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Older adults with amnestic mild cognitive impairment (aMCI) who in addition to their memory deficits also suffer from frontal-executive dysfunctions have a higher risk of developing dementia later in their lives than older adults with aMCI without executive deficits and older adults with non-amnestic MCI (naMCI). Handgrip strength (HGS) is also correlated with the risk of cognitive decline in the elderly. Hence, the current study aimed to investigate the associations between HGS and executive functioning in individuals with aMCI, naMCI and healthy controls. Older, right-handed adults with amnestic MCI (aMCI), non-amnestic MCI (naMCI), and healthy controls (HC) conducted a handgrip strength measurement via a handheld dynamometer. Executive functions were assessed with the Trail Making Test (TMT A&B). Normalized handgrip strength (nHGS, normalized to Body Mass Index (BMI)) was calculated and its associations with executive functions (operationalized through z-scores of TMT B/A ratio) were investigated through partial correlation analyses (i.e., accounting for age, sex, and severity of depressive symptoms). A positive and low-to-moderate correlation between right nHGS (rp (22) = 0.364; p = 0.063) and left nHGS (rp (22) = 0.420; p = 0.037) and executive functioning in older adults with aMCI but not in naMCI or HC was observed. Our results suggest that higher levels of nHGS are linked to better executive functioning in aMCI but not naMCI and HC. This relationship is perhaps driven by alterations in the integrity of the hippocampal-prefrontal network occurring in older adults with aMCI. Further research is needed to provide empirical evidence for this assumption.
In his short paper of 1886, the neogrammarian linguist Delbruck sketches his views on normal language processing and their relevance for the interpretation of some of the symptoms of progressive anomic aphasia. In particular, he discusses proper name impairments, verb and abstract noun superiority and the predominance of semantically related errors. Furthermore, he suggests that part of speech, morphology and word order may be preserved in this condition. This historical document has been lost in oblivion but the original ideas and their relevance for contemporary discussions merit a revival.
This paper describes the proof calculus LD for clausal propositional logic, which is a linearized form of the well-known DPLL calculus extended by clause learning. It is motivated by the demand to model how current SAT solvers built on clause learning are working, while abstracting from decision heuristics and implementation details. The calculus is proved sound and terminating. Further, it is shown that both the original DPLL calculus and the conflict-directed backtracking calculus with clause learning, as it is implemented in many current SAT solvers, are complete and proof-confluent instances of the LD calculus.
Computer-based simulation models are frequently used in hydrological research and engineering but also in other fields of environmental sciences. New case studies often require existing model concepts to be adapted. Extensions may be necessary due to the peculiarities of the studied natural system or subtleties of anthropogenic control. In other cases, simplifications must be made in response to scarce data, incomplete knowledge, or restrictions set by the spatio-temporal scale of application. This paper introduces an open-source modeling framework called ECHSE designed to cope with the above-mentioned challenges. It provides a lightweight infrastructure for the rapid development of new, reusable simulation tools and, more importantly, the safe modification of existing formulations. ECHSE-based models treat the simulated system as a collection of interacting objects. Although feedbacks are generally supported, the majority of the objects' interactions is expected to be of the feed-forward type. Therefore, the ECHSE software is particularly useful in the context of hydrological catchment modeling. Conversely, it is unsuitable, e.g., for fully hydrodynamic simulations and groundwater flow modeling. The focus of the paper is put on a comprehensible outline of the ECHSE's fundamental concepts and limitations. For the purpose of illustration, a specific, ECHSE-based solution for hydrological catchment modeling is presented which has undergone testing in a number of river basins. (C) 2015 Elsevier Ltd. All rights reserved.
A few months before his death, A. v. Humboldt attended the celebration in honor of the 127th birthday of George Washington at the US legation in Berlin. A letter to the American Envoy, Joseph A. Wright (1810 – 1867), underlines Humboldt’s admiration for the fi rst president of the United States. At the same time Humboldt asked the diplomat to mail a letter to the German-American Bernard Moses (1832 – 1897) in Clinton, Louisiana, who had named his son Alexander Humboldt Moses (grave on the Hebrew Rest Cemetery #2 in New Orleans, burial plot A, 12, 5). It appears to be possible that the Moses family still owns Humboldt’s letter.
In a recent paper, the Lefschetz number for endomorphisms (modulo trace class operators) of sequences of trace class curvature was introduced. We show that this is a well defined, canonical extension of the classical Lefschetz number and establish the homotopy invariance of this number. Moreover, we apply the results to show that the Lefschetz fixed point formula holds for geometric quasiendomorphisms of elliptic quasicomplexes.
The nutrient concentration in seeds determines many aspects of potential success of the sexual reproductive phase of plants, including the seed predation probability, efficiency of seed dispersal and seedling performance. Despite considerable research interest in latitudinal gradients of foliar nutrients, a similar gradient for seeds remains unexplored. We investigated a potential latitudinal gradient in seed nutrient concentrations within the widespread European understorey forest herb Anemone nemorosa L. We sampled seeds of A. nemorosa in 15 populations along a 1900-km long latitudinal gradient at three to seven seed collection dates post-anthesis and investigated the relative effects of growing degree-hours > 5 degrees C, soil characteristics and latitude on seed nutrient concentrations. Seed nitrogen, nitrogen:phosphorus ratio and calcium concentration decreased towards northern latitudes, while carbon:nitrogen ratios increased. When taking differences in growing degree-hours and measured soil characteristics into account and only considering the most mature seeds, the latitudinal decline remained particularly significant for seed nitrogen concentration. We argue that the decline in seed nitrogen concentration can be attributed to northward decreasing seed provisioning due to lower soil nitrogen availability or greater investment in clonal reproduction. This pattern may have large implications for the reproductive performance of this forest herb as the degree of seed provisioning ultimately co-determines seedling survival and reproductive success.
A total of 271 pollen records were selected from a large collection of both raw and digitized pollen spectra from eastern continental Asia (70 degrees-135 degrees E and 18 degrees-55 degrees N). Following pollen percentage recalculations, taxonomic homogenization, and age-depth model revision, the pollen spectra were interpolated at a 500-year resolution and a taxonomically harmonized and temporally standardized fossil pollen dataset established with 226 pollen taxa, covering the last 22 cal lea. Of the 271 pollen records, 85% were published since 1990, with reliable chronologies and high temporal resolutions; of these, 50% have raw data with complete pollen assemblages, ensuring the quality of this dataset The pollen records available for each 500-year time slice are well distributed over all main vegetation types and climatic zones of the study area, making their pollen spectra suitable for paleovegetation and paleoclimate research. Such a dataset can be used as an example for the development of similar datasets for other regions of the world.
We use the prolonged Greek crisis as a case study to understand how a lasting economic shock affects the innovation strategies of firms in economies with moderate innovation activities. Adopting the 3-stage CDM model, we explore the link between R&D, innovation, and productivity for different size groups of Greek manufacturing firms during the prolonged crisis. At the first stage, we find that the continuation of the crisis is harmful for the R&D engagement of smaller firms while it increased the willingness for R&D activities among the larger ones. At the second stage, among smaller firms the knowledge production remains unaffected by R&D investments, while among larger firms the R&D decision is positively correlated with the probability of producing innovation, albeit the relationship is weakened as the crisis continues. At the third stage, innovation output benefits only larger firms in terms of labor productivity, while the innovation-productivity nexus is insignificant for smaller firms during the lasting crisis.
Many Android applications embed webpages via WebView components and execute JavaScript code within Android. Hybrid applications leverage dedicated APIs to load a resource and render it in a WebView. Furthermore, Android objects can be shared with the JavaScript world. However, bridging the interfaces of the Android and JavaScript world might also incur severe security threats: Potentially untrusted webpages and their JavaScript might interfere with the Android environment and its access to native features.
No general analysis is currently available to assess the implications of such hybrid apps bridging the two worlds. To understand the semantics and effects of hybrid apps, we perform a large-scale study on the usage of the hybridization APIs in the wild. We analyze and categorize the parameters to hybridization APIs for 7,500 randomly selected and the 196 most popular applications from the Google Playstore as well as 1000 malware samples. Our results advance the general understanding of hybrid applications, as well as implications for potential program analyses, and the current security situation: We discovered thousands of flows of sensitive data from Android to JavaScript, the vast majority of which could flow to potentially untrustworthy code. Our analysis identified numerous web pages embedding vulnerabilities, which we exemplarily exploited. Additionally, we discovered a multitude of applications in which potentially untrusted JavaScript code may interfere with (trusted) Android objects, both in benign and malign applications.
A large landslide (frozen debris avalanche) occurred at Assapaat on the south coast of the Nuussuaq Peninsula in Central West Greenland on June 13, 2021, at 04:04 local time. We present a compilation of available data from field observations, photos, remote sensing, and seismic monitoring to describe the event. Analysis of these data in combination with an analysis of pre- and post-failure digital elevation models results in the first description of this type of landslide. The frozen debris avalanche initiated as a 6.9 * 10(6) m(3) failure of permafrozen talus slope and underlying colluvium and till at 600-880 m elevation. It entrained a large volume of permafrozen colluvium along its 2.4 km path in two subsequent entrainment phases accumulating a total volume between 18.3 * 10(6) and 25.9 * 10(6) m(3). About 3.9 * 10(6) m(3) is estimated to have entered the Vaigat strait; however, no tsunami was reported, or is evident in the field. This is probably because the second stage of entrainment along with a flattening of slope angle reduced the mobility of the frozen debris avalanche. We hypothesise that the initial talus slope failure is dynamically conditioned by warming of the ice matrix that binds the permafrozen talus slope. When the slope ice temperature rises to a critical level, its shear resistance is reduced, resulting in an unstable talus slope prone to failure. Likewise, we attribute the large-scale entrainment to increasing slope temperature and take the frozen debris avalanche as a strong sign that the permafrost in this region is increasingly at a critical state. Global warming is enhanced in the Arctic and frequent landslide events in the past decade in Western Greenland let us hypothesise that continued warming will lead to an increase in the frequency and magnitude of these types of landslides. Essential data for critical arctic slopes such as precipitation, snowmelt, and ground and surface temperature are still missing to further test this hypothesis. It is thus strongly required that research funds are made available to better predict the change of landslide threat in the Arctic.
A lamin in lower eukaryotes?
