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In vitro transcribed (IVT)-mRNA has been accepted as a promising therapeutic modality. Advances in facile and rapid production technologies make IVT-mRNA an appealing alternative to protein- or virus-based medicines.
Robust expression levels, lack of genotoxicity, and their manageable immunogenicity benefit its clinical applicability.
We postulated that innate immune responses of therapeutically relevant human cells can be tailored or abrogated by combinations of 5'-end and internal IVT-mRNA modifications.
Using primary human macrophages as targets, our data show the particular importance of uridine modifications for IVT-mRNA performance.
Among five nucleotide modification schemes tested, 5-methoxy-uridine outperformed other modifications up to 4-fold increased transgene expression, triggering moderate proinflammatory and non-detectable antiviral responses.
Macrophage responses against IVT-mRNAs exhibiting high immunogenicity (e.g., pseudouridine) could be minimized upon HPLC purification. Conversely, 5'-end modifications had only modest effects on mRNA expression and immune responses.
Our results revealed how the uptake of chemically modified IVT-mRNA impacts human macrophages, responding with distinct patterns of innate immune responses concomitant with increased transient transgene expression.
We anticipate our findings are instrumental to predictively address specific cell responses required for a wide range of therapeutic applications from eliciting controlled immunogenicity in mRNA vaccines to, e.g., completely abrogating cell activation in protein replacement therapies.
Monocytes and macrophages are key players in maintaining immune homeostasis. Identifying strategies to manipulate their functions via gene delivery is thus of great interest for immunological research and biomedical applications. We set out to establish conditions for mRNA transfection in hard-to-transfect primary human monocytes and monocyte-derived macrophages due to the great potential of gene expression from in vitro transcribed mRNA for modulating cell phenotypes. mRNA doses, nucleotide modifications, and different carriers were systematically explored in order to optimize high mRNA transfer rates while minimizing cell stress and immune activation. We selected three commercially available mRNA transfection reagents including liposome and polymer-based formulations, covering different application spectra. Our results demonstrate that liposomal reagents can particularly combine high gene transfer rates with only moderate immune cell activation. For the latter, use of specific nucleotide modifications proved essential. In addition to improving efficacy of gene transfer, our findings address discrete aspects of innate immune activation using cytokine and surface marker expression, as well as cell viability as key readouts to judge overall transfection efficiency. The impact of this study goes beyond optimizing transfection conditions for immune cells, by providing a framework for assessing new gene carrier systems for monocyte and macrophage, tailored to specific applications.
Monocytes and macrophages are key players in maintaining immune homeostasis. Identifying strategies to manipulate their functions via gene delivery is thus of great interest for immunological research and biomedical applications. We set out to establish conditions for mRNA transfection in hard-to-transfect primary human monocytes and monocyte-derived macrophages due to the great potential of gene expression from in vitro transcribed mRNA for modulating cell phenotypes. mRNA doses, nucleotide modifications, and different carriers were systematically explored in order to optimize high mRNA transfer rates while minimizing cell stress and immune activation. We selected three commercially available mRNA transfection reagents including liposome and polymer-based formulations, covering different application spectra. Our results demonstrate that liposomal reagents can particularly combine high gene transfer rates with only moderate immune cell activation. For the latter, use of specific nucleotide modifications proved essential. In addition to improving efficacy of gene transfer, our findings address discrete aspects of innate immune activation using cytokine and surface marker expression, as well as cell viability as key readouts to judge overall transfection efficiency. The impact of this study goes beyond optimizing transfection conditions for immune cells, by providing a framework for assessing new gene carrier systems for monocyte and macrophage, tailored to specific applications.
This work explores the use of different generative AI tools in the design of MOOC courses. Authors in this experience employed a variety of AI-based tools, including natural language processing tools (e.g. Chat-GPT), and multimedia content authoring tools (e.g. DALLE-2, Midjourney, Tome.ai) to assist in the course design process. The aim was to address the unique challenges of MOOC course design, which includes to create engaging and effective content, to design interactive learning activities, and to assess student learning outcomes. The authors identified positive results with the incorporation of AI-based tools, which significantly improved the quality and effectiveness of MOOC course design. The tools proved particularly effective in analyzing and categorizing course content, identifying key learning objectives, and designing interactive learning activities that engaged students and facilitated learning. Moreover, the use of AI-based tools, streamlined the course design process, significantly reducing the time required to design and prepare the courses. In conclusion, the integration of generative AI tools into the MOOC course design process holds great potential for improving the quality and efficiency of these courses. Researchers and course designers should consider the advantages of incorporating generative AI tools into their design process to enhance their course offerings and facilitate student learning outcomes while also reducing the time and effort required for course development.
Background Small-sided games have been suggested as a viable alternative to conventional endurance training to enhance endurance performance in youth soccer players. This has important implications for long-term athlete development because it suggests that players can increase aerobic endurance through activities that closely resemble their sport of choice. Data Sources The data sources utilised were Google Scholar, PubMed and Microsoft Academic. Study Eligibility Criteria Studies were eligible for inclusion if interventions were carried out in male soccer players (aged < 18years) and compared the effects of small-sided games and conventional endurance training on aerobic endurance performance. We defined small-sided games as modified [soccer] games played on reduced pitch areas, often using adapted rules and involving a smaller number of players than traditional games. We defined conventional endurance training as continuous running or extensive interval training consisting of work durations>3min. Study Appraisal and Synthesis Methods The inverse-variance random-effects model for meta-analyses was used because it allocates a proportionate weight to trials based on the size of their individual standard errors and facilitates analysis whilst accounting for heterogeneity across studies. Effect sizes were represented by the standardised mean difference and presented alongside 95% confidence intervals. Results Seven studies were included in this meta-analysis. Both modes of training were effective in increasing endurance performance. Within-mode effect sizes were both of moderate magnitude [small-sided games: 0.82 (95% confidence interval 0.05, 1.60), Z=2.07 (p=0.04); conventional endurance training: 0.89 (95% confidence interval 0.06, 1.72), Z=2.10 (p=0.04)]. There were only trivial differences [0.04 (95% confidence interval -0.36, 0.43), Z=0.18 (p=0.86)] between the effects on aerobic endurance performance of small-sided games and conventional endurance training. Subgroup analyses showed mostly trivial differences between the training methods across key programming variables such as set duration (>= or < 4 min) and recovery period between sets (>= or< 3min). Programmes that were longer than 8 weeks favoured small-sided games [effect size=0.45 (95% confidence interval -0.12, 1.02), Z=1.54 (p=0.12)], with the opposite being true for conventional endurance training [effect size=-0.33 (95% confidence interval -0.79, 0.14), Z=1.39 (p=0.16)]. Programmes with more than 4 sets per session favoured small-sided games [effect size=0.53 (95% confidence interval -0.52, 1.58), Z=0.98 (p=0.33)] with only a trivial difference between those with 4, or fewer, sets [effect size=-0.13 (95% confidence interval -0.52, 0.26), Z=0.65 (p=0.52)]. Conclusions Small-sided games are as effective as conventional endurance training for increasing aerobic endurance performance in male youth soccer players. This is important for practitioners as it means that small-sided games can allow both endurance and skills training to be carried out simultaneously, thus providing a more efficient training stimulus. Small-sided games offer the same benefits as conventional endurance training with two sessions per week, with4 sets of 4 min of activity, interspersed with recovery periods of 3min, recommended in this population.
Growth and maturation affect long term physical performance, making the appraisal of athletic ability difficult. We sought to longitudinally track youth soccer players to assess the developmental trajectory of athletic performance over a 6-year period in an English Premier League academy. Age-specific z-scores were calculated for sprint and jump performance from a sample of male youth soccer players (n = 140). A case study approach was used to analyse the longitudinal curves of the six players with the longest tenure. The trajectories of the sprint times of players 1 and 3 were characterised by a marked difference in respective performance levels up until peak height velocity (PHV) when player 1 achieved a substantial increase in sprint speed and player 3 experienced a large decrease. Player 5 was consistently a better performer than player 2 until PHV when the sprint and jump performance of the former markedly decreased and he was overtaken by the latter. Fluctuations in players' physical performance can occur quickly and in drastic fashion. Coaches must be aware that suppressed, or inflated, performance could be temporary and selection and deselection decisions should not be made based on information gathered over a short time period.
Background
Jump training (JT) can be used to enhance the ability of skeletal muscle to exert maximal force in as short a time as possible. Despite its usefulness as a method of performance enhancement in athletes, only a small number of studies have investigated its effects on muscle power in older adults.
Objectives
The aims of this meta-analysis were to measure the effect of JT on muscular power in older adults (≥ 50 years), and to establish appropriate programming guidelines for this population.
Data Sources
The data sources utilised were Google Scholar, PubMed, and Microsoft Academic.
Study Eligibility Criteria
Studies were eligible for inclusion if they comprised JT interventions in healthy adults (≥ 50 years) who were free of any medical condition that could impair movement.
Study Appraisal and Synthesis Methods
The inverse variance random-effects model for meta-analyses was used because it allocates a proportionate weight to trials based on the size of their individual standard errors and facilitates analysis while accounting for heterogeneity across studies. Effect sizes (ESs), calculated from a measure of muscular power, were represented by the standardised mean difference and were presented alongside 95% confidence intervals (CIs).
Results
Thirteen training groups across nine studies were included in this meta-analysis. The magnitude of the main effect was ‘moderate’ (0.66, 95% CI 0.33, 0.98). ESs were larger in non-obese participants (body mass index [BMI] < 30 vs. ≥ 30 kg/m2; 1.03 [95% CI 0.34, 1.73] vs. 0.53 [95% CI − 0.03, 1.09]). Among the studies included in this review, just one reported an acute injury, which did not result in the participant ceasing their involvement. JT was more effective in programmes with more than one exercise (range 1–4 exercises; ES = 0.74 [95% CI − 0.49, 1.96] vs. 0.53 [95% CI 0.29, 0.78]), more than two sets per exercise (range 1–4 sets; ES = 0.91 [95% CI 0.04, 1.77] vs. 0.68 [95% CI 0.15, 1.21]), more than three jumps per set (range 1–14 jumps; ES = 1.02 [95% CI 0.16, 1.87] vs. 0.53 [95% CI − 0.03, 1.09]) and more than 25 jumps per session (range 6–200 jumps; ES = 0.88 [95% CI 0.05, 1.70] vs. 0.49 [95% CI 0.14, 0.83]).
Conclusions
JT is safe and effective in older adults. Practitioners should construct varied JT programmes that include more than one exercise and comprise more than two sets per exercise, more than three jumps per set, and 60 s of recovery between sets. An upper limit of three sets per exercise and ten jumps per set is recommended. Up to three training sessions per week can be performed.
Purpose
This randomised controlled trial examined the effect of an 8-week volume-equated programme of Nordic hamstring exercise (NHE) training, executed at frequencies of 1- or 2-days per week, on fitness (10 m and 40 m sprint, '505' change of direction [COD] and standing long jump [SLJ]) in male youth soccer players (mean age: 16.4 0.81 years).
Method
Players were divided into an experimental group (n = 16) which was further subdivided into 1-day (n = 8) and 2-day (n = 8) per week training groups and a control group (n = 8).
Results
There were significant group-by-time interactions for 10-m sprint (p<0.001, eta(2) = 0.120, d = 2.05 [0.57 to 3.53]), 40-m sprint (p = 0.001, eta(2) = 0.041, d = 1.09 [-0.23 to 2.4]) and COD (p = 0.002, eta(2) = 0.063, d = 1.25 [-0.09 to 2.59). The experimental group demonstrated a 'very large' effect size (d = 3.02 [1.5 to 4.54]) in 10-m sprint, and 'large' effect sizes in 40-m sprint (d = 1.94 [0.98 to 2.90]) and COD (d = 1.84 [0.85 to 2.83). The control group showed no significant changes. There were no significant differences between the 1-day and 2-day training groups. In three of the four tests (40 m, COD, SLJ) the 2-day group demonstrated larger effect sizes. Ratings of perceived exertion (RPE) were significantly lower in the 2-day group (p<0.001, 3.46 [1.83 to 5.04).
Conclusion
The NHE increases fitness in youth soccer players and there may be advantages to spreading training over two days instead of one.
River restoration is a main emphasis of river management in European countries. Cross-national comparisons of its implementation are still rare in scientific literature. Based on French and German national censuses, this study compares river restoration practices and monitoring by analysing 102 French and 270 German projects. This comparison aims to draw a spatial and temporal framework of restoration practices in both countries to identify potential drivers of cross-national similarities and differences. The results underline four major trends: (1) a lag of almost 15 years in river restoration implementation between France and Germany, with a consequently higher share of projects in Germany than in France, (2) substantial similarities in restored reach characteristics, short reach length, small rivers, and in "agricultural" areas, (3) good correspondences between stressors identified and restoration measures implemented. Morphological alterations were the most important highlighted stressors. River morphology enhancement, especially instream enhancements, were the most frequently implemented restoration measures. Some differences exist in specific restoration practices, as river continuity restoration were most frequently implemented in French projects, while large wood introduction or channel re-braiding were most frequently implemented in German projects, and (4) some quantitative and qualitative differences in monitoring practices and a significant lack of project monitoring, especially in Germany compared to France. These similarities and differences between Germany and France in restoration application and monitoring possibly result from a complex set of drivers that might be difficult to untangle (e.g., environmental, technical, political, cultural).
