bluuebunny/crossref_metadata_2025 huggingface dataset:
Schätzen Entscheider im Gesundheitswesen die Niederlassungssituation falsch ein?
Authors: Redaèlli Marcus , Cizmowski Maren , Vollmar Horst Christian , Tamayo Miguel , Shukri Arim , Stock Stephanie , Bödecker August Wilhelm
Published: March 2020

Hintergrund Ziel der Untersuchung war die Abbildung von Motiven zur hausärztlichen Niederlassung aus der aktuellen Sicht nach Niederlassung (Erwartungen erfüllt) sowie vor Niederlassung (Motivation). Zudem sollten hinderliche bzw. förderliche Faktoren einer Niederlassung identifiziert werden.

Methoden Mittels Mixed-Methods-Ansatz (Fokusgruppen, Einzelinterviews) der Zielgruppe wurden Erfahrungen, Meinungen und Motivationen zur hausärztlichen Niederlassung erfasst, anschließend wurde ein prä-getesteter Fragebogen eingesetzt. Eine Vollerhebung von 675 identifizierten Hausärzten aus der Datenbank der Kassenärztlichen Vereinigung Nordrhein wurde durchgeführt. Das Einschlusskriterium war: Niederlassung 5 Jahren vor Befragungszeitraum (09/2015). Der Fragebogen enthielt 17 Fragen zur Niederlassungsmotivation, 11 zu biografischen Aspekten.

Ergebnisse Die Anzahl der auswertbaren Datensätze betrug 437 (64,7 %). Die höchsten Zustimmungswerte, im Sinne von förderlich für die Niederlassungsmotivation, erhielten „Wegfall der Dienste im Krankenhaus“ (97,2 %) und „eigener Chef sein“ (96,2 %). Als eher hinderlich wurden „Rechte und Pflichten als Vertragsarzt“ (8,5 %) und „vertragsärztlicher Notdienst/Bereitschaftsdienst“ (22,7 %) wahrgenommen. Im Sinne der Erfüllung von Erwartungen stellten sich „Wegfall der Dienste“ (95,6 %) und „Vielfalt der zu behandelnden Altersgruppen“ (88,9 %) heraus. Insgesamt würden sich 97 %, unabhängig vom Erfüllungsgrad ihrer Wünsche, wieder niederlassen und fast 3 Viertel entschieden sich erst nach dem Studium für die hausärztliche Tätigkeit.

Schlussfolgerungen Die Tatsache, dass die Flucht aus dem stationären Sektor als Hauptantrieb zur Niederlassung zählt, muss nachdenklich stimmen. Da dieser Befragungsansatz eine Vollerhebung von hausärztlich Niedergelassenen aus einem 5-jährigen Zeitraum darstellt, kann festgestellt werden, dass aufgrund der Altersstruktur der Befragten die derzeitigen Anreizstrukturen einer Niederlassung neu überdacht werden sollten.
Die Plastische Chirurgie im 2. Staatsexamen
Authors: Arsalan-Werner Annika , Sterz Jasmina , Stefanescu Maria-Christina , Sauerbier Michael , Rüsseler Miriam
Published: March 2020

Hintergrund Der nationale kompetenzbasierten Lernzielkatalog Chirurgie (NKLC) beinhaltet 230 Lernziele mit verschiedenen zugeordneten Kompetenzebenen, die am Ende des Medizinstudiums unabhängig vom späteren Berufswunsch erreicht sein müssen. Das Lernverhalten der Studenten orientiert sich an den Prüfungsinhalten von summativen Prüfungen („Assessment drives learning“), weshalb eine Ausrichtung des 2. schriftlichen Staatsexamens an definierten Lernzielen sinnvoll scheint. Diese Studie analysiert den Anteil an plastisch-chirurgischen Lernzielen im NKLC und stellt die Ergebnisse den Prüfungsfragen im 2. Staatsexamen gegenüber.

Material und Methoden Die Examensfragen von Herbst 2009 bis Herbst 2014 (Anzahl der Examina = 11) wurden retrospektiv ausgewertet. Separat davon analysierten 5 Fachärzte für Plastische und Ästhetische Chirurgie die plastisch-chirurgischen Lernziele des NKLC. Anschließend wurden in den untersuchten Staatsexamina die Fragen untersucht, die sich auf diese plastisch-chirurgischen Lernziele bezogen. Die Analyse umfasste die Gesamtzahl der Fragen, die Anzahl der Fragen pro Examen sowie pro Lernziel und Kompetenzebene.

Ergebnisse Dem Fach Plastische Chirurgie wurden 34 Lernziele des NKLC (14,8 % aller Lernziele des NKLC) zugeordnet. Eins dieser Lernziele („Verbrühung und Verbrennung“) wird ausschließlich von der Plastischen Chirurgie abgedeckt. 96 Fragen (2,8 % aller 3480 gestellten Fragen) adressierten diese 34 Lernziele. Pro Examen wurden durchschnittlich 8,7 ± 4,0 Fragen (Min. 4; Max. 15) mit Bezug zur Plastischen Chirurgie gestellt. Die meisten Fragen bezogen sich auf das Lernziel „Fehlbildungen und angeborene Entwicklungsstörungen von Skelett- und Bindegewebe“ mit 16 Fragen insgesamt. Im Studienzeitraum wurden insgesamt 6 Lernziele mit Bezug zur Plastischen Chirurgie gar nicht geprüft (2,6 % aller Lernziele des NKLC).