(2012)
Lamins are the major components of the nuclear lamina and serve not only as a mechanical support, but are also involved in chromatin organization, epigenetic regulation, transcription and mitotic events. Despite these universal tasks, lamins have so far been found only in metazoans. Yet, recently we have identified Dictyostelium NE81 as the first lamin-like protein in a lower eukaryote. Based on the current knowledge, we draw a model for nuclear envelope organization in Dictyostelium in this Extra View and we review the experimental data that justified this classification. Furthermore we provide unpublished data underscoring the requirement of posttranslational CaaX-box processing for proper protein localization at the nuclear envelope. Sequence comparison of NE81 sequences from four Dictyostelia with bona fide lamins illustrates the evolutional relationship between these proteins. Under certain conditions these usually unicellular social amoebae congregate to form a multicellular body. We propose that the evolution of the lamin-like NE81 went along with the invention of multicellularity.
Lakes are dominant and diverse landscape features in the Arctic, but conventional land cover classification schemes typically map them as a single uniform class. Here, we present a detailed lake-centric geospatial database for an Arctic watershed in northern Alaska. We developed a GIS dataset consisting of 4362 lakes that provides information on lake morphometry, hydrologic connectivity, surface area dynamics, surrounding terrestrial ecotypes, and other important conditions describing Arctic lakes. Analyzing the geospatial database relative to fish and bird survey data shows relations to lake depth and hydrologic connectivity, which are being used to guide research and aid in the management of aquatic resources in the National Petroleum Reserve in Alaska. Further development of similar geospatial databases is needed to better understand and plan for the impacts of ongoing climate and land-use changes occurring across lake-rich landscapes in the Arctic.
From the Drosophila virilis late puff region 31C, we microcloned two neighbouring genes, Kil-1 and Kil-2, that encode putative Kunitz serine protease inhibitor like proteins. The Kil-1 gene is expressed exclusively in prepupal salivary glands. Using a size mutant of the KIL-1 protein and MALDI-TOF analysis, we demonstrate that during pupation this protein is released from the prepupal salivary glands into the pupation fluid covering the surface of the pupa. 3-D- structure predictions are consistent with the known crystal structure of the human Kunitz type protease inhibitor 2KNT. This is the first experimental proof for the extra-corporal presence of a distinct Drosophila prepupal salivary gland protein. Possible functions of KIL-1 in the context of the control of proteolytic activities in the pupation fluid are discussed. (C) 2004 Elsevier Ltd. All rights reserved
The M-type kinesin isoform, Kif9, has recently been implicated in maintaining a physical connection between the centrosome and nucleus in Dictyostelium discoideum. However, the mechanism by which Kif9 functions to link these two organelles remains obscure. Here we demonstrate that the Kif9 protein is localized to the nuclear envelope and is concentrated in the region underlying the centrosome point of attachment. Nuclear anchorage appears mediated through a specialized transmembrane domain located in the carboxyl terminus. Kif9 interacts with microtubules in in vitro binding assays and effects an endwise depolymerization of the polymer. These results suggest a model whereby Kif9 is anchored to the nucleus and generates a pulling force that reels the centrosome up against the nucleus. This is a novel activity for a kinesin motor, one important for progression of cells into mitosis and to ensure centrosome-nuclear parity in a multinuclear environment.
Context. The spectroscopic class of subdwarf A-type (sdA) stars has come into focus in recent years because of their possible link to extremely low-mass white dwarfs, a rare class of objects resulting from binary evolution. Although most sdA stars are consistent with metal-poor halo main-sequence stars, the formation and evolution of a fraction of these stars are still matters of debate. Aims. The identification of photometric variability can help to put further constraints on the evolutionary status of sdA stars, in particular through the analysis of pulsations. Moreover, the binary ratio, which can be deduced from eclipsing binaries and ellipsoidal variables, is important as input for stellar models. In order to search for variability due to either binarity or pulsations in objects of the spectroscopic sdA class, we have extracted all available high precision light curves from the Kepler K2 mission.
Methods. We have performed a thorough time series analysis on all available light curves, employing three different methods. Frequencies with a signal-to-noise ratio higher than four have been used for further analysis.
Results. From the 25 targets, 13 turned out to be variables of different kinds (i.e., classical pulsating stars, ellipsoidal and cataclysmic variables, eclipsing binaries, and rotationally induced variables). For the remaining 12 objects, a variability threshold was determined.
Transposable elements (TEs) make up a large proportion of eukaryotic genomes. As their mobilization creates genetic variation that threatens genome integrity, TEs are epigenetically silenced through several pathways, and this may spread to neighboring sequences. JUMONJI (JMJ) proteins can function as antisilencing factors and prevent silencing of genes next to TEs. Whether TE silencing is counterbalanced by the activity of antisilencing factors is still unclear. Here, we characterize JMJ24 as a regulator of TE silencing. We show that loss of JMJ24 results in increased silencing of the DNA transposon AtMu1c, while overexpression of JMJ24 reduces silencing. JMJ24 has a JumonjiC (JmjC) domain and two RING domains. JMJ24 autoubiquitinates in vitro, demonstrating E3 ligase activity of the RING domain(s). JMJ24-JmjC binds the N-terminal tail of histone H3, and full-length JMJ24 binds histone H3 in vivo. JMJ24 activity is anticorrelated with histone H3 Lys 9 dimethylation (H3K9me2) levels at AtMu1c. Double mutant analyses with epigenetic silencing mutants suggest that JMJ24 antagonizes histone H3K9me2 and requires H3K9 methyltransferases for its activity on AtMu1c. Genome-wide transcriptome analysis indicates that JMJ24 affects silencing at additional TEs. Our results suggest that the JmjC domain of JMJ24 has lost demethylase activity but has been retained as a binding domain for histone H3. This is in line with phylogenetic analyses indicating that JMJ24 (with the mutated JmjC domain) is widely conserved in angiosperms. Taken together, this study assigns a role in TE silencing to a conserved JmjC-domain protein with E3 ligase activity, but no demethylase activity.
We present a new autoclave that enables in situ characterization of hydrothermal fluids at high pressures and high temperatures at synchrotron x-ray radiation sources. The autoclave has been specifically designed to enable x-ray absorption spectroscopy in fluids with applications to mineral solubility and element speciation analysis in hydrothermal fluids in complex compositions. However, other applications, such as Raman spectroscopy, in high-pressure fluids are also possible with the autoclave. First experiments were run at pressures between 100 and 600 bars and at temperatures between 25 degrees C and 550 degrees C, and preliminary results on scheelite dissolution in fluids of different compositions show that the autoclave is well suited to study the behavior of ore-forming metals at P-T conditions relevant to the Earth's crust.
We demonstrate a recycling system for synthetic nicotinamide cofactor analogues using a soluble hydrogenase with turnover number of >1000 for reduction of the cofactor analogues by H-2.
Coupling this system to an ene reductase, we show quantitative conversion of N-ethylmaleimide to N-ethylsuccinimide.
The biocatalyst system retained >50% activity after 7 h.
A hydrochemical approach to quantify the role of return flow in a surface flow-dominated catchment
(2017)
Stormflow generation in headwater catchments dominated by subsurface flow has been studied extensively, yet catchments dominated by surface flow have received less attention. We addressed this by testing whether stormflow chemistry is controlled by either (a) the event-water signature of overland flow, or (b) the pre-event water signature of return flow. We used a high-resolution hydrochemical data set of stormflow and end-members of multiple storms in an end-member mixing analysis to determine the number of end-members needed to explain stormflow, characterize and identify potential end-members, calculate their contributions to stormflow, and develop a conceptual model of stormflow. The arrangement and relative positioning of end-members in stormflow mixing space suggest that saturation excess overland flow (26-48%) and return flow from two different subsurface storage pools (17-53%) are both similarly important for stormflow. These results suggest that pipes and fractures are important flow paths to rapidly release stored water and highlight the value of within-event resolution hydrochemical data to assess the full range and dynamics of flow paths.
We prove a homology vanishing theorem for graphs with positive Bakry-' Emery curvature, analogous to a classic result of Bochner on manifolds [3]. Specifically, we prove that if a graph has positive curvature at every vertex, then its first homology group is trivial, where the notion of homology that we use for graphs is the path homology developed by Grigor'yan, Lin, Muranov, and Yau [11]. We moreover prove that the fundamental group is finite for graphs with positive Bakry-' Emery curvature, analogous to a classic result of Myers on manifolds [22]. The proofs draw on several separate areas of graph theory, including graph coverings, gain graphs, and cycle spaces, in addition to the Bakry-Emery curvature, path homology, and graph homotopy. The main results follow as a consequence of several different relationships developed among these different areas. Specifically, we show that a graph with positive curvature cannot have a non-trivial infinite cover preserving 3-cycles and 4-cycles, and give a combinatorial interpretation of the first path homology in terms of the cycle space of a graph. Furthermore, we relate gain graphs to graph homotopy and the fundamental group developed by Grigor'yan, Lin, Muranov, and Yau [12], and obtain an alternative proof of their result that the abelianization of the fundamental group of a graph is isomorphic to the first path homology over the integers.
The determination of low-molecular weight substances (haptens) is demonstrated with a homogeneous time-resolved immunoassay using antibody-induced luminescence quenching. Our novel assay technology uses the newly developed monoclonal antibody (G24-BA9) to quench the luminescence of europium trisbipyridine (EuTBP). We performed a competitive biotin immunoassay including an EuTBP-biotin conjugate, the anti-EuTBP antibody G24-BA9 and streptavidin as assay components. Steric hindrance allows only the binding of either G24-BA9 (to the EuTBP moiety) or streptavidin (to the biotin moiety) to the EuTBP-biotin conjugate. Addition of the analyte biotin resulted in the binding of streptavidin to biotin and a concomitant preferred binding of G24-BA9 to EuTBP-biotin. Since G24-BA9 quenches the luminescence of EuTBP within the conjugate, the luminescence signal could be used to indicate and quantify the presence of free biotin in the system. All experiments were carried out in solution in the presence of 5% serum demonstrating the possibility of using our novel assay for a very fast determination of low molecular weight substances in biological fluids.
