bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissipative control for nonlinear Markovian jump systems with mixed time‐delays: The discrete‐time case
Authors: Ma Lifeng , Fang Xiaoli , Yuan Yuan , Zhang Jie , Bo Yuming
Published: February 2020

This article is concerned with the dissipative control problem for discrete‐time nonlinear Markovian jump systems subject to both discrete and distributed time‐delays. The purpose is to design a state feedback controller that is capable of guaranteeing the required closed‐loop stability and dissipativity performances simultaneously. By resorting to Lyapunov functional methodology and completing square technique, sufficient conditions are established for the existence of the desired state feedback controller in terms of certain Hamilton‐Jacobi inequalities (HJIs). Within the provided framework, the required controller parameters can be obtained by solving the corresponding HJIs. Finally, two numerical simulation examples are presented to demonstrate the correctness and effectiveness of the developed control paradigm.
Enhanced hydrologic simulation may not improve downscaled soil moisture patterns without improved soil characterization
Authors: Pauly Matthew J. , Niemann Jeffrey D. , Scalia Joseph , Green Timothy R. , Erskine Robert H. , Jones Andrew S. , Grazaitis Peter J.
Published: February 2020

Fine‐resolution soil moisture maps (10–30 m grid cells) are useful for many applications, including agricultural production and off‐road vehicle mobility. Fine‐resolution maps of soil moisture can be produced by downscaling coarse‐resolution soil moisture data from remote sensing. Soil moisture downscaling has been conducted by modeling key hydrologic processes in the soil, but current downscaling methods neglect two key aspects of soil hydrology: surface runoff and residual water content. The objective of this study is to understand how these hydrologic considerations affect spatial patterns of soil moisture and whether their inclusion improves downscaling performance. The Equilibrium Moisture from Topography, Vegetation, and Soil (EMT+VS) downscaling model is used to address these questions. Surface runoff is introduced to the model by implementing an infiltration capacity based on the saturated hydraulic conductivity. Residual water content is included by assuming that all hydrologic processes cease when soil moisture is at or below the residual water content. The pre‐existing EMT+VS model is compared with the new models using data from northeastern Colorado. The results show that both model additions introduce more complex dependence on the spatial variability of soil texture, which is difficult to estimate accurately. Including surface runoff provides only a small improvement in model performance, and residual water content shows almost no effect on the performance in this case. Thus, the simplifying assumptions of the pre‐existing model provide an appropriate level of complexity, given the uncertainties of the spatial input data.
Strategies to Construct a Chemical‐Fuel‐Driven Self‐Assembly
Authors: Wang Guangtong , Liu Shaoqin
Published: February 2020

Fuel‐driven self‐assembly widely exists in the biological world since functional micro‐ or nanostructures in living bodies are usually transiently formed by biomolecular self‐assembly far from thermodynamic equilibrium driven by active molecules (chemical fuel), for example, adenosine triphosphate (ATP). Therefore, research focusing on artificial fuel‐driven self‐assembly has drawn extensive attention in recent years. Compared with spontaneous molecular self‐assembly at thermodynamic equilibrium, constructing a fuel‐driven self‐assembly remains complicated because it requires a delicately designed chemical reaction network mainly involving an “activation” and a “deactivation”. In this Minireview, we will review recent developments in fuel‐driven self‐assembly and generalize several strategies for constructing such a self‐assembly. Besides that, the functional micro‐ or nanostructures and materials achieved by these fuel‐driven self‐assemblies will also be discussed.
Copper(I) Complexes of Anionic Tridentate CNC Pincer Ligands
Authors: Adiraju Venkata A. K. , Jin Weichang , Yousufuddin Muhammed , Dias H. V. Rasika
Published: February 2020

New monoanionic CNC pincer ligands, [N{SiMe2CH2(RIm)}2]– (R = tBu, iPr, Ph) featuring three different N‐heterocyclic carbenes and a disilylamido moiety is reported. Treatment of the lithium salt of [N{SiMe2CH2(RIm)}2]– with CuIOTf afforded the corresponding copper complexes [N{SiMe2CH2(RIm)}2]Cu in 41–56 % yield. X‐ray crystal structures of [N{SiMe2CH2(RIm)}2]Cu show that they are monomeric and feature three‐coordinate, pseudo T‐shaped copper(I) sites. The X‐ray crystal structure of one of the precursor lithium complexes, [N{SiMe2CH2(tBuIm)}2]Li is also presented.
Management of pediatric blunt abdominal trauma in a Dutch level one trauma center
Authors: Spijkerman Roy , Bulthuis Lauren C. M. , Hesselink Lillian , Nijdam Thomas M. P. , Leenen Luke P. H. , de Bruin Ivar G. J. M.
Published: February 2020

Purpose

Most children with intra-abdominal injuries can be managed non-operatively. However, in Europe, there are many different healthcare systems for the treatment of pediatric trauma patients. Therefore, the aim of this study was to describe the management strategies and outcomes of all pediatric patients with blunt intra-abdominal injuries in our unique dedicated pediatric trauma center with a pediatric trauma surgeon.

Methods

We performed a retrospective, single-center, cohort study to investigate the management of pediatric patients with blunt abdominal trauma. From the National Trauma Registration database, we retrospectively identified pediatric (≤ 18 years) patients with blunt abdominal injuries admitted to the UMCU from January 2012 till January 2018.

