bluuebunny/crossref_metadata_2025 huggingface dataset:
Die Dunkle Triade der Persönlichkeit – Ein Korrelat des
Bösen?
Authors: Jauk Emanuel , Hiebler-Ragger Michaela , Unterrainer Human-Friedrich , Kapfhammer Hans-Peter
Published: June 2018

Vor gut 15 Jahren fassten die kanadischen Psychologen Delroy Paulhus und Kevin
Williams die Persönlichkeitsmerkmale Narzissmus, Machiavellismus und
Psychopathie als „Dunkle Triade der Persönlichkeit“ zusammen. Der mystisch
anmutende Begriff verweist auf eine neugierige Hinwendung zu unliebsamen oder
bedrohlichen Aspekten menschlichen Erlebens und Verhaltens – zum „Bösen“. Die
Dunkle Triade zog in Forschung und Öffentlichkeit große Faszination auf
sich.
Arbeitsplatz Forensische Psychiatrie – eine Hölle auf
Erden?
Authors: Spindler Peter
Published: June 2018

Unser Ruf ist nicht besonders gut. Gefängnissen geht es nicht besser. Es gibt
wenige, die immer schon davon geträumt haben, „in der Forensik“ zu arbeiten. Die
allermeisten verschlägt es dorthin. Mir selbst ist vom Gedanken, „dort“ zu
arbeiten, noch das Bild vom dunklen Loch in Erinnerung. Eine Institution, aus
der man nicht wieder rauskommt, auch als Arzt nicht. Vor allem fürchtete ich,
„danach“ nirgendwo anders mehr arbeiten zu können. So ist es tatsächlich
gekommen.
Psychotherapie depressiver Störungen als neurobiologischer Prozess – Erkenntnisse aus der Hirnbildgebung
Authors: Rubart Antonie , Hohagen Fritz , Zurowski Bartosz
Published: June 2018

Die Depression – eine der häufigsten psychischen Erkrankungen in Deutschland. Dieser Beitrag vermittelt Grundwissen über die Bildgebung in der Psychotherapieforschung und beschreibt Erklärungsmodelle für neurobiologische Prozesse mit der Möglichkeit der Vorhersage des Therapieerfolgs mittels bildgebender Verfahren.
Risk, Prediction and Prevention of Hereditary Breast Cancer – Large-Scale Genomic Studies in Times of Big and Smart Data
Authors: Wunderle Marius , Olmes Gregor , Nabieva Naiba , Häberle Lothar , Jud Sebastian , Hein Alexander , Rauh Claudia , Hack Carolin , Erber Ramona , Ekici Arif , Hoyer Juliane , Vasileiou Georgia , Kraus Cornelia , Reis André , Hartmann Arndt , Schulz-Wendtland Rüdiger , Lux Michael , Beckmann Matthias , Fasching Peter
Published: June 2018

Over the last two decades genetic testing for mutations in BRCA1 and BRCA2 has become standard of care for women and men who are at familial risk for breast or ovarian cancer. Currently, genetic testing more often also includes so-called panel genes, which are assumed to be moderate-risk genes for breast cancer. Recently, new large-scale studies provided more information about the risk estimation of those genes. The utilization of information on panel genes with regard to their association with the individual breast cancer risk might become part of future clinical practice. Furthermore, large efforts have been made to understand the influence of common genetic variants with a low impact on breast cancer risk. For this purpose, almost 450 000 individuals have been genotyped for almost 500 000 genetic variants in the OncoArray project. Based on first results it can be assumed that – together with previously identified common variants – more than 170 breast cancer risk single nucleotide polymorphisms can explain up to 18% of familial breast cancer risk. The knowledge about genetic and non-genetic risk factors and its implementation in clinical practice could especially be of use for individualized prevention. This includes an individualized risk prediction as well as the individualized selection of screening methods regarding imaging and possible lifestyle interventions. The aim of this review is to summarize the most recent developments in this area and to provide an overview on breast cancer risk genes, risk prediction models and their utilization for the individual patient.
Inferior Vena Cava Filters and Prevention of Recurrent Pulmonary Embolism
Authors: Kishore Sirish , Trost David , Madoff David , Winokur Ronald , Malhotra Anuj
Published: June 2018

Although inferior vena cava (IVC) filters have a clear role in preventing recurrent pulmonary embolism (PE) in patients with venous thromboembolism who cannot be anticoagulated, the role of filters in patients who are candidates for anticoagulation is controversial. With limited and conflicting data, practitioners often have to make an educated patient-specific decision when encountering this scenario. This article reviews the available data on the efficacy and risks associated with adjunctive IVC filter use to prevent recurrent PE.
Intervention in Massive Pulmonary Embolus: Catheter Thrombectomy/Thromboaspiration versus Systemic Lysis versus Surgical Thrombectomy
Authors: Edwards Martin , Plotnik Adam , Moriarty John
Published: June 2018

Massive pulmonary embolus (PE), defined as hemodynamic shock from acute PE, is a life-threatening condition. Deaths from massive PE, especially when unsuspected, occur within minutes to hours of onset and as such prompt intervention can be lifesaving. Acute massive PE patients have traditionally been candidates for treatment with intravenous systemic thrombolysis to improve pulmonary artery pressure, arteriovenous oxygenation, and pulmonary perfusion in an effort to reduce mortality. However, patients with contraindications to systemic thrombolysis or those who have failed thrombolysis may benefit from other techniques including endovascular and surgical embolectomy. This article will review the current medical management as well as catheter-directed therapies and surgical embolectomy in the treatment of patients with massive PE.
Catheter-Directed Thrombolysis for Submassive Pulmonary Embolism
Authors: Chiarello Matthew , Sista Akhilesh
Published: June 2018

