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Landslides in deglaciated and deglaciating mountains represent a major hazard, but their distribution at the spatial scale of entire mountain belts has rarely been studied. Traditional models of landslide distribution assume that landslides are concentrated in the steepest, wettest, and most tectonically active parts of the orogens, where glaciers reached their greatest thickness.
However, based on mapping large landslides (>0.9 km(2)) over an unprecedentedly large area of Southern Patagonia (similar to 305,000 km(2)), we show that the distribution of landslides can have the opposite trend.
We show that the largest landslides within the limits of the former Patagonian Ice Sheet (PIS) cluster along its eastern margins occupying lower, tectonically less active, and arid part of the Patagonian Andes. In contrast to the heavily glaciated, highest elevations of the mountain range, the peripheral regions have been glaciated only episodically, leaving a larger volume of unstable sedimentary and volcanic rocks that are subject to ongoing slope instability.
Incorporation of noncanonical amino acids (ncAAs) with bioorthogonal reactive groups by amber suppression allows the generation of synthetic proteins with desired novel properties. Such modified molecules are in high demand for basic research and therapeutic applications such as cancer treatment and in vivo imaging. The positioning of the ncAA-responsive codon within the protein's coding sequence is critical in order to maintain protein function, achieve high yields of ncAA-containing protein, and allow effective conjugation. Cell-free ncAA incorporation is of particular interest due to the open nature of cell-free systems and their concurrent ease of manipulation. In this study, we report a straightforward workflow to inquire ncAA positions in regard to incorporation efficiency and protein functionality in a Chinese hamster ovary (CHO) cell-free system. As a model, the well-established orthogonal translation components Escherichia coli tyrosyl-tRNA synthetase (TyrRS) and tRNATyr(CUA) were used to site-specifically incorporate the ncAA p-azido-l-phenylalanine (AzF) in response to UAG codons. A total of seven ncAA sites within an anti-epidermal growth factor receptor (EGFR) single-chain variable fragment (scFv) N-terminally fused to the red fluorescent protein mRFP1 and C-terminally fused to the green fluorescent protein sfGFP were investigated for ncAA incorporation efficiency and impact on antigen binding. The characterized cell-free dual fluorescence reporter system allows screening for ncAA incorporation sites with high incorporation efficiency that maintain protein activity. It is parallelizable, scalable, and easy to operate. We propose that the established CHO-based cell-free dual fluorescence reporter system can be of particular interest for the development of antibody-drug conjugates (ADCs).
Law smells
(2022)
Building on the computer science concept of code smells, we initiate the study of law smells, i.e., patterns in legal texts that pose threats to the comprehensibility and maintainability of the law. With five intuitive law smells as running examples-namely, duplicated phrase, long element, large reference tree, ambiguous syntax, and natural language obsession-, we develop a comprehensive law smell taxonomy. This taxonomy classifies law smells by when they can be detected, which aspects of law they relate to, and how they can be discovered. We introduce text-based and graph-based methods to identify instances of law smells, confirming their utility in practice using the United States Code as a test case. Our work demonstrates how ideas from software engineering can be leveraged to assess and improve the quality of legal code, thus drawing attention to an understudied area in the intersection of law and computer science and highlighting the potential of computational legal drafting.