One of the rules-of-thumb of colloid and surface physics is that most surfaces are charged when in contact with a solvent, usually water. This is the case, for instance, in charge-stabilized colloidal suspensions, where the surface of the colloidal particles are charged (usually with a charge of hundreds to thousands of e, the elementary charge), monolayers of ionic surfactants sitting at an air-water interface (where the water-loving head groups become charged by releasing counterions), or bilayers containing charged phospholipids (as cell membranes). In this work, we look at some model-systems that, although being a simplified version of reality, are expected to capture some of the physical properties of real charged systems (colloids and electrolytes). We initially study the simple double layer, composed by a charged wall in the presence of its counterions. The charges at the wall are smeared out and the dielectric constant is the same everywhere. The Poisson-Boltzmann (PB) approach gives asymptotically exact counterion density profiles around charged objects in the weak-coupling limit of systems with low-valent counterions, surfaces with low charge density and high temperature (or small Bjerrum length). Using Monte Carlo simulations, we obtain the profiles around the charged wall and compare it with both Poisson-Boltzmann (in the low coupling limit) and the novel strong coupling (SC) theory in the opposite limit of high couplings. In the latter limit, the simulations show that the SC leads in fact to asymptotically correct density profiles. We also compare the Monte Carlo data with previously calculated corrections to the Poisson-Boltzmann theory. We also discuss in detail the methods used to perform the computer simulations. After studying the simple double layer in detail, we introduce a dielectric jump at the charged wall and investigate its effect on the counterion density distribution. As we will show, the Poisson-Boltzmann description of the double layer remains a good approximation at low coupling values, while the strong coupling theory is shown to lead to the correct density profiles close to the wall (and at all couplings). For very large couplings, only systems where the difference between the dielectric constants of the wall and of the solvent is small are shown to be well described by SC. Another experimentally relevant modification to the simple double layer is to make the charges at the plane discrete. The counterions are still assumed to be point-like, but we constraint the distance of approach between ions in the plane and counterions to a minimum distance D. The ratio between D and the distance between neighboring ions in the plane is, as we will see, one of the important quantities in determining the influence of the discrete nature of the charges at the wall over the density profiles. Another parameter that plays an important role, as in the previous case, is the coupling as we will demonstrate, systems with higher coupling are more subject to discretization effects than systems with low coupling parameter. After studying the isolated double layer, we look at the interaction between two double layers. The system is composed by two equally charged walls at distance d, with the counterions confined between them. The charge at the walls is smeared out and the dielectric constant is the same everywhere. Using Monte-Carlo simulations we obtain the inter-plate pressure in the global parameter space, and the pressure is shown to be negative (attraction) at certain conditions. The simulations also show that the equilibrium plate separation (where the pressure changes from attractive to repulsive) exhibits a novel unbinding transition. We compare the Monte Carlo results with the strong-coupling theory, which is shown to describe well the bound states of systems with moderate and high couplings. The regime where the two walls are very close to each other is also shown to be well described by the SC theory. Finally, Using a field-theoretic approach, we derive the exact low-density ("virial") expansion of a binary mixture of positively and negatively charged hard spheres (two-component hard-core plasma, TCPHC). The free energy obtained is valid for systems where the diameters d_+ and d_- and the charge valences q_+ and q_- of positive and negative ions are unconstrained, i.e., the same expression can be used to treat dilute salt solutions (where typically d_+ ~ d_- and q_+ ~ q_-) as well as colloidal suspensions (where the difference in size and valence between macroions and counterions can be very large). We also discuss some applications of our results.
The B fields in OB stars (BOB) survey is an ESO large programme collecting spectropolarimetric observations for a large number of early-type stars in order to study the occurrence rate, properties, and ultimately the origin of magnetic fields in massive stars. As of July 2014, a total of 98 objects were observed over 20 nights with FORS2 and HARPSpol. Our preliminary results indicate that the fraction of magnetic OB stars with an organised, detectable field is low. This conclusion, now independently reached by two different surveys, has profound implications for any theoretical model attempting to explain the field formation in these objects. We discuss in this contribution some important issues addressed by our observations (e.g., the lower bound of the field strength) and the discovery of some remarkable objects.
In this article we analyze several examples of the syntactic structure ansí un...(Eng. such a...) apparently calqued from the German expression so ein... that can be found in different Judeo-Spanish texts since the second half of 19th Century. Although the eldest examples appeared in Judeo-Spanish translations of German novels, published in Vienna – what suggests that they could be mere cases derived from a kind of translation too attached to the original –, we can also find more examples in Sephardic texts produced outside the German speaking area (Bosnia, Bulgaria, etc.), not being necessarily translations of a German original. Dealing with all these cases, we will try to trace (and explain) the spread of the ansí un syntactic structure in modern Judeo-Spanish prose.
Elucidating the molecular basis of enhanced growth in the Arabidopsis thaliana accession Bur-0
(2021)
The life cycle of flowering plants is a dynamic process that involves successful passing through several developmental phases and tremendous progress has been made to reveal cellular and molecular regulatory mechanisms underlying these phases, morphogenesis, and growth. Although several key regulators of plant growth or developmental phase transitions have been identified in Arabidopsis, little is known about factors that become active during embryogenesis, seed development and also during further postembryonic growth. Much less is known about accession-specific factors that determine plant architecture and organ size. Bur-0 has been reported as a natural Arabidopsis thaliana accession with exceptionally big seeds and a large rosette; its phenotype makes it an interesting candidate to study growth and developmental aspects in plants, however, the molecular basis underlying this big phenotype remains to be elucidated. Thus, the general aim of this PhD project was to investigate and unravel the molecular mechanisms underlying the big phenotype in Bur-0.
Several natural Arabidopsis accessions and late flowering mutant lines were analysed in this study, including Bur-0. Phenotypes were characterized by determining rosette size, seed size, flowering time, SAM size and growth in different photoperiods, during embryonic and postembryonic development. Our results demonstrate that Bur-0 stands out as an interesting accession with simultaneously larger rosettes, larger SAM, later flowering phenotype and larger seeds, but also larger embryos. Interestingly, inter-accession crosses (F1) resulted in bigger seeds than the parental self-crossed accessions, particularly when Bur-0 was used as the female parental genotype, suggesting parental effects on seed size that might be maternally controlled. Furthermore, developmental stage-based comparisons revealed that the large embryo size of Bur-0 is achieved during late embryogenesis and the large rosette size is achieved during late postembryonic growth. Interestingly, developmental phase progression analyses revealed that from germination onwards, the length of developmental phases during postembryonic growth is delayed in Bur-0, suggesting that in general, the mechanisms that regulate developmental phase progression are shared across developmental phases.
On the other hand, a detailed physiological characterization in different tissues at different developmental stages revealed accession-specific physiological and metabolic traits that underlie accession-specific phenotypes and in particular, more carbon resources during embryonic and postembryonic development were found in Bur-0, suggesting an important role of carbohydrates in determination of the bigger Bur-0 phenotype. Additionally, differences in the cellular organization, nuclei DNA content, as well as ploidy level were analyzed in different tissues/cell types and we found that the large organ size in Bur-0 can be mainly attributed to its larger cells and also to higher cell proliferation in the SAM, but not to a different ploidy level.
Furthermore, RNA-seq analysis of embryos at torpedo and mature stage, as well as SAMs at vegetative and floral transition stage from Bur-0 and Col-0 was conducted to identify accession-specific genetic determinants of plant phenotypes, shared across tissues and developmental stages during embryonic and postembryonic growth. Potential candidate genes were identified and further validation of transcriptome data by expression analyses of candidate genes as well as known key regulators of organ size and growth during embryonic and postembryonic development confirmed that the high confidence transcriptome datasets generated in this study are reliable for elucidation of molecular mechanisms regulating plant growth and accession-specific phenotypes in Arabidopsis.
Taken together, this PhD project contributes to the plant development research field providing a detailed analysis of mechanisms underlying plant growth and development at different levels of biological organization, focusing on Arabidopsis accessions with remarkable phenotypical differences. For this, the natural accession Bur-0 was an ideal outlier candidate and different mechanisms at organ and tissue level, cell level, metabolism, transcript and gene expression level were identified, providing a better understanding of different factors involved in plant growth regulation and mechanisms underlying different growth patterns in nature.
In flowering plants, sugars act as carbon sources providing energy for developing embryos and seeds. Although most studies focus on carbon metabolism in whole seeds, knowledge about how particular sugars contribute to the developmental transitions during embryogenesis is scarce. To develop a quantitative understanding of how carbon composition changes during embryo development, and to determine how sugar status contributes to final seed or embryo size, we performed metabolic profiling of hand-dissected embryos at late torpedo and mature stages, and dormant seeds, in two Arabidopsis thaliana accessions with medium [Columbia-0 (Col-0)] and large [Burren-0 (Bur-0)] seed sizes, respectively. Our results show that, in both accessions, metabolite profiles of embryos largely differ from those of dormant seeds. We found that developmental transitions from torpedo to mature embryos, and further to dormant seeds, are associated with major metabolic switches in carbon reserve accumulation. While glucose, sucrose, and starch predominantly accumulated during seed dormancy, fructose levels were strongly elevated in mature embryos. Interestingly, Bur-0 seeds contain larger mature embryos than Col-0 seeds. Fructose and starch were accumulated to significantly higher levels in mature Bur-0 than Col-0 embryos, suggesting that they contribute to the enlarged mature Bur-0 embryos. Furthermore, we found that Bur-0 embryos accumulated a higher level of sucrose compared to hexose sugars and that changes in sucrose metabolism are mediated by sucrose synthase (SUS), with SUS genes acting non-redundantly, and in a tissue-specific manner to utilize sucrose during late embryogenesis.
The coupling of the internal mechanisms of cell polarization to cell shape deformations and subsequent cell crawling poses many interdisciplinary scientific challenges. Several mathematical approaches have been proposed to model the coupling of both processes, where one of the most successful methods relies on a phase field that encodes the morphology of the cell, together with the integration of partial differential equations that account for the polarization mechanism inside the cell domain as defined by the phase field. This approach has been previously employed to model the motion of single cells of the social amoeba Dictyostelium discoideum, a widely used model organism to study actin-driven motility and chemotaxis of eukaryotic cells. Besides single cell motility, Dictyostelium discoideum is also well-known for its collective behavior. Here, we extend the previously introduced model for single cell motility to describe the collective motion of large populations of interacting amoebae by including repulsive interactions between the cells. We performed numerical simulations of this model, first characterizing the motion of single cells in terms of their polarity and velocity vectors. We then systematically studied the collisions between two cells that provided the basic interaction scenarios also observed in larger ensembles of interacting amoebae. Finally, the relevance of the cell density was analyzed, revealing a systematic decrease of the motility with density, associated with the formation of transient cell clusters that emerge in this system even though our model does not include any attractive interactions between cells. This model is a prototypical active matter system for the investigation of the emergent collective dynamics of deformable, self-driven cells with a highly complex, nonlinear coupling of cell shape deformations, self-propulsion and repulsive cell-cell interactions. Understanding these self-organization processes of cells like their autonomous aggregation is of high relevance as collective amoeboid motility is part of wound healing, embryonic morphogenesis or pathological processes like the spreading of metastatic cancer cells.
We analyze the role of megathrust geometry on slip estimation using the 1960 Chile earthquake (M-W = 9.5) as an example. A variable slip distribution for this earthquake has been derived by Barrientos and Ward (1990) applying an elastic dislocation model with a planar fault geometry. Their model shows slip patches at 80-110 km depth, isolated from the seismogenic zone, interpreted as aseismic slip. We invert the same geodetic data set using a finite element model (FEM) with precise geometry derived from geophysical data. Isoparametric FEM is implemented to constrain the slip distribution of curve-shaped elements. Slip resolved by our precise geometry model is limited to the shallow region of the plate interface suggesting that the deep patches of moment were most likely an artifact of the planar geometry. Our study emphasizes the importance of fault geometry on slip estimation of large earthquakes.
We use Global Positioning System (GPS) velocities and kinematic Finite Element models (FE-models) to infer the state of locking between the converging Nazca and South America plates in South-Central Chile (36 degrees S -46 degrees S) and to evaluate its spatial and temporal variability. GPS velocities provide information on earthquake-cycle deformation over the last decade in areas affected by the megathrust events of 1960 (M-w = 9.5) and 2010 (M-w = 8.8). Our data confirm that a change in surface velocity patterns of these two seismotectonic segments can be related to their different stages in the seismic cycle: Accordingly, the northern (2010) segment was in a final stage of interseismic loading whereas the southern (1960) segment is still in a postseismic stage and undergoes a prolonged viscoelastic mantle relaxation. After correcting the signals for mantle relaxation, the residual GPS velocity pattern suggests that the plate interface accumulates slip deficit in a spatially and presumably temporally variable way towards the next great event. Though some similarity exist between locking and 1960 coseismic slip, extrapolating the current, decadal scale slip deficit accumulation towards the similar to 300-yr recurrence times of giant events here does neither yield the slip distribution nor the moment magnitude of the 1960 earthquake. This suggests that either the locking pattern is evolving in time (to reconcile a slip deficit distribution similar to the 1960 earthquake) or that some asperities are not persistent over multiple events. The accumulated moment deficit since 1960 suggests that highly locked patches in the 1960 segment are already capable of producing a M similar to 8 event if triggered to fail by stress transfer from the 2010 event.
The Maule earthquake of 27th February 2010 (M-w = 8.8) affected similar to 500 km of the Nazca-South America plate boundary in south-central Chile producing spectacular crustal deformation. Here, we present a detailed estimate of static coseismic surface offsets as measured by survey and continuous GPS, both in near- and far-field regions. Earthquake slip along the megathrust has been inferred from a Joint inversion of our new data together with published GPS, InSAR, and land-level changes data using Green's functions generated by a spherical finite-element model with realistic subduction zone geometry. The combination of the data sets provided a good resolution, indicating that most of the slip was well resolved. Coseismic slip was concentrated north of the epicenter with up to 16 m of slip, whereas to the south it reached over 10 m within two minor patches. A comparison of coseismic slip with the slip deficit accumulated since the last great earthquake in 1835 suggests that the 2010 event closed a mature seismic gap. Slip deficit distribution shows an apparent local overshoot that highlight cycle-to-cycle variability, which has to be taken into account when anticipating future events from interseismic observations. Rupture propagation was obviously not affected by bathymetric features of the incoming plate. Instead, splay faults in the upper plate seem to have limited rupture propagation in the updip and along-strike directions. Additionally, we found that along-strike gradients in slip are spatially correlated with geometrical inflections of the megathrust. Our study suggests that persistent tectonic features may control strain accumulation and release along subduction megathrusts.
In June 2019, more than a hundred plant researchers met in Cologne, Germany, for the 6th European Workshop on Plant Chromatin (EWPC). This conference brought together a highly dynamic community of researchers with the common aim to understand how chromatin organization controls gene expression, development, and plant responses to the environment. New evidence showing how epigenetic states are set, perpetuated, and inherited were presented, and novel data related to the three-dimensional organization of chromatin within the nucleus were discussed. At the level of the nucleosome, its composition by different histone variants and their specialized histone deposition complexes were addressed as well as the mechanisms involved in histone post-translational modifications and their role in gene expression. The keynote lecture on plant DNA methylation by Julie Law (SALK Institute) and the tribute session to Lars Hennig, honoring the memory of one of the founders of the EWPC who contributed to promote the plant chromatin and epigenetic field in Europe, added a very special note to this gathering. In this perspective article we summarize some of the most outstanding data and advances on plant chromatin research presented at this workshop.