Schlussfolgerung Lerninhalte, die die Plastische Chirurgie betreffen, werden wenig geprüft und es kann daher davon ausgegangen werden, dass diese auch von den Studierenden unzureichend erlernt werden. Damit ist das Fach in der 2. Schriftlichen Staatsexamensprüfung unterrepräsentiert und es erscheint eine vermehrte Prüfung der plastisch-chirurgischen Lernziele nötig.
A Novel Partogram for Stages 1 and 2 of Labor Based on Fetal Head Station Measured by Ultrasound: A Prospective Multicenter Cohort Study
Authors: Haberman Shoshana , Atallah Fouad , Nizard Jacky , Buhule Olive , Albert Paul , Gonen Ron , Ville Yves , Paltieli Yoav
Published: March 2020

Objective This study was aimed to describe continuous labor curves, including second stage, based on fetal head station.

Study Design We performed a prospective multicenter cohort study. The inclusion criteria were women with singleton uncomplicated cephalic term pregnancies in labor, who delivered vaginally. We used a device that combines ultrasound imaging with position-tracking technology to monitor the head station noninvasively throughout labor. We collected data on demographics, labor parameters, and delivery and neonatal outcomes.

Results A total of 613 women delivered vaginally, 327 (53.3%) were nulliparous, while 286 (46.7%) were multiparous. Time to delivery (TTD) diminished progressively with descent of the fetal head. When the head is engaged, the labor curve of multiparous women demonstrated a more prominent downward shift in curve as compared with nulliparous women. When comparing multipara and nullipara at engagement level, the median TTD was 1 and 1.62 hours, respectively. In 95% of women with unengaged head during the second stage, TTD of nulliparous and multiparous women were less than 3.8 and 3 hours, respectively.

Conclusion While current labor curves end at full dilatation, the described curves were developed throughout stages 1 and 2 of labor. The TTD, according to the station curves, shows an acceleration of labor, once passed the engagement level, especially in multiparous women.
An Anatomical Study of Primary Pattern of Arteries of Upper Limb With Relevance to Their Variations
Authors: Bidarkotimath Suresh , Avadhani Ramakrishna , Kumar Arunachalam
Published: March 2020

A detailed description of the vascular pattern of upper limbs especially their variations in their origin, course and branching pattern is of utmost importance anatomically in general and clinically in particular. These variations have drawn attention of surgeons, physicians, radiologist and interventionists due to the advanced surgical procedures practicd in vascular surgeries, plastic (reconstructive) surgeries and also for diagnostic and therapeutic approaches. 50 cadavers (100 upper limbs) were used for the study, which were dissected as the part of routine dissection for teaching undergraduate students at our institution. Length of the normal and variant arteries with mean, standard deviation, 'p' and 't' values are noted in each of the limbs. The following variations are observed - i) high division of brachial artery ii) higher origin of profunda brachii artery, iii) high origin of radial artery, iv) absence of common interosseous artery. The variations are of particular importance to the surgeons operating in the area, especially for those involved in vascular reconstructive surgeries. So it is prudent to do pre-operative studies of the brachial and antebrachial arteries and their branching patterns, to prevent possible complications post operatively.
Inter-Rater Reliabilty of Neonatal Infant Pain Scale (NIPS) as a Multidimensional Behavioral Pain Tool
Authors: G. Malarvizhi , Vatsa Manju , M. Roseline , S. Nithin , Paul Sarah
Published: March 2020

Evaluation of pain in human neonate is complex and difficult because pain is a subjective phenomenon. Neonates cannot verbalize pain rather they express through cry and body movements. However measurement of pain provides a value of pain. There is no gold standard in pain assessment tool. JCAHO recommends selection of a valid and reliable and also age appropriate pain assessment tool.

To determine the interobserver reliabity and clinical utility of NIPS scale To analyze the inter-rater reliability, reproducibility of NIPS scale between three observers prospective observation study was designed to establish reliability and validity of NIPS among 27 neonates who underwent venipuncture, Hepatitis vaccination (intramuscular) and heel prick at a tertiary care level III NICU. The baseline data and behavioral responses to procedural pain were rated by three observers trained in NIPS scale.

At the end of 100 observation across the various time intervals and three phases, inter-rater reliability of NIPS scale among the three observers were. 82,.81,.75. Acceptable psychometric properties are reported for the tool which includes cronbach's alpha levels of. 9,.85,.9 between the observers. CNIPS was found to be highly reliable and valid multidimensional scale and practical and has good clinical utility.
The FAFA Trial: A Phase 2 Randomized Clinical Trial on the Effect of a Fan Blowing Air on the Face to Relieve Dyspnea in Filipino Patients with Terminal Cancer
Authors: Ting Frederic Ivan , Estreller Sachiko , Strebel Heinrik Martin Jude
Published: March 2020

Introduction Fan therapy has been suggested by some studies as one of the nonpharmacological supportive interventions to alleviate breathlessness for dyspneic patients with terminal cancer. Unfortunately, data among Asians are limited and there are currently no published data showing that this intervention works among Filipinos—thus this study.

Study Design This study was an open-label, randomized, placebo-controlled, crossover Phase 2 trial. The experimental group had a fan blowing air directly to the patient’s face for 5 minutes, and the control group had a fan blowing air to the patient’s legs. Treatment crossover was done after a washout period of 1 hour. The primary outcome, which is dyspnea, was measured subjectively using the Modified Borg Scale (MBS). Differences in the patient’s respiratory rate (RR) and oxygen saturation were also measured.