Acute pulmonary embolism (PE) is a leading cause of morbidity and mortality in the United States. PE associated with right ventricular strain, termed submassive or intermediate-risk PE, is associated with an increased rate of clinical deterioration and short-term mortality. Trials have demonstrated systemic thrombolytics may improve patient outcomes, but they carry a risk of major hemorrhage. Catheter-directed thrombolysis (CDT) may offer similar efficacy to and a lower risk of catastrophic hemorrhage than systemic thrombolysis. Three prospective trials have evaluated CDT for submassive PE; ULTIMA, SEATTLE II, and PERFECT. These trials provide evidence that CDT may improve radiographic efficacy endpoints in submassive PE with acceptable rates of major hemorrhage. However, the lack of clinical endpoints, long-term follow-up, and adequate sample size limit their generalizability. Future trials should be adequately powered and controlled so that the short- and long-term effectiveness and safety of CDT can be definitively determined.
The Lectin Pathway in Thrombotic Conditions—A Systematic Review
Authors: Larsen Julie , Hvas Christine , Hvas Anne-Mette
Published: June 2018

The lectin pathway of the complement system can activate the coagulation system in vitro, but the role of the lectin pathway in haemostatic activation and thrombosis in vivo is not clear. We performed a systematic review of the existing literature on associations between the lectin pathway and arterial and venous thrombosis, in accordance with the Assessing the Methodological Quality of Systematic Reviews guidelines. PubMed and Embase were searched from January 1990 to March 2017. We included original studies on human study populations investigating associations between the lectin pathway (protein serum levels, genotype or gene expression) and thrombotic conditions or laboratory coagulation markers. Exclusion criteria were case studies including fewer than five cases, conference abstracts or any other language than English. In total, 43 studies were included which investigated associations between the lectin pathway and cardiovascular thrombotic events (CVEs) (n = 22), ischaemic stroke (n = 9), CVE and stroke (n = 1) and other conditions (systemic lupus erythematosus [n = 6], sepsis-related coagulopathy [n = 3], pulmonary embolism [n = 1], asparaginase treatment [n = 1]). Studies on the lectin pathway and CVE risk reported discrepant results, as both high and low mannose-binding lectin (MBL) serum levels were found to correlate with increased CVE risk. In ischaemic stroke patients, occurrence of stroke as well as increased stroke severity and poor outcome were consistently associated with high serum MBL. For other thromboembolic conditions, only few studies were identified. In conclusion, lectin pathway activation may negatively influence outcome after ischaemic stroke and possibly contribute to CVE risk. Further research is warranted to elucidate the role of the lectin pathway in other thrombotic conditions.
Inhibition of Protease-Activated Receptor (PAR1) Reduces Activation of the Endothelium, Coagulation, Fibrinolysis and Inflammation during Human Endotoxemia
Authors: Schoergenhofer Christian , Schwameis Michael , Gelbenegger Georg , Buchtele Nina , Thaler Barbara , Mussbacher Marion , Schabbauer Gernot , Wojta Johann , Jilma-Stohlawetz Petra , Jilma Bernd
Published: June 2018

The protease-activated receptor-1 (PAR-1) is critically involved in the co-activation of coagulation and inflammatory responses. Vorapaxar is a reversible, orally active, low molecular weight, competitive antagonist of PAR-1.We investigated the effects of PAR-1 inhibition by vorapaxar on the inflammatory response, the activation of coagulation, fibrinolysis and endothelium during experimental endotoxemia. In this randomized, double blind, crossover trial, 16 healthy volunteers received a bolus infusion of 2 ng/kg lipopolysaccharide (LPS) ± placebo/vorapaxar with a washout period of 8 weeks. Vorapaxar dosing was guided by thrombin receptor-activating peptide-6-induced whole blood aggregometry. Participants received 10 mg vorapaxar or placebo as an initial dose and, depending on the aggregometry, potentially an additional 10 mg. Goal was > 80% inhibition of aggregation compared with baseline. Vorapaxar significantly reduced the LPS-induced increase in pro-thrombin fragments F1 + 2 by a median of 27% (quartiles: 11–49%), thrombin–anti-thrombin concentrations by 22% (–3 to 46%) and plasmin–anti-plasmin levels by 38% (23–53%). PAR-1 inhibition dampened peak concentrations of tumour necrosis factor -α, interleukin-6 and consequently C-reactive protein by 66% (−11–71%), 50% (15–79%) and 23% (16–38%), respectively. Vorapaxar decreased maximum von Willebrand factor levels by 29% (26–51%) and soluble E-selectin concentrations by 30% (25–38%) after LPS infusion. PAR-1 inhibition did not affect thrombomodulin, soluble P-selectin and platelet factor-4 concentrations.