Results

A total of 121 pediatric patients were included in the study. The median [interquartile range (IQR)] age of patients was 12 (8–16) years, and the median ISS was 16 (9–25). High-grade liver injuries were found in 12 patients. Three patients had a pancreas injury grade V. Furthermore, 2 (1.6%) patients had urethra injuries and 10 (8.2%) hollow viscus injuries were found. Eighteen (14.9%) patients required a laparotomy and 4 (3.3%) patients underwent angiographic embolization. In 6 (5.0%) patients, complications were found and in 4 (3.3%) children intervention was needed for their complication. No mortality was seen in patients treated non-operatively. One patient died in the operative management group.

Conclusions

In conclusion, it is safe to treat most children with blunt abdominal injuries non-operatively if monitoring is adequate. These decisions should be made by the clinicians operating on these children, who should be an integral part of the entire group of treating physicians. Surgical interventions are only needed in case of hemodynamic instability or specific injuries such as bowel perforation.
Nächtliche Verkehrslärmbelästigung in Deutschland: individuelle und regionale Unterschiede in der NAKO Gesundheitsstudie
Authors: Wolf Kathrin , Kraus Ute , Dzolan Mihovil , Bolte Gabriele , Lakes Tobia , Schikowski Tamara , Greiser Karin Halina , Kuß Oliver , Ahrens Wolfgang , Bamberg Fabian , Becher Heiko , Berger Klaus , Brenner Hermann , Castell Stefanie , Damms-Machado Antje , Fischer Beate , Franzke Claus-Werner , Gastell Sylvia , Günther Kathrin , Holleczek Bernd , Jaeschke Lina , Kaaks Rudolf , Keil Thomas , Kemmling Yvonne , Krist Lilian , Legath Nicole , Leitzmann Michael , Lieb Wolfgang , Loeffler Markus , Meinke-Franze Claudia , Michels Karin B. , Mikolajczyk Rafael , Moebus Susanne , Mueller Ulrich , Obi Nadia , Pischon Tobias , Rathmann Wolfgang , Schipf Sabine , Schmidt Börge , Schulze Matthias , Thiele Inke , Thierry Sigrid , Waniek Sabina , Wigmann Claudia , Wirkner Kerstin , Zschocke Johannes , Peters Annette , Schneider Alexandra
Published: February 2020

Hintergrund

Lärmbelästigung geht mit gesundheitlicher Beeinträchtigung und reduziertem Wohlbefinden einher. Die subjektive Lärmbelästigung steht im Zusammenhang mit der objektiven Lärmbelastung sowie individuellen und regionalen Faktoren.

Fragestellung

Wie viele Teilnehmende der NAKO Gesundheitsstudie fühlen sich durch nächtlichen Verkehrslärm belästigt und welche Faktoren stehen damit im Zusammenhang?

Material und Methoden

Diese Querschnittsanalyse basiert auf Daten von 86.080 NAKO-Teilnehmenden aus 18 Studienzentren, die von 2014 bis 2017 untersucht wurden. Um die Beziehungen zwischen individuellen und regionalen Faktoren und Verkehrslärmbelästigung in den Kategorien nicht belästigt, leicht/mittel und stark/sehr stark belästigt zu untersuchen, wurden multinomiale logistische Regressionsmodelle mit wechselseitiger Adjustierung der Faktoren verwendet.

Ergebnisse

Zwei Drittel der Teilnehmenden fühlten sich nicht durch Verkehrslärm belästigt; jeder Zehnte berichtete von starker/sehr starker Belästigung, mit den höchsten Anteilen in Berlin-Mitte und Leipzig. Die stärksten Assoziationen mit Lärmbelästigung wurden für Faktoren der individuellen Wohnsituation beobachtet, wie z. B. die Position des Schlafraums zur Hauptstraße (OR für leicht/mittel belästigt: 4,26 [95 % KI: 4,01; 4,52]; OR für stark/sehr stark belästigt: 13,36 [95 % KI: 12,47; 14,32] im Vergleich zu Garten/Innenhof). Teilnehmende im Alter von 40–60 Jahren oder der mittleren und niedrigen Einkommensklasse fühlten sich eher durch Verkehrslärm belästigt als jüngere bzw. ältere Teilnehmende oder solche mit hoher Einkommensklasse.

Diskussion

Teilnehmende der NAKO Gesundheitsstudie wiesen Unterschiede in der Belästigung durch nächtlichen Verkehrslärm in Bezug auf individuelle und regionale Faktoren auf.
Einsatz von sedierenden Medikamenten und bewegungseinschränkenden Maßnahmen bei Patienten mit Demenz im Akutkrankenhaus
Authors: Lüdecke Daniel , Kofahl Christopher
Published: February 2020

Hintergrund

Auf Menschen mit Demenz mit stationär behandlungsbedürftiger Akuterkrankung ist der Großteil der Akutkrankenhäuser kaum vorbereitet. Dies birgt die Gefahr der Überforderung für das Personal. Demenzerkrankungen sind der häufigste Grund dafür, dass Krankenhauspersonal sedierende Medikamente verabreicht und bewegungseinschränkende Maßnahmen einsetzt.

Zielsetzung

Die vorliegende Studie untersucht Faktoren, die den (unangemessenen) Einsatz von sedierenden Medikamenten und bewegungseinschränkenden Maßnahmen beeinflussen.