Results A total of 48 patients were enrolled in this trial. The mean age of the patients enrolled was 51 years, and the most common primary tumor was lung cancer (21%). In the control group, results showed that the mean difference before and after intervention in the MBS was 0.15, and the mean difference in RR was 0.25. On the other hand, the intervention group showed a statistically significant decrease in the patient’s dyspnea as evidenced by a mean MBS decrease of 2.79 (p < 0.0001), and a mean RR decrease of 1.88 (p < 0.0001).

Conclusion The results of this study reveal that fan on face (FAFA) therapy in terminally ill Filipino cancer patients in addition to the prescribed standard of care can significantly alleviate their level of dyspnea. Thus, FAFA therapy should be considered as an adjunct to standard of care for these patients.
Correlation functions of the XXZ spin chain with the twisted boundary condition
Authors: Qiao Yi , Xin Zhirong , Xu Xiaotian , Hao Kun , Yang Tao , Cao Junpeng , Yang Wen-Li
Published: March 2020

The scalar products, form factors, and correlation functions of the XXZ spin chain with a twisted (or antiperiodic) boundary condition are obtained based on the inhomogeneous T–Q relation and the Bethe states constructed via the off-diagonal Bethe ansatz. It is shown that the scalar product of two off-shell Bethe states, the form factors, and the two-point correlation functions can be expressed as the summation of certain determinants. The corresponding homogeneous limits are studied. The results are also checked by the numerical calculations.
An innovative framework for electrical energy storage system selection for remote area electrification with renewable energy system: Case of a remote village in India
Authors: Maisanam Anil Kumar Singh , Biswas Agnimitra , Sharma Kaushal Kumar
Published: March 2020

Electrical energy storage is a promising solution to overcome the intermittency and demand-supply mismatch problem in hybrid renewable energy systems. The objective of the present study is to prioritize ten electrical energy storage systems by using an innovative ranking framework, considering different criteria. Further, a techno-economic study of a hybrid renewable energy system is performed for rural area electrification, where the present selection strategy of the storage system is incorporated in the system design. Due to the conflicting nature of these criteria, a fuzzy assisted Technique for Order of Preference by Similarity to Ideal Solution method based framework is employed for its prioritization. The effect of variation of the weights on the criteria is also investigated through a sensitivity analysis. The framework is used to design an optimum hybrid renewable energy system for a remote village in India using the Hybrid Optimization Model for Electric Renewables tool. The results of the ranking show that pumped hydro storage, compressed air energy storage, and lead-acid batteries are the top three electrical energy storage systems that present more benefits for renewable energy integration for the present case. Moreover, adopting a storage system selection strategy can further reduce the cost of energy of the system. Therefore, the present framework provides a systematic procedure of storage system selection for renewable energy integration by considering different conflicting criteria for case-specific application.
Mechanobiology of dynamic enzyme systems
Authors: Butler Peter J.
Published: March 2020

This Perspective paper advances a hypothesis of mechanosensation by endothelial cells in which the cell is a dynamic crowded system, driven by continuous enzyme activity, that can be shifted from one non-equilibrium state to another by external force. The nature of the shift will depend on the direction, rate of change, and magnitude of the force. Whether force induces a pathophysiological or physiological change in cell biology will be determined by whether the dynamics of a cellular system can accommodate the dynamics and magnitude of the force application. The complex interplay of non-static cytoskeletal structures governs internal cellular rheology, dynamic spatial reorganization, and chemical kinetics of proteins such as integrins, and a flaccid membrane that is dynamically supported; each may constitute the necessary dynamic properties able to sense external fluid shear stress and reorganize in two and three dimensions. The resulting reorganization of enzyme systems in the cell membrane and cytoplasm may drive the cell to a new physiological state. This review focuses on endothelial cell mechanotransduction of shear stress, but may lead to new avenues of investigation of mechanobiology in general requiring new tools for interrogation of mechanobiological systems, tools that will enable the synthesis of large amounts of spatial and temporal data at the molecular, cellular, and system levels.
Theoretical analysis and numerical simulations of turbulent jets in a wave environment
Authors: Barile Sara , De Padova Diana , Mossa Michele , Sibilla Stefano
Published: March 2020

A thorough understanding of the mixing and diffusion of turbulent jets released in a wave flow field is still lacking in the literature. This issue is undoubtedly of interest because, although stagnant ambient conditions are well known, they are almost never present in real coastal environmental problems, where the presence of waves or currents is common. As a result, jets cannot be analyzed without considering the surrounding environment, which is only rarely under stagnant conditions. The aim of the present research is to analyze from a theoretical point of view a pure jet vertically discharged in a wave motion field. Specifically, starting from the fundamental Navier–Stokes equations governing the problem joined to the continuity equation, the equations of motion and the integral equations of momentum, energy, and moment of momentum are derived. Therefore, the laws of variation of the jet length and velocity scales are deduced. Results from experiments and numerical simulations of a jet issuing in a wave environment demonstrate the validity of the proposed laws.
Electric dipole image forces in three-layer systems: The classical electrostatic model
Authors: Gabovich Alexander M. , Li Mai Suan , Szymczak Henryk , Voitenko Alexander I.
Published: March 2020