PAR-1 inhibition significantly reduced the activation of coagulation, fibrinolysis, the inflammatory response and endothelial activation during experimental human endotoxemia.
Factor V Has Anticoagulant Activity in Plasma in the Presence of TFPIα: Difference between FV1 and FV2
Authors: van Doorn Peter , Rosing Jan , Duckers Connie , Hackeng Tilman , Simioni Paolo , Castoldi Elisabetta
Published: June 2018

Background Activated factor V (FVa) is a potent procoagulant cofactor in the prothrombinase complex, whereas its precursor factor V (FV) stimulates the inhibition of factor Xa (FXa) by tissue factor pathway inhibitor-α (TFPIα), presumably by promoting TFPIα binding to phospholipids. Plasma FV comprises two glycosylation isoforms (FV1 and FV2) with low and high phospholipid-binding affinity, respectively. The FV1/FV2 ratio is increased in carriers of the FV R2 haplotype.

Objective This article demonstrates the TFPIα-cofactor function of FV in plasma and compares FV1 and FV2.

Materials and Methods Thrombin generation at low TF concentration was measured in FV-depleted plasma reconstituted with 0 to 100% FV, FV1 or FV2, and in 122 individuals genotyped for the R2 haplotype. The TFPIα-cofactor activities of FV1 and FV2 were also investigated in a model system of TFPIα-mediated FXa inhibition.

Results In the FV titration, thrombin generation first increased (up to 5% FV) and then progressively decreased at higher FV concentrations. This anticoagulant effect of FV, which was also observed with FV2 but not with FV1, was largely abolished by anti-TFPIα antibodies, suggesting that it reflects TFPIα-cofactor activity of FV. In the model system of TFPIα-mediated FXa inhibition, FV2 was a more potent TFPIα-cofactor than FV1, in line with their respective phospholipid affinities. Accordingly, FV R2 carriers had higher thrombin generation than non-carriers, even after correction for demographics and plasma levels of coagulation factors and inhibitors.

Conclusion FV (and particularly its FV2 isoform) contributes to the TFPIα-dependent down-regulation of thrombin generation in plasma triggered with low TF.
New Anticoagulant Agents: Incidence of Adverse Drug Reactions and New Signals Thereof
Authors: Jiménez-Serranía María-Isabel , Martínez-García Raquel , Corzo-Delibes Francisco , Martín Arias Luis , Treceño-Lobato Carlos
Published: June 2018

The aim of this study was to evaluate the adverse drug reaction (ADR) incidence rate and new signals thereof for classic compared with new anticoagulants in real-life ambulatory settings. The authors performed an observational cross-sectional study in two cohorts of surveyed patients treated with vitamin K antagonists (VKAs; acenocoumarol or warfarin) or nonvitamin K antagonist oral anticoagulants (NOACs; apixaban, edoxaban, rivaroxaban, dabigatran etexilate). Descriptive, clinical, and ADRs data were reported and analyzed through a bivariate analysis (odds ratio [OR]) to compare the ADRs incidence rate and an adaptation of Bayesian methodology (false discovery rate [FDR] < 0.05) to detect new signals. A total of 334 patients were surveyed—average international normalized ratio (INR) of 2.6—and 45.4% taking new anticoagulants. Note that 835 ADRs were reported; 2.5 per patient (2.8 in the VKA cohort, 2.1 in the NOAC cohort). The authors obtained higher risk of epistaxis (OR, 2.18; 95% confidence interval [CI], 1.01–4.74) and hematoma (OR, 2.43; 95% CI, 1.39–4.25) with VKAs and lower risk of global bleeding symptoms with NOACs (OR, 0.45; 95% CI, 0.28–0.71). After standardizing the data, a significant risk of diarrhea with VKAs was observed (OR, 3.37; 95% CI, 1.09–10.41). They also detected an intense positive signal regarding the use of VKAs and osteoporosis (FDR < 0.001), specifically acenocoumarol (FDR < 0.002). NOACs presented lower risk of bleeding, especially dabigatran (FDR < 0.031), and of dermatological pathologies with apixaban being the safest (FDR = 0.050). The lower risk of global bleeding and a potential protective effect against osteoporosis in patients treated with NOACs postulate them as safer than VKAs.
Sudden Cardiac and Noncardiac Death in Sports: Epidemiology, Causes, Pathogenesis, and Prevention
Authors: Favaloro Emmanuel , Sanchis-Gomar Fabian , Lippi Giuseppe
Published: June 2018

Although few doubts remain that physical exercise should be widely promoted for maintenance of health and fitness, the risk of adverse events such as sudden death (especially due to cardiac causes, i.e., sudden cardiac death [SCD]) during exercise remains tangible. The overall risk of sudden death in athletes is relatively low (i.e., usually comprised between 0.1 and 38/100,000 person-years), and globally comparable to that of the general population. However, up to 20% of all sudden death cases are still recorded while exercising. The most frequent underlying disorders encountered in SCD are hypertrophic cardiomyopathy and coronary artery disease (CAD), representing three quarters of all conditions. The risk related to CAD increases with aging (>35 years old), while that attributable to cardiomyopathies or fatal arrhythmias is especially frequent among young people (<35 years old). Taken together, these findings would lead to the conclusion that physical exercise may be seen as an acute trigger of myocardial ischemia or arrhythmias in some predisposed individuals. Nonetheless, the prevalence of coronary atherosclerosis seems to be higher in athletes than in sedentary subjects with comparable risk profile. On the contrary, coronary plaques in physically active subjects appear more stable, thereby attenuating the risk of rupture and subsequent myocardial ischemia. These findings, along with evidence of a considerable increase of peak coronary blood flow during exercise, make it very likely that an imbalance between oxygen demand and supply may be the most frequent cause of myocardial ischemia in athletes suffering SCD and/or cardiac arrest. Therefore, all subjects who wish to practice moderate- to high-intensity exercise are recommended to undergo preparticipation screening and annual follow-up.
Buildup of speaking skills in an online learning community: a network-analytic exploration
Authors: Shafipour Rasoul , Baten Raiyan Abdul , Hasan Md Kamrul , Ghoshal Gourab , Mateos Gonzalo , Hoque Mohammed Ehsan
Published: June 2018