In nature, plants often encounter chronic or recurring stressful conditions. Recent results indicate that plants can remember a past exposure to stress to be better prepared for a future stress incident. However, the molecular basis of this is poorly understood. Here, we report the involvement of chromatin modifications in the maintenance of acquired thermotolerance (heat stress [HS] memory). HS memory is associated with the accumulation of histone H3 lysine 4 di- and trimethylation at memory-related loci. This accumulation outlasts their transcriptional activity and marks them as recently transcriptionally active. High accumulation of H3K4 methylation is associated with hyper-induction of gene expression upon a recurring HS. This transcriptional memory and the sustained accumulation of H3K4 methylation depend on HSFA2, a transcription factor that is required for HS memory, but not initial heat responses. Interestingly, HSFA2 associates with memory-related loci transiently during the early stages following HS. In summary, we show that transcriptional memory after HS is associated with sustained H3K4 hyper-methylation and depends on a hit-and-run transcription factor, thus providing a molecular framework for HS memory.
The article examines the work of Rabbi Yitzhak Isaac Halevy, arguably the most significant Orthodox response to the Wissenschaft des Judentums school of historiography. Halevy himself exemplified the Orthodox struggle against Wissenschaft, yet his work expressed a commitment to modern historiographical discipline that suggested an internalization of some of the very same premises adopted by Wissenschaft. While criticizing the representatives of Wissenschaft, Halevy was, at the same time, fighting for the internalization of its innovative characteristics into Orthodox society. He saw himself as a leader of a movement working towards the development of Orthodox Jewish studies and his application of modern historiographic principles from an Orthodox worldview as creating critical Orthodox historiography. Halevy’s approach promotes an understanding of Orthodoxy as a complex phenomenon, of which the struggle against modern secularization is just one of many characteristics.
We elaborate a boundary Fourier method for studying an analogue of the Hilbert problem for analytic functions within the framework of generalised Cauchy-Riemann equations. The boundary value problem need not satisfy the Shapiro-Lopatinskij condition and so it fails to be Fredholm in Sobolev spaces. We show a solvability condition of the Hilbert problem, which looks like those for ill-posed problems, and construct an explicit formula for approximate solutions.
Background: The outcrossing rate is a key determinant of the population-genetic structure of species and their long-term evolutionary trajectories. However, determining the outcrossing rate using current methods based on PCRgenotyping individual offspring of focal plants for multiple polymorphic markers is laborious and time-consuming.
Results: We have developed an amplicon-based, high-throughput enabled method for estimating the outcrossing rate and have applied this to an example of scented versus non-scented Capsella (Shepherd’s Purse) genotypes. Our results show that the method is able to robustly capture differences in outcrossing rates. They also highlight potential biases in the estimates resulting from differential haplotype sharing of the focal plants with the pollen-donor population at individual amplicons.
Conclusions: This novel method for estimating outcrossing rates will allow determining this key population-genetic parameter with high-throughput across many genotypes in a population, enabling studies into the genetic determinants of successful pollinator attraction and outcrossing.
A highly K+-selective two-photon fluorescent probe for the in vitro monitoring of physiological K+ levels in the range of 1-100 mM is reported. The two-photon excited fluorescence (TPEF) probe shows a fluorescence enhancement (FE) by a factor of about three in the presence of 160 mM K+, independently of one-photon (OP, 430 nm) or two-photon (TP, 860 nm) excitation and comparable K+-induced FEs in the presence of competitive Na+ ions. The estimated dissociation constant (K-d) values in Na+-free solutions (K-d(OP)=(28 +/- 5) mM and K-d(TP)=(36 +/- 6) mM) and in combined K+/Na+ solutions (K-d(OP)=(38 +/- 8) mM and K-d(TP)=(46 +/- 25) mM) reflecting the high K+/Na+ selectivity of the fluorescent probe. The TP absorption cross-section (sigma(2PA)) of the TPEF probe+160 mMK(+) is 26 GM at 860 nm. Therefore, the TPEF probe is a suitable tool for the in vitro determination of K+.
Herein, we report the synthesis of two phenylaza-[18]crown-6 lariat ethers with a coumarin fluorophore (1 and 2) and we reveal that compound 1 is an excellent probe for K+ ions under simulated physiological conditions. The presence of a 2-methoxyethoxy lariat group at the ortho position of the anilino moiety is crucial to the substantially increased stability of compounds 1 and 2 over their lariat-free phenylaza-[18] crown-6 ether analogues. Probe 1 shows a high K+/Na+ selectivity and a 2.5-fold fluorescence enhancement was observed in the presence of 100 mm K+ ions. A fluorescent membrane sensor, which was prepared by incorporating probe 1 into a hydrogel, showed a fully reversible response, a response time of 150 s, and a signal change of 7.8% per 1 mm K+ within the range 1-10 mm K+. The membrane was easily fabricated (only a single sensing layer on a solid polyester support), yet no leaching was observed. Moreover, compound 1 rapidly permeated into cells, was cytocompatible, and was suitable for the fluorescent imaging of K+ ions on both the extracellular and intracellular levels.
A desirable goal is to synthesize easily accessible and highly K+/Na+-selective fluoroionophores to monitor physiological K+ levels in vitro and in vivo. Therefore, highly K+/Na+-selective ionophores have to be developed. Herein, we obtained in a sequence of only four synthetic steps a set of K+-responsive fluorescent probes 4, 5 and 6. In a systematic study, we investigated the influence of the alkoxy substitution in ortho position of the aniline moiety in -conjugated aniline-1,2,3-triazole-coumarin-fluoroionophores 4, 5 and 6 [R=MeO (4), EtO (5) and iPrO (6)] towards the K+-complex stability and K+/Na+ selectivity. The highest K+-complex stability showed fluoroionophore 4 with a dissociation constant K-d of 19mm, but the K-d value increases to 31mm in combined K+/Na+ solutions, indicating a poor K+/Na+ selectivity. By contrast, 6 showed even in the presence of competitive Na+ ions equal K-d values (K-d(K+)=45mm and K-d(K+/Na+)=45mm) and equal K+-induced fluorescence enhancement factors (FEFs=2.3). Thus, the fluorescent probe 6 showed an outstanding K+/Na+ selectivity and is a suitable fluorescent tool to measure physiological K+ levels in the range of 10-80mm in vitro. Further, the isopropoxy-substituted N-phenylaza[18]crown-6 ionophore in 6 is a highly K+-selective building block with a feasible synthetic route.
Background: Leishmania tarentolae, a unicellular eukaryotic protozoan, has been established as a novel host for recombinant protein production in recent years. Current protocols for protein expression in Leishmania are, however, time consuming and require extensive lab work in order to identify well-expressing cell lines. Here we established an alternative protein expression work-flow that employs recently engineered infrared fluorescence protein (IFP) as a suitable and easy-to-handle reporter protein for recombinant protein expression in Leishmania. As model proteins we tested three proteins from the plant Arabidopsis thaliana, including a NAC and a type-B ARR transcription factor. Results: IFP and IFP fusion proteins were expressed in Leishmania and rapidly detected in cells by deconvolution microscopy and in culture by infrared imaging of 96-well microtiter plates using small cell culture volumes (2 mu L
Although the use of stable transformation technology has led to great insight into gene function, its application in high-throughput studies remains arduous. Agro-infiltration have been widely used in species such as Nicotiana benthamiana for the rapid detection of gene expression and protein interaction analysis, but this technique does not work efficiently in other plant species, including Arabidopsis thaliana. As an efficient high-throughput transient expression system is currently lacking in the model plant species A. thaliana, we developed a method that is characterized by high efficiency, reproducibility, and suitability for transient expression of a variety of functional proteins in A. thaliana and 7 other plant species, including Brassica oleracea, Capsella rubella, Thellungiella salsuginea, Thellungiella halophila, Solanum tuberosum, Capsicum annuum, and N. benthamiana. Efficiency of this method was independently verified in three independent research facilities, pointing to the robustness of this technique. Furthermore, in addition to demonstrating the utility of this technique in a range of species, we also present a case study employing this method to assess protein-protein interactions in the sucrose biosynthesis pathway in Arabidopsis.
Lacustrine sediments have been widely used to investigate past climatic and environmental changes on millennial to seasonal time scales. Sedimentary archives of lakes in mountainous regions may also record non-climatic events such as earthquakes. We argue herein that a set of 64 annual laminae couplets reconciles a stratigraphically inconsistent accelerator mass spectrometry (AMS) C-14 chronology in a similar to 4-m-long sediment core from Lake Mengda, in the north-eastern Tibetan Plateau. The laminations suggest the lake was formed by a large landslide, triggered by the 1927 Gulang earthquake (M = 8.0). The lake sediment sequence can be separated into three units based on lithologic, sedimentary, and isotopic characteristics. Starting from the bottom of the sequence, these are: (1) unweathered, coarse, sandy valley-floor deposits or landslide debris that pre-date the lake, (2) landslide-induced, fine-grained soil or reworked landslide debris with a high organic content, and (3) lacustrine sediments with low organic content and laminations. These annual laminations provide a high-resolution record of anthropogenic and environmental changes during the twentieth century, recording enhanced sediment input associated with two phases of construction activities. The high mean sedimentation rates of up to 4.8 mm year(-1) underscore the potential for reconstructing such distinct sediment pulses in remote, forested, and seemingly undisturbed mountain catchments.
A comprehensive hydrometeorological dataset is presented spanning the period 1 January 201131 December 2014 to improve the understanding of the hydrological processes leading to flash floods and the relation between rainfall, runoff, erosion and sediment transport in a mesoscale catchment (Auzon, 116 km(2)) of the Mediterranean region. Badlands are present in the Auzon catchment and well connected to high-gradient channels of bedrock rivers which promotes the transfer of suspended solids downstream. The number of observed variables, the various sensors involved (both in situ and remote) and the space-time resolution (similar to km(2), similar to min) of this comprehensive dataset make it a unique contribution to research communities focused on hydrometeorology, surface hydrology and erosion. Given that rainfall is highly variable in space and time in this region, the observation system enables assessment of the hydrological response to rainfall fields. Indeed, (i) rainfall data are provided by rain gauges (both a research network of 21 rain gauges with a 5 min time step and an operational network of 10 rain gauges with a 5 min or 1 h time step), S-band Doppler dual-polarization radars (1 km(2), 5 min resolution), disdrometers (16 sensors working at 30 s or 1 min time step) and Micro Rain Radars (5 sensors, 100m height resolution). Additionally, during the special observation period (SOP-1) of the HyMeX (Hydrological Cycle in the Mediterranean Experiment) project, two X-band radars provided precipitation measurements at very fine spatial and temporal scales (1 ha, 5 min). (ii) Other meteorological data are taken from the operational surface weather observation stations of Meteo-France (including 2m air temperature, atmospheric pressure, 2 m relative humidity, 10m wind speed and direction, global radiation) at the hourly time resolution (six stations in the region of interest). (iii) The monitoring of surface hydrology and suspended sediment is multi-scale and based on nested catchments. Three hydrometric stations estimate water discharge at a 2-10 min time resolution. Two of these stations also measure additional physico-chemical variables (turbidity, temperature, conductivity) and water samples are collected automatically during floods, allowing further geochemical characterization of water and suspended solids. Two experimental plots monitor overland flow and erosion at 1 min time resolution on a hillslope with vineyard. A network of 11 sensors installed in the intermittent hydrographic network continuously measures water level and water temperature in headwater subcatchments (from 0.17 to 116 km(2)) at a time resolution of 2-5 min. A network of soil moisture sensors enables the continuous measurement of soil volumetric water content at 20 min time resolution at 9 sites. Additionally, concomitant observations (soil moisture measurements and stream gauging) were performed during floods between 2012 and 2014. Finally, this dataset is considered appropriate for understanding the rainfall variability in time and space at fine scales, improving areal rainfall estimations and progressing in distributed hydrological and erosion modelling.