Methoden

Eine nichtrandomisierte Fall-Kontroll-Studie wurde in 2 internistischen Abteilungen in Hamburg durchgeführt. In der Interventionsgruppe wurde ein spezielles Versorgungskonzept für Menschen mit Demenz implementiert. Die Versorgungsart in der Kontrollgruppe entsprach der Regelversorgung. Mit logistischen Regressionen wurden Zusammenhänge zwischen Faktoren wie Alter, Demenzschweregrad, Verhaltensauffälligkeiten, Barthel-Index oder Versorgungsart und dem Einsatz sedierender Medikamente bzw. bewegungseinschränkender Maßnahmen untersucht.

Ergebnisse

Herausfordernde Verhaltensweisen (OR = 1,32) und die Zugehörigkeit zur Kontrollgruppe (OR = 1,94) sind signifikant mit dem Einsatz sedierender Medikamente assoziiert. Ein geringerer Barthel-Index, längere Aufenthaltsdauer und die eine Behandlung in der Kontrollgruppe sind signifikant mit einer höheren Wahrscheinlichkeit des Einsatzes bewegungseinschränkender Maßnahmen assoziiert.

Diskussion

Der Einsatz sedierender Medikamente als auch bewegungseinschränkender Maßnahmen variiert stark zwischen Interventions- und Kontrollgruppe. Andere Studien, die zu ähnlichen Ergebnissen kommen, sehen verschiedene Bausteine spezieller Versorgungskonzepte als Gründe für diese Unterschiede. Dazu zählen neben der baulichen Gestaltung und räumlichen Aspekten auch demenzspezifische Schulungsangebote und ein angemessener Personalschlüssel. Dies vermag auch Unruhe und herausfordernde Verhaltensweisen aufseiten der Patienten zu reduzieren. Der Verzicht auf Sedierung und bewegungseinschränkende Maßnahmen hat nicht zuletzt auch positive Auswirkungen auf die Lebensqualität von Menschen mit Demenz.
Alzheimer’s disease: targeting the glutamatergic system
Authors: Conway Myra E.
Published: February 2020

Alzheimer’s disease (AD) is a debilitating neurodegenerative disease that causes a progressive decline in memory, language and problem solving. For decades mechanism-based therapies have primarily focused on amyloid β (Aβ) processing and pathways that govern neurofibrillary tangle generation. With the potential exception to Aducanumab, a monotherapy to target Aβ, clinical trials in these areas have been challenging and have failed to demonstrate efficacy. Currently, the prescribed therapies for AD are those that target the cholinesterase and glutamatergic systems that can moderately reduce cognitive decline, dependent on the individual. In the brain, over 40% of neuronal synapses are glutamatergic, where the glutamate level is tightly regulated through metabolite exchange in neuronal, astrocytic and endothelial cells. In AD brain, Aβ can interrupt effective glutamate uptake by astrocytes, which evokes a cascade of events that leads to neuronal swelling, destruction of membrane integrity and ultimately cell death. Much work has focussed on the post-synaptic response with little insight into how glutamate is regulated more broadly in the brain and the influence of anaplerotic pathways that finely tune these mechanisms. The role of blood branched chain amino acids (BCAA) in regulating neurotransmitter profiles under disease conditions also warrant discussion. Here, we review the importance of the branched chain aminotransferase proteins in regulating brain glutamate and the potential consequence of dysregulated metabolism in the context of BCAA or glutamate accumulation. We explore how the reported benefits of BCAA supplementation or restriction in improving cognitive function in other neurological diseases may have potential application in AD. Given that memantine, the glutamate receptor agonist, shows clinical relevance it is now timely to research related pathways, an understanding of which could identify novel approaches to treatment of AD.
Bivs, Space and ‘In’
Authors: Mac Cumhaill Clare
Published: February 2020

I present a novel anti-sceptical BIV argument by focusing on conditions on the production and use of the locative preposition ‘in’. I distinguish two uses of ‘in’—material and descriptive phenomenological—and I explain in what respect movement is central to the concept that our use of ‘in’ expresses. I go on to argue that a functionalist semantics of the intelligible use of ‘in’ demands a materialist philosophy of action in the spirit of G.E.M. Anscombe, but also why the structure of space is not irrelevant either; appeal to the structure of space unsettles the causal-empirical assumptions that ground the picture of subjectivity and agency that the biv narrative assumes. Finally, I explain why a functionalist semantics demands a Naïve Realist metaphysics of perception, consistent with some of Putnam’s last writings on philosophy of perception.
Evaluation of wild barley introgression lines for agronomic traits related to nitrogen fertilization
Authors: Zahn Sarah , Koblenz Barbara , Christen Olaf , Pillen Klaus , Maurer Andreas
Published: February 2020

In the coming decades, climate change and resources constraints will make profitable and economically reliable agriculture more and more challenging. To evaluate the potential of exotic alleles to maintain performance under low nitrogen input, we investigated a set of 41 introgression lines (S42ILs) originating from the hybridization of the German spring barley ‘Scarlett’ and the Israeli wild barley ‘ISR42-8’. These lines were assessed in field trials for yield, yield components, grain protein content and chlorophyll content during growing seasons 2015 and 2016 in two different test sites in Germany under low and high nitrogen supply levels, N0 and N1. Our analyses revealed 17 regions for putative quantitative trait loci (QTL), linked to one or multiple traits, across all chromosomes. In particular, lines S42IL_119 and S42IL_121 exhibited an enhanced thousand grain weight of 7% and 9% under N1 and N0, respectively. In addition, six QTL were found for grain number per ear leading to a decline of grain number of up to 20%. Furthermore, three new QTL for chlorophyll content could be identified on chromosomes 1H and 2H. The present study revealed QTL effects of wild barley introgressions in a spring barley elite background, especially under low nitrogen. The selection for nitrogen efficient lines with beneficial exotic alleles represents the first step towards the development of spring barley cultivars genetically adapted to nitrogen limitations.
Supererogation and sequence
Authors: Bales Adam , Benn Claire
Published: February 2020