In June 2019, more than a hundred plant researchers met in Cologne, Germany, for the 6th European Workshop on Plant Chromatin (EWPC). This conference brought together a highly dynamic community of researchers with the common aim to understand how chromatin organization controls gene expression, development, and plant responses to the environment. New evidence showing how epigenetic states are set, perpetuated, and inherited were presented, and novel data related to the three-dimensional organization of chromatin within the nucleus were discussed. At the level of the nucleosome, its composition by different histone variants and their specialized histone deposition complexes were addressed as well as the mechanisms involved in histone post-translational modifications and their role in gene expression. The keynote lecture on plant DNA methylation by Julie Law (SALK Institute) and the tribute session to Lars Hennig, honoring the memory of one of the founders of the EWPC who contributed to promote the plant chromatin and epigenetic field in Europe, added a very special note to this gathering. In this perspective article we summarize some of the most outstanding data and advances on plant chromatin research presented at this workshop.
We present K-s-band light curves for 299 Cepheids in the Small Magellanic Cloud (SMC) of which 288 are new discoveries that we have identified using multi-epoch near-infrared photometry obtained by the VISTA survey of the Magellanic Clouds system (VMC). The new Cepheids have periods in the range from 0.34 to 9.1 d and cover the magnitude interval 12.9 <= currency sign < K-s > <= currency sign 17.6 mag. Our method was developed using variable stars previously identified by the optical microlensing survey OGLE. We focus on searching new Cepheids in external regions of the SMC for which complete VMC K-s-band observations are available and no comprehensive identification of different types of variable stars from other surveys exists yet.
The Pathological Narcissism Inventory (PNI) is a multidimensional measure for assessing grandiose and vulnerable features in narcissistic pathology. The aim of the present research was to construct and validate a German translation of the PNI and to provide further information on the PNI's nomological net. Findings from a first study confirm the psychometric soundness of the PNI and replicate its seven-factor first-order structure. A second-order structure was also supported but with several equivalent models. A second study investigating associations with a broad range of measures (DSM Axis I and II constructs, emotions, personality traits, interpersonal and dysfunctional behaviors, and well-being) supported the concurrent validity of the PNI. Discriminant validity with the Narcissistic Personality Inventory was also shown. Finally, in a third study an extension in a clinical inpatient sample provided further evidence that the PNI is a useful tool to assess the more pathological end of narcissism.
Current climate warming is affecting arctic regions at a faster rate than the rest of the world. This has profound effects on permafrost that underlies most of the arctic land area. Permafrost thawing can lead to the liberation of considerable amounts of greenhouse gases as well as to significant changes in the geomorphology, hydrology, and ecology of the corresponding landscapes, which may in turn act as a positive feedback to the climate system. Vast areas of the east Siberian lowlands, which are underlain by permafrost of the Yedoma-type Ice Complex, are particularly sensitive to climate warming because of the high ice content of these permafrost deposits. Thermokarst and thermal erosion are two major types of permafrost degradation in periglacial landscapes. The associated landforms are prominent indicators of climate-induced environmental variations on the regional scale. Thermokarst lakes and basins (alasses) as well as thermo-erosional valleys are widely distributed in the coastal lowlands adjacent to the Laptev Sea. This thesis investigates the spatial distribution and morphometric properties of these degradational features to reconstruct their evolutionary conditions during the Holocene and to deduce information on the potential impact of future permafrost degradation under the projected climate warming. The methodological approach is a combination of remote sensing, geoinformation, and field investigations, which integrates analyses on local to regional spatial scales. Thermokarst and thermal erosion have affected the study region to a great extent. In the Ice Complex area of the Lena River Delta, thermokarst basins cover a much larger area than do present thermokarst lakes on Yedoma uplands (20.0 and 2.2 %, respectively), which indicates that the conditions for large-area thermokarst development were more suitable in the past. This is supported by the reconstruction of the development of an individual alas in the Lena River Delta, which reveals a prolonged phase of high thermokarst activity since the Pleistocene/Holocene transition that created a large and deep basin. After the drainage of the primary thermokarst lake during the mid-Holocene, permafrost aggradation and degradation have occurred in parallel and in shorter alternating stages within the alas, resulting in a complex thermokarst landscape. Though more dynamic than during the first phase, late Holocene thermokarst activity in the alas was not capable of degrading large portions of Pleistocene Ice Complex deposits and substantially altering the Yedoma relief. Further thermokarst development in existing alasses is restricted to thin layers of Holocene ice-rich alas sediments, because the Ice Complex deposits underneath the large primary thermokarst lakes have thawed completely and the underlying deposits are ice-poor fluvial sands. Thermokarst processes on undisturbed Yedoma uplands have the highest impact on the alteration of Ice Complex deposits, but will be limited to smaller areal extents in the future because of the reduced availability of large undisturbed upland surfaces with poor drainage. On Kurungnakh Island in the central Lena River Delta, the area of Yedoma uplands available for future thermokarst development amounts to only 33.7 %. The increasing proximity of newly developing thermokarst lakes on Yedoma uplands to existing degradational features and other topographic lows decreases the possibility for thermokarst lakes to reach large sizes before drainage occurs. Drainage of thermokarst lakes due to thermal erosion is common in the study region, but thermo-erosional valleys also provide water to thermokarst lakes and alasses. Besides these direct hydrological interactions between thermokarst and thermal erosion on the local scale, an interdependence between both processes exists on the regional scale. A regional analysis of extensive networks of thermo-erosional valleys in three lowland regions of the Laptev Sea with a total study area of 5,800 km² found that these features are more common in areas with higher slopes and relief gradients, whereas thermokarst development is more pronounced in flat lowlands with lower relief gradients. The combined results of this thesis highlight the need for comprehensive analyses of both, thermokarst and thermal erosion, in order to assess past and future impacts and feedbacks of the degradation of ice-rich permafrost on hydrology and climate of a certain region.
Thermal erosion is a major mechanism of permafrost degradation, resulting in characteristic landforms. We inventory thermo-erosional valleys in ice-rich coastal lowlands adjacent to the Siberian Laptev Sea based on remote sensing, Geographic Information System (GIS), and field investigations for a first regional assessment of their spatial distribution and characteristics. Three study areas with similar geological (Yedoma Ice Complex) but diverse geomorphological conditions vary in valley areal extent, incision depth, and branching geometry. The most extensive valley networks are incised deeply (up to 35 m) into the broad inclined lowland around Mamontov Klyk. The flat, low-lying plain forming the Buor Khaya Peninsula is more degraded by thermokarst and characterized by long valleys of lower depth with short tributaries. Small, isolated Yedoma Ice Complex remnants in the Lena River Delta predominantly exhibit shorter but deep valleys. Based on these hydrographical network and topography assessments, we discuss geomorphological and hydrological connections to erosion processes. Relative catchment size along with regional slope interact with other Holocene relief-forming processes such as thermokarst and neotectonics. Our findings suggest that thermo-erosional valleys are prominent, hitherto overlooked permafrost degradation landforms that add to impacts on biogeochemical cycling, sediment transport, and hydrology in the degrading Siberian Yedoma Ice Complex.
Metabolomic networks in plants : transitions from pattern recognition to biological interpretation
(2006)
Nowadays techniques for non-targeted metabolite profiling allow for the generation of huge amounts of relevant data essential for the construction of dynamic metabolomic networks. Thus, metabolomics, besides transcriptomics or proteomics, provides a major tool for the characterization of postgenomic processes. In this work, we introduce comparative correlation analysis as a complementary approach to characterize the physiological states of various organs of diverse plant species with focus on specific participation of metabolites in different reaction networks. The correlations observed are induced by diminutive fluctuations in environmental conditions, which propagate through the system and induce specific patterns depending on the genomic background. In order to examine this hypothesis, numeric examples of such fluctuations are computed and compared with experimentally obtained metabolite data.
Contactless pressure monitoring based on Forster resonance energy transfer between donor/acceptor pairs immobilized within elastomers is demonstrated. The donor/acceptor energy transfer is employed by dispersing terbium(III) tris[(2-hydroxybenzoyl)-2-aminoethyl] amine complex (LLC, donor) and CdSe/ZnS quantum dots (QD655, acceptor) in styrene-ethylene/buthylene-styrene (SEBS) and poly(dimethylsiloxane) (PDMS). The continuous monitoring of QD luminescence showed a reversible intensity change as the pressure signal is alternated between two stable states indicating a pressure sensitivity of 6350 cps kPa(-1). Time-resolved measurements show the pressure impact on the FRET signal due to an increase of decay time (270 ms up to 420 ms) for the donor signal and parallel drop of decay time (170 mu s to 155 mu s) for the acceptor signal as the net pressure applied. The LLC/QD655 sensors enable a contactless readout as well as space resolved monitoring to enable miniaturization towards smaller integrated stretchable opto-electronics. Elastic FRET sensors can potentially lead to developing profitable analysis systems capable to outdo conventional wired electronic systems (inductive, capacitive, ultrasonic and photoelectric sensors) especially for point-of-care diagnostics, biological monitoring required for wearable electronics.
Hemolysis, the rupturing of red blood cells, can result from numerous medical conditions (in vivo) or occur after collecting blood specimen or extracting plasma and serum out of whole blood (in vitro). In clinical laboratory practice, hemolysis can be a serious problem due to its potential to bias detection of various analytes or biomarkers. Here we present the first "mix-and-measure' method to assess the degree of hemolysis in biosamples using luminescence spectroscopy. Luminescent terbium complexes (LTC) were studied in the presence of free hemoglobin (Hb) as indicators for hemolysis in TRIS-buffer, and in fresh human plasma with absorption, excitation and emission measurements. Our findings indicate dynamic as well as resonance energy transfer (FRET) between the LTC and the porphyrin ligand of hemoglobin. This transfer leads to a decrease in luminescence intensity and decay time even at nanomolar hemoglobin concentrations either in buffer or plasma. Luminescent terbium complexes are very sensitive to free hemoglobin in buffer and blood plasma. Due to the instant change in luminescence properties of the LTC in presence of Hb it is possible to access the concentration of hemoglobin via spectroscopic methods without incubation time or further treatment of the sample thus enabling a rapid and sensitive detection of hemolysis in clinical diagnostics.
Hemolysis, the rupturing of red blood cells, can result from numerous medical conditions (in vivo) or occur after collecting blood specimen or extracting plasma and serum out of whole blood (in vitro). In clinical laboratory practice, hemolysis can be a serious problem due to its potential to bias detection of various analytes or biomarkers. Here we present the first ‘‘mix-and-measure’’ method to assess the degree of hemolysis in biosamples using luminescence spectroscopy. Luminescent terbium complexes (LTC) were studied in the presence of free hemoglobin (Hb) as indicators for hemolysis in TRIS-buffer, and in fresh human plasma with absorption, excitation and emission measurements. Our findings indicate dynamic as well as resonance energy transfer (FRET) between the LTC and the porphyrin ligand of hemoglobin. This transfer leads to a decrease in luminescence intensity and decay time even at nanomolar hemoglobin concentrations either in buffer or plasma. Luminescent terbium complexes are very sensitive to free hemoglobin in buffer and blood plasma. Due to the instant change in luminescence properties of the LTC in presence of Hb it is possible to access the concentration of hemoglobin via spectroscopic methods without incubation time or further treatment of the sample thus enabling a rapid and sensitive detection of hemolysis in clinical diagnostics.
Forster resonance energy transfer (FRET) from luminescent terbium complexes (LTC) as donors to semiconductor quantum dots (QDs) as acceptors allows extraordinary large FRET efficiencies due to the long Forster distances afforded. Moreover, time-gated detection permits an efficient suppression of autofluorescent background leading to sub-picomolar detection limits even within multiplexed detection formats. These characteristics make FRET-systems with LTC and QDs excellent candidates for clinical diagnostics. So far, such proofs of principle for highly sensitive multiplexed biosensing have only been performed under optimized buffer conditions and interactions between real-life clinical media such as human serum or plasma and LTC-QD-FRET-systems have not yet been taken into account. Here we present an extensive spectroscopic analysis of absorption, excitation and emission spectra along with the luminescence decay times of both the single components as well as the assembled FRET-systems in TRIS-buffer, TRIS-buffer with 2% bovine serum albumin, and fresh human plasma. Moreover, we evaluated homogeneous LTC-QD FRET assays in QD conjugates assembled with either the well-known, specific biotin-streptavidin biological interaction or, alternatively, the metal-affinity coordination of histidine to zinc. In the case of conjugates assembled with biotin-streptavidin no significant interference with the optical and binding properties occurs whereas the histidine-zinc system appears to be affected by human plasma.
LiCSBAS
(2020)
For the past five years, the 2-satellite Sentinel-1 constellation has provided abundant and useful Synthetic Aperture Radar (SAR) data, which have the potential to reveal global ground surface deformation at high spatial and temporal resolutions. However, for most users, fully exploiting the large amount of associated data is challenging, especially over wide areas. To help address this challenge, we have developed LiCSBAS, an open-source SAR interferometry (InSAR) time series analysis package that integrates with the automated Sentinel-1 InSAR processor (LiCSAR). LiCSBAS utilizes freely available LiCSAR products, and users can save processing time and disk space while obtaining the results of InSAR time series analysis. In the LiCSBAS processing scheme, interferograms with many unwrapping errors are automatically identified by loop closure and removed. Reliable time series and velocities are derived with the aid of masking using several noise indices. The easy implementation of atmospheric corrections to reduce noise is achieved with the Generic Atmospheric Correction Online Service for InSAR (GACOS). Using case studies in southern Tohoku and the Echigo Plain, Japan, we demonstrate that LiCSBAS applied to LiCSAR products can detect both large-scale (>100 km) and localized (~km) relative displacements with an accuracy of <1 cm/epoch and ~2 mm/yr. We detect displacements with different temporal characteristics, including linear, periodic, and episodic, in Niigata, Ojiya, and Sanjo City, respectively. LiCSBAS and LiCSAR products facilitate greater exploitation of globally available and abundant SAR datasets and enhance their applications for scientific research and societal benefit.