General exact analytical expressions have been derived for the image force energy Wi(Z, φ) of a point dipole in a classical three-layer system composed of dispersionless media with arbitrary constant dielectric permittivities εi. Here, i = 1–3 is the layer number, and Z and φ are the dipole coordinate and orientation angle, respectively. It was found that the long-range asymptotics Wi(Z→∞,φ) in both covers (i = 1, 3) are reached unexpectedly far from the interlayer (i = 2). Another specific feature of the solution consists in that the interference of the fields created by polarization charges emerging at both interfaces leads to the appearance of a constant contribution inside the interlayer with a non-standard dependence on the dipole orientation angle φ. It was shown that by changing the dielectric constants of the structure components, one can realize two peculiar regimes of the Wi(Z, φ) behavior in the covers; namely, there arises either a potential barrier preventing adsorption or a well far from the interface, both being of a totally electrostatic origin, i.e., without involving the Pauli exchange repulsion, which is taken into account in the conventional theories of physical adsorption. The results obtained provide a fresh insight into the physics of adsorption in physical electronics, chemical physics, and electrochemistry.
Analytic solution to charge-exchange source terms between Maxwellian and kappa-distributed velocity distributions in the heliosphere
Authors: DeStefano Anthony Michael , Heerikhuisen Jacob
Published: March 2020

Many space and astrophysical environments are dominated by magnetohydrodynamic plasma interactions that are virtually collisionless. However, pseudo-elastic collisions are present through mechanisms of ion-neutral charge-exchange. In this paper, we investigate how charge-exchange collisions affect the balance of momentum and energy between ions and neutrals within the plasma. Our primary application is the heliosphere, where the transfer of momentum and energy between protons and interstellar hydrogen ultimately modifies its shape and structure. We derive analytical formulas for charge-exchange coupling between protons with suprathermal tails, modeled as a kappa distribution, and a relatively cool population of thermal hydrogen that is moving with respect to the plasma. We discuss differences in the energy and momentum transfer rates depending on whether the plasma is modeled by a Maxwellian or kappa distribution.
Electrically driven lasing in metal halide perovskites: Challenges and outlook
Authors: Gunnarsson William B. , Rand Barry P.
Published: March 2020

Metal halide perovskite semiconductors have shown great potential as emissive layers in light-emitting diodes and gain media in optically pumped lasers, and thus represent a possible foundation for a non-epitaxial electrically driven laser diode. However, degradation of perovskite-based devices and inability to maintain high-efficiency operation at large current densities have so far inhibited realization of this goal. This report will explore the causes underlying these observations—specifically, Joule heating, electric field-induced quenching, charge injection imbalance, and Auger recombination—and consider approaches to achieve an electrically driven perovskite laser diode.
Effective Hamiltonians derived from equation-of-motion coupled-cluster wave functions: Theory and application to the Hubbard and Heisenberg Hamiltonians
Authors: Pokhilko Pavel , Krylov Anna I.
Published: March 2020

Effective Hamiltonians, which are commonly used for fitting experimental observables, provide a coarse-grained representation of exact many-electron states obtained in quantum chemistry calculations; however, the mapping between the two is not trivial. In this contribution, we apply Bloch’s formalism to equation-of-motion coupled-cluster wave functions to rigorously derive effective Hamiltonians in Bloch’s and des Cloizeaux’s forms. We report the key equations and illustrate the theory by application to systems with two or three unpaired electrons, which give rise to electronic states of covalent and ionic characters. We show that Hubbard’s and Heisenberg’s Hamiltonians can be extracted directly from the so-obtained effective Hamiltonians. By establishing a quantitative connection between many-body states and simple models, the approach facilitates the analysis of the correlated wave functions. We propose a simple diagnostic for assessing the validity of the model space choice based on the overlaps between the target- and model-space states. Artifacts affecting the quality of electronic structure calculations such as spin contamination are also discussed.
Estimation of the critical condition for expansion/contraction of single Shockley stacking faults in 4H-SiC PiN diodes
Authors: Iijima A. , Kimoto T.
Published: March 2020

The critical condition for expansion/contraction of single Shockley-type stacking faults (1SSFs) was experimentally estimated by monitoring the electroluminescence from 1SSFs in 4H-SiC PiN diodes with different p/n structures while varying the current density and the temperature. The “threshold current density” for expansion/contraction of 1SSF was determined by observing the 1SSF behavior, and it was converted to the “threshold excess carrier density” using the numerical calculation by device simulation. The threshold excess carrier density was almost independent of the diode structures though the threshold current densities were very different among the various diodes, which means that the 1SSF behavior does not depend on the current density but on the excess carrier density. The threshold excess carrier density at room temperature was estimated to be about 4×1014 cm−3, which agrees with the result calculated by a theoretical model previously proposed. In addition, the conduction type- and the doping concentration-dependences of the threshold excess carrier density were discussed.
Electric field effect on the magnetic domain wall creep velocity in Pt/Co/Pd structures with different Co thicknesses
Authors: Koyama T. , Ieda J. , Chiba D.
Published: March 2020