The planetary nebula N66 in the Large Magellanic Cloud is an extraordinary object, as it is the only confirmed PN where the central star is a Wolf-Rayet star of the nitrogen sequence, i.e. of type [WN]. Moreover, the star showed a dramatic brightness outburst in 1993-1994. In a previous paper (Hamann et al. 2003) we analyzed the changing stellar spectra and found evidence that the central star is most likely a binary system where a white dwarf presently accretes matter from a non-degenerate companion at a high rate. Thus the object is a candidate for a future type Ia supernova in our cosmic neighborhood. In the present paper we analyze the morphology and kinematics of the nebula, using images and high-resolution spectra obtained with the Hubble Space Telescope (HST) and the Very Large Telescope (ESO-VLT). The object presents a complex multipolar structure, dominated by very bright lobes located at both sides of the central star and separated by a narrow waist. In addition there is a pair of very extended and twisted loops, also pointing in opposite directions; their symmetry axis and collimation angle differs from those of the bright lobes. High resolution spectroscopy reveals two main velocity components, "approaching" material at an average heliocentric radial velocity Of V-rad = 248 30 km s(-1) and similarly bright "receding" material at V-rad = 331 +/- 25 km s(-1). A systemic velocity of about 300 km s(-1) is derived. Opposite lobes and loops possess opposite velocities. Furthermore there are knots and filaments of complex structure and kinematics. Close to the central star, nebular gas is found, receding at very high velocity (125 km s(-1) relative to the system). The morphology and kinematics of LMC-N66 can be explained as the result of episodic bipolar ejections with changing axis. The bipolar structures could have been produced by collimated streams ejected from a precessing central source. We suggest that the precession could have been produced by an external torque, possibly due to a binary companion. Young, fast-moving nebular knots close to the star appear slightly He- and N-richer than the main body of the nebula, but are still hydrogen-rich in contrast to the helium-dominated atmosphere of the [WN]- type central star. In the binary scenario, this nebular matter must have been accreted from the non-degenerate companion and re-ejected before it was fully burnt
Parallel File Systems like PVFS2 are a necessary compo nent for high-performance computing. The design of ef ;cient communication layers for these systems is still of great research interest. This paper presents a low- latency messaging method for PVFS2 dedicated for Gigabit Ether net networks and discusses relevant design issues. In con trast to other approaches, we argue that zero-copying can be achieved also for big messages without use of a rendez vous protocol. Further, ef;ciency within the communica tion layer like a small call stack plays an important role.
There is much recent interest in the idea that we represent our knowledge together with the sensory and motor features that were activated during its acquisition. This paper reviews the evidence for such "embodiment" in the domain of numerical cognition, a traditional stronghold of abstract theories of knowledge representation. The focus is on spatial-numerical associations, such as the SNARC effect (small numbers are associated with left space, larger numbers with right space). Using empirical evidence from behavioral research, I first describe sensory and motor biases induced by SNARC, thus identifying numbers as embodied concepts. Next, I propose a hierarchical relationship between grounded, embodied, and situated aspects of number knowledge. This hierarchical conceptualization helps to understand the variety of SNARC-related findings and yields testable predictions about numerical cognition. I report several such tests, ranging from cross-cultural comparisons of horizontal and vertical SNARC effects (Shaki and Fischer in J Exp Psychol Hum Percept Perform 38(3): 804-809, 2012) to motor cortical activation studies in adults with left- and right-hand counting preferences (Tschentscher et al. in NeuroImage 59: 3139-3148, 2012). It is concluded that the diagnostic features for each level of the proposed hierarchical knowledge representation, together with the spatial associations of numbers, make the domain of numerical knowledge an ideal testing ground for embodied cognition research.
Motivation: Full-length DNA and protein sequences that span the entire length of a gene are ideally used for multiple sequence alignments (MSAs) and the subsequent inference of their relationships. Frequently, however, MSAs contain a substantial amount of missing data. For example, expressed sequence tags (ESTs), which are partial sequences of expressed genes, are the predominant source of sequence data for many organisms. The patterns of missing data typical for EST-derived alignments greatly compromise the accuracy of estimated phylogenies. Results: We present a statistical method for inferring phylogenetic trees from EST-based incomplete MSA data. We propose a class of hierarchical models for modeling pairwise distances between the sequences, and develop a fully Bayesian approach for estimation of the model parameters. Once the distance matrix is estimated, the phylogenetic tree may be constructed by applying neighbor-joining (or any other algorithm of choice). We also show that maximizing the marginal likelihood from the Bayesian approach yields similar results to a pro. le likelihood estimation. The proposed methods are illustrated using simulated protein families, for which the true phylogeny is known, and one real protein family.
We discuss an efficient Hierarchical Effective Mode (HEM) representation of a high-dimensional harmonic oscillator bath, which describes phonon-driven vibrational relaxation of an adsorbate-surface system, namely, deuterium adsorbed on Si(100). Starting from the original Hamiltonian of the adsorbate-surface system, the HEM representation is constructed via iterative orthogonal transformations, which are efficiently implemented with Householder matrices. The detailed description of the HEM representation and its construction are given in the second quantization representation. The hierarchical nature of this representation allows access to the exact quantum dynamics of the adsorbate-surface system over finite time intervals, controllable via the truncation order of the hierarchy. To study the convergence properties of the effective mode representation, we solve the time-dependent Schrodinger equation of the truncated system-bath HEM Hamiltonian, with the help of the multilayer extension of the Multiconfigurational Time-Dependent Hartree (ML-MCTDH) method. The results of the HEM representation are compared with those obtained with a quantum-mechanical tier-model. The convergence of the HEM representation with respect to the truncation order of the hierarchy is discussed for different initial conditions of the adsorbate-surface system. The combination of the HEM representation with the ML-MCTDH method provides information on the time evolution of the system (adsorbate) and multiple effective modes of the bath (surface). This permits insight into mechanisms of vibration-phonon coupling of the adsorbate-surface system, as well as inter-mode couplings of the effective bath.
A short and convenient synthesis of metallochlorin-C-60 dyads based on a Heck-type hetero coupling at the 3(2) position of a chlorin is described. p-Bromobenzaldehyde was treated with Zn-metalated 13(2)- demethoxycarbonylmethylpheophorbide a, using a palladium acetate/LiCl catalyst mixture under phase-transfer conditions in DMF at 70 degrees C. The resulting asymmetric olefin was obtained in a high trans/cis ratio. The desired trans isomer was separated and subsequently transformed into a donor-acceptor dyad by a 1,3-dipolar cycloaddition to C-60 in the presence of sarcosine in refluxing toluene. The resulting dyads are expected to undergo efficient photoinduced electron transfer and can potentially be utilized in solar energy conversion devices.
A holistic design and verification environment to investigate driving assistance systems is presented, with an emphasis on system-on-chip architectures for video applications. Starting with an executable specification of a driving assistance application, subsequent transformations are performed across different levels of abstraction until the final implementation is achieved. The hardware/software partitioning is facilitated through the integration of OpenCV and SystemC in the same design environment, as well as OpenCV and Linux in the run-time system. We built a rapid prototyping, FPGA-based camera system, which allows designs to be explored and evaluated in realistic conditions. Using lane departure and the corresponding performance speedup, we show that our platform reduces the design time, while improving the verification efforts.
Reliable hydrological monitoring is the basis for sound water management in drained wetlands. Since statistical methods cannot be employed for unobserved or sparsely monitored areas, the primary design (first set-up) may be arbitrary in most instances. The objective of this paper is therefore to provide a guideline for designing the initial hydrological monitoring network. A scheme is developed that handles different parts of monitoring and hydrometry in wetlands, focusing on the positioning of surface water and groundwater gauges. For placement of the former, control units are used which correspond to areas whose water levels can be regulated separately. The latter are arranged depending on hydrological response units, defined by combinations of soil type and land use, and the chosen surface water monitoring sites. A practical application of the approach is shown for an investigation area in the Spreewald region in north-east Germany. The presented scheme leaves a certain degree of freedom to its user, allowing the inclusion of expert knowledge or special concerns. Based on easily obtainable data, the developed hydrological network serves as a first step in the iterative procedure of monitoring network optimisation. Copyright (c) 2013 John Wiley & Sons, Ltd.
Supramolecular polymers or fibers are non-covalent assemblies of unimeric building blocks connected by secondary interactions such as hydrogen bonds or pi-pi interactions. Such structures hold enormous potential in the development of future materials, as their non-covalent nature makes them highly modular and adaptive. Within this review we aim to provide a broad overview over the area of linear supramolecular polymers including the different mechanisms of their polymerization as well as methods essential for their characterization. The different non-covalent interactions able to form supramolecular polymers are discussed, and key examples for each species are shown. Particular emphasis is laid on the development of living supramolecular polymerization able to produce fibers with a controlled length and low length dispersity, and even enable the production of supramolecular block copolymers. Another important and very recent field is the development of out-of-equilibrium supramolecular polymers, where the polymerization process can be temporally controlled enabling access to highly adaptive materials.
To gain a deeper understanding of the mechanisms behind biomass accumulation, it is important to study plant growth behavior. Manually phenotyping large sets of plants requires important human resources and expertise and is typically not feasible for detection of weak growth phenotypes. Here, we established an automated growth phenotyping pipeline for Arabidopsis thaliana to aid researchers in comparing growth behaviors of different genotypes.