LiCSBAS
(2020)
For the past five years, the 2-satellite Sentinel-1 constellation has provided abundant and useful Synthetic Aperture Radar (SAR) data, which have the potential to reveal global ground surface deformation at high spatial and temporal resolutions. However, for most users, fully exploiting the large amount of associated data is challenging, especially over wide areas. To help address this challenge, we have developed LiCSBAS, an open-source SAR interferometry (InSAR) time series analysis package that integrates with the automated Sentinel-1 InSAR processor (LiCSAR). LiCSBAS utilizes freely available LiCSAR products, and users can save processing time and disk space while obtaining the results of InSAR time series analysis. In the LiCSBAS processing scheme, interferograms with many unwrapping errors are automatically identified by loop closure and removed. Reliable time series and velocities are derived with the aid of masking using several noise indices. The easy implementation of atmospheric corrections to reduce noise is achieved with the Generic Atmospheric Correction Online Service for InSAR (GACOS). Using case studies in southern Tohoku and the Echigo Plain, Japan, we demonstrate that LiCSBAS applied to LiCSAR products can detect both large-scale (>100 km) and localized (similar to km) relative displacements with an accuracy of <1 cm/epoch and similar to 2 mm/yr. We detect displacements with different temporal characteristics, including linear, periodic, and episodic, in Niigata, Ojiya, and Sanjo City, respectively. LiCSBAS and LiCSAR products facilitate greater exploitation of globally available and abundant SAR datasets and enhance their applications for scientific research and societal benefit.
Import and decomposition of dissolved organic carbon in pre-dams of drinking water reservoirs
(2017)
Dissolved organic carbon (DOC) depicts a key component in the aquatic carbon cycle as well as for drinking water production from surface waters. DOC concentrations increased in water bodies of the northern hemisphere in the last decades, posing ecological consequences and water quality problems. Within the pelagic zone of lakes and reservoirs, the DOC pool is greatly affected by biological activity as DOC is simultaneously produced and decomposed. This thesis aimed for a conceptual understanding of organic carbon cycling and DOC quality changes under differing hydrological and trophic conditions. Further, the occurrence of aquatic priming was investigated, which has been proposed as a potential process facilitating the microbial decomposition of stable allochthonous DOC within the pelagic zone.
To study organic carbon cycling under different hydrological conditions, quantitative and qualitative investigations were carried out in three pre-dams of drinking water reservoirs exhibiting a gradient in DOC concentrations and trophic states. All pre-dams were mainly autotrophic in their epilimnia. Discharge and temperature were identified as the key factors regulating net production and respiration in the upper water layers of the pre-dams. Considerable high autochthonous production was observed during the summer season under higher trophic status and base flow conditions. Up to 30% of the total gained organic carbon was produced within the epilimnia. Consequently, this affected the DOC quality within the pre-dams over the year and enhanced characteristics of algae-derived DOC were observed during base flow in summer. Allochthonous derived DOC dominated at high discharges and oligotrophic conditions when production and respiration were low. These results underline that also small impoundments with typically low water residence times are hotspots of carbon cycling, significantly altering water quality in dependence of discharge conditions, temperature and trophic status. Further, it highlights that these factors need to be considered in future water management as increasing temperatures and altered precipitation patterns are predicted in the context of climate change.
Under base flow conditions, heterotrophic bacteria preferentially utilized older DOC components with a conventional radiocarbon age of 195-395 years before present (i.e. before 1950). In contrast, younger carbon components (modern, i.e. produced after 1950) were mineralized following a storm flow event. This highlights that age and recalcitrance of DOC are independent from each other. To assess the ages of the microbially consumed DOC, a simplified method was developed to recover the respired CO2 from heterotrophic bacterioplankton for carbon isotope analyses (13C, 14C). The advantages of the method comprise the operation of replicate incubations at in-situ temperatures using standard laboratory equipment and thus enabling an application in a broad range of conditions.
Aquatic priming was investigated in laboratory experiments during the microbial decomposition of two terrestrial DOC substrates (peat water and soil leachate). Thereby, natural phytoplankton served as a source of labile organic matter and the total DOC pool increased throughout the experiments due to exudation and cell lysis of the growing phytoplankton. A priming effect for both terrestrial DOC substrates was revealed via carbon isotope analysis and mixing models. Thereby, priming was more pronounced for the peat water than for the soil leachate. This indicates that the DOC source and the amount of the added labile organic matter might influence the magnitude of a priming effect. Additional analysis via high-resolution mass spectrometry revealed that oxidized, unsaturated compounds were more strongly decomposed under priming (i.e. in phytoplankton presence). Given the observed increase in DOC concentrations during the experiments, it can be concluded that aquatic priming is not easily detectable via net concentration changes alone and could be considered as a qualitative effect.
The knowledge gained from this thesis contributes to the understanding of aquatic carbon cycling and demonstrated how DOC dynamics in freshwaters vary with hydrological, seasonal and trophic conditions. It further demonstrated that aquatic priming contributes to the microbial transformation of organic carbon and the observed decay of allochthonous DOC during transport in inland waters.
Background: The pathophysiology behind the subacute but persistent hypercoagulable state after traumatic brain injury (TBI) is poorly understood but contributes to morbidity induced by venous thromboembolism. Because platelets and their microvesicles have been hypothesized to play a role in post-traumatic hypercoagulability, administration of commonly used agents may ameliorate this coagulability. We hypothesized that utilization of aspirin, ketorolac, amitriptyline, unfractionated heparin, or enoxaparin would modulate the platelet aggregation response after TBI. Methods: Concussive TBI was induced by weight drop. Mice were then randomized to receive aspirin, ketorolac, amitriptyline, heparin, enoxaparin, or saline control at 2 and 8 h after TBI. Mice were sacrificed at 6 or 24 h after injury to determine coagulability by rotational thromboelastometry (ROTEM), platelet function testing with impedance aggregometry, and microvesicle enumeration. Platelet sphingolipid metabolites were analyzed by mass spectrometry. Results: ROTEM demonstrated increased platelet contribution to maximum clot firmness at 6 h after TBI in mice that received aspirin or amitriptyline, but this did not persist at 24 h. By contrast, adenosine diphosphate- and arachidonic acid-induced platelet aggregation at 6 h was significantly lower in mice receiving ketorolac, aspirin, and amitriptyline compared with mice receiving saline at 6 h after injury and only arachidonic acid-initiated platelet aggregation was decreased by aspirin at 24 h. There were no differences in microvesicle production at either time point. Platelet sphingosine-1-phosphate levels were decreased at 6 h in the group receiving amitriptyline and increased at 24 h along with platelet ceramide levels at 24 h in the amitriptyline group. Conclusion: After TBI, amitriptyline decreased platelet aggregability and increased contribution to clot in a manner similar to aspirin. The amitriptyline effects on platelet function and sphingolipid metabolites may represent a possible role of the acid sphingomyelinase in the hypercoagulability observed after injury. In addition, inhibition of platelet reactivity may be an underappreciated benefit of low molecular weight heparins, such as enoxaparin. (C) 2019 Elsevier Inc. All rights reserved.
I address uncertainties on the spatial distribution and mass of the dust formed in η Carinae's Homunculus nebula with data being combined from several space- and ground-based facilities spanning near-infrared to sub-mm wavelengths, in terms of observational constraints and modeling. Until these aspects are better understood, the mass loss history and mechanisms responsible for η Car's enormous eruption(s) remain poorly constrained.
To undergo diffusive shock acceleration, electrons need to be preaccelerated to increase their energies by several orders of magnitude, else their gyroradii will be smaller than the finite width of the shock. In oblique shocks, where the upstream magnetic field orientation is neither parallel nor perpendicular to the shock normal, electrons can escape to the shock upstream, modifying the shock foot to a region called the electron foreshock. To determine the preacceleration in this region, we undertake particle-in-cell simulations of oblique shocks while varying the obliquity and in-plane angles. We show that while the proportion of reflected electrons is negligible for theta (Bn) = 74.degrees 3, it increases to R similar to 5% for theta (Bn) = 30 degrees, and that, via the electron acoustic instability, these electrons power electrostatic waves upstream with energy density proportional to R (0.6) and a wavelength approximate to 2 lambda (se), where lambda (se) is the electron skin length. While the initial reflection mechanism is typically a combination of shock-surfing acceleration and magnetic mirroring, we show that once the electrostatic waves have been generated upstream, they themselves can increase the momenta of upstream electrons parallel to the magnetic field. In less than or similar to 1% of cases, upstream electrons are prematurely turned away from the shock and never injected downstream. In contrast, a similar fraction is rescattered back toward the shock after reflection, reinteracts with the shock with energies much greater than thermal, and crosses into the downstream.
Thermal electrons have gyroradii many orders of magnitude smaller than the finite width of a shock, thus need to be pre-accelerated before they can cross it and be accelerated by diffusive shock acceleration. One region where pre-acceleration may occur is the inner foreshock, which upstream electrons must pass through before any potential downstream crossing. In this paper, we perform a large-scale particle-in-cell simulation that generates a single shock with parameters motivated from supernova remnants. Within the foreshock, reflected electrons excite the oblique whistler instability and produce electromagnetic whistler waves, which comove with the upstream flow and as nonlinear structures eventually reach radii of up to 5 ion-gyroradii. We show that the inner electromagnetic configuration of the whistlers evolves into complex nonlinear structures bound by a strong magnetic field around four times the upstream value. Although these nonlinear structures do not in general interact with cospatial upstream electrons, they resonate with electrons that have been reflected at the shock. We show that they can scatter, or even trap, reflected electrons, confining around 0.8% of the total upstream electron population to the region close to the shock where they can undergo substantial pre-acceleration. This acceleration process is similar to, yet approximately three times more efficient than, stochastic shock drift acceleration.
The safe upper limit for inclusion of vitamin A in complete diets for growing dogs is uncertain, with the result that current recommendations range from 5.24 to 104.80 mu mol retinol (5000 to 100 000 IU vitamin A)/4184 kJ (1000 kcal) metabolisable energy (ME). The aim of the present study was to determine the effect of feeding four concentrations of vitamin A to puppies from weaning until 1 year of age. A total of forty-nine puppies, of two breeds, Labrador Retriever and Miniature Schnauzer, were randomly assigned to one of four treatment groups. Following weaning at 8 weeks of age, puppies were fed a complete food supplemented with retinyl acetate diluted in vegetable oil and fed at 1ml oil/100 g diet to achieve an intake of 5.24, 13.10, 78.60 and 104.80 mu mol retinol (5000, 12 500, 75 000 and 100 000 IU vitamin A)/4184 kJ (1000 kcal) ME. Fasted blood and urine samples were collected at 8, 10, 12, 14, 16, 20, 26, 36 and 52 weeks of age and analysed for markers of vitamin A metabolism and markers of safety including haematological and biochemical variables, bone-specific alkaline phosphatase, cross-linked carboxyterminal telopeptides of type I collagen and dual-energy X-ray absorptiometry. Clinical examinations were conducted every 4 weeks. Data were analysed by means of a mixed model analysis with Bonferroni corrections for multiple endpoints. There was no effect of vitamin A concentration on any of the parameters, with the exception of total serum retinyl esters, and no effect of dose on the number, type and duration of adverse events. We therefore propose that 104.80 mu mol retinol (100 000 IU vitamin A)/4184 kJ (1000 kcal) is a suitable safe upper limit for use in the formulation of diets designed for puppy growth.
The safe upper limit for inclusion of vitamin A in complete diets for growing dogs is uncertain, with the result that current recommendations range from 5.24 to 104.80 mu mol retinol (5000 to 100 000 IU vitamin A)/4184 kJ (1000 kcal) metabolisable energy (ME). The aim of the present study was to determine the effect of feeding four concentrations of vitamin A to puppies from weaning until 1 year of age. A total of forty-nine puppies, of two breeds, Labrador Retriever and Miniature Schnauzer, were randomly assigned to one of four treatment groups. Following weaning at 8 weeks of age, puppies were fed a complete food supplemented with retinyl acetate diluted in vegetable oil and fed at 1ml oil/100 g diet to achieve an intake of 5.24, 13.10, 78.60 and 104.80 mu mol retinol (5000, 12 500, 75 000 and 100 000 IU vitamin A)/4184 kJ (1000 kcal) ME. Fasted blood and urine samples were collected at 8, 10, 12, 14, 16, 20, 26, 36 and 52 weeks of age and analysed for markers of vitamin A metabolism and markers of safety including haematological and biochemical variables, bone-specific alkaline phosphatase, cross-linked carboxyterminal telopeptides of type I collagen and dual-energy X-ray absorptiometry. Clinical examinations were conducted every 4 weeks. Data were analysed by means of a mixed model analysis with Bonferroni corrections for multiple endpoints. There was no effect of vitamin A concentration on any of the parameters, with the exception of total serum retinyl esters, and no effect of dose on the number, type and duration of adverse events. We therefore propose that 104.80 mu mol retinol (100 000 IU vitamin A)/4184 kJ (1000 kcal) is a suitable safe upper limit for use in the formulation of diets designed for puppy growth.
Hα observations of Rigel obtained on 184 nights during the past ten years with the 1-m telescope and ´echelle spectrograph of Ritter Observatory are surveyed. The line profiles were classified in terms of morphology. About 1/4 of them are of P Cygni type, about 15% inverse P Cygni, about 25% double-peaked, about 1/3 pure absorption, and a few are single emission lines. Transformation of the profile from one type to another typically takes a few days. Although the line stays in absorption for extended intervals, only one high-velocity absorption event of the intensity reported by Kaufer et al. (1996a) was observed, in late 2006. Late in this event, Hα absorption occurred farther to the red than the red wing of a plausible photospheric absorption component, an indication of infalling material. In general, as the absorption events come to an end, the emission typically returns with an inverse P Cygni profile. The Hα profile class shows no obvious correlation with the radial velocity of C II λ6578, a photospheric absorption line.
This paper provides an overview of analytical techniques used to determine isoflavones (IFs) in foods and biological fluids with main emphasis on sample preparation methods. Factors influencing the content of IFs in food including processing and natural variability are summarized and an insight into IF databases is given. Comparisons of dietary intake of IFs in Asian and Western populations, in special subgroups like vegetarians, vegans, and infants are made and our knowledge on their absorption, distribution, metabolism, and excretion by the human body is presented. The influences of the gut microflora, age, gender, background diet, food matrix, and the chemical nature of the IFs on the metabolism of IFs are described. Potential mechanisms by which IFs may exert their actions are reviewed, and genetic polymorphism as determinants of biological response to soy IFs is discussed. The effects of IFs on a range of health outcomes including atherosclerosis, breast, intestinal, and prostate cancers, menopausal symptoms, bone health, and cognition are reviewed on the basis of the available in vitro, in vivo animal and human data.