Studies in learning communities have consistently found evidence that peer-interactions contribute to students’ performance outcomes. A particularly important competence in the modern context is the ability to communicate ideas effectively. One metric of this is speaking, which is an important skill in professional and casual settings. In this study, we explore peer-interaction effects in online networks on speaking skill development. In particular, we present an evidence for gradual buildup of skills in a small-group setting that has not been reported in the literature. Evaluating the development of such skills requires studying objective evidence, for which purpose, we introduce a novel dataset of six online communities consisting of 158 participants focusing on improving their speaking skills. They video-record speeches for 5 prompts in 10 days and exchange comments and performance-ratings with their peers. We ask (i) whether the participants’ ratings are affected by their interaction patterns with peers, and (ii) whether there is any gradual buildup of speaking skills in the communities towards homogeneity. To analyze the data, we employ tools from the emerging field of Graph Signal Processing (GSP). GSP enjoys a distinction from Social Network Analysis in that the latter is concerned primarily with the connection structures of graphs, while the former studies signals on top of graphs. We study the performance ratings of the participants as graph signals atop underlying interaction topologies. Total variation analysis of the graph signals show that the participants’ rating differences decrease with time (slope = −0.04, p < 0.01), while average ratings increase (slope = 0.07, p < 0.05)—thereby gradually building up the ratings towards community-wide homogeneity. We provide evidence for peer-influence through a prediction formulation. Our consensus-based prediction model outperforms baseline network-agnostic regression models by about 23% in predicting performance ratings. This in turn shows that participants’ ratings are affected by their peers’ ratings and the associated interaction patterns, corroborating previous findings. Then, we formulate a consensus-based diffusion model that captures these observations of peer-influence from our analyses. We anticipate that this study will open up future avenues for a broader exploration of peer-influenced skill development mechanisms, and potentially help design innovative interventions in small-groups to maximize peer-effects.
Demonstration of a chamber for strain mapping of steel specimens under mechanical load in a hydrogen environment by synchrotron radiation
Authors: Connolly Matthew , Park Jun-Sang , Bradley Peter , Lauria Damian , Slifka Andrew , Drexler Elizabeth
Published: June 2018

We demonstrate a hydrogen gas chamber suitable for lattice strain measurements and capturing radiographs of a steel specimen under a mechanical load using high energy synchrotron x-rays. The chamber is suitable for static and cyclic mechanical loading. Experiments were conducted at the 1-ID-E end station of the Advanced Photon Source, Argonne National Laboratory. Diffraction patterns show a high signal-to-noise ratio suitable for lattice strain measurements for the specimen and with minimal scattering and overlap from the gas chamber manufactured from aluminum. In situ radiographs of a specimen in the hydrogen chamber show the ability to track a growing crack and to map the lattice strain around the crack with high spatial and strain resolution.
Readout models for BaFBr0.85I0.15:Eu image plates
Authors: Stoeckl M. , Solodov A. A.
Published: June 2018

The linearity of the photostimulated luminescence process makes repeated image-plate scanning a viable technique to extract a more dynamic range. In order to obtain a response estimate, two semi-empirical models for the readout fading of an image plate are introduced; they relate the depth distribution of activated photostimulated luminescence centers within an image plate to the recorded signal. Model parameters are estimated from image-plate scan series with BAS-MS image plates and the Typhoon FLA 7000 scanner for the hard x-ray image-plate diagnostic over a collection of experiments providing x-ray energy spectra whose approximate shape is a double exponential.
Enhancement-mode two-channel triple quantum dot from an undoped Si/Si0.8Ge0.2 quantum well hetero-structure
Authors: Studenikin S. A. , Gaudreau L. , Kataoka K. , Austing D. G. , Sachrajda A. S.
Published: June 2018

We demonstrate coupled triple dot operation and charge sensing capability for the recently introduced quantum dot technology employing undoped Si/Si0.8Ge0.2 hetero-structures which also incorporate a single metal-gate layer to simplify fabrication [Lu et al., Appl. Phys. Lett. 109, 093102 (2016)]. Si/SiGe hetero-structures with a Ge concentration of 20% rather than the more usual 30% typically encountered offer higher electron mobility. The devices consist of two in-plane parallel electron channels that host a double dot in one channel and a single dot in the other channel. In a device where the channels are sufficiently close a triple dot in a triangular configuration is induced leading to regions in the charge stability diagram where three charge-addition lines of different slope approach each other and anti-cross. In a device where the channels are further apart, the single dot charge-senses the double dot with relative change of ∼2% in the sensor current.
Thermodynamic modeling of the solar wind plasma in the presence of envelope-modulated low-frequency Alfvén waves
Authors: Nariyuki Y.
Published: June 2018

