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Institute
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The Great Hungarian Plain was a crossroads of cultural transformations that have shaped European prehistory. Here we analyse a 5,000-year transect of human genomes, sampled from petrous bones giving consistently excellent endogenous DNA yields, from 13 Hungarian Neolithic, Copper, Bronze and Iron Age burials including two to high (similar to 22x) and seven to similar to 1x coverage, to investigate the impact of these on Europe's genetic landscape. These data suggest genomic shifts with the advent of the Neolithic, Bronze and Iron Ages, with interleaved periods of genome stability. The earliest Neolithic context genome shows a European hunter-gatherer genetic signature and a restricted ancestral population size, suggesting direct contact between cultures after the arrival of the first farmers into Europe. The latest, Iron Age, sample reveals an eastern genomic influence concordant with introduced Steppe burial rites. We observe transition towards lighter pigmentation and surprisingly, no Neolithic presence of lactase persistence.
We extend the scope of European palaeogenomics by sequencing the genomes of Late Upper Palaeolithic (13,300 years old, 1.4-fold coverage) and Mesolithic (9,700 years old, 15.4-fold) males from western Georgia in the Caucasus and a Late Upper Palaeolithic (13,700 years old, 9.5-fold) male from Switzerland. While we detect Late Palaeolithic-Mesolithic genomic continuity in both regions, we find that Caucasus hunter-gatherers (CHG) belong to a distinct ancient clade that split from western hunter-gatherers similar to 45 kya, shortly after the expansion of anatomically modern humans into Europe and from the ancestors of Neolithic farmers similar to 25 kya, around the Last Glacial Maximum. CHG genomes significantly contributed to the Yamnaya steppe herders who migrated into Europe similar to 3,000 BC, supporting a formative Caucasus influence on this important Early Bronze age culture. CHG left their imprint on modern populations from the Caucasus and also central and south Asia possibly marking the arrival of Indo-Aryan languages.
In this study, we analyze interactions in lake and lake catchment systems of a continuous permafrost area. We assessed colored dissolved organic matter (CDOM) absorption at 440 nm (a(440)(CDOM)) and absorption slope (S300-500) in lakes using field sampling and optical remote sensing data for an area of 350 km(2) in Central Yamal, Siberia. Applying a CDOM algorithm (ratio of green and red band reflectance) for two high spatial resolution multispectral GeoEye-1 and Worldview-2 satellite images, we were able to extrapolate the a()(CDOM) data from 18 lakes sampled in the field to 356 lakes in the study area (model R-2 = 0.79). Values of a(440)(CDOM) in 356 lakes varied from 0.48 to 8.35 m(-1) with a median of 1.43 m(-1). This a()(CDOM) dataset was used to relate lake CDOM to 17 lake and lake catchment parameters derived from optical and radar remote sensing data and from digital elevation model analysis in order to establish the parameters controlling CDOM in lakes on the Yamal Peninsula. Regression tree model and boosted regression tree analysis showed that the activity of cryogenic processes (thermocirques) in the lake shores and lake water level were the two most important controls, explaining 48.4% and 28.4% of lake CDOM, respectively (R-2 = 0.61). Activation of thermocirques led to a large input of terrestrial organic matter and sediments from catchments and thawed permafrost to lakes (n = 15, mean a(440)(CDOM) = 5.3 m(-1)). Large lakes on the floodplain with a connection to Mordy-Yakha River received more CDOM (n = 7, mean a(440)(CDOM) = 3.8 m(-1)) compared to lakes located on higher terraces.
The knowledge of transformation pathways and identification of transformation products (TPs) of veterinary drugs is important for animal health, food, and environmental matters. The active agent Monensin (MON) belongs to the ionophore antibiotics and is widely used as a veterinary drug against coccidiosis in broiler farming. However, no electrochemically (EC) generated TPs of MON have been described so far. In this study, the online coupling of EC and mass spectrometry (MS) was used for the generation of oxidative TPs. EC-conditions were optimized with respect to working electrode material, solvent, modifier, and potential polarity. Subsequent LC/HRMS (liquid chromatography/high resolution mass spectrometry) and MS/MS experiments were performed to identify the structures of derived TPs by a suspected target analysis. The obtained EC-results were compared to TPs observed in metabolism tests with microsomes and hydrolysis experiments of MON. Five previously undescribed TPs of MON were identified in our EC/MS based study and one TP, which was already known from literature and found by a microsomal assay, could be confirmed. Two and three further TPs were found as products in microsomal tests and following hydrolysis, respectively. We found decarboxylation, O-demethylation and acid-catalyzed ring-opening reactions to be the major mechanisms of MON transformation.
Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based Nanogels
(2019)
Polyglycerol-based thermoresponsive nanogels (tNGs) have been shown to have excellent skin hydration properties and to be valuable delivery systems for sustained release of drugs into skin. In this study, we compared the skin penetration of tacrolimus formulated in tNGs with a commercial 0.1% tacrolimus ointment. The penetration of the drug was investigated in ex vivo abdominal and breast skin, while different methods for skin barrier disruption were investigated to improve skin permeability or simulate inflammatory conditions with compromised skin barrier. The amount of penetrated tacrolimus was measured in skin extracts by liquid chromatography tandem-mass spectrometry (LC-MS/MS), whereas the inflammatory markers IL-6 and IL-8 were detected by enzyme-linked immunosorbent assay (ELISA). Higher amounts of tacrolimus penetrated in breast as compared to abdominal skin or in barrier-disrupted as compared to intact skin, confirming that the stratum corneum is the main barrier for tacrolimus skin penetration. The anti-proliferative effect of the penetrated drug was measured in skin tissue/Jurkat cells co-cultures. Interestingly, tNGs exhibited similar anti-proliferative effects as the 0.1% tacrolimus ointment. We conclude that polyglycerol-based nanogels represent an interesting alternative to paraffin-based formulations for the treatment of inflammatory skin conditions.
In this paper, we investigate the continuous version of modified iterative Runge–Kutta-type methods for nonlinear inverse ill-posed problems proposed in a previous work. The convergence analysis is proved under the tangential cone condition, a modified discrepancy principle, i.e., the stopping time T is a solution of ∥𝐹(𝑥𝛿(𝑇))−𝑦𝛿∥=𝜏𝛿+ for some 𝛿+>𝛿, and an appropriate source condition. We yield the optimal rate of convergence.
This paper investigates the predictions of the Derivational Complexity Hypothesis by studying the acquisition of wh-questions in 4- and 5-year-old Akan-speaking children in an experimental approach using an elicited production and an elicited imitation task. Akan has two types of wh-question structures (wh-in-situ and wh-ex-situ questions), which allows an investigation of children’s acquisition of these two question structures and their preferences for one or the other. Our results show that adults prefer to use wh-ex-situ questions over wh-in-situ questions. The results from the children show that both age groups have the two question structures in their linguistic repertoire. However, they differ in their preferences in usage in the elicited production task: while the 5-year-olds preferred the wh-in-situ structure over the wh-ex-situ structure, the 4-year-olds showed a selective preference for the wh-in-situ structure in who-questions. These findings suggest a developmental change in wh-question preferences in Akan-learning children between 4 and 5 years of age with a so far unobserved u-shaped developmental pattern. In the elicited imitation task, all groups showed a strong tendency to maintain the structure of in-situ and ex-situ questions in repeating grammatical questions. When repairing ungrammatical ex-situ questions, structural changes to grammatical in-situ questions were hardly observed but the insertion of missing morphemes while keeping the ex-situ structure. Together, our findings provide only partial support for the Derivational Complexity Hypothesis.
Sediment archives in the terrestrial and marine realm are regularly analyzed to infer changes in climate, tectonic, or anthropogenic boundary conditions of the past. However, contradictory observations have been made regarding whether short period events are faithfully preserved in stratigraphic archives; for instance, in marine sediments offshore large river systems. On the one hand, short period events are hypothesized to be non-detectable in the signature of terrestrially derived sediments due to buffering during sediment transport along large river systems. On the other hand, several studies have detected signals of short period events in marine records offshore large river systems. We propose that this apparent discrepancy is related to the lack of a differentiation between different types of signals and the lack of distinction between river response times and signal propagation times. In this review, we (1) expand the definition of the term ‘signal’ and group signals in sub-categories related to hydraulic grain size characteristics, (2) clarify the different types of ‘times’ and suggest a precise and consistent terminology for future use, and (3) compile and discuss factors influencing the times of signal transfer along sediment routing systems and how those times vary with hydraulic grain size characteristics. Unraveling different types of signals and distinctive time periods related to signal propagation addresses the discrepancies mentioned above and allows a more comprehensive exploration of event preservation in stratigraphy – a prerequisite for reliable environmental reconstructions from terrestrially derived sedimentary records.
Deans at Institutions of Higher Education are seldom recipients of effective or specific professional management training, institutional mentorship, and coaching despite an increasing demand on them to play a more dynamic leadership role in the face of ever-changing local and global challenges. To address this deficiency, the inaugural Malaysian Chapter of the International Deans’ Course (MyIDC) was held in three parts over 2019 and 2020. In this paper, findings related to feedback on the programme are presented and discussed. Responses from the participants from two sets of surveys, and written feedback provided by two IDC international trainers involved in MyIDC were analysed. These reveal potential areas of improvement for the forthcoming MyIDC programme, such as in terms of planning and organisation, duration, content, and delivery. The article explores the lessons learnt from the MyIDC 2019/2020 training programme and discusses the improvements that can be made arising from the feedback received.
During the National Multiplication Training in Kenya in 2018, participants raised concerns about attrition, completion rates and quality of PhD programmes in Kenya’s public universities. This led the authors of this article to further examine the question of PhD completion rates. Available data underlined that PhD students across various disciplines in Kenya’s public universities take unnecessarily long to complete their studies due to a myriad of factors that are related to their supervisors, university guidelines for post-graduate studies, or the students themselves. This article examines inertia areas along the PhD training pathway at three public universities in Kenya and provides suggestions on structural and operational changes universities must make to shorten completion periods.