Morally supererogatory acts are those that go above and beyond the call of duty. More specifically: they are acts that, on any individual occasion, are good to do and also both permissible to do and permissible to refrain from doing. We challenge the way in which discussions of supererogation typically consider our choices and actions in isolation. Instead we consider sequences of supererogatory acts and omissions and show that some such sequences are themselves problematic. This gives rise to the following puzzle: what problem can we have with a sequences of actions if each individual act or omission is itself permissible? In this paper, we develop a response to this question, by exploring whether solutions analogous to those proposed in the rational choice literature are available in the case of supererogatory sequences. Our investigation leads us to the view that making sense of the supererogatory requires accepting that there are global moral norms that apply to sequences of acts alongside the local moral norms that apply to individual acts.
Rapid Solidification Microstructure and Carbide Precipitation Behavior in Electron Beam Melted High-Speed Steel
Authors: Jin J. , Gao R. , Peng H. , Guo H. , Gong S. , Chen B.
Published: February 2020

The solidified microstructure and carbide precipitation behavior in an S390 high-speed steel processed by electron beam melting (EBM) have been fully characterized. The as-EBM microstructure consists of discontinuous network of very fine primary carbides dispersed in auto-tempered martensite matrix together with a limited amount of retained austenite. The carbide network consists of M2C/M6C and MC carbides. Both the columnar and near-equiaxed grain structures were found in as-EBM microstructure and the presence of inter-dendritic eutectic carbides assisted in revealing the dendritic solidification nature. The top-layer microstructure observation confirmed that the columnar dendritic structured grains were located adjacent to the micro-melt pool boundary, indicating an epitaxial growth with the average growth direction parallel to the maximum thermal gradient. At the center of the micro-melt pool, the near-equiaxed grains were developed by dendritic growth parallel to the beam traveling direction. The carbide decomposition was revealed by scanning transmission electron microscopy and confirmed by transmission Kikuchi diffraction. The MC carbides (rich in V followed by W) nucleated at the interface between M2C (W, Fe, Mo, and Co in the order of significance) and the matrix and then grew from the outside inward, but their nucleation might occur from the M2C carbide itself. The thermal effect induced by the adjacent scan lines seems to trigger a solid-state phase transformation of MC → M2C + γ-Fe. The elemental migration was theoretically calculated and compared with the experimental results. The high hardness of ~ 65 HRC and good transverse rupture strength of ~ 2500 MPa in as-EBM S390 means that EBM processing can be used to fabricate highly alloyed tool steels. With the help of the post-processing heat treatment, the best Rockwell hardness of 73.1±0.2 HRC and transverse rupture strength of 3012±34 MPa can be obtained.
Wat als prostaatkanker in de familie voorkomt?
Authors: Cremers Ruben G. H. M. , Blanker Marco H. , Bloemendal Maaike M.
Published: February 2020

Samenvatting

In de algemene populatie geldt het advies om bij een verzoek om PSA-bepaling eerst de voors en tegens goed af te wegen, eventueel ondersteund door online tools, zoals te vinden zijn op https://www.thuisarts.nl/keuzehulpen/psa/. De familieanamnese is daarbij van belang voor het inschatten van een mogelijk erfelijk verhoogde kans op een agressieve prostaatkanker. Zowel het voorkomen als ook de mate van agressiviteit van de prostaatkankers dient daarbij uitgevraagd te worden, als ook tumoren die aan BRCA2-mutaties gerelateerd zijn (mammacarcinoom en ovariumcarcinoom bij vrouwelijke familieleden). Een (mogelijk) verhoogd erfelijk risico op agressieve prostaatkanker kan worden gebruikt om af te wijken van het algemene advies: bij eerstegraads verwanten van prostaatkankerpatiënten in HPC-families wordt tweejaarlijks PSA-onderzoek vanaf 50 jaar (of vanaf 5 jaar vóór de jongste prostaatkankerpatiënt in de familie) geadviseerd. Het vóórkomen van niet-agressieve prostaatkankers in de familie is biologisch gezien geen reden om af te wijken van het algemene advies ten aanzien van prostaatkankerscreening.
Case report: manic episode with psychotic symptoms induced by hyponatremia
Authors: Mauracher Laurin , Rettenbacher Maria
Published: February 2020

In the literature, several cases of an association between hyponatremia and psychotic symptoms have been reported. We present the case of a young Caucasian male presenting with rapid, incoherent speech, religious and megalomanic delusions, and emotional lability. The patient was described by his relatives as being healthy until a few days before admission. He had no significant medical or psychiatric history, except a short drug-induced psychotic episode a few years earlier. Somatic workup showed moderate hyponatremia, but no other abnormalities. Tests for narcotics, in particular, were also negative. Antipsychotic treatment with risperidone was initiated. After normalization of sodium levels using intravenous saline, the patient remitted within a few days and risperidone was discontinued on day 3. He was discharged by day 13 without further pharmacological treatment.