Alfvénic fluctuation is a typical state of the solar wind turbulence. Due to its finite amplitude and envelope modulation, the Alfvénic fluctuation becomes compressible. In the present study, an analytical model of the specific heat ratio in the presence of envelope-modulated Alfvén waves is derived. Ion kinetic effects are modeled by using a semi-ideal (perfect) gas model, in which the specific heat ratio depends on temperature. It is shown that the fourth order polynomial approximation is in good agreement with the kinetic theory. The resultant model is also applied to the fast solar wind plasma.
High-density convergent plasma sputtering device for a liquid metal target using an unheated glass plate
Authors: Motomura T. , Tabaru T.
Published: June 2018

A high-density convergent plasma sputtering device has been developed for a liquid metal target, using an unheated glass plate. The convergent magnetic field lines, which are produced by an external solenoid coil and a permanent magnet positioned behind the liquid metal target, effectively transport high-density plasmas near the target. In this study, a liquid gallium target was sputtered with nitrogen plasmas, without additive gas required for depositing gallium nitride films on the unheated substrates. The deposition rate of the GaN film was estimated at ∼13 nm/min at a gas pressure of 0.2 Pa. A strong diffraction peak was observed along the GaN (002) axis, with the use of an unheated glass plate and a target-substrate distance of ∼45 mm.
Axial plasma jet characterization on a microsecond x-pinch
Authors: Jaar G. S. , Appartaim R. K.
Published: June 2018

The jets produced on a microsecond x-pinch (quarter period T1/4 ∼ 1 μs, dI/dt ∼ 0.35 kA/ns) have been studied through light-field schlieren imaging and optical framing photographs across 4 different materials: Al, Ti, Mo, and W. The axial velocity of the jets was measured and exhibited no dependence on atomic number (Z) of the wire material. There may be a dependence on another factor(s), namely, the current rise rate. The average axial jet velocity across all four materials was measured to be 2.9 ± 0.5 × 106 cm/s. The average jet diameter and the average radial jet expansion rate displayed inverse relationships with Z, which may be attributed to radiative cooling and inertia. Asymmetry between the anode and cathode jet behavior was observed and is thought to be caused by electron beam activity. The mean divergence angle of the jet was found to vary with wire material and correlated inversely with the thermal conductivity of the cold wire. Optical images indicated a two-layer structure in Al jets which may be caused by standing shocks and resemble phenomena observed in astrophysical jet formation and collimation. Kinks in the jets have also been observed which may be caused by m = 1 MHD instability modes or by the interaction of the jet with the electrode plasma.
Compressibility of the protein-water interface
Authors: Persson Filip , Halle Bertil
Published: June 2018

The compressibility of a protein relates to its stability, flexibility, and hydrophobic interactions, but the measurement, interpretation, and computation of this important thermodynamic parameter present technical and conceptual challenges. Here, we present a theoretical analysis of protein compressibility and apply it to molecular dynamics simulations of four globular proteins. Using additively weighted Voronoi tessellation, we decompose the solution compressibility into contributions from the protein and its hydration shells. We find that positively cross-correlated protein-water volume fluctuations account for more than half of the protein compressibility that governs the protein’s pressure response, while the self correlations correspond to small (∼0.7%) fluctuations of the protein volume. The self compressibility is nearly the same as for ice, whereas the total protein compressibility, including cross correlations, is ∼45% of the bulk-water value. Taking the inhomogeneous solvent density into account, we decompose the experimentally accessible protein partial compressibility into intrinsic, hydration, and molecular exchange contributions and show how they can be computed with good statistical accuracy despite the dominant bulk-water contribution. The exchange contribution describes how the protein solution responds to an applied pressure by redistributing water molecules from lower to higher density; it is negligibly small for native proteins, but potentially important for non-native states. Because the hydration shell is an open system, the conventional closed-system compressibility definitions yield a pseudo-compressibility. We define an intrinsic shell compressibility, unaffected by occupation number fluctuations, and show that it approaches the bulk-water value exponentially with a decay “length” of one shell, less than the bulk-water compressibility correlation length. In the first hydration shell, the intrinsic compressibility is 25%–30% lower than in bulk water, whereas its self part is 15%–20% lower. These large reductions are caused mainly by the proximity to the more rigid protein and are not a consequence of the perturbed water structure.
Statistics for real-time deformability cytometry: Clustering, dimensionality reduction, and significance testing
Authors: Herbig M. , Mietke A. , Müller P. , Otto O.
Published: June 2018

Real-time deformability (RT-DC) is a method for high-throughput mechanical and morphological phenotyping of cells in suspension. While analysis rates exceeding 1000 cells per second allow for a label-free characterization of complex biological samples, e.g., whole blood, data evaluation has so far been limited to a few geometrical and material parameters such as cell size, deformation, and elastic Young's modulus. But as a microscopy-based technology, RT-DC actually generates and yields multidimensional datasets that require automated and unbiased tools to obtain morphological and rheological cell information. Here, we present a statistical framework to shed light on this complex parameter space and to extract quantitative results under various experimental conditions. As model systems, we apply cell lines as well as primary cells and highlight more than 11 parameters that can be obtained from RT-DC data. These parameters are used to identify sub-populations in heterogeneous samples using Gaussian mixture models, to perform a dimensionality reduction using principal component analysis, and to quantify the statistical significance applying linear mixed models to datasets of multiple replicates.
Proton dynamics and the phase diagram of dense water ice
Authors: Hernandez J.-A. , Caracas R.
Published: June 2018