The electric field (EF) modulation of magnetic domain wall (DW) creep velocity v in the Pt/Co/Pd structure with perpendicular magnetic anisotropy (MA) has been studied. The structures with different Co thicknesses tCo up to ∼1 nm are investigated. In all samples, applying a gate voltage induces a clear change in v. Thicker samples provide a higher v modulation efficiency, and the v modulation magnitude of more than a factor of 100 times is observed in the thickest tCo of 0.98 nm. The parameter characterizing the creep motion is significantly affected by the EF, resulting in the modulation of v. Unlike the v case, the MA modulation efficiency decreases with increasing tCo. The present results are discussed based on the EF-induced change in the interfacial Dzyaloshinskii–Moriya interaction (iDMI), which has been recently demonstrated in the same structure, and tCo dependence of the DW energy. The tCo dependence of the v modulation suggests that the EF effect on the iDMI is more important than the MA.
Assessing the role of live poultry trade in community-structured transmission of avian influenza in China
Authors: Yang Qiqi , Zhao Xiang , Lemey Philippe , Suchard Marc A. , Bi Yuhai , Shi Weifeng , Liu Di , Qi Wenbao , Zhang Guogang , Stenseth Nils Chr. , Pybus Oliver G. , Tian Huaiyu
Published: March 2020

Significance

The emergence and transmission of avian influenza viruses (AIVs) pose a threat to public health and result in enormous economic losses. Here we discover an association between the community structure of the poultry trade network and AIV transmission in China by combining virus genomes and statistical modeling of the poultry trade. Importantly, we are able to “replicate” this finding by comparing the dynamics of three strains of AIV (H5N1, H7N9, and H5N6) that currently cocirculate in poultry in China. Given the detection of a continuous process of AIV geographic spread among poultry, our results indicate that at the national scale there are repeatable and potentially predictable patterns that can be used to shape future strategies for AIV control and prevention.
A hepatocyte differentiation model reveals two subtypes of liver cancer with different oncofetal properties and therapeutic targets
Authors: Liu Ming , Yan Qian , Sun Yi , Nam Yoonhee , Hu Liang , Loong Jane HC , Ouyang Qi , Zhang Yu , Li Hao-Long , Kong Fan-En , Li Lei , Li Yan , Li Mei-Mei , Cheng Wei , Jiang Ling-Xi , Fang Shuo , Yang Xiao-Dong , Mo Jia-Qiang , Gong Yuan-Feng , Tang Yun-Qiang , Li Yan , Yuan Yun-Fei , Ma Ning-Fang , Lin Ge , Ma Stephanie , Wang Ji-Guang , Guan Xin-Yuan
Published: March 2020

Significance

Developmental signaling pathways play important roles in cancer initiation and therapeutic resistance. Poorly differentiated hepatocellular carcinomas (HCCs) usually show phenotypic resemblance to their ancestral precursor cells and are associated with poor clinical outcome. In a recent study, a dynamic oncofetal-like gene expression signature during liver development was identified from an in vitro hepatocyte differentiation model. Two subtypes of liver cancer with different oncofetal properties and upstream oncogenic drivers were found in clinical patients with poor prognosis. Clinically available small-molecule inhibitors HLM6474 and SIS3 specifically targeting the oncofetal drivers extensively down-regulated subtype-specific developmental signaling and significantly inhibited tumorigenicity. Further treatment of HCC patients with specified small-molecular inhibitors according to subtype-specific biomarkers might accurately block the tumor-initiating steps and eliminate tumor progression.
Composition-based prediction and rational manipulation of prion-like domain recruitment to stress granules
Authors: Boncella Amy E. , Shattuck Jenifer E. , Cascarina Sean M. , Paul Kacy R. , Baer Matthew H. , Fomicheva Anastasia , Lamb Andrew K. , Ross Eric D.
Published: March 2020

Significance

Many RNA-binding proteins contain aggregation-prone prion-like domains (PrLDs), and mutations in several of these have been linked to degenerative diseases. Additionally, many of these proteins are associated with stress granules, which are membraneless organelles that form under stress, in part through reversible protein assembly. Although the mechanisms of stress granule assembly are unclear, PrLDs can play a role in this process. In order to further understand how PrLDs respond to stress, we analyzed the assembly propensities of a selection of different PrLDs from yeast. We find that many PrLDs are efficiently recruited to stress-induced assemblies and that this recruitment is predominantly dependent on the amino acid composition of the PrLDs.
Carbon export from leaves is controlled via ubiquitination and phosphorylation of sucrose transporter SUC2
Authors: Xu Qiyu , Yin Shijiao , Ma Yue , Song Min , Song Yingjie , Mu Shuaicheng , Li Yunsong , Liu Xiaohui , Ren Yunjuan , Gao Chen , Chen Shaolin , Liesche Johannes
Published: March 2020

Significance

Plants depend on strict regulation of carbon transport to keep the activities of different parts in balance under various environmental conditions. In most crops and the model plant
Arabidopsis thaliana
, sucrose transporters (SUCs) that are strategically positioned in the leaf veins are responsible for carbon export from photosynthetically active leaves. Despite their central role, relatively little is known about the regulation of SUCs. This study identified two regulatory proteins of
Arabidopsis
SUC2 and investigated how they modulate sucrose transport activity. Both proteins proved important for the environmental acclimation of leaf carbon export. Furthermore, the increased biomass and yield of plants lacking a regulator observed here demonstrate that manipulation of SUC regulation can be a viable path to enhance plant productivity.
Plasmodium
chaperonin TRiC/CCT identified as a target of the antihistamine clemastine using parallel chemoproteomic strategy
Authors: Lu Kuan-Yi , Quan Baiyi , Sylvester Kayla , Srivastava Tamanna , Fitzgerald Michael C. , Derbyshire Emily R.
Published: March 2020