Dysfunction of voltage-gated ion channels, particularly sodium and calcium channels, has been implicated in the pathogenesis of bipolar disorder. We therefore assume a causal relationship between hyponatremia and manic-psychotic symptoms in our patient. Hyponatremia was most likely induced by excessive water intake during a period of fasting in the context of a wellness practice.
Propeller influence on the aeroelastic stability of High Altitude Long Endurance aircraft
Authors: Teixeira P.C. , Cesnik C.E.S.
Published: February 2020

This work investigates the propeller’s influence on the stability of High Altitude Long Endurance aircraft, incorporating all resultant loads at the propeller hub, propeller slipstream, and gyroscopic loads. Such effects are usually neglected in the aeroelastic simulation of HALE aircraft. For that goal, a previously developed framework, which couples a geometrically nonlinear structural solver with an Unsteady Vortex Lattice method (uVLM) for lifting surfaces and a Viscous Vortex Particle (VVP) method for propeller slipstream, was employed to generate time-data series. Also, a method, based on a combination of Proper Orthogonal Decomposition and system identification, to extract dynamic information (frequencies, damping, and modes) of the aircraft from a time-series signal is proposed and successfully tested for a purely structural case, for which reference data is available. The method is then applied to investigate the stability of aeroelastic cases. The results demonstrate that the presence of propellers can influence the aeroelastic stability of a Very Flexible Aircraft.
THE EFFECTS OF FOREIGN LANGUAGE PROFICIENCY ON PUBLIC ATTITUDES: EVIDENCE FROM THE CHINESE-SPEAKING WORLD
Authors: Hu Yue , Liu Amy H.
Published: February 2020

What explains public attitudes towards a former aggressor state? Conventional wisdom would suggest the prevalence of negative sentiments rooted in historical hatred. In this article we contend that when individuals are proficient in a foreign language—e.g. a lingua franca—they have an alternative channel through which they are exposed to positive narratives put forth by other parties regarding the former aggressor state. And as a result, their attitudes towards the former aggressor state are more positive than those held by their linguistically limited counterparts. To test our argument, we focus on public attitudes towards the Japanese in Mainland China, Singapore, and Taiwan—three Chinese-ethnic majority political units that experienced Japanese aggression leading up to and during World War II. Using survey data, we demonstrate that individuals who are proficient in the English language are much more likely to hold positive attitudes of the Japanese. These results are robust even when we consider whether some individuals are predisposed to being cosmopolitan; whether some individuals have more opportunities to learn English; and whether the linguistic effects are symptomatic of American soft power.
Dinocyst stratigraphy of the Valanginian–Aptian Rurikfjellet and Helvetiafjellet formations on Spitsbergen, Arctic Norway
Authors: Śliwińska Kasia K. , Jelby Mads E. , Grundvåg Sten-Andreas , Nøhr-Hansen Henrik , Alsen Peter , Olaussen Snorre
Published: February 2020

In order to improve the understanding of how the high northern latitudes responded to the escalating warming which led to the middle Cretaceous super greenhouse climate, more temperature proxy records from the High Arctic are needed. One of the current obstacles in obtaining such records is poor age control on the Lower Cretaceous strata in the Boreal region. Here, we provide a biostratigraphic framework for the Rurikfjellet and Helvetiafjellet formations representing the lower part of the Lower Cretaceous succession on Spitsbergen. We also attempt to date the boundary between the Agardhfjellet and the Rurikfjellet formations. This study is based on dinoflagellate cysts (dinocysts) from three onshore cores (DH1, DH2 and DH5R) and three outcrop sections (Bohemanflya, Myklegardfjellet and Ullaberget). Relatively abundant and well-preserved dinocyst assemblages from the Rurikfjellet Formation date this unit as early Valanginian – early Barremian. The dinocyst assemblages from the Helvetiafjellet Formation are significantly impoverished and are characterized by reworking, but collectively indicate a Barremian–Aptian age for this formation.
De novoprotein design, a retrospective
Authors: Korendovych Ivan V. , DeGrado William F.
Published: February 2020

Proteins are molecular machines whose function depends on their ability to achieve complex folds with precisely defined structural and dynamic properties. The rational design of proteins from first-principles, orde novo, was once considered to be impossible, but today proteins with a variety of folds and functions have been realized. We review the evolution of the field from its earliest days, placing particular emphasis on how this endeavor has illuminated our understanding of the principles underlying the folding and function of natural proteins, and is informing the design of macromolecules with unprecedented structures and properties. An initial set of milestones inde novoprotein design focused on the construction of sequences that folded in water and membranes to adopt folded conformations. The first proteins were designed from first-principles using very simple physical models. As computers became more powerful, the use of the rotamer approximation allowed one to discover amino acid sequences that stabilize the desired fold. As the crystallographic database of protein structures expanded in subsequent years, it became possible to construct proteins by assembling short backbone fragments that frequently recur in Nature. The second set of milestones inde novodesign involves the discovery of complex functions. Proteins have been designed to bind a variety of metals, porphyrins, and other cofactors. The design of proteins that catalyze hydrolysis and oxygen-dependent reactions has progressed significantly. However,de novodesign of catalysts for energetically demanding reactions, or even proteins that bind with high affinity and specificity to highly functionalized complex polar molecules remains an importnant challenge that is now being achieved. Finally, the protein design contributed significantly to our understanding of membrane protein folding and transport of ions across membranes. The area of membrane protein design, or more generally of biomimetic polymers that function in mixed or non-aqueous environments, is now becoming increasingly possible.
Habitual versus affective motivations in obsessive-compulsive disorder and alcohol use disorder
Authors: Ferreira Gabriela M. , Lee Rico S.C. , Piquet-Pessôa Marcelo , de Menezes Gabriela B. , Moreira-de-Oliveira Maria E. , Albertella Lucy , Yücel Murat , dos Santos Cruz Marcelo , dos Santos-Ribeiro Samara , Fontenelle Leonardo F.
Published: February 2020