All the different phases of water ice between 2 GPa and several megabars are based on a single body-centered cubic sub-lattice of oxygen atoms. They differ only by the behavior of the hydrogen atoms. In this study, we investigate the dynamics of the H atoms at high pressures and temperatures in water ice from first-principles molecular dynamics simulations. We provide a detailed analysis of the O—H⋯O bonding dynamics over the entire stability domain of the body-centered cubic (bcc) water ices and compute transport properties and vibrational density-of-states. We report the first ab initio evidence for a plastic phase of water and we propose a coherent phase diagram for bcc water ices compatible with the two groups of melting curves and with the multiple anomalies reported in ice VII around 15 GPa.
Propagation dynamics of successive emissions in laboratory and astrophysical jets and problem of their collimation
Authors: Kalashnikov I. , Chardonnet P. , Chechetkin V. , Dodin A. , Krauz V.
Published: June 2018

This paper presents the results of numerical simulation of the propagation of a sequence of plasma knots in laboratory conditions and in the astrophysical environment. The physical and geometric parameters of the simulation have been chosen close to the parameters of the PF-3 facility (Kurchatov Institute) and the jet of the star RW Aur. We found that the low-density region formed after the first knot propagation plays an important role in the collimation of the subsequent ones. Assuming only the thermal expansion of the subsequent emissions, qualitative estimates of the time taken to fill this area with the surrounding matter and the angle of jet scattering have been made. These estimates are consistent with observations and results of our modeling.
Laser entrance window transmission and reflection measurements for preheating in magnetized liner inertial fusion
Authors: Davies J. R. , Bahr R. E. , Barnak D. H. , Betti R. , Bonino M. J. , Campbell E. M. , Hansen E. C. , Harding D. R. , Peebles J. L. , Sefkow A. B. , Seka W. , Chang P.-Y. , Geissel M. , Harvey-Thompson A. J.
Published: June 2018

Laser-driven magnetized liner inertial fusion (MagLIF) is being developed on the OMEGA Laser System to study scaling. MagLIF targets require a preheat laser entrance window that can hold the gas in the target yet allow sufficient laser energy to enter the gas. For OMEGA MagLIF targets, 1.8-μm-thick polyimide foils were found to be sufficient to hold a fuel pressure of up to 14 atm. Transmission and reflection of an OMEGA beam incident on such foils were measured with a calorimeter and time-resolved spectrometers for 2.5-ns square-shaped pulses, with energies from 60 to 200 J, focused to intensities from 0.65 to 2.2 × 1014 W/cm2. The laser energy transmitted in every case exceeded that required to achieve the goal of preheating the gas to 100 eV. The time-resolved measurements showed an initial period with very low, decreasing transmission, the duration of which decreased with increasing intensity, followed by a rapid transition to full transmission, accompanied by brief sidescattering of the transmitted light with a significant red shift. Reflection was always negligible. Two-dimensional radiation–hydrodynamic simulations, using 3-D ray tracing with inverse bremsstrahlung energy deposition, did not capture the rapid transition to full transmission, showing instead a slow increase in transmission, without significant sidescatter or red shift. We propose that full transmission is achieved by self-focusing followed by ponderomotive blowout of the plasma.
Characterization of xenon ion and neutral interactions in a well-characterized experiment
Authors: Patino Marlene I. , Wirz Richard E.
Published: June 2018

Interactions between fast ions and slow neutral atoms are commonly dominated by charge-exchange and momentum-exchange collisions, which are important to understanding and simulating the performance and behavior of many plasma devices. To investigate these interactions, this work developed a simple, well-characterized experiment that accurately measures the behavior of high energy xenon ions incident on a background of xenon neutral atoms. By using well-defined operating conditions and a simple geometry, these results serve as canonical data for the development and validation of plasma models and models of neutral beam sources that need to ensure accurate treatment of angular scattering distributions of charge-exchange and momentum-exchange ions and neutrals. The energies used in this study are relevant for electric propulsion devices ∼1.5 keV and can be used to improve models of ion-neutral interactions in the plume. By comparing these results to both analytical and computational models of ion-neutral interactions, we discovered the importance of (1) accurately treating the differential cross-sections for momentum-exchange and charge-exchange collisions over a large range of neutral background pressures and (2) properly considering commonly overlooked interactions, such as ion-induced electron emission from nearby surfaces and neutral-neutral ionization collisions.
The spatial range of protein hydration
Authors: Persson Filip , Söderhjelm Pär , Halle Bertil
Published: June 2018