The Cenozoic East African Rift System (EARS) is an exceptional example of active continental extension, providing opportunities for furthering our understanding of hydrocarbon plays within rifts. It is divided into structurally distinct western and eastern branches. The western branch comprises deep rift basins separated by transfer zones, commonly localised onto pre-existing structures, offering good regional scale hydrocarbon traps. At a basin-scale, local discrete inherited structures might also play an important role on fault localisation and hydrocarbon distribution. Here, we consider the evolution of the Central basin of the Malawi Rift, in particular the influence of pre-existing structural fabrics. Integrating basin-scale multichannel 2D, and high resolution seismic datasets we constrain the border, Mlowe-Nkhata, fault system (MNF) to the west of the basin and smaller Mbamba fault (MF) to the east and document their evolution. Intra basin structures define a series of horsts, which initiated as convergent transfers, along the basin axis. The horsts are offset along a NE SW striking transfer fault parallel to and along strike of the onshore Karoo (Permo-Triassic) Ruhuhu graben. Discrete pre-existing structures probably determined its location and, oriented obliquely to the extension orientation it accommodated predominantly strike-slip deformation, with more slowly accrued dip-slip. To the north of this transfer fault, the overall basin architecture is asymmetric, thickening to the west throughout; while to the south, an initially symmetric graben architecture became increasingly asymmetric in sediment distribution as strain localised onto the western MNF. The presence of the axial horst increasingly focussed sediment supply to the west. As the transfer fault increased its displacement, so this axial supply was interrupted, effectively starving the south-east while ponding sediments between the western horst margin and the transfer fault. This asymmetric bathymetry and partitioned sedimentation continues to the present-day, overprinting the early basin symmetry and configuration. Sediments deposited earlier become increasingly dissected and fault juxtapositions changed at a small (10-100 m) scale. The observed influence of basin-scale transfer faults on sediment dispersal and fault compartmentalization due to pre-existing structures oblique to the extension orientation is relevant to analogous exploration settings. (C) 2016 Elsevier Ltd. All rights reserved.
We investigate the controls on the architecture of coarse-grained delta progradational units (PUs) in the Pliocene Loreto basin (Baja California Sur, Mexico), a half-graben located on the western margin of the Gulf of California. Dorsey et al. (1997b) argued that delta progradation and transgression cycles in the basin were driven by episodic fault-controlled subsidence along the basin-bounding Loreto fault. Here we test this hypothesis by a detailed analysis of the sedimentary architecture of 11 exceptionally well-exposed, vertically arranged fluvio-deltaic PUs, each of which shows lateral facies transition from proximal alluvial facies palaeo-seaward into distal pro-delta facies. Of these 11 PUs, seven exhibit a lateral transition from a shoal water to Gilbert-delta facies associations as they are traced palaeo-seaward. This transition is characterised by down-transport development of foresets, which grow in height up to 35 m. Foreset units thicken in a basinward direction, with initially an oblique topset-foreset geometry that becomes increasingly sigmoidal. Each delta is capped by a shell bed that records drowning of the delta top. This systematic transition in delta architecture records increasing water depth through time during individual episodes of progradation. A mechanism that explains this transition is an accelerating rate of fault-controlled subsidence during each PU. During episodes of low slip rate, shoal-water deltas prograde across the submerged topography of the underlying delta unit. As displacement rate accelerates, increasing bathymetry at the delta front leads to steepening of foresets and initiation of Gilbert deltas. Subsequent delta drowning results from sediment starvation at the shoreline at high slip rates because of sediment trapping upstream. The observed delta architecture suggests that the long-term (> 100 kyr) history of slip on the Loreto fault was characterised by repetitive episodes of accelerating displacement accumulation. Such episodic fault behaviour is most likely to be because of variations in temporal and spatial strain partitioning between the Loreto fault and other faults in the Gulf of California. A physical explanation for the acceleration phenomenon involves evolving frictional properties on the episodically active Loreto fault
The evolution of through-going normal-fault arrays from initial nucleation to growth and subsequent interaction and mechanical linkage is well documented in many extensional provinces. Over time, these processes. lead to predictable spatial and temporal variations in the amount and rate of displacement accumulated along strike of individual fault segments, which should be manifested in the patterns of footwall exhumation. Here, we investigate the along-strike and vertical distribution of low-temperature apatite (U-Th)/He (AHe) cooling ages along the bounding fault system, the Livingstone fault, of the Karonga Basin of the northern Malawi Rift. The fault evolution and linkage from rift initiation to the present day has been previously constrained through investigations of the hanging wall basin fill. The new cooling ages from the footwall of the Livingstone fault can be related to the adjacent depocentre evolution and across a relay zone between two palaeo-fault segments. Our data are complimented by published apatite fission track (AFT) data and reveal significant variation in rock cooling history along-strike: the centre of the footwall yields younger cooling ages than the former tips of earlier fault segments that are now linked. This suggests that low-temperature thermochronology can detect fault interactions along strike. That these former segment boundaries are preserved within exhumed footwall rocks is a function of the relatively recent linkage of the system. Our study highlights that changes in AHe (and potentially AFT) ages associated with the along-strike displacement profile can occur over relatively short horizontal distances (of a few kilometres). This is fundamentally important in the assessment of the vertical cooling history of footwalls in extensional systems: temporal differences in the rate of tectonically driven exhumation at a given location along fault strike may be of greater importance in controlling changes in rates of vertical exhumation than commonly invoked climatic fluctuations. (C) 2016 Elsevier B.V. All rights reserved.
We examine the effect that the shape of the source brightness profile has on the magnitude fluctuations of images in quasar lens systems due to microlensing. We do this by convolving a variety of accretion disk models (including Gaussian disks, uniform disks, "cones," and a Shakura-Sunyaev thermal model) with two magnification maps in the source plane, one with convergence kappa = 0.4 and shear gamma = 0.4 (positive parity) and the other with kappa = gamma = 0.6 ( negative parity). By looking at magnification histograms of the convolutions and using chi(2) tests to determine the number of observations that would be necessary to distinguish histograms associated with different disk models, we find that, for circular disk models, the microlensing fluctuations are relatively insensitive to all properties of the models except the half-light radius of the disk. Shakura-Sunyaev models are sufficiently well constrained by observed quasar properties that we can estimate the half-light radius at optical wavelengths for a typical quasar. If Shakura-Sunyaev models are appropriate, the half-light radii are very much smaller than the Einstein rings of intervening stars, and the quasar can be reasonably taken to be a point source except in the immediate vicinity of caustic-crossing events
The goal of this study was to determine how trilinguals select the language they intend to use in a language switching context. Two accounts are examined: (a) a language-specific account, according to which language selection considers the activation level of words of the intended language only (i.e., language co-activation without language competition), and (b) a language non-specific account, where activated words from both the intended and non-intended languages compete for selection (i.e., language co-activation with language competition). Results showed that, in both groups, all three languages competed for selection and that selection was achieved by inhibiting the currently non-relevant languages. Moreover, extending findings from previous research, the study reveals that, in both Experiments 1 and 2, the amount of inhibition was influenced not only by language proficiency but also by the typological similarity between languages. Overall, the study shows that language switching performance can be accounted for by a strategic and flexible inhibitory account. In particular, the controlling system is “strategic” in the sense that it aims at preventing potential conflicting situations, such as typological closeness between languages, and it is “flexible” in that it adjusts languages’ activation levels, depending on the conflict to be solved.
For several decades, researchers have tried to explain how speakers of more than one language (multilinguals) manage to keep their languages separate and to switch from one language to the other depending on the context. This ability of multilingual speakers to use the intended language, while avoiding interference from the other language(s) has recently been termed “language control”.
A multitude of studies showed that when bilinguals process one language, the other language is also activated and might compete for selection. According to the most influential model of language control developed over the last two decades, competition from the non-intended language is solved via inhibition. In particular, the Inhibitory Control (IC) model proposed by Green (1998) puts forward that the amount of inhibition applied to the non-relevant language depends on its dominance, in that the stronger the language the greater the strength of inhibition applied to it. Within this account, the cost required to reactivate a previously inhibited language depends on the amount of inhibition previously exerted on it, that is, reactivation costs are greater for a stronger compared to a weaker language. In a nutshell, according to the IC model, language control is determined by language dominance.
The goal of the present dissertation is to investigate the extent to which language control in multilinguals is affected by language dominance and whether and how other factors might influence this process. Three main factors are considered in this work: (i) the time speakers have to prepare for a certain language or PREPARATION TIME, (ii) the type of languages involved in the interactional context or LANGUAGE TYPOLOGY, and (iii) the PROCESSING MODALITY, that is, whether the way languages are controlled differs between reception and production.
The results obtained in the four manuscripts, either published or in revision, indicate that language dominance alone does not suffice to explain language switching patterns. In particular, the present thesis shows that language control is profoundly affected by each of the three variables described above. More generally, the findings obtained in the present dissertation indicate that language control in multilingual speakers is a much more dynamic system than previously believed and is not exclusively determined by language dominance, as predicted by the IC model (Green, 1998).
Much research on language control in bilinguals has relied on the interpretation of the costs of switching between two languages. Of the two types of costs that are linked to language control, switching costs are assumed to be transient in nature and modulated by trial-specific manipulations (e.g., by preparation time), while mixing costs are supposed to be more stable and less affected by trial-specific manipulations. The present study investigated the effect of preparation time on switching and mixing costs, revealing that both types of costs can be influenced by trial-specific manipulations.
Much research on language control in bilinguals has relied on the interpretation of the costs of switching between two languages. Of the two types of costs that are linked to language control, switching costs are assumed to be transient in nature and modulated by trial-specific manipulations (e.g., by preparation time), while mixing costs are supposed to be more stable and less affected by trial-specific manipulations. The present study investigated the effect of preparation time on switching and mixing costs, revealing that both types of costs can be influenced by trial-specific manipulations.
Continuous exercise (CON) and high-intensity interval exercise (HIIE) can be safely performed with type 1 diabetes mellitus (T1DM). Additionally, continuous glucose monitoring (CGM) systems may serve as a tool to reduce the risk of exercise-induced hypoglycemia. It is unclear if CGM is accurate during CON and HIIE at different mean workloads. Seven T1DM patients performed CON and HIIE at 5% below (L) and above (M) the first lactate turn point (LTP1), and 5% below the second lactate turn point (LTP2) (H) on a cycle ergometer. Glucose was measured via CGM and in capillary blood (BG). Differences were found in comparison of CGM vs. BG in three out of the six tests (p < 0.05). In CON, bias and levels of agreement for L, M, and H were found at: 0.85 (-3.44, 5.15) mmol.L-1, -0.45 (-3.95, 3.05) mmol.L-1, -0.31 (-8.83, 8.20) mmol.L-1 and at 1.17 (-2.06, 4.40) mmol.L-1, 0.11 (-5.79, 6.01) mmol.L-1, 1.48 (-2.60, 5.57) mmol.L-1 in HIIE for the same intensities. Clinically-acceptable results (except for CON H) were found. CGM estimated BG to be clinically acceptable, except for CON H. Additionally, using CGM may increase avoidance of exercise-induced hypoglycemia, but usual BG control should be performed during intense exercise.
Continuous exercise (CON) and high-intensity interval exercise (HIIE) can be safely performed with type 1 diabetes mellitus (T1DM). Additionally, continuous glucose monitoring (CGM) systems may serve as a tool to reduce the risk of exercise-induced hypoglycemia. It is unclear if CGM is accurate during CON and HIIE at different mean workloads. Seven T1DM patients performed CON and HIIE at 5% below (L) and above (M) the first lactate turn point (LTP1), and 5% below the second lactate turn point (LTP2) (H) on a cycle ergometer. Glucose was measured via CGM and in capillary blood (BG). Differences were found in comparison of CGM vs. BG in three out of the six tests (p < 0.05). In CON, bias and levels of agreement for L, M, and H were found at: 0.85 (−3.44, 5.15) mmol·L−1, −0.45 (−3.95, 3.05) mmol·L−1, −0.31 (−8.83, 8.20) mmol·L−1 and at 1.17 (−2.06, 4.40) mmol·L−1, 0.11 (−5.79, 6.01) mmol·L−1, 1.48 (−2.60, 5.57) mmol·L−1 in HIIE for the same intensities. Clinically-acceptable results (except for CON H) were found. CGM estimated BG to be clinically acceptable, except for CON H. Additionally, using CGM may increase avoidance of exercise-induced hypoglycemia, but usual BG control should be performed during intense exercise.
Introduction
We investigated blood glucose (BG) and hormone response to aerobic high-intensity interval exercise (HIIE) and moderate continuous exercise (CON) matched for mean load and duration in type 1 diabetes mellitus (T1DM).
Material and Methods
Seven trained male subjects with T1DM performed a maximal incremental exercise test and HIIE and CON at 3 different mean intensities below (A) and above (B) the first lactate turn point and below the second lactate turn point (C) on a cycle ergometer. Subjects were adjusted to ultra-long-acting insulin Degludec (Tresiba/Novo Nordisk, Denmark). Before exercise, standardized meals were administered, and short-acting insulin dose was reduced by 25% (A), 50% (B), and 75% (C) dependent on mean exercise intensity. During exercise, BG, adrenaline, noradrenaline, dopamine, cortisol, glucagon, and insulin-like growth factor-1, blood lactate, heart rate, and gas exchange variables were measured. For 24 h after exercise, interstitial glucose was measured by continuous glucose monitoring system.
Results
BG decrease during HIIE was significantly smaller for B (p = 0.024) and tended to be smaller for A and C compared to CON. No differences were found for post-exercise interstitial glucose, acute hormone response, and carbohydrate utilization between HIIE and CON for A, B, and C. In HIIE, blood lactate for A (p = 0.006) and B (p = 0.004) and respiratory exchange ratio for A (p = 0.003) and B (p = 0.003) were significantly higher compared to CON but not for C.
Conclusion
Hypoglycemia did not occur during or after HIIE and CON when using ultra-long-acting insulin and applying our methodological approach for exercise prescription. HIIE led to a smaller BG decrease compared to CON, although both exercises modes were matched for mean load and duration, even despite markedly higher peak workloads applied in HIIE. Therefore, HIIE and CON could be safely performed in T1DM.
Introduction
We investigated blood glucose (BG) and hormone response to aerobic high-intensity interval exercise (HIIE) and moderate continuous exercise (CON) matched for mean load and duration in type 1 diabetes mellitus (T1DM).
Material and Methods
Seven trained male subjects with T1DM performed a maximal incremental exercise test and HIIE and CON at 3 different mean intensities below (A) and above (B) the first lactate turn point and below the second lactate turn point (C) on a cycle ergometer. Subjects were adjusted to ultra-long-acting insulin Degludec (Tresiba/ Novo Nordisk, Denmark). Before exercise, standardized meals were administered, and short-acting insulin dose was reduced by 25% (A), 50% (B), and 75% (C) dependent on mean exercise intensity. During exercise, BG, adrenaline, noradrenaline, dopamine, cortisol, glucagon, and insulin-like growth factor-1, blood lactate, heart rate, and gas exchange variables were measured. For 24 h after exercise, interstitial glucose was measured by continuous glucose monitoring system.