Objective

To (1) confirm whether the Habit, Reward, and Fear Scale is able to generate a 3-factor solution in a population of obsessive-compulsive disorder and alcohol use disorder (AUD) patients; (2) compare these clinical groups in their habit, reward, and fear motivations; and (3) investigate whether homogenous subgroups can be identified to resolve heterogeneity within and across disorders based on the motivations driving ritualistic and drinking behaviors.

Methods

One hundred and thirty-four obsessive-compulsive disorder (n = 76) or AUD (n = 58) patients were assessed with a battery of scales including the Habit, Reward, and Fear Scale, the Yale-Brown Obsessive-Compulsive Scale, the Alcohol Dependence Scale, the Behavioral Inhibition/Activation System Scale, and the Urgency, (lack of
) Premeditation, (lack of
) Perseverance, Sensation Seeking, and Positive Urgency Impulsive Behavior Scale.

Results

A 3-factor solution reflecting habit, reward, and fear subscores explained 56.6% of the total variance of the Habit, Reward, and Fear Scale. Although the habit and fear subscores were significantly higher in obsessive-compulsive disorder (OCD) and the reward subscores were significantly greater in AUD patients, a cluster analysis identified that the 3 clusters were each characterized by differing proportions of OCD and AUD patients.

Conclusions

While affective (reward- and fear-driven) and nonaffective (habitual) motivations for repetitive behaviors seem dissociable from each other, it is possible to identify subgroups in a transdiagnostic manner based on motivations that do not match perfectly motivations that usually described in OCD and AUD patients.
Devout Neoliberalism?! Explaining Egypt's Muslim Brotherhood's Socio-economic Perspective and Policies
Authors: al-Anani Khalil
Published: February 2020

How can we explain the neoliberal orientation of Islamist movements in the Middle East? This paper attempts to answer this question by exploring the case of the Muslim Brotherhood in Egypt. It analyzes in depth the Brotherhood's socio-economic vision and policies when it was in power between 2012 and 2013. It argues that the Brotherhood adopted a market-oriented vision, which encouraged the private sector, liberalized the economy, and appealed to foreign investments. As a socio-political movement, the Brotherhood attempted to strike a balance between its constituency, which is rooted in the lower, middle, and upper-middle classes, and its commitment to neoliberal policies. However, this paradoxical balance burdened the movement and affected its popularity. The article also contends that the Brotherhood's neoliberal leanings can be explained by three key factors: the movement's pragmatism, its “devout” bourgeoisie, and the appeal for international acceptance and recognition.
The Project Talent Twin and Sibling Study: Zygosity and New Data Collection
Authors: Prescott Carol A. , Walters Ellen E. , Arpawong Thalida Em , Zavala Catalina , Gruenewald Tara L. , Gatz Margaret
Published: February 2020

The Project Talent Twin and Sibling (PTTS) study includes 4481 multiples and their 522 nontwin siblings from 2233 families. The sample was drawn from Project Talent, a U.S. national longitudinal study of 377,000 individuals born 1942–1946, first assessed in 1960 and representative of U.S. students in secondary school (Grades 9–12). In addition to the twins and triplets, the 1960 dataset includes 84,000 siblings from 40,000 other families. This design is both genetically informative and unique in facilitating separation of the ‘common’ environment into three sources of variation: shared by all siblings within a family, specific to twin-pairs, and associated with school/community-level factors. We term this the GIFTS model for genetics, individual, family, twin, and school sources of variance. In our article published in a previous Twin Research and Human Genetics special issue, we described data collections conducted with the full Project Talent sample during 1960–1974, methods for the recent linking of siblings within families, identification of twins, and the design of a 54-year follow-up of the PTTS sample, when participants were 68–72 years old. In the current article, we summarize participation and data available from this 2014 collection, describe our method for assigning zygosity using survey responses and yearbook photographs, illustrate the GIFTS model applied to 1960 vocabulary scores from more than 80,000 adolescent twins, siblings and schoolmates and summarize the next wave of PTTS data collection being conducted as part of the larger Project Talent Aging Study.
Changes in Extreme Precipitation and Landslides Over High Mountain Asia
Authors: Kirschbaum D. , Kapnick S. B. , Stanley T. , Pascale S.
Published: February 2020

High Mountain Asia is impacted by extreme monsoonal rainfall that triggers landslides in large proportions relative to global distributions, resulting in substantial human impacts and damage to infrastructure each year. Previous landslide research has qualitatively estimated how patterns in landslide activity may change based on climate change scenarios. We present the first quantitative view of potential modulation in future landslide activity over the High Mountain Asia region leveraging a new landslide hazard model and precipitation data from satellite and Global Climate Model sources. In doing so, we find that the rate of increase in landslide activity at the end of the century is expected to be greatest over areas covered by current glaciers and glacial lakes, potentially exacerbating the impacts of cascading hazards on populations downstream. This work demonstrates the potential of Global Climate Models and satellite‐based precipitation estimates to characterize landslide hazards at time scales affected by climate change.
Evaporative Resistance is of Equal Importance as Surface Albedo in High‐Latitude Surface Temperatures Due to Cloud Feedbacks
Authors: Kim Jinhyuk E. , Laguë Marysa M. , Pennypacker Sam , Dawson Eliza , Swann Abigail L. S.
Published: February 2020