The antihistamine clemastine inhibits multiple stages of the
Plasmodium
parasite that causes malaria, but the molecular targets responsible for its parasite inhibition were unknown. Here, we applied parallel chemoproteomic platforms to discover the mechanism of action of clemastine and identify that clemastine binds to the
Plasmodium falciparum
TCP-1 ring complex or chaperonin containing TCP-1 (TRiC/CCT), an essential heterooligomeric complex required for de novo cytoskeletal protein folding. Clemastine destabilized all eight
P. falciparum
TRiC subunits based on thermal proteome profiling (TPP). Further analysis using stability of proteins from rates of oxidation (SPROX) revealed a clemastine-induced thermodynamic stabilization of the
Plasmodium
TRiC delta subunit, suggesting an interaction with this protein subunit. We demonstrate that clemastine reduces levels of the major TRiC substrate tubulin in
P. falciparum
parasites. In addition, clemastine treatment leads to disorientation of
Plasmodium
mitotic spindles during the asexual reproduction and results in aberrant tubulin morphology suggesting protein aggregation. This clemastine-induced disruption of TRiC function is not observed in human host cells, demonstrating a species selectivity required for targeting an intracellular human pathogen. Our findings encourage larger efforts to apply chemoproteomic methods to assist in target identification of antimalarial drugs and highlight the potential to selectively target
Plasmodium
TRiC-mediated protein folding for malaria intervention.
Charge-dependent interactions of monomeric and filamentous actin with lipid bilayers
Authors: Schroer Carsten F. E. , Baldauf Lucia , van Buren Lennard , Wassenaar Tsjerk A. , Melo Manuel N. , Koenderink Gijsje H. , Marrink Siewert J.
Published: March 2020

The cytoskeletal protein actin polymerizes into filaments that are essential for the mechanical stability of mammalian cells. In vitro experiments showed that direct interactions between actin filaments and lipid bilayers are possible and that the net charge of the bilayer as well as the presence of divalent ions in the buffer play an important role. In vivo, colocalization of actin filaments and divalent ions are suppressed, and cells rely on linker proteins to connect the plasma membrane to the actin network. Little is known, however, about why this is the case and what microscopic interactions are important. A deeper understanding is highly beneficial, first, to obtain understanding in the biological design of cells and, second, as a possible basis for the building of artificial cortices for the stabilization of synthetic cells. Here, we report the results of coarse-grained molecular dynamics simulations of monomeric and filamentous actin in the vicinity of differently charged lipid bilayers. We observe that charges on the lipid head groups strongly determine the ability of actin to adsorb to the bilayer. The inclusion of divalent ions leads to a reversal of the binding affinity. Our in silico results are validated experimentally by reconstitution assays with actin on lipid bilayer membranes and provide a molecular-level understanding of the actin–membrane interaction.
Nf1deletion results in depletion of theLhx6transcription factor and a specific loss of parvalbumin+cortical interneurons
Authors: Angara Kartik , Pai Emily Ling-Lin , Bilinovich Stephanie M. , Stafford April M. , Nguyen Julie T. , Li Katie X. , Paul Anirban , Rubenstein John L. , Vogt Daniel
Published: March 2020

Significance

NF1 is a monogenic disorder caused by mutations in theNF1gene. While it affects multiple organs and tissues, how brain symptoms arise has been complicated to uncover. Since brain glial and inhibitory neuron cells have been implicated in NF1, we conditionally deleted the mouseNf1gene in progenitors that give rise to both of these cell types. We found that glial cells were impacted when both copies ofNf1were deleted, while properties of a specific group of inhibitory neurons were altered when either one or both copies ofNf1were deleted. These data demonstrate phenotypes that may contribute to NF1 and uncover roles for theNf1gene in brain development.
Early globalized industrial chain revealed by residual submicron pigment particles in Chinese imperial blue-and-white porcelains
Authors: Jiang Xiaochenyang , Weng Yanjun , Wu Xiaohong , Cui Jianfeng , Lyu Hongshu , Jiang Jianxin , Song Guodong , Jin Hetian , Qin Dashu , Wang Changsui
Published: March 2020

Significance

Our knowledge of the pigment provenance of blue-and-white porcelain is based primarily on the Fe/Mn criteria, which contradicts the archaeological concept (including typological evidence like blue hue, bleeding effect, iron spots) and historical records. Here we propose a reliable method for tracing cobalt sources through the microstructural analysis of submicron residual pigment particles to avoid influence from elemental fractionation. An application of the method to the Xuande imperial productions demonstrates that an intentional approach of mixing imported and domestic cobalt ores was adopted, which could rationalize all of the apparent contradictions between compositional data and conventional authentication. Our findings further suggest that the overseas pigments continued to play an irreplaceable role from 15th century onward as the globalized trading network began to break free of regional political affairs.
Cell-penetrating peptide inhibits retromer-mediated human papillomavirus trafficking during virus entry
Authors: Zhang Pengwei , Moreno Ruben , Lambert Paul F. , DiMaio Daniel
Published: March 2020