Results
BG decrease during HIIE was significantly smaller for B (p = 0.024) and tended to be smaller for A and C compared to CON. No differences were found for post-exercise interstitial glucose, acute hormone response, and carbohydrate utilization between HIIE and CON for A, B, and C. In HIIE, blood lactate for A (p = 0.006) and B (p = 0.004) and respiratory exchange ratio for A (p = 0.003) and B (p = 0.003) were significantly higher compared to CON but not for C.
Conclusion
Hypoglycemia did not occur during or after HIIE and CON when using ultra-long-acting insulin and applying our methodological approach for exercise prescription. HIIE led to a smaller BG decrease compared to CON, although both exercises modes were matched for mean load and duration, even despite markedly higher peak workloads applied in HIIE. Therefore, HIIE and CON could be safely performed in T1DM.
Introduction
We investigated blood glucose (BG) and hormone response to aerobic high-intensity interval exercise (HIIE) and moderate continuous exercise (CON) matched for mean load and duration in type 1 diabetes mellitus (T1DM).
Material and Methods
Seven trained male subjects with T1DM performed a maximal incremental exercise test and HIIE and CON at 3 different mean intensities below (A) and above (B) the first lactate turn point and below the second lactate turn point (C) on a cycle ergometer. Subjects were adjusted to ultra-long-acting insulin Degludec (Tresiba/ Novo Nordisk, Denmark). Before exercise, standardized meals were administered, and short-acting insulin dose was reduced by 25% (A), 50% (B), and 75% (C) dependent on mean exercise intensity. During exercise, BG, adrenaline, noradrenaline, dopamine, cortisol, glucagon, and insulin-like growth factor-1, blood lactate, heart rate, and gas exchange variables were measured. For 24 h after exercise, interstitial glucose was measured by continuous glucose monitoring system.
Results
BG decrease during HIIE was significantly smaller for B (p = 0.024) and tended to be smaller for A and C compared to CON. No differences were found for post-exercise interstitial glucose, acute hormone response, and carbohydrate utilization between HIIE and CON for A, B, and C. In HIIE, blood lactate for A (p = 0.006) and B (p = 0.004) and respiratory exchange ratio for A (p = 0.003) and B (p = 0.003) were significantly higher compared to CON but not for C.
Conclusion
Hypoglycemia did not occur during or after HIIE and CON when using ultra-long-acting insulin and applying our methodological approach for exercise prescription. HIIE led to a smaller BG decrease compared to CON, although both exercises modes were matched for mean load and duration, even despite markedly higher peak workloads applied in HIIE. Therefore, HIIE and CON could be safely performed in T1DM.
Introduction
We investigated blood glucose (BG) and hormone response to aerobic high-intensity interval exercise (HIIE) and moderate continuous exercise (CON) matched for mean load and duration in type 1 diabetes mellitus (T1DM).
Material and Methods
Seven trained male subjects with T1DM performed a maximal incremental exercise test and HIIE and CON at 3 different mean intensities below (A) and above (B) the first lactate turn point and below the second lactate turn point (C) on a cycle ergometer. Subjects were adjusted to ultra-long-acting insulin Degludec (Tresiba/Novo Nordisk, Denmark). Before exercise, standardized meals were administered, and short-acting insulin dose was reduced by 25% (A), 50% (B), and 75% (C) dependent on mean exercise intensity. During exercise, BG, adrenaline, noradrenaline, dopamine, cortisol, glucagon, and insulin-like growth factor-1, blood lactate, heart rate, and gas exchange variables were measured. For 24 h after exercise, interstitial glucose was measured by continuous glucose monitoring system.
Results
BG decrease during HIIE was significantly smaller for B (p = 0.024) and tended to be smaller for A and C compared to CON. No differences were found for post-exercise interstitial glucose, acute hormone response, and carbohydrate utilization between HIIE and CON for A, B, and C. In HIIE, blood lactate for A (p = 0.006) and B (p = 0.004) and respiratory exchange ratio for A (p = 0.003) and B (p = 0.003) were significantly higher compared to CON but not for C.
Conclusion
Hypoglycemia did not occur during or after HIIE and CON when using ultra-long-acting insulin and applying our methodological approach for exercise prescription. HIIE led to a smaller BG decrease compared to CON, although both exercises modes were matched for mean load and duration, even despite markedly higher peak workloads applied in HIIE. Therefore, HIIE and CON could be safely performed in T1DM.
When we fixate our gaze on a stable object, our eyes move continuously with extremely small involuntary and autonomic movements, that even we are unaware of during their occurrence. One of the roles of these fixational eye movements is to prevent the adaptation of the visual system to continuous illumination and inhibit fading of the image. These random, small movements are restricted at long time scales so as to keep the target at the centre of the field of view. In addition, the synchronisation properties between both eyes are related to binocular coordination in order to provide stereopsis. We investigated the roles of different time scale behaviours, especially how they are expressed in the different spatial directions (vertical versus horizontal). We also tested the synchronisation between both eyes. Results show different scaling behaviour between horizontal and vertical movements. When the small ballistic movements, i.e., microsaccades, are removed, the scaling behaviour in both axes becomes similar. Our findings suggest that microsaccades enhance the persistence at short time scales mostly in the horizontal component and much less in the vertical component. We also applied the phase synchronisation decay method to study the synchronisation between six combinations of binocular fixational eye movement components. We found that the vertical-vertical components of right and left eyes are significantly more synchronised than the horizontal-horizontal components. These differences may be due to the need for continuously moving the eyes in the horizontal plane in order to match the stereoscopic image for different viewing distances.
Reactions of trifluoromethanesulfonamide with alpha-methylstyrene, 2-methylpent-1-ene, and cycloocta-1,5-diene in the system t-BuOCl-NaI were studied. In the reaction with alpha-methylstyrene 1-iodo-2-phenylpropan-2-ol was the only isolated product. The reaction with 2-methylpent-1-ene gave a mixture of N,N'-(2-methylpentane-1,2-diyl)bis(trifluoromethanesulfonamide), trifluoro-N-(2-hydroxy-2-methylpentyl)-methanesulfonamide, and N,N'-[oxybis(2-methylpentan-2,1-diyl)]bis(trifluoromethanesulfonamide). Trifluoromethanesulfonamide reacted with cycloocta-1,5-diene to produce a mixture of 2,5-diiodo-9-(trifluoromethylsulfonyl)-9-azabicyclo[4.2.1]nonane and 2,5-diiodo-9-oxabicyclo[4.2.1]nonane; this reaction may be regarded as the first example of direct assembly of bicyclononane skeleton.
In the oxidative system (t-BuOCl+NaI) trifluoromethanesulfonamide is regio- and stereoselectively added to only one double bond of cyclopentadiene and 1,3-cyclohexadiene giving rise to 1,1,1-trifluoro-N-(5-iodocyclopent-2-en-1-yl)methanesulfonamide 7 and trans-N,N'-cyclohex-3-en-1,2-diylbis(1,1,1-trifluoromethanesulfonamide) 8. The structure of 7 and 8 was determined by X-ray, NMR, and MS. With 1,4-cyclohexadiene, addition to both double bonds occurs with the formation of N,N'-(4-chloro-5-iodocyclohexan-1,2-diyl)bis(1,1,1-trifluoromethanesulfonamide) 9. Under the action of sodium iodide in acetone, the latter product undergoes halogenophilic attack with the reduction of the CHI group and elimination of HCl to give trans-N,N'-cyclohex-4-en-1,2-diylbis(1,1,1-trifluoromethanesulfonamide) 10, whose structure was also determined by X-ray analysis. 1,3,5-Cycloheptatriene under these conditions is oxidized to benzaldehyde and does not react with trifluoromethanesulfonamide.
Reliable baseline information necessary for the monitoring and conservation of Sumatran elephants is scarce. We here combine non-invasive molecular genetics methods and capture-recapture modeling to estimate elephant population size, distribution, sex ratio, and age structure for the Bukit Tigapuluh landscape in Sumatra, Indonesia. Two separate subpopulations were found, for which we estimated a population size of 99 (95% CI = [86, 125], PCCL = 38.59%) and 44 elephants (95% CI = [37, 56], PCCL = 43.18%), respectively. Low elephant densities are likely the result of patchy habitat usage and anthropogenically increased mortality, the latter assumption being supported by strong skews in both sex ratio and age structure as well as direct evidence of elephant killing. Still, the Bukit Tigapuluh landscape currently holds the largest known population of elephants in central Sumatra, representing one of the most important areas for their conservation in Indonesia. Conservation of both the elephant population and their habitat in this region should thus be of high priority. We identified several threats to the population, including (i) the risk of inbreeding and subsequent loss of genetic diversity, (ii) illegal elephant killing, and (iii) the lack of protected habitat. In order to overcome these challenges we suggest: (i) the implementation of a meta-population management program, (ii) monitoring and safeguarding elephants and improving law enforcement, and (iii) providing sufficient safe habitat to mitigate human-elephant-conflict (HEC) and ensure elephant survival.
This thesis presents a comprehensive exploration of the application of DNA origami nanofork antennas (DONAs) in the field of spectroscopy, with a particular focus on the structural analysis of Cytochrome C (CytC) at the single-molecule level. The research encapsulates the design, optimization, and application of DONAs in enhancing the sensitivity and specificity of Raman spectroscopy, thereby offering new insights into protein structures and interactions.
The initial phase of the study involved the meticulous optimization of DNA origami structures. This process was pivotal in developing nanoscale tools that could significantly enhance the capabilities of Raman spectroscopy. The optimized DNA origami nanoforks, in both dimer and aggregate forms, demonstrated an enhanced ability to detect and analyze molecular vibrations, contributing to a more nuanced understanding of protein dynamics.
A key aspect of this research was the comparative analysis between the dimer and aggregate forms of DONAs. This comparison revealed that while both configurations effectively identified oxidation and spin states of CytC, the aggregate form offered a broader range of detectable molecular states due to its prolonged signal emission and increased number of molecules. This extended duration of signal emission in the aggregates was attributed to the collective hotspot area, enhancing overall signal stability and sensitivity.
Furthermore, the study delved into the analysis of the Amide III band using the DONA system. Observations included a transient shift in the Amide III band's frequency, suggesting dynamic alterations in the secondary structure of CytC. These shifts, indicative of transitions between different protein structures, were crucial in understanding the protein’s functional mechanisms and interactions.
The research presented in this thesis not only contributes significantly to the field of spectroscopy but also illustrates the potential of interdisciplinary approaches in biosensing. The use of DNA origami-based systems in spectroscopy has opened new avenues for research, offering a detailed and comprehensive understanding of protein structures and interactions. The insights gained from this research are expected to have lasting implications in scientific fields ranging from drug development to the study of complex biochemical pathways. This thesis thus stands as a testament to the power of integrating nanotechnology, biochemistry, and spectroscopic techniques in addressing complex scientific questions.
The phenolic compounds as food components represent the largest group of secondary metabolites in plant foods. The phenolic compounds, e.g. chlorogenic acid (CQA), are susceptible to oxidation by enzymes specially, polyphenol oxidase (PPO) and at alkaline conditions. Both enzymatic and non-enzymatic oxidations occur in the presence of oxygen and produce quinone, which normally further react with other quinone to produce colored compounds (dimers), as well as is capable of undergoing a nucleophilic addition to proteins. The interactions of proteins with the phenolic compounds have received considerable attention in the recent years where, plant phenolic compounds have drawn increasing attention due to their antioxidant properties and their noticeable effects in the prevention of various oxidative stress associated diseases. Green coffee beans are one of the richest sources of chlorogenic acids. Therefore, a green coffee extract would provide an eligible food relevant source for phenolic compounds for modification of proteins. The interaction between 5-CQA and amino acid lysine showed decrease in both free CQA and amino acid groups and only a slight effect on the antioxidative capacity depending on the reaction time was found. Furthermore, this interaction showed a large number of intermediary substances of low intensities. The reaction of lysine with 5-CQA in a model system initially leads to formation of 3-CQA and 4-CQA (both are isomers of 5-CQA), oxidation giving rise to the formation of a dimer which subsequently forms an adduct with lysine to finally result in a benzacridine derivative as reported and confirmed with the aid of HPLC coupled with ESI-MSn. The benzacridine derivative containing a trihydroxy structural element, was found to be yellow, being very reactive with oxygen yielding semiquinone and quinone type of products with characteristic green colors. Finally, the optimal conditions for this interaction as assessed by both the loss of CQA and free amino groups of lysine can be given at pH 7 and 25°C, the interaction increasing with incubation time and depending also on the amount of tyrosinase present. Green coffee bean has a higher diversity and content of phenolics, where besides the CQA isomers and their esters, other conjugates like feruloylquinic acids were also identified, thus documenting differences in phenolic profiles for the two coffee types (Coffea arabica and Coffea robusta). Coffee proteins are modified by interactions with phenolic compounds during the extraction, where those from C. arabica are more susceptible to these interactions compared to C. robusta, and the polyphenol oxidase activity seems to be a crucial factor for the formation of these addition products. Moreover, In-gel digestion combined with MALDI-TOF-MS revealed that the most reactive and susceptible protein fractions to covalent reactions are the α-chains of the 11S storage protein. Thus, based on these results and those supplied by other research groups, a tentative list of possible adduct structures was derived. The diversity of the different CQA derivatives present in green coffee beans complicates the series of reactions occurring, providing a broad palette of reaction products. These interactions influence the properties of protein, where they exposed changes in the solubility and hydrophobicity of proteins compared to faba bean proteins (as control). Modification of milk whey protein products (primarily b-lactoglobulin) with coffee specific phenolics and commercial CQA under enzymatic and alkaline conditions seems to be affecting their chemical, structural and functional properties, where both modifications led to reduced free amino-,thiol groups and tryptophan content. We propose that the disulfide-thiol exchange in the C-terminus of b-lactoglobulin may be initiated by the redox conditions provided in the presence of CQA. The protein structure b-lactoglobulin thereupon becomes more disordered as simulated by molecular dynamic calculation. This unfolding process may additionally be supported by the reaction of the CQA at the proposed sites of modification of -amino groups of lysine (K77, K91, K138, K47) and the thiol group of cysteine (C121). These covalent modifications also decreased the solubility and hydrophobicity of b-lactoglobulin, moreover they provide modified protein samples with a high antioxidative power, thermally more stable as reflected by a higher Td, require less amount of energy to unfold and when emulsified with lutein esters, exhibit their higher stability against UV light. The MALDI-TOF and SDS-PAGE results revealed that proteins treated at alkaline conditions were more strongly modified than those treated under enzymatic conditions. Finally, the results showed a slight change in emulsifying properties of modified proteins.