Deep lipidomics in human plasma: cardiometabolic disease risk and effect of dietary fat modulation
(2022)
Background: In blood and tissues, dietary and endogenously generated fatty acids (FAs) occur in free form or as part of complex lipid molecules that collectively represent the lipidome of the respective tissue. We assessed associations of plasma lipids derived from high-resolution lipidomics with incident cardiometabolic diseases and subsequently tested if the identified risk-associated lipids were sensitive to dietary fat modification. Methods: The EPIC Potsdam cohort study (European Prospective Investigation into Cancer and Nutrition) comprises 27 548 participants recruited within an age range of 35 to 65 years from the general population around Potsdam, Germany. We generated 2 disease-specific case cohorts on the basis of a fixed random subsample (n=1262) and all respective cohort-wide identified incident primary cardiovascular disease (composite of fatal and nonfatal myocardial infarction and stroke; n=551) and type 2 diabetes (n=775) cases. We estimated the associations of baseline plasma concentrations of 282 class-specific FA abundances (calculated from 940 distinct molecular species across 15 lipid classes) with the outcomes in multivariable-adjusted Cox models. We tested the effect of an isoenergetic dietary fat modification on risk-associated lipids in the DIVAS randomized controlled trial (Dietary Intervention and Vascular Function; n=113). Participants consumed either a diet rich in saturated FAs (control), monounsaturated FAs, or a mixture of monounsaturated and n-6 polyunsaturated FAs for 16 weeks. Results: Sixty-nine lipids associated (false discovery rate<0.05) with at least 1 outcome (both, 8; only cardiovascular disease, 49; only type 2 diabetes, 12). In brief, several monoacylglycerols and FA16:0 and FA18:0 in diacylglycerols were associated with both outcomes; cholesteryl esters, free fatty acids, and sphingolipids were largely cardiovascular disease specific; and several (glycero)phospholipids were type 2 diabetes specific. In addition, 19 risk-associated lipids were affected (false discovery rate<0.05) by the diets rich in unsaturated dietary FAs compared with the saturated fat diet (17 in a direction consistent with a potential beneficial effect on long-term cardiometabolic risk). For example, the monounsaturated FA-rich diet decreased diacylglycerol(FA16:0) by 0.4 (95% CI, 0.5-0.3) SD units and increased triacylglycerol(FA22:1) by 0.5 (95% CI, 0.4-0.7) SD units. Conclusions: We identified several lipids associated with cardiometabolic disease risk. A subset was beneficially altered by a dietary fat intervention that supports the substitution of dietary saturated FAs with unsaturated FAs as a potential tool for primary disease prevention.
In seismic risk assessment, the sources of uncertainty associated with building exposure modelling have not received as much attention as other components related to hazard and vulnerability. Conventional practices such as assuming absolute portfolio compositions (i.e., proportions per building class) from expert-based assumptions over aggregated data crudely disregard the contribution of uncertainty of the exposure upon earthquake loss models. In this work, we introduce the concept that the degree of knowledge of a building stock can be described within a Bayesian probabilistic approach that integrates both expert-based prior distributions and data collection on individual buildings. We investigate the impact of the epistemic uncertainty in the portfolio composition on scenario-based earthquake loss models through an exposure-oriented logic tree arrangement based on synthetic building portfolios. For illustrative purposes, we consider the residential building stock of Valparaiso (Chile) subjected to seismic ground-shaking from one subduction earthquake. We have found that building class reconnaissance, either from prior assumptions by desktop studies with aggregated data (top-down approach), or from building-by-building data collection (bottom-up approach), plays a fundamental role in the statistical modelling of exposure. To model the vulnerability of such a heterogeneous building stock, we require that their associated set of structural fragility functions handle multiple spectral periods. Thereby, we also discuss the relevance and specific uncertainty upon generating either uncorrelated or spatially cross-correlated ground motion fields within this framework. We successively show how various epistemic uncertainties embedded within these probabilistic exposure models are differently propagated throughout the computed direct financial losses. This work calls for further efforts to redesign desktop exposure studies, while also highlighting the importance of exposure data collection with standardized and iterative approaches.
Gut zwei Jahrzehnte nach dem Millenniumsgipfel der Vereinten Nationen bleiben berechtigte Zweifel an der Wirksamkeit von Entwicklungszusammenarbeit (EZ). Ist das Politikfeld von den Realitäten überholt worden? Welchen Beitrag haben Entwicklungstheorien für die Weiterentwicklung von Entwicklungspolitik leisten können? Der Beitrag zieht eine Bilanz, die von der ersten Entwicklungsdekade in den 1960er-Jahren bis zu den Folgen der Covid-19-Pandemie reicht. Er plädiert für eine herrschaftskritische Weiterentwicklung des Entwicklungsbegriffs und für eine Stärkung globaler Kooperation.