The analysis pipeline includes automated image analysis of two-dimensional digital plant images and evaluation of manually annotated information of growth stages. It employs linear mixed-effects models to quantify genotype effects on total rosette area and relative leaf growth rate (RLGR) and ANOVAs to quantify effects on developmental times.
Using the system, a single researcher can phenotype up to 7000 plants d(-1). Technical variance is very low (typically < 2%). We show quantitative results for the growth-impaired starch-excessmutant sex4-3 and the growth-enhancedmutant grf9.
We show that recordings of environmental and developmental variables reduce noise levels in the phenotyping datasets significantly and that careful examination of predictor variables (such as d after sowing or germination) is crucial to avoid exaggerations of recorded phenotypes and thus biased conclusions.
The study reports a group-randomized trial of a theatre-based intervention to prevent sexual abuse targeting first and second grade primary school children in Germany. A sample of 148 first and second graders saw a live performance of a play designed to promote skills in dealing with abuse-prone interactions with adults, watched a recording of the play on DVD or were assigned to a no intervention control group. Both the live performance and the DVD groups showed significant increases in the target variables (distinguishing good/bad touch and secrets, getting help, rejecting unwanted touch) from baseline to post-intervention and a follow-up after 2 weeks, while the control group did not show changes. The live performance and DVD groups participated in a further follow-up 30 weeks post-intervention, which showed sustained effects of the intervention. The findings indicate that with appropriately culture-sensitive measures, Sexual abuse prevention programmes can have Sustainable effects with young primary school children.
A ground motion logic tree for seismic hazard analysis in the stable cratonic region of Europe
(2020)
Regions of low seismicity present a particular challenge for probabilistic seismic hazard analysis when identifying suitable ground motion models (GMMs) and quantifying their epistemic uncertainty. The 2020 European Seismic Hazard Model adopts a scaled backbone approach to characterise this uncertainty for shallow seismicity in Europe, incorporating region-to-region source and attenuation variability based on European strong motion data. This approach, however, may not be suited to stable cratonic region of northeastern Europe (encompassing Finland, Sweden and the Baltic countries), where exploration of various global geophysical datasets reveals that its crustal properties are distinctly different from the rest of Europe, and are instead more closely represented by those of the Central and Eastern United States. Building upon the suite of models developed by the recent NGA East project, we construct a new scaled backbone ground motion model and calibrate its corresponding epistemic uncertainties. The resulting logic tree is shown to provide comparable hazard outcomes to the epistemic uncertainty modelling strategy adopted for the Eastern United States, despite the different approaches taken. Comparison with previous GMM selections for northeastern Europe, however, highlights key differences in short period accelerations resulting from new assumptions regarding the characteristics of the reference rock and its influence on site amplification.
In the present study, the effects of ionic liquids (ILs) on the stability of nanoparticles in several IL compositions were investigated. In this context, we examined the primary role of ILs in the synthesis of metal/metal oxide nanoparticles and their dispersions extensively. However, the focus of the discussion in this communication centers mainly on the effect of EMIM Ethyl Sulfate on growth and stability of nanoparticles. The dispersion properties of ILs based on their ability to aid the synthesis of uniformly dispersed nanoparticles have been further explored to produce nanoparticles of an effective catalyst useful in water purification, soil remediation and battery applications. Two independent protocols were developed for the synthesis of nanoparticles, namely (a) one pot process via chemical reduction (b) dispersion of the inorganic material in ILs. The protocols are simple, sustainable and environmentally friendly because the processes are conducted in ILs as harmless non-toxic green solvent materials. The catalysts were analyzed by x-ray diffraction, electron microscopy, UV visible spectroscopy and dynamic light scattering as the main methodologies.
Plants located adjacent to agricultural fields are important for maintaining biodiversity in semi-natural landscapes. To avoid undesired impacts on these plants due to herbicide application on the arable fields, regulatory risk assessments are conducted prior to registration to ensure proposed uses of plant protection products do not present an unacceptable risk. The current risk assessment approach for these non-target terrestrial plants (NTTPs) examines impacts at the individual-level as a surrogate approach for protecting the plant community due to the inherent difficulties of directly assessing population or community level impacts. However, modelling approaches are suitable higher tier tools to upscale individual-level effects to community level. IBC-grass is a sophisticated plant community model, which has already been applied in several studies. However, as it is a console application software, it was not deemed sufficiently user-friendly for risk managers and assessors to be conveniently operated without prior expertise in ecological models. Here, we present a user-friendly and open source graphical user interface (GUI) for the application of IBC-grass in regulatory herbicide risk assessment. It facilitates the use of the plant community model for predicting long-term impacts of herbicide applications on NTTP communities. The GUI offers two options to integrate herbicide impacts: (1) dose responses based on current standard experiments (acc. to testing guidelines) and (2) based on specific effect intensities. Both options represent suitable higher tier options for future risk assessments of NTTPs as well as for research on the ecological relevance of effects.
A grammar of authority?
(2021)
Directive Speech Acts (dsas) are a major feature of historical pragmatics, specifically in research on historical (im)politeness. However, for Classical French, there is a lack of research on related phenomena. In our contribution, we present two recently constructed corpora covering the period of Classical French, sermo and apwcf. We present these corpora in terms of their genre characteristics on a communicative-functional and socio-pragmatic level. Based on the observation that, both in sermo and apwcf, dsas frequently occur together with terms of address, we analyse and manually code a sample based on this co-occurrence, and we compare the results with regard to special features in the individual corpora. The emerging patterns show a clear correspondence between socio-pragmatic factors and the linguistic means used to realise dsas. We propose that these results can be interpreted as signs of an underlying "grammar of authority".
Our goal was to reconstruct the late eighteenth century forest vegetation of the Prignitz region (NE Germany) at a scale of 1:50,000. We also wanted to relate the historical forest vegetation to the actual and potential natural vegetation. For these purposes, we selected 15 woody species and transferred relevant data found in historical records from various sources together with the recent localities of (very) old individuals belonging to these woody species into ArcView GIS. Following multi-step data processing including the generation of a point density layer using a moving window with kernel estimation and derivation of vegetation units applying Boolean algebra rules together with information on site conditions, we derived 17 forest communities corresponding to the potential natural vegetation. We were able to reconstruct the historical forest vegetation for 90% of the forest area ca. 1780. Only two of the 17 forest communities covered large parts of the forested area. The oak forest with Agrostis capillaris covered about 44% of the total forest area, and alder forests on fenland made up about 37%. Oak-hornbeam forests with Stellaria holostea comprised slightly less than 6% of the forest area, while all other forest communities comprised less than 1%. The historical forest vegetation is more similar to the potential forest vegetation and quite different from the actual forest vegetation because coniferous tree species currently cover approximately two-thirds of the actual forest area. The most beneficial result of this study is the map of high-resolution historical vegetation units that may serve as the basis for various further studies, e.g., modelling long-term changes in biodiversity at the landscape scale.
Deep hydrothermal Mo, W, and base metal mineralization at the Sweet Home mine (Detroit City portal) formed in response to magmatic activity during the Oligocene. Microthermometric data of fluid inclusions trapped in greisen quartz and fluorite suggest that the early-stage mineralization at the Sweet Home mine precipitated from low- to medium-salinity (1.5-11.5 wt% equiv. NaCl), CO2-bearing fluids at temperatures between 360 and 415 degrees C and at depths of at least 3.5 km. Stable isotope and noble gas isotope data indicate that greisen formation and base metal mineralization at the Sweet Home mine was related to fluids of different origins. Early magmatic fluids were the principal source for mantle-derived volatiles (CO2, H2S/SO2, noble gases), which subsequently mixed with significant amounts of heated meteoric water. Mixing of magmatic fluids with meteoric water is constrained by delta H-2(w)-delta O-18(w) relationships of fluid inclusions. The deep hydrothermal mineralization at the Sweet Home mine shows features similar to deep hydrothermal vein mineralization at Climax-type Mo deposits or on their periphery. This suggests that fluid migration and the deposition of ore and gangue minerals in the Sweet Home mine was triggered by a deep-seated magmatic intrusion. The findings of this study are in good agreement with the results of previous fluid inclusion studies of the mineralization of the Sweet Home mine and from Climax-type Mo porphyry deposits in the Colorado Mineral Belt.
Ophiostomatoid fungi are vectored by their bark-beetle associates and colonize different host tree species. To survive and proliferate in the host, they have evolved mechanisms for detoxification and elimination of host defence compounds, efficient nutrient sequestration, and, in pathogenic species, virulence towards plants. Here, we assembled a draft genome of the spruce pathogen Ophiostoma bicolor. For our comparative and phylogenetic analyses, we mined the genomes of closely related species (Ophiostoma piceae, Ophiostoma ulmi, Ophiostoma novo-ulmi, and Grosmannia clavigera). Our aim was to acquire a genomic and evolutionary perspective of gene families important in host colonization. Genome comparisons showed that both the nuclear and mitochondrial genomes in our assembly were largely complete. Our O. bicolor 25.3 Mbp draft genome had 10 018 predicted genes, 6041 proteins with gene ontology (GO) annotation, 269 carbohydrate-active enzymes (CAZymes), 559 peptidases and inhibitors, and 1373 genes likely involved in pathogen-host interactions. Phylogenetic analyses of selected protein families revealed core sets of cytochrome P450 genes, ABC transporters and backbone genes involved in secondary metabolite (SM) biosynthesis (polyketide synthases (PKS) and non-ribosomal synthases), and species-specific gene losses and duplications. Phylogenetic analyses of protein families of interest provided insight into evolutionary adaptations to host biochemistry in ophiostomatoid fungi.
Liverwort Blasia pusilla L. recruits soil nitrogen-fixing cyanobacteria of genus Nostoc as symbiotic partners. In this work we compared Nostoc community composition inside the plants and in the soil around them from two distant locations in Northern Norway. STRR fingerprinting and 16S rDNA phylogeny reconstruction showed a remarkable local diversity among isolates assigned to several Nostoc clades. An extensive web of negative allelopathic interactions was recorded at an agricultural site, but not at the undisturbed natural site. The cell extracts of the cyanobacteria did not show antimicrobial activities, but four isolates were shown to be cytotoxic to human cells. The secondary metabolite profiles of the isolates were mapped by MALDI-TOF MS, and the most prominent ions were further analyzed by Q-TOF for MS/MS aided identification. Symbiotic isolates produced a great variety of small peptide-like substances, most of which lack any record in the databases. Among identified compounds we found microcystin and nodularin variants toxic to eukaryotic cells. Microcystin producing chemotypes were dominating as symbiotic recruits but not in the free-living community. In addition, we were able to identify several novel aeruginosins and banyaside-like compounds, as well as nostocyclopeptides and nosperin.