Aldehyde oxidases are molybdenum and flavin dependent enzymes characterized by a very wide substrate specificity and performing diverse reactions that include oxidations (e.g., aldehydes and azaheterocycles), hydrolysis of amide bonds, and reductions (e.g., nitro, S-oxides and N-oxides). Oxidation reactions and amide hydrolysis occur at the molybdenum site while the reductions are proposed to occur at the flavin site. AOX activity affects the metabolism of different drugs and xenobiotics, some of which designed to resist other liver metabolizing enzymes (e.g., cytochrome P450 monooxygenase isoenzymes), raising its importance in drug development. This work consists of a comprehensive overview on aldehyde oxidases, concerning the genetic evolution of AOX, its diversity among the human population, the crystal structures available, the known catalytic reactions and the consequences in pre-clinical pharmacokinetic and pharmacodynamic studies. Analysis of the different animal models generally used for pre-clinical trials and comparison between the human (hAOX1), mouse homologs as well as the related xanthine oxidase (XOR) are extensively considered. The data reviewed also include a systematic analysis of representative classes of molecules that are hAOX1 substrates as well as of typical and well characterized hAOX1 inhibitors. The considerations made on the basis of a structural and functional analysis are correlated with reported kinetic and metabolic data for typical classes of drugs, searching for potential structural determinants that may dictate substrate and/or inhibitor specificities.
Human aldehyde oxidase (hAOX1) is a molybdenum enzyme with high toxicological importance, but its physiological role is still unknown. hAOX1 metabolizes different classes of xenobiotics and is one of the main drug-metabolizing enzymes in the liver, along with cytochrome P450. hAOX1 oxidizes and inactivates a large number of drug molecules and has been responsible for the failure of several phase I clinical trials. The interindividual variability of drug-metabolizing enzymes caused by single nucleotide polymorphisms (SNPs) is highly relevant in pharmaceutical treatments. In this study, we present the crystal structure of the inactive variant G1269R, revealing the first structure of a molybdenum cofactor (Moco)-free form of hAOX1. These data allowed to model, for the first time, the flexible Gate 1 that controls access to the active site. Furthermore, we inspected the thermostability of wild-type hAOX1 and hAOX1 with various SNPs (L438V, R1231H, G1269R or S1271L) by CD spectroscopy and ThermoFAD, revealing that amino acid exchanges close to the Moco site can impact protein stability up to 10 degrees C. These results correlated with biochemical and structural data and enhance our understanding of hAOX1 and the effect of SNPs in the gene encoding this enzyme in the human population. EnzymesAldehyde oxidase (); xanthine dehydrogenase (); xanthine oxidase (). DatabasesStructural data are available in the Protein Data Bank under the accession number .
Narcissists are assumed to lack the motivation and ability to share and understand the mental states of others. Prior empirical research, however, has yielded inconclusive findings and has differed with respect to the specific aspects of narcissism and socioemotional cognition that have been examined. Here, we propose a differentiated facet approach that can be applied across research traditions and that distinguishes between facets of narcissism (agentic vs. antagonistic) on the one hand, and facets of socioemotional cognition ability (SECA; self-perceived vs. actual) on the other. Using five nonclinical samples in two studies (total N = 602), we investigated the effect of facets of grandiose narcissism on aspects of socioemotional cognition across measures of affective and cognitive empathy, Theory of Mind, and emotional intelligence, while also controlling for general reasoning ability. Across both studies, agentic facets of narcissism were found to be positively related to perceived SECA, whereas antagonistic facets of narcissism were found to be negatively related to perceived SECA. However, both narcissism facets were negatively related to actual SECA. Exploratory condition-based regression analyses further showed that agentic narcissists had a higher directed discrepancy between perceived and actual SECA: They self-enhanced their socio-emotional capacities. Implications of these results for the multifaceted theoretical understanding of the narcissism-SECA link are discussed.
Many complex networks display strong heterogeneity in the degree (connectivity) distribution. Heterogeneity in the degree distribution often reduces the average distance between nodes but, paradoxically, may suppress synchronization in networks of oscillators coupled symmetrically with uniform coupling strength. Here we offer a solution to this apparent paradox. Our analysis is partially based on the identification of a diffusive process underlying the communication between oscillators and reveals a striking relation between this process and the condition for the linear stability of the synchronized states. We show that, for a given degree distribution, the maximum synchronizability is achieved when the network of couplings is weighted and directed and the overall cost involved in the couplings is minimum. This enhanced synchronizability is solely determined by the mean degree and does not depend on the degree distribution and system size. Numerical verification of the main results is provided for representative classes of small-world and scale-free networks
Heterogeneity in the degree (connectivity) distribution has been shown to suppress synchronization in networks of symmetrically coupled oscillators with uniform coupling strength (unweighted coupling). Here we uncover a condition for enhanced synchronization in weighted networks with asymmetric coupling. We show that, in the optimum regime, synchronizability is solely determined by the average degree and does not depend on the system size and the details of the degree distribution. In scale-free networks, where the average degree may increase with heterogeneity, synchronizability is drastically enhanced and may become positively correlated with heterogeneity, while the overall cost involved in the network coupling is significantly reduced as compared to the case of unwcighted coupling
Geochemistry and Ar-40/Ar-39 age of Early Carboniferous dolerite sills in the southern Baltic Sea
(2015)
The Early Carboniferous magmatic event in the southern Baltic Sea is manifested by dolerite intrusions. The presumable area in which the dolerite intrusions occur ranges from 30 to 60 km in east-west direction, and is about 100 km in north-south direction. The dolerites were sampled in well D1-1 and investigated by applying chemical analysis and Ar-40/Ar-39 step-heating dating. Dolerites are classified as alkali and sodic, characterized by high TiO2 (3.92, 3.99 wt%) and P2O5 (1.67, 1.77 wt%) and low MgO (4.89, 4.91 wt%) concentrations, enriched in light rare earth elements, originated from an enriched mantle magma source and emplaced in a continental rift tectonic setting. The 351 +/- 11 Ma Ar-40/Ar-39 plateau age for groundmass plagioclase indicates a considerable age gap with the 310-250 Ma magmatism in southern Scandinavia and northern Germany. The magmatic rocks in the Baltic Sedimentary Basin are coeval with alkaline intrusions of NE Poland. Both magmatic provinces lie in the northwestward prolongation of the Pripyat-Dnieper-Donetsk Rift (370-359 Ma) and may constitute a later phase of magmatic activity of this propagating rift system.
Each year we are bombarded with B.Sc. and Ph.D. applications from students that want to improve the world. They have learned that their future depends on changing the type of fuel we use and that solar energy is our future. The hope and energy of these young people will transform future energy technologies, but it will not happen quickly. Organic photovoltaic devices are easy to sketch, but the materials, processing steps, and ways of measuring the properties of the materials are very complicated. It is not trivial to make a systematic measurement that will change the way other research groups think or practice. In approaching this chapter, we thought about what a new researcher would need to know about organic photovoltaic devices and materials in order to have a good start in the subject. Then, we simplified that to focus on what a new researcher would need to know about poly-3-hexylthiophene: phenyl-C61-butyric acid methyl ester blends (P3HT: PCBM) to make research progress with these materials. This chapter is by no means authoritative or a compendium of all things on P3HT: PCBM. We have selected to explain how the sample fabrication techniques lead to control of morphology and structural features and how these morphological features have specific optical and electronic consequences for organic photovoltaic device applications.
How to reuse inclusive stem Moocs in blended settings to engage young girls to scientific careers
(2023)
The FOSTWOM project (2019–2022), an ERASMUS+ funding, gave METID (Politecnico di Milano) and the MOOC Técnico (Instituto Superior Técnico, University of Lisbon), together with other partners, the opportunity to support the design and creation of gender-inclusive MOOCs. Among other project outputs, we designed a toolkit and a framework that enabled the production of two MOOCs for undergraduate and graduate students in Science, Technology, Engineering and Maths (STEM) and used them as academic content free of gender stereotypes about intellectual ability. In this short paper, the authors aim to 1) briefly share the main outputs of the project; 2) tell the story of how the FOSTWOM approach together with 3) a motivational strategy, the Heroine’s Learning Journey, proved to be effective in the context of rural and marginal areas in Brazil, with young girls as a specific target audience.
Inflammatory cytokines play an important role in intervertebral disc degeneration. Although largely produced by immune cells, nucleus pulposus (NP) cells can also secrete them under various conditions, for example, under free swelling. Thus, tissue hypotonicity may be an inflammatory trigger for NP cells. The aim of this study was to investigate whether decreased tonicity under restricted swelling conditions (as occurring in early disc degeneration) could initiate an inflammatory cascade that mediates further degeneration. Healthy bovine NP tissue was balanced against different PEG concentrations (0-30%) to obtain various tissue tonicities. Samples were then placed in an artificial annulus (fixed volume) and were cultured for 3, 7, or 21 days, with free swelling NP as control. Tissue content (water, glycosaminoglycan, collagen) was analyzed, and both the tissue and medium were screened for tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), prostaglandin-E-2 (PGE(2)), and nitric oxide (NO). A range of tonicities (isotonic to hypotonic) was present at day 3 in the PEG-treated samples. However, during culture, the tonicity range narrowed as GAGs leached from the tissue. TNF-alpha and IL-1 beta were below detection limits in all conditions, while mid- and downstream inflammatory cytokines were detected. This may suggest that the extracellular environment directly affects NP cells instead of inducing a classical inflammatory cascade. Furthermore, IL-8 increased in swelling restricted samples, while IL-6 and PGE(2) were elevated in free swelling controls. These findings may suggest the involvement of different mechanisms in disc degeneration with intact AF compared to herniation, and encourage further investigation. (c) 2019 The Authors. Journal of Orthopaedic Research (R) Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res
Question: Is there a relationship between size and death in the Iona-lived, deep-rooted tree, Acacia erioloba, in a semi-arid savanna? What is the size-class distribution of A. erioloba mortality? Does the mortality distribution differ from total tree size distribution? Does A. erioloba mortality distribution match the mortality distributions recorded thus far in other environments? Location: Dronfield Ranch, near Kimberley, Kalahari, South Africa. Methods: A combination of aerial photographs and a satellite image covering 61 year was used to provide long-term spatial data on mortality. We used aerial photographs of the study area from 1940, 1964, 1984, 1993 and a satellite image from 2001 to follow three plots covering 510 ha. We were able to identify and individually follow ca. 3000 individual trees from 1940 till 2001. Results: The total number of trees increased over time. No relationship between total number of trees and mean tree size was detected. There were no trends over time in total number of deaths per plot or in size distributions of dead trees. Kolmogorov-Smirnov tests showed no differences in size class distributions for living trees through time. The size distribution of dead trees was significantly different from the size distribution of all trees present on the plots. Overall, the number of dead trees was low in small size classes, reached a peak value when canopy area was 20 - 30 m(2), and declined in lamer size-classes. Mortality as a ratio of dead vs. total trees peaked at intermediate canopy sizes too. Conclusion: A. erioloba mortality was size-dependent, peaking at intermediate sizes. The mortality distribution differs from all other tree mortality distributions recorded thus far. We suggest that a possible mechanism for this unusual mortality distribution is intraspecific competition for water in this semi-arid environment.
High diffusion-sensitizing magnetic field gradients have been more and more often applied nowadays to achieve a better characterization of the microstructure. As the resulting spin-echo signal significantly deviates from the conventional Gaussian form, various models have been employed to interpret these deviations and to relate them with the microstructural properties of a sample. In this paper, we argue that the non-Gaussian behavior of the signal is a generic universal feature of the Bloch-Torrey equation. We provide a simple yet rigorous description of the localization regime emerging at high extended gradients and identify its origin as a symmetry breaking at the reflecting boundary. We compare the consequent non-Gaussian signal decay to other diffusion NMR regimes such as slow-diffusion, motional-narrowing and diffusion-diffraction regimes. We emphasize limitations of conventional perturbative techniques and advocate for non-perturbative approaches which may pave a way to new imaging modalities in this field.
The synthesis of new N,N-dimethyl carbamoyl 5-aryloxytetrazoles have been reported. Their dynamic H-1-NMR via rotation about C-N bonds in moiety of urea group [a; CO-NMe2 and b; (2-tetrazolyl)N-CO rotations] in the solvents CDCl3 (223-333 K) and DMSO (298-363 K) is studied. Accordingly, the free energies of activation, obtained 16.5 and 16.9 kcal mol(-1) respectively, attributed to the conformational isomerization about the Me2N-C=O bond (a rotation). Moreover, a and b barrier to rotations in 5-((4-methylphenoxy)-N,N-dimethyl-2H-tetrazole-2-carboxamide (P) also were computed at level of B3LYP using 6-311++G** basis set. The optimized geometry parameters are in good agreement with X-ray structure data. The computation of energy barrier for a and b was determined 16.9 and 2.5 kcal mol(-1), respectively. The former is completely in agreement with the result obtained via dynamic NMR. X-ray structure analysis data demonstrate that just 2-acylated tetrazole was formed in the case of 5-(p-tolyloxy)-N,N-dimethyl-2H-tetrazole-2-carboxamide. X-ray data also revealed a planar trigonal orientation of the Me2N group which is coplanar to carbonyl group with the partial double-bond C-N character. It also demonstrates the synperiplanar position of C=O group with tetrazolyl ring. On average, in solution the plane containing carbonyl bond is almost perpendicular to the plane of the tetrazolyl ring (because of steric effects as confirmed by B3LY12/6-311++G**) while the plane containing Me2N group is coplanar with carbonyl bond which is in contrast with similar urea derivatives and it demonstrates the unusually high rotational energy barrier of these compounds. (C) 2016 Elsevier B.V. All rights reserved.