Hot, compact, hydrogen-deficient pre-white dwarfs (pre-WDs) with effective temperatures of Teff > 70 000 K and a surface gravity of 5.0 < logg < 7.0 are rather rare objects despite recent and ongoing surveys. It is believed that they are the outcome of either single star evolution (late helium-shell flash or late helium-core flash) or binary star evolution (double WD merger). Their study is interesting because the surface elemental abundances reflect the physics of thermonuclear flashes and merger events. Spectroscopically they are divided in three different classes, namely PG1159, O(He), or He-sdO. We present a spectroscopic analysis of five such stars that turned out to have atmospheric parameters in the range Teff = 70 000-80 000 K and logg = 5.2-6.3. The three investigated He-sdOs have a relatively high hydrogen mass fraction (10%) that is unexplained by both single (He core flash) and binary evolution (He-WD merger) scenarios. The O(He) star JL 9 is probably a binary helium-WD merger, but its hydrogen content (6%) is also at odds with merger models. We found that RL 104 is the 'coolest' (Teff = 80 000 K) member of the PG1159 class in a pre-WD stage. Its optical spectrum is remarkable because it exhibits C※ IV lines involving Rydberg states with principal quantum numbers up to n = 22. Its rather low mass (0.48-0.02+0.03 M·) is difficult to reconcile with the common evolutionary scenario for PG1159 stars due to it being the outcome of a (very) late He-shell flash. The same mass-problem faces a merger model of a close He-sdO plus CO WD binary that predicts PG1159-like abundances. Perhaps RL 104 originates from a very late He-shell flash in a CO/He WD formed by a merger of two low-mass He-WDs.
The benefits of counting butterflies: recommendations for a successful citizen science project
(2022)
Citizen science (CS) projects, being popular across many fields of science, have recently also become a popular tool to collect biodiversity data. Although the benefits of such projects for science and policy making are well understood, relatively little is known about the benefits participants get from these projects as well as their personal backgrounds and motivations. Furthermore, very little is known about their expectations. We here examine these aspects, with the citizen science project "German Butterfly Monitoring" as an example. A questionnaire was sent to all participants of the project and the responses to the questionnaire indicated the following: center dot Most transect walkers do not have a professional background in this field, though they do have a high educational level, and are close to retirement, with a high number of females; center dot An important motivation to join the project is to preserve the natural environment and to contribute to scientific knowledge; center dot Participants benefit by enhancing their knowledge about butterflies and especially their ability to identify different species (taxonomic knowledge); center dot Participants do not have specific expectations regarding the project beyond proper management and coordination, but have an intrinsic sense of working for a greater good. The willingness to join a project is higher if the project contributes to the solution of a problem discussed in the media (here, insect decline). Based on our findings from the analysis of the questionnaire we can derive a set of recommendations for establishing a successful CS project. These include the importance of good communication, e.g., by explaining what the (scientific) purpose of the project is and what problems are to be solved with the help of the data collected in the project. The motivation to join a CS project is mostly intrinsic and CS is a good tool to engage people during difficult times such as the COVID-19 pandemic, giving participants the feeling of doing something useful.
In this paper, we employ an experimental paradigm using insights from the psychology of reasoning to investigate the question whether certain modals generate and draw attention to alternatives. The article extends and builds on the methodology and findings of Mascarenhas & Picat (2019). Based on experimental results, they argue that the English epistemic modal might raises alternatives. We apply the same methodology to the English modal allowed to to test different hypotheses regarding the involvement of alternatives in deontic modality. We find commonalities and differences between the two modals we tested. We discuss theoretical consequences for existing semantic analyses of these modals, and argue that reasoning tasks can serve as a diagnostic tool to discover which natural language expressions involve alternatives.