Arctic vegetation is known to influence Arctic surface temperatures through albedo. However, it is less clear how plant evaporative resistance and albedo independently influence surface climate at high latitudes. We use surface properties derived from two common Arctic tree types to simulate the climate response to a change in land surface albedo and evaporative resistance in factorial combinations. We find that lower evaporative resistances lead to an increase of low clouds. The reflection of light due to the difference in albedos between vegetation types is similar to the loss of incident sunlight due to increased cloud cover resulting from lower evaporative resistance from vegetation change. Our results demonstrate that realistic changes in evaporative resistance can have an equal impact on surface temperature to changes in albedo and that cloud feedbacks play a first‐order role in determining the surface climate response to changes in Arctic land cover.
Simulation of Plasmaspheric Plume Impact on Dayside Magnetic Reconnection
Authors: Dargent J. , Aunai N. , Lavraud B. , Toledo‐Redondo S. , Califano F.
Published: February 2020

During periods of strong magnetic activity, cold dense plasma from the plasmasphere typically forms a plume extending toward the dayside magnetopause, eventually reaching it. In this work, we present a large‐scale two‐dimensional fully kinetic particle‐in‐cell simulation of a reconnecting magnetopause hit by a propagating plasmaspheric plume. The simulation is designed so that it undergoes four distinct phases: initial unsteady state, steady state prior to plume arrival at the magnetospause, plume interaction, and steady state once the plume is well engulfed in the reconnection site. We show the evolution of the magnetopause's dynamics subjected to the modification of the inflowing plasma. Our main result is that the change in the plasma temperature (cold protons in the plume) has no effects on the magnetic reconnection rate, which on average depends only on the inflowing magnetic field and total ion density, before, during, and after the impact.
Decoupling the Role of Inertia, Friction, and Cohesion in Dense Granular Avalanche Pressure Build‐up on Obstacles
Authors: Kyburz M. L. , Sovilla Betty , Gaume Johan , Ancey Christophe
Published: February 2020

Understanding the physical processes involved in snow avalanche‐obstacle interaction is essential to be able to estimate the pressure exerted on structures. Although avalanche impact pressure has been measured in field experiments for decades, the underlying physical principles are still elusive. Previous studies suggest that pressure is increased due to the formation of an influenced flow region around the structure, the mobilized domain, which varies in size depending on snow properties such as snow cohesion. Here, we aim to better understand how cohesion, friction, velocity, and their interplay affect avalanche pressure buildup on structures. This is achieved by simulating the avalanche‐obstacle interaction with a newly developed numerical model based on the discrete element method, using a cohesive bond contact law. The relevance of the model is tested by comparing simulated impact pressures with field measurements from the Vallée de la Sionne experimental site. Our results show that at the macroscale, impact pressure consists of the inertial, frictional, and cohesive contributions. The inertial and frictional contributions arise due to the existence, shape, and dimension of the mobilized domain. The cohesive contribution increases the particle contact forces inside the domain, leading up to a doubling of the pressure. Based on these physical processes, we propose a novel scaling law to reduce the problem of calculating the pressure induced by cohesive flows, to the calculation of cohesionless flows. These findings enhance our understanding of the interaction of cohesive granular flows, such as snow avalanches, and structures at the microscale and macroscale.
Impacts of the Cryosphere and Atmosphere on Observed Microseisms Generated in the Southern Ocean
Authors: Turner Ross J. , Gal Martin , Hemer Mark A. , Reading Anya M.
Published: February 2020

The Southern Ocean (in the region 60–180° E) south of the Indian Ocean, Australia, and the West Pacific is noted for the frequent occurrence and severity of its storms. These storms give rise to high‐amplitude secondary microseisms from sources, including the deep ocean regions, and primary microseisms where the swells impinge on submarine topographic features. A better understanding of the varying microseism wavefield enables improvements to seismic imaging and development of proxy observables to complement sparse in situ wave observations and hindcast models of the global ocean wave climate. We analyze 12–26 years of seismic data from 11 seismic stations either on the East Antarctic coast or sited in the Indian Ocean, Australia, and New Zealand. The power spectral density of the seismic wavefield is calculated to explore how the time‐changing microseism intensity varies with (i) sea ice coverage surrounding Antarctica and (ii) the Southern Annular Mode (SAM) climate index. Variations in sea ice extent are found to be the dominant control on the microseism intensity at Antarctic stations, which exhibit a seasonal pattern phase‐shifted by 4–5 months compared to stations in other continents. Peaks in extremal intensity at East Antarctic stations occur in March–April, with the highest peaks for secondary microseisms occurring during negative SAM events. This relationship between microseism intensity and the SAM index is opposite to that observed on the Antarctic Peninsula. This work informs the complexity of microseism amplitudes in the Southern Hemisphere and assists ongoing interdisciplinary investigations of interannual variability and long‐term trends.
RASSF10 is frequently epigenetically inactivated in kidney cancer and its knockout promotes neoplasia in cancer prone mice
Authors: Richter Antje M. , Woods Michelle L. , Küster Miriam M. , Walesch Sara K. , Braun Thomas , Boettger Thomas , Dammann Reinhard H.
Published: February 2020