Based on results of previous investigations of tephra-tuff volcaniclastic deposits and a geophysical survey in the surroundings of the Zelezna hurka Quaternary volcano, West Bohemia, we performed detailed geophysical Surveys using gravimetry, magnetometry and electrical conductivity techniques. Striking anomalies were revealed in a morphological depression near Mytina, West Bohemia, as a strong evidence of the assumed maar-diatreme structure. The sharp isometric gravity low of -2.30 mGal, as well as the corresponding positive magnetic anomaly of 200 nT with a negative rim on its northern side indicate a steeply clipping geological body of low density and containing magnetic rocks/minerals. Magnetic survey also showed pronounced local anomalies outside the depression that can reflect relicts of the tephra rim of the maar. This geophysical evidence was then proven by an exploratory drilling near the centre of the gravity anomaly. Macroscopic on-site evaluation of the core, and more detailed sedimentological, petrochemical, palynological and microbiological laboratory analyses further confirmed the existence of a maar structure filled by 84 m of lake sediments reflecting a Succession of several warm and cold climatic periods. Results Of palynological analyses confirm the presence of a continuous palaeoclimate archive, with at least three successive warmer periods of most probably interstadial character from the upper Quaternary Saalian complex. Therefore. the recovered sediment sequence holds strong potential for in-depth palaeoclimate reconstruction and deep biosphere studies. At the bottom of the Mytina-1 (MY- 1) borehole (84-85.5 M), Country rock debris Was found, containing also volcanic bombs and lapilli. The discovered volcanic Structure is considered to be the first known Quaternary maar-diatreme volcano on the territory of the Bohemian Massif. Because of hidden active magmatic processes in combination with earthquake swarm seismicity ca. 20-30 km north of the Mytina maar, reconstruction of the palaeovolcanological evolution is important for evaluation of hazard potential of the NE and E Part of the Cheb Basin.
Laboratory mice are the most commonly used animal model for Staphylococcus aureus infection studies. We have previously shown that laboratory mice from global vendors are frequently colonized with S. aureus. Laboratory mice originate from wild house mice. Hence, we investigated whether wild rodents, including house mice, as well as shrews are naturally colonized with S. aureus and whether S. aureus adapts to the wild animal host. 295 animals of ten different species were caught in different locations over four years (2012-2015) in Germany, France and the Czech Republic. 45 animals were positive for S. aureus (15.3%). Three animals were co-colonized with two different isolates, resulting in 48 S. aureus isolates in total. Positive animals were found in Germany and the Czech Republic in each studied year. The S. aureus isolates belonged to ten different spa types, which grouped into six lineages (clonal complex (CC) 49, CC88, CC130, CC1956, sequence type (ST) 890, ST3033). CC49 isolates were most abundant (17/48, 35.4%), followed by CC1956 (14/48, 29.2%) and ST890 (9/48, 18.8%). The wild animal isolates lacked certain properties that are common among human isolates, e.g., a phage-encoded immune evasion cluster, superantigen genes on mobile genetic elements and antibiotic resistance genes, which suggests long-term adaptation to the wild animal host. One CC130 isolate contained the mecC gene, implying wild rodents might be both reservoir and vector for methicillin-resistant. In conclusion, we demonstrated that wild rodents and shrews are naturally colonized with S. aureus, and that those S. aureus isolates show signs of host adaptation.
The work is designed to investigate the impacts and sensitivity of climate change on water resources, droughts and hydropower production in Malawi, the South-Eastern region which is highly vulnerable to climate change. It is observed that rainfall is decreasing and temperature is increasing which calls for the understanding of what these changes may impact the water resources, drought occurrences and hydropower generation in the region. The study is conducted in the Greater Lake Malawi Basin (Lake Malawi and Shire River Basins) and is divided into three projects. The first study is assessing the variability and trends of both meteorological and hydrological droughts from 1970-2013 in Lake Malawi and Shire River basins using the standardized precipitation index (SPI) and standardized precipitation and evaporation Index (SPEI) for meteorological droughts and the lake level change index (LLCI) for hydrological droughts. And later the relationship of the meteorological and hydrological droughts is established.
While the second study extends the drought analysis into the future by examining the potential future meteorological water balance and associated drought characteristics such as the drought intensity (DI), drought months (DM), and drought events (DE) in the Greater Lake Malawi Basin. The sensitivity of drought to changes of rainfall and temperature is also assessed using the scenario-neutral approach. The climate change projections from 20 Coordinated Regional Climate Downscaling Experiment (CORDEX) models for Africa based on two scenarios (RCP4.5 and RCP8.5) for the periods 2021–2050 and 2071–2100 are used. The study also investigates the effect of bias-correction (i.e., empirical quantile mapping) on the ability of the climate model ensemble in reproducing observed drought characteristics as compared to raw climate projections.
The sensitivity of key hydrologic variables and hydropower generation to climate change in Lake Malawi and Shire River basins is assessed in third study. The study adapts the mesoscale Hydrological Model (mHM) which is applied separately in the Upper Lake Malawi and Shire River basins. A particular Lake Malawi model, which focuses on reservoir routing and lake water balance, has been developed and is interlinked between the two basins. Similar to second study, the scenario-neutral approach is also applied to determine the sensitivity of climate change on water resources more particularly Lake Malawi level and Shire River flow which later helps to estimate the hydropower production susceptibility.
Results suggest that meteorological droughts are increasing due to a decrease in precipitation which is exacerbated by an increase in temperature (potential evapotranspiration). The hydrological system of Lake Malawi seems to have a >24-month memory towards meteorological conditions since the 36-months SPEI can predict hydrological droughts ten-months in advance. The study has found the critical lake level that would trigger hydrological drought to be 474.1 m.a.s.l.
Despite the differences in the internal structures and uncertainties that exist among the climate models, they all agree on an increase of meteorological droughts in the future in terms of higher DI and longer events (DM). DI is projected to increase between +25% and +50% during 2021-2050 and between +131% and +388% during 2071-2100. This translates into +3 to +5, and +7 to +8 more drought months per year during both periods, respectively. With longer lasting drought events, DE is decreasing. Projected droughts based on RCP8.5 are 1.7 times more severe than droughts based on RCP4.5.
It is also found that an annual temperature increase of 1°C decreases mean lake level and outflow by 0.3 m and 17%, respectively, signifying the importance of intensified evaporation for Lake Malawi’s water budget. Meanwhile, a +5% (-5%) deviation in annual rainfall changes mean lake level by +0.7 m (-0.6 m). The combined effects of temperature increase and rainfall decrease result in significantly lower flows on Shire River. The hydrological river regime may change from perennial to seasonal with the combination of annual temperature increase and precipitation decrease beyond 1.5°C (3.5°C) and -20% (-15%). The study further projects a reduction in annual hydropower production between 1% (RCP8.5) and 2.5% (RCP4.5) during 2021–2050 and between 5% (RCP4.5) and 24% (RCP8.5) during 2071–2100.
The findings are later linked to global policies more particularly the United Nations Framework Convention on Climate Change (UNFCCC)’s Paris Agreement and the United Nations (UN)’s Sustainable Development Goals (SDGs), and how the failure to adhere the restriction of temperature increase below the global limit of 1.5°C will affect drought and the water resources in Malawi consequently impact the hydropower production. As a result, the achievement of most of the SDGs will be compromised.
The results show that it is of great importance that a further development of hydro energy on the Shire River should take into account the effects of climate change. The information generation is important for decision making more especially supporting the climate action required to fight against climate change. The frequency of extreme climate events due to climate change has reached the climate emergency as saving lives and livelihoods require urgent action.
Meteorological and hydrological drought assessment in Lake Malawi and Shire River basins (1970-2013)
(2020)
The study assesses the variability and trends of both meteorological and hydrological droughts from 1970 to 2013 in Lake Malawi and Shire River basins using the standardized precipitation index (SPI) and standardized precipitation and evaporation index (SPEI) for meteorological droughts and the lake level change index (LLCI) for hydrological droughts. Trends and slopes in droughts and drought drivers are estimated using Mann-Kendall test and Sen's slope, respectively. Results suggest that meteorological droughts are increasing due to a decrease in precipitation which is exacerbated by an increase in temperature (potential evapotranspiration). The hydrological system of Lake Malawi seems to have a >24-month memory towards meteorological conditions, since the 36-month SPEI can predict hydrological droughts 10 months in advance. The study has found the critical lake level that would trigger hydrological drought to be 474.1 m a.s.l. The increase in drought is a concern as this will have serious impacts on water resources and hydropower supply in Malawi.
The sensitivity of key hydrologic variables and hydropower generation to climate change in the Lake Malawi and Shire River basins is assessed. The study adapts the mesoscale Hydrological Model (mHM) which is applied separately in the Upper Lake Malawi and Shire River basins. A particular Lake Malawi model, which focuses on reservoir routing and lake water balance, has been developed and is interlinked between the two basins. Climate change projections from 20 Coordinated Regional Climate Downscaling Experiment (CORDEX) models for Africa based on two scenarios (RCP4.5 and RCP8.5) for the periods 2021-2050 and 2071-2100 are used. An annual temperature increase of 1 degrees C decreases mean lake level and outflow by 0.3 m and 17%, respectively, signifying the importance of intensified evaporation for Lake Malawi's water budget. Meanwhile, a +5% (-5%) deviation in annual rainfall changes mean lake level by +0.7 m (-0.6 m). The combined effects of temperature increase and rainfall decrease result in significantly lower flows in the Shire River. The hydrological river regime may change from perennial to seasonal with the combination of annual temperature increase and precipitation decrease beyond 1.5 degrees C (3.5 degrees C) and -20% (-15%). The study further projects a reduction in annual hydropower production between 1% (RCP8.5) and 2.5% (RCP4.5) during 2021-2050 and between 5% (RCP4.5) and 24% (RCP8.5) during 2071-2100. The results show that it is of great importance that a further development of hydro energy on the Shire River should take into account the effects of climate change, e.g., longer low flow periods and/or higher discharge fluctuations, and thus uncertainty in the amount of electricity produced.
The study examined the potential future changes of drought characteristics in the Greater Lake Malawi Basin in Southeast Africa. This region strongly depends on water resources to generate electricity and food. Future projections (considering both moderate and high emission scenarios) of temperature and precipitation from an ensemble of 16 bias-corrected climate model combinations were blended with a scenario-neutral response surface approach to analyses changes in: (i) the meteorological conditions, (ii) the meteorological water balance, and (iii) selected drought characteristics such as drought intensity, drought months, and drought events, which were derived from the Standardized Precipitation and Evapotranspiration Index. Changes were analyzed for a near-term (2021-2050) and far-term period (2071-2100) with reference to 1976-2005. The effect of bias-correction (i.e., empirical quantile mapping) on the ability of the climate model ensemble to reproduce observed drought characteristics as compared to raw climate projections was also investigated. Results suggest that the bias-correction improves the climate models in terms of reproducing temperature and precipitation statistics but not drought characteristics. Still, despite the differences in the internal structures and uncertainties that exist among the climate models, they all agree on an increase of meteorological droughts in the future in terms of higher drought intensity and longer events. Drought intensity is projected to increase between +25 and +50% during 2021-2050 and between +131 and +388% during 2071-2100. This translates into +3 to +5, and +7 to +8 more drought months per year during both periods, respectively. With longer lasting drought events, the number of drought events decreases. Projected droughts based on the high emission scenario are 1.7 times more severe than droughts based on the moderate scenario. That means that droughts in this region will likely become more severe in the coming decades. Despite the inherent high uncertainties of climate projections, the results provide a basis in planning and (water-)managing activities for climate change adaptation measures in Malawi. This is of particular relevance for water management issues referring hydro power generation and food production, both for rain-fed and irrigated agriculture.
The study examined the potential future changes of drought characteristics in the Greater Lake Malawi Basin in Southeast Africa. This region strongly depends on water resources to generate electricity and food. Future projections (considering both moderate and high emission scenarios) of temperature and precipitation from an ensemble of 16 bias-corrected climate model combinations were blended with a scenario-neutral response surface approach to analyses changes in: (i) the meteorological conditions, (ii) the meteorological water balance, and (iii) selected drought characteristics such as drought intensity, drought months, and drought events, which were derived from the Standardized Precipitation and Evapotranspiration Index. Changes were analyzed for a near-term (2021–2050) and far-term period (2071–2100) with reference to 1976–2005. The effect of bias-correction (i.e., empirical quantile mapping) on the ability of the climate model ensemble to reproduce observed drought characteristics as compared to raw climate projections was also investigated. Results suggest that the bias-correction improves the climate models in terms of reproducing temperature and precipitation statistics but not drought characteristics. Still, despite the differences in the internal structures and uncertainties that exist among the climate models, they all agree on an increase of meteorological droughts in the future in terms of higher drought intensity and longer events. Drought intensity is projected to increase between +25 and +50% during 2021–2050 and between +131 and +388% during 2071–2100. This translates into +3 to +5, and +7 to +8 more drought months per year during both periods, respectively. With longer lasting drought events, the number of drought events decreases. Projected droughts based on the high emission scenario are 1.7 times more severe than droughts based on the moderate scenario. That means that droughts in this region will likely become more severe in the coming decades. Despite the inherent high uncertainties of climate projections, the results provide a basis in planning and (water-)managing activities for climate change adaptation measures in Malawi. This is of particular relevance for water management issues referring hydro power generation and food production, both for rain-fed and irrigated agriculture.
The study examined the potential future changes of drought characteristics in the Greater Lake Malawi Basin in Southeast Africa. This region strongly depends on water resources to generate electricity and food. Future projections (considering both moderate and high emission scenarios) of temperature and precipitation from an ensemble of 16 bias-corrected climate model combinations were blended with a scenario-neutral response surface approach to analyses changes in: (i) the meteorological conditions, (ii) the meteorological water balance, and (iii) selected drought characteristics such as drought intensity, drought months, and drought events, which were derived from the Standardized Precipitation and Evapotranspiration Index. Changes were analyzed for a near-term (2021–2050) and far-term period (2071–2100) with reference to 1976–2005. The effect of bias-correction (i.e., empirical quantile mapping) on the ability of the climate model ensemble to reproduce observed drought characteristics as compared to raw climate projections was also investigated. Results suggest that the bias-correction improves the climate models in terms of reproducing temperature and precipitation statistics but not drought characteristics. Still, despite the differences in the internal structures and uncertainties that exist among the climate models, they all agree on an increase of meteorological droughts in the future in terms of higher drought intensity and longer events. Drought intensity is projected to increase between +25 and +50% during 2021–2050 and between +131 and +388% during 2071–2100. This translates into +3 to +5, and +7 to +8 more drought months per year during both periods, respectively. With longer lasting drought events, the number of drought events decreases. Projected droughts based on the high emission scenario are 1.7 times more severe than droughts based on the moderate scenario. That means that droughts in this region will likely become more severe in the coming decades. Despite the inherent high uncertainties of climate projections, the results provide a basis in planning and (water-)managing activities for climate change adaptation measures in Malawi. This is of particular relevance for water management issues referring hydro power generation and food production, both for rain-fed and irrigated agriculture.