Proteins interact with their aqueous surroundings, thereby modifying the physical properties of the solvent. The extent of this perturbation has been investigated by numerous methods in the past half-century, but a consensus has still not emerged regarding the spatial range of the perturbation. To a large extent, the disparate views found in the current literature can be traced to the lack of a rigorous definition of the perturbation range. Stating that a particular solvent property differs from its bulk value at a certain distance from the protein is not particularly helpful since such findings depend on the sensitivity and precision of the technique used to probe the system. What is needed is a well-defined decay length, an intrinsic property of the protein in a dilute aqueous solution, that specifies the length scale on which a given physical property approaches its bulk-water value. Based on molecular dynamics simulations of four small globular proteins, we present such an analysis of the structural and dynamic properties of the hydrogen-bonded solvent network. The results demonstrate unequivocally that the solvent perturbation is short-ranged, with all investigated properties having exponential decay lengths of less than one hydration shell. The short range of the perturbation is a consequence of the high energy density of bulk water, rendering this solvent highly resistant to structural perturbations. The electric field from the protein, which under certain conditions can be long-ranged, induces a weak alignment of water dipoles, which, however, is merely the linear dielectric response of bulk water and, therefore, should not be thought of as a structural perturbation. By decomposing the first hydration shell into polarity-based subsets, we find that the hydration structure of the nonpolar parts of the protein surface is similar to that of small nonpolar solutes. For all four examined proteins, the mean number of water-water hydrogen bonds in the nonpolar subset is within 1% of the value in bulk water, suggesting that the fragmentation and topography of the nonpolar protein-water interface has evolved to minimize the propensity for protein aggregation by reducing the unfavorable free energy of hydrophobic hydration.
Microwave probe stations with three-dimensional control of the magnetic field to study high-frequency dynamics in nanoscale devices
Authors: Banuazizi Seyed Amir Hossein , Åkerman Johan
Published: June 2018

We present two microwave probe stations with motorized rotary stages for adjusting the magnitude and angle of the applied magnetic field. In the first system, the magnetic field is provided by an electromagnet and can be adjusted from 0 to ∼1.4 T while its polar angle (θ) can be varied from 0° to 360°. In the second system, the magnetic field is provided by a Halbach array permanent magnet, which can be rotated and translated to cover the full range of polar (θ) and azimuthal (φ) angles with a tunable field magnitude up to ∼1 T. Both systems are equipped with microwave probes, bias-Ts, amplifiers, and spectrum analyzers to allow for microwave characterization up to 40 GHz, as well as software to automatically perform continuous large sets of electrical and microwave measurements.
Contribution of aquatic shredders to leaf litter decomposition in Atlantic island streams depends on shredder density and litter quality
Authors: Raposeiro Pedro Miguel , Ferreira Verónica , Gea Guillermo , Gonçalves Vítor
Published: June 2018

It has been widely reported that shredders play an important role in leaf decomposition, especially in continental temperate streams. However, the paucity of shredders in many oceanic island streams leads to a greater contribution of microbes to litter decomposition in these streams. In this study, we investigated the importance of shredder presence and density (three levels) and leaf litter identity (Alnus glutinosa, Clethra arborea and Acacia melanoxylon) on leaf litter decomposition in one stream located in the Azores Archipelago. Coarse and fine mesh bags were used to allow natural colonisation of leaf litter by benthic macroinvertebrates or to exclude macroinvertebrates respectively. Treatments with one and three shredders were accomplished by enclosing one or three shredders in the fine mesh bags. Rates of litter decomposition differed significantly among shredder density treatments only for A. glutinosa and C. arborea. Decomposition rates were significantly faster for the natural within-stream shredder density treatment than for other shredder treatments. Shredder density differed significantly among litter species, being higher in A. glutinosa than in C. arborea and A. melanoxylon. The results indicate that when shredders are present at high densities in oceanic island streams they can substantially contribute to the decomposition of high-quality leaf litter, whereas the decomposition of hard leaf litter is mostly performed by the microbial community.
Determining the minimum sampling frequency for ground measurements of burn severity
Authors: Holmes Alexander W. , Rüdiger Christoph , Harris Sarah , Tapper Nigel
Published: June 2018

Understanding burn severity is essential to provide an overview of the precursory conditions leading to fires as well as understanding the constraints placed on fire management services when mitigating their effects. Determining the minimum sampling frequency for ground measurements is not only essential for accurately assessing burn severity, but also for fire managers to better allocate resources and reduce the time and costs associated with sampling. In this study, field sampling methods for assessing burn severity are analysed statistically for 10 burn sites across Victoria, Australia, with varying spatial extents, topography and vegetation. Random and transect sampling methods are compared against each other using a Monte Carlo simulation to determine the minimum sample size needed for a difference of 0.02 (2%) in the severity classes proportions relative to the population proportions. We show that, on average, transect sampling requires a sampling rate of 3.16% compared with 0.59% for random sampling. We also find that sites smaller than 400 ha require a sampling rate of between 1.4 and 2.8 times that of sites larger than 400 ha to achieve the same error. The information obtained from this study will assist fire managers to better allocate resources for assessing burn severity.
Proterozoic Milankovitch cycles and the history of the solar system
Authors: Meyers Stephen R. , Malinverno Alberto
Published: June 2018

Significance

Periodic variations in Earth’s orbit and rotation axis occur over tens of thousands of years, producing rhythmic climate changes known as Milankovitch cycles. The geologic record of these climate cycles is a powerful tool for reconstructing geologic time, for understanding ancient climate change, and for evaluating the history of our solar system, but their reliability dramatically decreases beyond 50 Ma. Here, we extend the analysis of Milankovitch cycles into the deepest stretches of Earth history, billions of years ago, while simultaneously reconstructing the history of solar system characteristics, including the distance between the Earth and Moon. Our results improve the temporal resolution of ancient Earth processes and enhance our knowledge of the solar system in deep time.
Altered p53 functionality in cancer-associated fibroblasts contributes to their cancer-supporting features
Authors: Arandkar Sharathchandra , Furth Noa , Elisha Yair , Nataraj Nishanth Belugali , van der Kuip Heiko , Yarden Yosef , Aulitzky Walter , Ulitsky Igor , Geiger Benjamin , Oren Moshe
Published: June 2018