Advances in the field of seismic interferometry have provided a basic theoretical interpretation to the full spectrum of the microtremor horizontal-to-vertical spectral ratio [H/V(f)]. The interpretation has been applied to ambient seismic noise data recorded both at the surface and at depth. The new algorithm, based on the diffuse wavefield assumption, has been used in inversion schemes to estimate seismic wave velocity profiles that are useful input information for engineering and exploration seismology both for earthquake hazard estimation and to characterize surficial sediments. However, until now, the developed algorithms are only suitable for on land environments with no offshore consideration. Here, the microtremor H/V(z, f) modelling is extended for applications to marine sedimentary environments for a 1-D layered medium. The layer propagator matrix formulation is used for the computation of the required Green’s functions. Therefore, in the presence of a water layer on top, the propagator matrix for the uppermost layer is defined to account for the properties of the water column. As an application example we analyse eight simple canonical layered earth models. Frequencies ranging from 0.2 to 50 Hz are considered as they cover a broad wavelength interval and aid in practice to investigate subsurface structures in the depth range from a few meters to a few hundreds of meters. Results show a marginal variation of 8 per cent at most for the fundamental frequency when a water layer is present. The water layer leads to variations in H/V peak amplitude of up to 50 per cent atop the solid layers.
The present study proposes a General Probabilistic Framework (GPF) for uncertainty and global sensitivity analysis of deterministic models in which, in addition to scalar inputs, non-scalar and correlated inputs can be considered as well. The analysis is conducted with the variance-based approach of Sobol/Saltelli where first and total sensitivity indices are estimated. The results of the framework can be used in a loop for model improvement, parameter estimation or model simplification. The framework is applied to SWAP, a 113 hydrological model for the transport of water, solutes and heat in unsaturated and saturated soils. The sources of uncertainty are grouped in five main classes: model structure (soil discretization), input (weather data), time-varying (crop) parameters, scalar parameters (soil properties) and observations (measured soil moisture). For each source of uncertainty, different realizations are created based on direct monitoring activities. Uncertainty of evapotranspiration, soil moisture in the root zone and bottom fluxes below the root zone are considered in the analysis. The results show that the sources of uncertainty are different for each output considered and it is necessary to consider multiple output variables for a proper assessment of the model. Improvements on the performance of the model can be achieved reducing the uncertainty in the observations, in the soil parameters and in the weather data. Overall, the study shows the capability of the GPF to quantify the relative contribution of the different sources of uncertainty and to identify the priorities required to improve the performance of the model. The proposed framework can be extended to a wide variety of modelling applications, also when direct measurements of model output are not available.
We consider the problem of representing arbitrary preferences in causal reasoning and planning systems. In planning, a preference may be seen as a goal or constraint that is desirable, but not necessary, to satisfy. To begin, we define a very general query language for histories, or interleaved sequences of world states and actions. Based on this, we specify a second language in which preferences are defined. A single preference defines a binary relation on histories, indicating that one history is preferred to the other. From this, one can define global preference orderings on the set of histories, the maximal elements of which are the preferred histories. The approach is very general and flexible; thus it constitutes a base language in terms of which higher-level preferences may be defined. To this end, we investigate two fundamental types of preferences that we call choice and temporal preferences. We consider concrete strategies for these types of preferences and encode them in terms of our framework. We suggest how to express aggregates in the approach, allowing, e.g. the expression of a preference for histories with lowest total action costs. Last, our approach can be used to express other approaches and so serves as a common framework in which such approaches can be expressed and compared. We illustrate this by indicating how an approach due to Son and Pontelli can be encoded in our approach, as well as the language PDDL3.
A 741-cm-long laminated sediment core, covering the last 10,800 years was collected from Lake Zigetang, central Tibetan Plateau (90.9 degrees E, 32.0 degrees N, 4560m a.s.l.), and analysed palynologically at 69 horizons. Biome reconstruction suggests a dominance of temperate steppe vegetation (mainly Artemisia and Poaceae) on the central Tibetan Plateau during the first half of the Holocene (10.8-4.4 cal. ka BP), while alpine steppes with desert elements (mainly Cyperaceae, Poaceae, Chenopodiaceae, and characteristic high-alpine herb families) tend to dominate the second half (4.4-0 cal. ka BP). The Artemisia/Cyperaceae ratio-a semi-quantitative measure for summer temperature-indicates a general cooling trend throughout the Holocene. Dense temperate steppe vegetation and maximum desert plant withdrawal, however, indicate that a suitable balance of wet and warm conditions for optimum vegetation growth likely occurred during the middle Holocene (7.3-4.4 cal. ka BP). Severe Early Holocene cold events have been reconstructed for 8.7-8.3 and similar to 7.4 cal. ka BP. (c) 2006 Elsevier Ltd and INQUA. All rights reserved.
P>The onset and progression of senescence are under genetic and environmental control. The Arabidopsis thaliana NAC transcription factor ANAC092 (also called AtNAC2 and ORE1) has recently been shown to control age-dependent senescence, but its mode of action has not been analysed yet. To explore the regulatory network administered by ANAC092 we performed microarray-based expression profiling using estradiol-inducible ANAC092 overexpression lines. Approximately 46% of the 170 genes up-regulated upon ANAC092 induction are known senescence-associated genes, suggesting that the NAC factor exerts its role in senescence through a regulatory network that includes many of the genes previously reported to be senescence regulated. We selected 39 candidate genes and confirmed their time-dependent response to enhanced ANAC092 expression by quantitative RT-PCR. We also found that the majority of them (24 genes) are up-regulated by salt stress, a major promoter of plant senescence, in a manner similar to that of ANAC092, which itself is salt responsive. Furthermore, 24 genes like ANAC092 turned out to be stage-dependently expressed during seed growth with low expression at early and elevated expression at late stages of seed development. Disruption of ANAC092 increased the rate of seed germination under saline conditions, whereas the opposite occurred in respective overexpression plants. We also detected a delay of salinity-induced chlorophyll loss in detached anac092-1 mutant leaves. Promoter-reporter (GUS) studies revealed transcriptional control of ANAC092 expression during leaf and flower ageing and in response to salt stress. We conclude that ANAC092 exerts its functions during senescence and seed germination through partly overlapping target gene sets.
Small-subunit (SSU) rRNA genes (rDNA) were amplified by PCR from a hot pool environmental DNA sample using Bacteria- or Archaea-specific rDNA primers. Unique rDNA types were identified by restriction fragment length polymorphism (RFLP) analysis and representative sequences were determined. Family 10 glycoside hydrolase consensus PCR primers were used to explore the occurrence and diversity of xylanase genes in the hot pool environmental DNA sample. Partial sequences for three different xylanases were obtained and genomic walking PCR (GWPCR), in combination with nested primer pairs, was used to obtained a unique 1,741-bp nucleotide sequence. Analysis of this sequence identified a putative XynA protein encoded by the xynA open reading frame. The single module novel xylanase shared sequence similarity to the family 10 glycoside hydrolases. The purified recombinant enzyme, XynA expressed in E. coli exhibited optimum activity at 100 degrees C and pH 6.0, and was extremely thermostable at 90 degrees C. The enzyme showed high specificity toward different xylans and xylooligosaccharides.
Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase; EC 4.1.1.39), the most abundant protein in nature, catalyzes the assimilation of CO(2) (worldwide about 10(11) t each year) by carboxylation of ribulose-1,5-bisphosphate. It is a hexadecamer consisting of eight large and eight small subunits. Although the Rubisco large subunit (rbcL) is encoded by a single gene on the multicopy chloroplast genome, the Rubisco small subunits (rbcS) are encoded by a family of nuclear genes. In Arabidopsis thaliana, the rbcS gene family comprises four members, that is, rbcS-1a, rbcS-1b, rbcS-2b, and rbcS-3b. We sequenced all Rubisco genes in 26 worldwide distributed A. thaliana accessions. In three of these accessions, we detected a gene duplication/loss event, where rbcS-1b was lost and substituted by a duplicate of rbcS-2b (called rbcS-2b*). By screening 74 additional accessions using a specific polymerase chain reaction assay, we detected five additional accessions with this duplication/loss event. In summary, we found the gene duplication/loss in 8 of 100 A. thaliana accessions, namely, Bch, Bu, Bur, Cvi, Fei, Lm, Sha, and Sorbo. We sequenced an about 1-kb promoter region for all Rubisco genes as well. This analysis revealed that the gene duplication/loss event was associated with promoter alterations (two insertions of 450 and 850 bp, one deletion of 730 bp) in rbcS-2b and a promoter deletion (2.3 kb) in rbcS-2b* in all eight affected accessions. The substitution of rbcS-1b by a duplicate of rbcS-2b (i.e., rbcS-2b*) might be caused by gene conversion. All four Rubisco genes evolve under purifying selection, as expected for central genes of the highly conserved photosystem of green plants. We inferred a single positive selected site, a tyrosine to aspartic acid substitution at position 72 in rbcS-1b. Exactly the same substitution compromises carboxylase activity in the cyanobacterium Anacystis nidulans. In A. thaliana, this substitution is associated with an inferred recombination. Functional implications of the substitution remain to be evaluated.
We generalize the popular ensemble Kalman filter to an ensemble transform filter, in which the prior distribution can take the form of a Gaussian mixture or a Gaussian kernel density estimator. The design of the filter is based on a continuous formulation of the Bayesian filter analysis step. We call the new filter algorithm the ensemble Gaussian-mixture filter (EGMF). The EGMF is implemented for three simple test problems (Brownian dynamics in one dimension, Langevin dynamics in two dimensions and the three-dimensional Lorenz-63 model). It is demonstrated that the EGMF is capable of tracking systems with non-Gaussian uni- and multimodal ensemble distributions.
A Gateway to the World
(2017)
In the second half of the 19th century, the French École centrale des arts et manufactures became one of the engineering schools that enjoyed a worldwide reputation. There were many foreigners among its students. This article focuses on the graduates born in the Ottoman Empire, particularly on Jews and Armenians. It analyses their backgrounds, their common features and their professional careers, tracing their links with other centraliens. The patterns in the Ottoman centraliens’ professional trajectories help us picture a world full of opportunities where highly qualified men could cross borders and build careers with ease, but where, at the same time, origins, allegiances, contacts and credentials mattered greatly.