Kidney cancer incidences are rising globally, thereby fueling the demand for targeted therapies and precision medicine. In our previous work, we have identified and characterized the Ras-Association Domain Family encoding ten members that are often aberrantly expressed in human cancers. In this study, we created and analyzed theRassf10knockout mice. Here we show thatRassf10haploinsufficiency promotes neoplasia formation in two established mouse cancer models (Rassf1A−/−and p53−/−). HaploinsufficientRassf10knockout mice were significantly prone to various diseases including lymphoma (Rassf1A−/−background) and thymoma (p53−/−background). Especially Rassf10−/−and p53-deficient mice exhibited threefold increased rates of kidney cysts compared with p53−/−controls. Moreover, we observed that in human kidney cancer,RASSF10is frequently epigenetically inactivated by its CpG island promoter hypermethylation. Primary tumors of renal clear cell and papillary cell carcinoma confirmed thatRASSF10methylation is associated with decreased expression in comparison to normal kidney tissue. In independent data sets, we could validate thatRASSF10inactivation clinically correlated with decreased survival and with progressed disease state of kidney cancer patients and polycystic kidney size. Functionally, we revealed that the loss ofRassf10was significantly associated with upregulation of KRAS signaling andMYCexpression. In summary, we could show thatRassf10functions as a haploinsufficient tumor suppressor. In combination with other markers,RASSF10silencing can serve as diagnostic and prognostic cancer biomarker in kidney diseases.
Lysosome biology in autophagy
Authors: Yim Willa Wen-You , Mizushima Noboru
Published: February 2020

Autophagy is a major intracellular degradation system that derives its degradative abilities from the lysosome. The most well-studied form of autophagy is macroautophagy, which delivers cytoplasmic material to lysosomes via the double-membraned autophagosome. Other forms of autophagy, namely chaperone-mediated autophagy and microautophagy, occur directly on the lysosome. Besides providing the means for degradation, lysosomes are also involved in autophagy regulation and can become substrates of autophagy when damaged. During autophagy, they exhibit notable changes, including increased acidification, enhanced enzymatic activity, and perinuclear localization. Despite their importance to autophagy, details on autophagy-specific regulation of lysosomes remain relatively scarce. This review aims to provide a summary of current understanding on the behaviour of lysosomes during autophagy and outline unexplored areas of autophagy-specific lysosome research.
Cryo-EM structures of PAC1 receptor reveal ligand binding mechanism
Authors: Wang Jia , Song Xianqiang , Zhang Dandan , Chen Xiaoqing , Li Xun , Sun Yaping , Li Cui , Song Yunpeng , Ding Yao , Ren Ruobing , Harrington Essa Hu , Hu Liaoyuan A. , Zhong Wenge , Xu Cen , Huang Xin , Wang Hong-Wei , Ma Yingli
Published: February 2020

The pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1R) belongs to the secretin receptor family and is widely distributed in the central neural system and peripheral organs. Abnormal activation of the receptor mediates trigeminovascular activation and sensitization, which is highly related to migraine, making PAC1R a potential therapeutic target. Elucidation of PAC1R activation mechanism would benefit discovery of therapeutic drugs for neuronal disorders. PAC1R activity is governed by pituitary adenylate cyclase-activating polypeptide (PACAP), known as a major vasodilator neuropeptide, and maxadilan, a native peptide from the sand fly, which is also capable of activating the receptor with similar potency. These peptide ligands have divergent sequences yet initiate convergent PAC1R activity. It is of interest to understand the mechanism of PAC1R ligand recognition and receptor activity regulation through structural biology. Here we report two near-atomic resolution cryo-EM structures of PAC1R activated by PACAP38 or maxadilan, providing structural insights into two distinct ligand binding modes. The structures illustrate flexibility of the extracellular domain (ECD) for ligands with distinct conformations, where ECD accommodates ligands in different orientations while extracellular loop 1 (ECL1) protrudes to further anchor the ligand bound in the orthosteric site. By structure-guided molecular modeling and mutagenesis, we tested residues in the ligand-binding pockets and identified clusters of residues that are critical for receptor activity. The structures reported here for the first time elucidate the mechanism of specificity and flexibility of ligand recognition and binding for PAC1R, and provide insights toward the design of therapeutic molecules targeting PAC1R.
Designing minimal genomes using whole-cell models
Authors: Rees-Garbutt Joshua , Chalkley Oliver , Landon Sophie , Purcell Oliver , Marucci Lucia , Grierson Claire
Published: February 2020

In the future, entire genomes tailored to specific functions and environments could be designed using computational tools. However, computational tools for genome design are currently scarce. Here we present algorithms that enable the use of design-simulate-test cycles for genome design, using genome minimisation as a proof-of-concept. Minimal genomes are ideal for this purpose as they have a simple functional assay whether the cell replicates or not. We used the first (and currently only published) whole-cell model for the bacterium Mycoplasma genitalium. Our computational design-simulate-test cycles discovered novel in silico minimal genomes which, if biologically correct, predict in vivo genomes smaller than JCVI-Syn3.0; a bacterium with, currently, the smallest genome that can be grown in pure culture. In the process, we identified 10 low essential genes and produced evidence for at least two Mycoplasma genitalium in silico minimal genomes. This work brings combined computational and laboratory genome engineering a step closer.