Significance

Human papillomaviruses (HPVs) are responsible for 5% of cancers, but no specific antiviral agents inhibit HPV infection. Based on our mechanistic understanding of HPV entry into cells, we designed a strategy to inhibit HPV infection. We demonstrate that short synthetic peptides derived from an HPV capsid protein enter cells, interfere with a protein interaction essential for intracellular virus trafficking, and prevent HPV from entering its proper intracellular transport pathway, thereby inhibiting infection in cultured cells and in mice. Thus, we have repurposed viral protein segments that normally mediate infection into a rationally designed agent that inhibits infection. The use of cell-penetrating peptides to disrupt essential intracellular protein-protein interactions may be broadly applicable in virology and in other situations.
The neural signature of numerosity by separating numerical and continuous magnitude extraction in visual cortex with frequency-tagged EEG
Authors: Van Rinsveld Amandine , Guillaume Mathieu , Kohler Peter J. , Schiltz Christine , Gevers Wim , Content Alain
Published: March 2020

The ability to handle approximate quantities, or number sense, has been recurrently linked to mathematical skills, although the nature of the mechanism allowing to extract numerical information (i.e., numerosity) from environmental stimuli is still debated. A set of objects is indeed not only characterized by its numerosity but also by other features, such as the summed area occupied by the elements, which often covary with numerosity. These intrinsic relations between numerosity and nonnumerical magnitudes led some authors to argue that numerosity is not independently processed but extracted through a weighting of continuous magnitudes. This view cannot be properly tested through classic behavioral and neuroimaging approaches due to these intrinsic correlations. The current study used a frequency-tagging EEG approach to separately measure responses to numerosity as well as to continuous magnitudes. We recorded occipital responses to numerosity, total area, and convex hull changes but not to density and dot size. We additionally applied a model predicting primary visual cortex responses to the set of stimuli. The model output was closely aligned with our electrophysiological data, since it predicted discrimination only for numerosity, total area, and convex hull. Our findings thus demonstrate that numerosity can be independently processed at an early stage in the visual cortex, even when completely isolated from other magnitude changes. The similar implicit discrimination for numerosity as for some continuous magnitudes, which correspond to basic visual percepts, shows that both can be extracted independently, hence substantiating the nature of numerosity as a primary feature of the visual scene.
Mechanophenotyping of 3D multicellular clusters using displacement arrays of rendered tractions
Authors: Leggett Susan E. , Patel Mohak , Valentin Thomas M. , Gamboa Lena , Khoo Amanda S. , Williams Evelyn Kendall , Franck Christian , Wong Ian Y.
Published: March 2020

Epithelial tissues mechanically deform the surrounding extracellular matrix during embryonic development, wound repair, and tumor invasion. Ex vivo measurements of such multicellular tractions within three-dimensional (3D) biomaterials could elucidate collective dissemination during disease progression and enable preclinical testing of targeted antimigration therapies. However, past 3D traction measurements have been low throughput due to the challenges of imaging and analyzing information-rich 3D material deformations. Here, we demonstrate a method to profile multicellular clusters in a 96-well-plate format based on spatially heterogeneous contractile, protrusive, and circumferential tractions. As a case study, we profile multicellular clusters across varying states of the epithelial–mesenchymal transition, revealing a successive loss of protrusive and circumferential tractions, as well as the formation of localized contractile tractions with elongated cluster morphologies. These cluster phenotypes were biochemically perturbed by using drugs, biasing toward traction signatures of different epithelial or mesenchymal states. This higher-throughput analysis is promising to systematically interrogate and perturb aberrant mechanobiology, which could be utilized with human-patient samples to guide personalized therapies.
Abrogation of prenucleation, transient oligomerization of the Huntingtin exon 1 protein by human profilin I
Authors: Ceccon Alberto , Tugarinov Vitali , Ghirlando Rodolfo , Clore G. Marius
Published: March 2020

Human profilin I reduces aggregation and concomitant toxicity of the polyglutamine-containing N-terminal region of the huntingtin protein encoded by exon 1 (htt
ex1
) and responsible for Huntington’s disease. Here, we investigate the interaction of profilin with htt
ex1
using NMR techniques designed to quantitatively analyze the kinetics and equilibria of chemical exchange at atomic resolution, including relaxation dispersion, exchange-induced shifts, and lifetime line broadening. We first show that the presence of two polyproline tracts in htt
ex1
, absent from a shorter huntingtin variant studied previously, modulates the kinetics of the transient branched oligomerization pathway that precedes nucleation, resulting in an increase in the populations of the on-pathway helical coiled-coil dimeric and tetrameric species (τ
ex
≤ 50 to 70 μs), while leaving the population of the off-pathway (nonproductive) dimeric species largely unaffected (τ
ex
∼750 μs). Next, we show that the affinity of a single molecule of profilin to the polyproline tracts is in the micromolar range (
K
diss
∼ 17 and ∼ 31 μM), but binding of a second molecule of profilin is negatively cooperative, with the affinity reduced ∼11-fold. The lifetime of a 1:1 complex of htt
ex1
with profilin, determined using a shorter huntingtin variant containing only a single polyproline tract, is shown to be on the submillisecond timescale (
τ
ex
∼ 600 μs and
K
diss
∼ 50 μM). Finally, we demonstrate that, in stable profilin–htt
ex1
complexes, the productive oligomerization pathway, leading to the formation of helical coiled-coil htt
ex1
tetramers, is completely abolished, and only the pathway resulting in “nonproductive” dimers remains active, thereby providing a mechanistic basis for how profilin reduces aggregation and toxicity of htt
ex1
.
Words from where?
Authors: Busby Nicole Louise
Published: March 2020