We present a catalogue of white dwarf candidates selected from the second data release of Gaia (DR2). We used a sample of spectroscopically confirmed white dwarfs from the Sloan Digital Sky Survey (SDSS) to map the entire space spanned by these objects in the Gaia Hertzsprung–Russell diagram. We then defined a set of cuts in absolute magnitude, colour, and a number of Gaia quality flags to remove the majority of contaminating objects. Finally, we adopt a method analogous to the one presented in our earlier SDSS photometric catalogues to calculate a probability of being a white dwarf (PWD) for all Gaia sources that passed the initial selection. The final catalogue is composed of 486641 stars with calculated PWD from which it is possible to select a sample of ≃260000 high-confidence white dwarf candidates in the magnitude range 8 < G < 21. By comparing this catalogue with a sample of SDSS white dwarf candidates, we estimate an upper limit in completeness of 85 per cent for white dwarfs with G ≤ 20 mag and Teff >7000 K, at high Galactic latitudes (|b| > 20°). However, the completeness drops at low Galactic latitudes, and the magnitude limit of the catalogue varies significantly across the sky as a function of Gaia’s scanning law. We also provide the list of objects within our sample with available SDSS spectroscopy. We use this spectroscopic sample to characterize the observed structure of the white dwarf distribution in the H–R diagram.
A Fuzzy Rule-Based Model for Remote Monitoring of Preterm in the Intensive Care Unit of Hospitals
(2019)
The use of Remote patient monitoring (RPM) systems to monitor critically ill patients in the Intensive Care Unit (ICU) has enabled quality and real-time healthcare management. Fuzzy logic as an approach to designing RPM systems provides a means for encapsulating the subjective decision-making process of medical experts in an algorithm suitable for computer implementation. In this paper, a remote monitoring system for preterm in neonatal ICU incubators is modeled and simulated. The model was designed with 4 input variables (body temperature, heart rate, respiratory rate, and oxygen level saturation), and 1 output variable (action performed represented as ACT). ACT decides whether-an alert is generated or not and also determines the message displayed when a notification is required. ACT classifies the clinical priority of the monitored preterm into 5 different fields: code blue, code red, code yellow, code green, and-code black. The model was simulated using a fuzzy logic toolbox of MATLAB R2015A. About 216 IF_THEN rules were formulated to monitor the inputs data fed into the model. The performance of the model was evaluated using-the confusion matrix to determine the model’s accuracy, precision, sensitivity, specificity, and false alarm rate. The-experimental results obtained shows that the fuzzy-based system is capable of producing satisfactory results when used for monitoring and classifying the clinical statuses of neonates in ICU incubators.
Sphingolipids are major components of the plasma membrane. In particular, ceramide serves as an essential building hub for complex sphingolipids, but also as an organizer of membrane domains segregating receptors and signalosomes. Sphingomyelin breakdown as a result of sphingomyelinase activation after ligation of a variety of receptors is the predominant source of ceramides released at the plasma membrane. This especially applies to T lymphocytes where formation of ceramide-enriched membrane microdomains modulates TCR signaling. Because ceramide release and redistribution occur very rapidly in response to receptor ligation, novel tools to further study these processes in living T cells are urgently needed. To meet this demand, we synthesized nontoxic, azido-functionalized ceramides allowing for bio-orthogonal click-reactions to fluorescently label incorporated ceramides, and thus investigate formation of ceramide-enriched domains. Azido-functionalized C-6-ceramides were incorporated into and localized within plasma membrane microdomains and proximal vesicles in T cells. They segregated into clusters after TCR, and especially CD28 ligation, indicating efficient sorting into plasma membrane domains associated with T cell activation; this was abolished upon sphingomyelinase inhibition. Importantly, T cell activation was not abrogated upon incorporation of the compound, which was efficiently excluded from the immune synapse center as has previously been seen in Ab-based studies using fixed cells. Therefore, the functionalized ceramides are novel, highly potent tools to study the subcellular redistribution of ceramides in the course of T cell activation. Moreover, they will certainly also be generally applicable to studies addressing rapid stimulation-mediated ceramide release in living cells.
Background/Aims: Cortisol plays an important role during pregnancy. It controls maternal glucose metabolism and fetal development. Cortisol metabolism is partially controlled by the 11b-HSD2. This enzyme is expressed in the kidney and human placenta. The activity of the enzyme is partially controlled by functional polymorphisms: the HSD11B2[CA]n microsatellite polymorphism. The impact of this functional gene polymorphism on cortisol metabolism and potential effects on the newborn's is unknown so far. Methods: In the current prospective birth cohort study in southern Asia, we analyzed the association of the HSD11B2[CA]n microsatellite polymorphisms in 187 mothers and their newborn's on maternal and newborn's serum cortisol concentrations. Results: Using multivariable regression analyses considering known confounding ( gestational age, newborn's gender, the labor uterine contraction states and the timing during the day of blood taking), we showed that the fetal HSD11B2[CA]n microsatellite polymorphisms in the first intron was related to maternal cortisol concentration ( R2=0.26, B=96.27, p=0.007), whereas as the newborn's cortisol concentrations were independent of fetal and maternal HSD11B2[CA] n microsatellite polymorphism. Conclusions: Our study showed for the first time that the fetal HSD11B2[CA]n microsatellite polymorphism of the HSD11B2 gene in healthy uncomplicated human pregnancy is associated with maternal cortisol concentration. This indicates that fetal genes controlling cortisol metabolism may affect maternal cortisol concentration and hence physiology in healthy pregnant women.
In this paper we evaluate different methods to predict soil erosion processes. We derived different layers of predictor variables for the study area in the Northern Chianti, Italy, describing the soil-lithologic complex, land use, and topographic characteristics. For a subcatchment of the Orme River, we mapped erosion processes by interpreting aerial photographs and field observations. These were classified as erosional response units (ERU), i.e. spatial areas of homogeneous erosion processes. The ERU were used as the response variable in the soil erosion modelling process. We applied two models i) bootstrap aggregation (Random Forest: RF), and ii) stochastic gradient boosting (TreeNet: TN) to predict the potential spatial distribution of erosion processes for the entire Orme River catchment. The models are statistically evaluated using training data and a set of performance parameters such as the area under the receiver operating characteristic curve (AUC), Cohen's Kappa, and pseudo R2. Variable importance and response curves provide further insight into controlling factors of erosion. Both models provided good performance in terms of classification and calibration; however, TN outperformed RF. Similar classes such as active and inactive landslides can be discriminated and well interpreted by considering response curves and relative variable importance. The spatial distribution of the predicted erosion susceptibilities generally follows topographic constraints and is similar for both models. Hence, the model-based delineation of ERU on the basis of soil and terrain information is a valuable tool in geomorphology; it provides insights into factors controlling erosion processes and may allow the extrapolation and prediction of erosion processes in unsurveyed areas.
Image feature detection is a key task in computer vision. Scale Invariant Feature Transform (SIFT) is a prevalent and well known algorithm for robust feature detection. However, it is computationally demanding and software implementations are not applicable for real-time performance. In this paper, a versatile and pipelined hardware implementation is proposed, that is capable of computing keypoints and rotation invariant descriptors on-chip. All computations are performed in single precision floating-point format which makes it possible to implement the original algorithm with little alteration. Various rotation resolutions and filter kernel sizes are supported for images of any resolution up to ultra-high definition. For full high definition images, 84 fps can be processed. Ultra high definition images can be processed at 21 fps.
Climate change and its impacts already pose considerable challenges for societies that will further increase with global warming (IPCC, 2014a, b). Uncertainties of the climatic response to greenhouse gas emissions include the potential passing of large-scale tipping points (e.g. Lenton et al., 2008; Levermann et al., 2012; Schellnhuber, 2010) and changes in extreme meteorological events (Field et al., 2012) with complex impacts on societies (Hallegatte et al., 2013). Thus climate change mitigation is considered a necessary societal response for avoiding uncontrollable impacts (Conference of the Parties, 2010). On the other hand, large-scale climate change mitigation itself implies fundamental changes in, for example, the global energy system. The associated challenges come on top of others that derive from equally important ethical imperatives like the fulfilment of increasing food demand that may draw on the same resources. For example, ensuring food security for a growing population may require an expansion of cropland, thereby reducing natural carbon sinks or the area available for bio-energy production. So far, available studies addressing this problem have relied on individual impact models, ignoring uncertainty in crop model and biome model projections. Here, we propose a probabilistic decision framework that allows for an evaluation of agricultural management and mitigation options in a multi-impact-model setting. Based on simulations generated within the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP), we outline how cross-sectorally consistent multi-model impact simulations could be used to generate the information required for robust decision making.
Using an illustrative future land use pattern, we discuss the trade-off between potential gains in crop production and associated losses in natural carbon sinks in the new multiple crop-and biome-model setting. In addition, crop and water model simulations are combined to explore irrigation increases as one possible measure of agricultural intensification that could limit the expansion of cropland required in response to climate change and growing food demand. This example shows that current impact model uncertainties pose an important challenge to long-term mitigation planning and must not be ignored in long-term strategic decision making.
We explore the interaction between oculomotor control and language comprehension on the sentence level using two well-tested computational accounts of parsing difficulty. Previous work (Boston, Hale, Vasishth, & Kliegl, 2011) has shown that surprisal (Hale, 2001; Levy, 2008) and cue-based memory retrieval (Lewis & Vasishth, 2005) are significant and complementary predictors of reading time in an eyetracking corpus. It remains an open question how the sentence processor interacts with oculomotor control. Using a simple linking hypothesis proposed in Reichle, Warren, and McConnell (2009), we integrated both measures with the eye movement model EMMA (Salvucci, 2001) inside the cognitive architecture ACT-R (Anderson et al., 2004). We built a reading model that could initiate short Time Out regressions (Mitchell, Shen, Green, & Hodgson, 2008) that compensate for slow postlexical processing. This simple interaction enabled the model to predict the re-reading of words based on parsing difficulty. The model was evaluated in different configurations on the prediction of frequency effects on the Potsdam Sentence Corpus. The extension of EMMA with postlexical processing improved its predictions and reproduced re-reading rates and durations with a reasonable fit to the data. This demonstration, based on simple and independently motivated assumptions, serves as a foundational step toward a precise investigation of the interaction between high-level language processing and eye movement control.