Significance

p53 research has primarily addressed its cell-autonomous tumor-suppressive features. Yet, recent evidence suggests that, in normal tissues, p53 can also exert cell nonautonomous tumor suppressor activities. Cancer-associated fibroblasts (CAFs) enhance the malignant features of adjacent cancer cells. Surprisingly, we found that the conversion of normal fibroblasts to CAFs entails nonmutational alteration of their p53, such that it now becomes cancer supportive rather than cancer inhibitory. This is achieved through reprogramming the transcriptional output of the CAF p53, rendering it a positive regulator of cancer-promoting genes and secreted proteins. Overall, our study highlights a function of nonmutated p53 in the tumor microenvironment and suggests that molecules that can “re-educate” the renegade p53 may have therapeutic value.
Spatially modulated ephrinA1:EphA2 signaling increases local contractility and global focal adhesion dynamics to promote cell motility
Authors: Chen Zhongwen , Oh Dongmyung , Biswas Kabir H. , Yu Cheng-Han , Zaidel-Bar Ronen , Groves Jay T.
Published: June 2018

Significance

Cell receptors are neither uniformly distributed nor uniformly activated across plasma membrane. However, very little is known about how their spatial arrangement affects cellular response to receptor signaling. EphA2 is a receptor tyrosine kinase whose activation depends on binding of EphrinA1 ligands on the opposing cell, and EphA2 signaling plays an important role in cancer metastasis. In adherent cells, integrin adhesions are a key element to regulate cell–matrix interactions and cell migration. However, our understanding of how their activities are spatiotemporally coordinated remains superficial. In this study, we combined microfabrication, live imaging, and single-molecule tracking to directly map the signal transduction from ephrinA1:EphA2 complex to integrin adhesions, and revealed a spatially controlled mechanism for EphA2–integrin signaling cross talk.
Gut microbiota regulates maturation of the adult enteric nervous system via enteric serotonin networks
Authors: De Vadder Filipe , Grasset Estelle , Mannerås Holm Louise , Karsenty Gérard , Macpherson Andrew J. , Olofsson Louise E. , Bäckhed Fredrik
Published: June 2018

Significance

The gut microbiota affects several physiological processes, including gut motility. Here we observed that germ-free mice have an immature enteric nervous system (ENS) that is normalized upon colonization with a normal microbiota. We identified the mechanism of communication between the microbiota and enteric neurons as the initiation of serotonin release and subsequent activation of the 5-HT
4
receptor. This demonstrates a strong interaction between the microbiota and the ENS and indicates potential mechanisms linking microbial dysbiosis to gastrointestinal disorders. The ability to modulate the microbiota, e.g., by diet, will open new perspectives of research in neurogastroenterology.
Transdifferentiation of human adult peripheral blood T cells into neurons
Authors: Tanabe Koji , Ang Cheen Euong , Chanda Soham , Olmos Victor Hipolito , Haag Daniel , Levinson Douglas F. , Südhof Thomas C. , Wernig Marius
Published: June 2018

Significance

Recent advances in genomics have revealed that many polygenetic diseases are caused by complex combinations of many common variants with individually small effects. Thus, building informative disease models requires the interrogation of many patient-derived genetic backgrounds in a disease-relevant cell type. Current approaches to obtaining human neurons are not easy to scale to many patients. Here we describe a facile, one-step conversion of human adult peripheral blood T cells directly into functional neurons using episomal vectors without the need for previous in vitro expansion. This approach is more amenable than induced pluripotent stem cell-based approaches for application to larger cohorts of individuals and will enable the development of functional assays to study complex human brain diseases.
Pronounced summer warming in northwest Greenland during the Holocene and Last Interglacial
Authors: McFarlin Jamie M. , Axford Yarrow , Osburn Magdalena R. , Kelly Meredith A. , Osterberg Erich C. , Farnsworth Lauren B.
Published: June 2018

Significance

Reconstructions of climate over Greenland during past warm periods provide crucial insights into the likely response of the Greenland Ice Sheet to future warming. However, limited preservation of interglacial archives due to extensive glacial scouring has hindered paleoclimate reconstructions along Greenland’s margins. Here, we report a Greenland lake sediment record that preserves both the present and previous interglacial periods. This record, combined with prior studies, demonstrates exceptionally strong warming over the northern Greenland Ice Sheet. Pronounced summer warming in this region helps explain ice sheet changes in the Early Holocene, while highlighting seemingly incongruous evidence for ice sheet extent and temperatures during the Last Interglacial. These findings may portend large future warming in this high-latitude region.
Uncovering pH at both sides of the root plasma membrane interface using noninvasive imaging
Authors: Martinière Alexandre , Gibrat Rémy , Sentenac Hervé , Dumont Xavier , Gaillard Isabelle , Paris Nadine
Published: June 2018

Significance

The pH on both sides of the plant plasma membrane was accurately measured in vivo using ratiometric fluorescent sensors. This enabled noninvasive access to membrane-associated pH and transmembrane delta pH values from the surface of the root up to the deepest cell layers beyond the Casparian strip barrier. We demonstrate that despite direct contact with the soil, the apoplastic pH close to the plasma membrane was maintained at values ranging from 6.0 to 6.4 in mature root cells, whereas the overall pH in the apoplastic space is far more acidic. Furthermore, we found that the cell wall plays a role in proton homeostasis in mature root.