This study investigated variation in receptive L2 English vocabulary among Norwegian university students in relation to their field of study and exposure to English, both within and outside of formal education. A survey comprising the Vocabulary Levels Test (Schmitt, Schmitt, & Clapham, 2001) and questions about sources of language acquisition was completed by 189 Norwegian university students. The results indicate that vocabulary knowledge varied between students whose courses required different amounts of English reading. Extramural exposure to English was found to be a stronger predictor of vocabulary scores than formal English education. Since vocabulary knowledge is an important predictor of reading comprehension, it is important to consider how much the observed variation in vocabulary knowledge might affect academic outcomes.
Effect of microsegregation on carbide-free bainitic transformation in a high-silicon cast steel
Authors: Tenaglia Nicolás E. , Massone Juan M. , Boeri Roberto E. , Speer John G.
Published: March 2020

A high silicon cast steel was studied in the as-cast condition in order to characterise its solidification macrostructure and microsegregation. The steel, poured into 32 mm-keel-block-shaped moulds, has a coarse solidification structure and marked microsegregation, containing low-alloyed areas with a total alloy content (Cr + Mn + Si) of 2.3 wt-% and high-alloyed zones of 5.3 wt-%. The bainitic transformation behaviour at 300°C was studied at different austempering times. The bainitic reaction occurs at different rates within the specimen volume, because of its chemical heterogeneity. An austempering heat treatment leads to an inhomogeneous carbide-free bainitic microstructure with different phase amounts, morphologies and sizes. The heterogeneous distribution of sizes and chemical compositions of retained austenite is speculated to benefit mechanical properties.
Ca2+ mediates extracellular vesicle biogenesis through alternate pathways in malignancy
Authors: Taylor Jack , Azimi Iman , Monteith Gregory , Bebawy Mary
Published: March 2020

Extracellular vesicles (EVs) are small membrane vesicles that serve as important intercellular signalling intermediaries in both malignant and non‐malignant cells. For EVs formed by the plasma membrane, their biogenesis is characterized by an increase in intracellular calcium followed by successive membrane and cytoskeletal changes. EV‐production is significantly higher in malignant cells relative to non‐malignant cells and previous work suggests this is dependent on increased calcium mobilization and activity of calpain. However, calcium‐signalling pathways involved in malignant and non‐malignant EV biogenesis remain unexplored. Here we demonstrate; malignant cells have high basal production of plasma membrane EVs compared to non‐malignant cells and this is driven by a calcium–calpain dependent pathway. Resting vesiculation in malignant cells occurs via mobilization of calcium from endoplasmic reticulum (ER) stores rather than from the activity of plasma membrane calcium channels. In the event of ER store depletion however, the store‐operated calcium entry (SOCE) pathway is activated to restore ER calcium stores. Depleting both ER calcium stores and blocking SOCE, inhibits EV biogenesis. In contrast, calcium signalling pathways are not activated in resting non‐malignant cells. Consequently, these cells are relatively low vesiculators in the resting state. Following cellular activation however, an increase in cytosolic calcium and activation of calpain increase in EV biogenesis. These findings contribute to furthering our understanding of extracellular vesicle biogenesis. As EVs are key mediators in the intercellular transfer of deleterious cancer traits such as cancer multidrug resistance (MDR), understanding the molecular mechanisms governing their biogenesis in cancer is the crucial first step in finding novel therapeutic targets that circumvent EV‐mediated MDR.
Comparison of different sloshing speedmeters
Authors: Huttner S H , Danilishin S L , Hild S , Strain K A
Published: March 2020

By numerical simulation, we compare the performance of four speedmeter interferometer configurations with potential application in future gravitational wave detectors. In the absence of optical loss, all four configurations can be adjusted to yield the same sensitivity in a fair comparison. Once we introduce a degree of practicality in the form of lossy optics and mode mismatch, however, the situation changes: the sloshing Sagnac and the speedmeter of Purdue and Chen have almost identical performance showing smaller degradation from the ideal than the speedmeter of Freise and the speedmeter of Miao. In a further step, we show that there is a similar hierarchy in the degree of improvement obtained through the application of 10  dB squeezing to the lossy speedmeters. In this case, the sensitivity of each speedmeter improves, but it is greatest for the sloshing Sagnac and the speedmeter of Purdue and Chen, in particular in the lower part of the target frequency range.
Noise model considering electrical feed-through under force rebalance closed-loop detection of MEMS gyroscope
Authors: Bu Feng , Wang Xi , Fan Bo , Guo Shuwen , Xu Dacheng , Xu Xiang , Zhao Heming
Published: March 2020

This study analyses the transfer path of electrical feed-through noise in the electromechanical amplitude modulation detection circuit of a micro-electro-mechanical system vibrating gyroscope. By considering the feed-through, circuit and mechanical thermal noises, a new noise model in the force-to-rebalance closed-loop detection is constructed, and the expression of the noise-equivalent rotation rate spectrum is given. In addition, the influences of factors such as circuit gain, feedback coefficient and frequency split on the contribution of noise are analysed. The analysis shows that the back-end injection noise is the main factor affecting angle random walk (ARW) for high Q-value gyroscopes. Through actual measurements, it was found that the feed-through noise at the carrier frequency of the feedback circuit was the main source of the back-end noise. After noise optimization, the ARW of the detection output decreased from 0.148

°

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hr

to 0.017

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, which was an improvement of about 8.7 times.