As resources are valuable assets, organizations have to decide which resources to allocate to business process tasks in a way that the process is executed not only effectively but also efficiently. Traditional role-based resource allocation leads to effective process executions, since each task is performed by a resource that has the required skills and competencies to do so. However, the resulting allocations are typically not as efficient as they could be, since optimization techniques have yet to find their way in traditional business process management scenarios. On the other hand, operations research provides a rich set of analytical methods for supporting problem-specific decisions on resource allocation. This paper provides a novel framework for creating transparency on existing tasks and resources, supporting individualized allocations for each activity in a process, and the possibility to integrate problem-specific analytical methods of the operations research domain. To validate the framework, the paper reports on the design and prototypical implementation of a software architecture, which extends a traditional process engine with a dedicated resource management component. This component allows us to define specific resource allocation problems at design time, and it also facilitates optimized resource allocation at run time. The framework is evaluated using a real-world parcel delivery process. The evaluation shows that the quality of the allocation results increase significantly with a technique from operations research in contrast to the traditional applied rule-based approach.
The outermost cell layer of plants, the epidermis, and its outer (lateral) membrane domain facing the environment are continuously challenged by biotic and abiotic stresses. Therefore, the epidermis and the outer membrane domain provide important selective and protective barriers. However, only a small number of specifically outer membrane-localized proteins are known. Similarly, molecular mechanisms underlying the trafficking and the polar placement of outer membrane domain proteins require further exploration. Here, we demonstrate that ACTIN7 (ACT7) mediates trafficking of the PENETRATION3 (PEN3) outer membrane protein from the trans-Golgi network (TGN) to the plasma membrane in the root epidermis of Arabidopsis (Arabidopsis thaliana) and that actin function contributes to PEN3 endocytic recycling. In contrast to such generic ACT7-dependent trafficking from the TGN, the EXOCYST84b (EXO84b) tethering factor mediates PEN3 outer-membrane polarity. Moreover, precise EXO84b placement at the outer membrane domain itself requires ACT7 function. Hence, our results uncover spatially and mechanistically distinct requirements for ACT7 function during outer lateral membrane cargo trafficking and polarity establishment. They further identify an exocyst tethering complex mediator of outer lateral membrane cargo polarity.
Text displayed in a video is an essential part for the high-level semantic information of the video content. Therefore, video text can be used as a valuable source for automated video indexing in digital video libraries. In this paper, we propose a workflow for video text detection and recognition. In the text detection stage, we have developed a fast localization-verification scheme, in which an edge-based multi-scale text detector first identifies potential text candidates with high recall rate. Then, detected candidate text lines are refined by using an image entropy-based filter. Finally, Stroke Width Transform (SWT)- and Support Vector Machine (SVM)-based verification procedures are applied to eliminate the false alarms. For text recognition, we have developed a novel skeleton-based binarization method in order to separate text from complex backgrounds to make it processible for standard OCR (Optical Character Recognition) software. Operability and accuracy of proposed text detection and binarization methods have been evaluated by using publicly available test data sets.
The termprocess modelis widely used, but rarely agreed upon. This paper proposes a framework for characterizing and building cognitive process models. Process models model not only inputs and outputs but also model the ongoing information transformations at a given level of abstraction. We argue that the following dimensions characterize process models: They have a scope that includes different levels of abstraction. They specify a hypothesized mental information transformation. They make predictions not only for the behavior of interest but also for processes. The models' predictions for the processes can be derived from the input, without reverse inference from the output data. Moreover, the presumed information transformation steps are not contradicting current knowledge of human cognitive capacities. Lastly, process models require a conceptual scope specifying levels of abstraction for the information entering the mind, the proposed mental events, and the behavior of interest. This framework can be used for refining models before testing them or after testing them empirically, and it does not rely on specific modeling paradigms. It can be a guideline for developing cognitive process models. Moreover, the framework can advance currently unresolved debates about which models belong to the category of process models.
When sampling animal movement paths, the frequency at which location measurements are attempted is a critical feature for data analysis. Important quantities derived from raw data, e.g. travel distance or sinuosity, can differ largely based on the temporal resolution of the data. Likewise, when movement models are fitted to data, parameter estimates have been demonstrated to vary with sampling rate. Thus, biological statements derived from such analyses can only be made with respect to the resolution of the underlying data, limiting extrapolation of results and comparison between studies. To address this problem, we investigate whether there are models that are robust against changes in temporal resolution. First, we propose a mathematically rigorous framework, in which we formally define robustness as a model property. We then use the framework for a thorough assessment of a range of basic random walk models, in which we also show how robustness relates to other probabilistic concepts. While we found robustness to be a strong condition met by few models only, we suggest a new method to extend models so as to make them robust. Our framework provides a new systematic, mathematically founded approach to the question if, and how, sampling rate of movement paths affects statistical inference.
A mathematical model of working-memory capacity limits is proposed on the key assumption of mutual interference between items in working memory. Interference is assumed to arise from overwriting of features shared by these items. The model was fit to time-accuracy data of memory-updating tasks from four experiments using nonlinear mixed effect (NLME) models as a framework. The model gave a good account of the data from a numerical and a spatial task version. The performance pattern in a combination of numerical and spatial updating could be explained by variations in the interference parameter: assuming less feature overlap between contents from different domains than between contents from the same domain, the model can account for double dissociations of content domains in dual-task experiments. Experiment 3 extended this idea to similarity within the verbal domain. The decline of memory accuracy with increasing memory load was steeper with phonologically similar than with dissimilar material, although processing speed was faster for the similar material. The model captured the similarity effects with a higher estimated interference parameter for the similar than for the dissimilar condition. The results are difficult to explain with alternative models, in particular models incorporating time-based decay and models assuming limited resource pools.
A form-function mismatch?
(2019)
Class IIa histone deacetylases (HDACs) show extremely low enzymatic activity and no commonly accepted endogenous substrate is known today. Increasing evidence suggests that these enzymes exert their effect rather through molecular recognition of acetylated proteins and recruiting other proteins like HDAC3 to the desired target location. Accordingly, class IIa HDACs like bromodomains have been suggested to act as “Readers” of acetyl marks, whereas enzymatically active HDACs of class I or IIb are called “Erasers” to highlight their capability to remove acetyl groups from acetylated histones or other proteins. Small-molecule ligands of class IIa histone deacetylases (HDACs) have gained tremendous attention during the last decade and have been suggested as pharmaceutical targets in several indication areas such as cancer, Huntington's disease and muscular atrophy. Up to now, only enzyme activity assays with artificial chemically activated trifluoroacetylated substrates are in use for the identification and characterization of new active compounds against class IIa HDACs. Here, we describe the first binding assay for this class of HDAC enzymes that involves a simple mix-and-measure procedure and an extraordinarily robust fluorescence lifetime readout based on [1,3]dioxolo[4,5-f]benzodioxole-based ligand probes. The principle of the assay is generic and can also be transferred to class I HDAC8.
High-throughput assays for drug screening applications have to fulfill particular specifications. Besides the capability to identify even compounds with low potency, one of the major issues is to minimize the number of false-positive hits in a screening campaign in order to reduce the logistic effort for the subsequent cherry picking and confirmation procedure. In this respect, fluorescence lifetime (FLT) appears as an ideal readout parameter that is supposed to be robust against autofluorescent and light-absorbing compounds, the most common source of systematic false positives. The extraordinary fluorescence features of the recently discovered [1,3]dioxolo[4,5-f][1,3]benzodioxole dyes were exploited to develop an FLT-based binding assay with exceptionally robust readout. The assay setup was comprehensively validated and shown to comply not only with all requirements for a powerful high-throughput screening assay but also to be suitable to determine accurate binding constants for inhibitors against enzymes of the histone deacetylase family. Using the described binding assay, the first inhibitors against three members of this enzyme family from Pseudomonas aeruginosa were identified. The compounds were characterized in terms of potency and selectivity profile. The novel ligand probe should also be applicable to other homologues of the histone deacetylase family that are inhibited by N-hydroxy-N'-phenyloctandiamide.
Winter cereals require prolonged cold to transition from vegetative to reproductive development. This process, referred to as vernalization, has been extensively studied in Arabidopsis (Arabidopsis thaliana). In Arabidopsis, a key flowering repressor called FLOWERING LOCUS C (FLC) quantitatively controls the vernalization requirement. By contrast, in cereals, the vernalization response is mainly regulated by the VERNALIZATION genes, VRN1 and VRN2. Here, we characterize ODDSOC2, a recently identified FLC ortholog in monocots, knowing that it belongs to the FLC lineage. By studying its expression in a diverse set of Brachypodium accessions, we find that it is a good predictor of the vernalization requirement. Analyses of transgenics demonstrated that BdODDSOC2 functions as a vernalization-regulated flowering repressor. In most Brachypodium accessions BdODDSOC2 is down-regulated by cold, and in one of the winter accessions in which this down-regulation was evident, BdODDSOC2 responded to cold before BdVRN1. When stably down-regulated, the mechanism is associated with spreading H3K27me3 modifications at the BdODDSOC2 chromatin. Finally, homoeolog-specific gene expression analyses identify TaAGL33 and its splice variant TaAGL22 as the FLC orthologs in wheat (Triticum aestivum) behaving most similar to Brachypodium ODDSOC2. Overall, our study suggests that ODDSOC2 is not only phylogenetically related to FLC in eudicots but also functions as a flowering repressor in the vernalization pathway of Brachypodium and likely other temperate grasses. These insights could prove useful in breeding efforts to refine the vernalization requirement of temperate cereals and adapt varieties to changing climates.
The investigation of metabolic fluxes and metabolite distributions within cells by means of tracer molecules is a valuable tool to unravel the complexity of biological systems. Technological advances in mass spectrometry (MS) technology such as atmospheric pressure chemical ionization (APCI) coupled with high resolution (HR), not only allows for highly sensitive analyses but also broadens the usefulness of tracer-based experiments, as interesting signals can be annotated de novo when not yet present in a compound library. However, several effects in the APCI ion source, i.e., fragmentation and rearrangement, lead to superimposed mass isotopologue distributions (MID) within the mass spectra, which need to be corrected during data evaluation as they will impair enrichment calculation otherwise. Here, we present and evaluate a novel software tool to automatically perform such corrections. We discuss the different effects, explain the implemented algorithm, and show its application on several experimental datasets. This adjustable tool is available as an R package from CRAN.