bluuebunny/crossref_metadata_2025 huggingface dataset:
Forschungsvorausverfügungen bei Demenz: Medizinethische Überlegungen zur Aufklärungspflicht
Authors: Gieselmann Astrid , Scholten Matthé , Gather Jakov , Vollmann Jochen
Published: February 2019

Der Deutsche Bundestag hat im November 2016 eine Änderung des Arzneimittelgesetzes beschlossen. Nach dieser Änderung soll gruppennützige Arzneimittelforschung mit nicht-einwilligungsfähigen Erwachsenen unter bestimmten Bedingungen erlaubt sein. Eine dieser Bedingungen ist, dass der Proband eine sogenannte Forschungsvorausverfügung abgefasst hat, in der er in die Studienteilnahme eingewilligt hat. Zudem soll der Proband vor der Abfassung der Forschungsvorausverfügung von einem Arzt über die Forschungsteilnahme aufgeklärt worden sein. Es ist die Auffassung vertreten worden, dass der Gesetzgeber auf eine Aufklärungspflicht hätte verzichten sollen. In diesem Artikel werden Gründe diskutiert, die für eine Aufklärungspflicht bei Forschungsvorausverfügungen sprechen. Zudem wird ein praktisch umsetzbarer Aufklärungsstandard vorgeschlagen, nach dem potentielle Studienteilnehmer nicht über spezifische Studien, sondern über bestimmte Studientypen aufgeklärt würden.
Sphincterotomy plus balloon dilation versus sphincterotomy alone for choledocholithiasis: a meta-analysis
Authors: Dong Shou Quan , Singh Tikka Prabhjot , Zhao Qiu , Li Juan Juan , Wang Hong Ling
Published: February 2019

Background Endoscopic sphincterotomy plus balloon dilation (ESBD) is considered to be a promising method for the removal of large common bile duct (CBD) stones. However, when compared with endoscopic sphincterotomy (EST) alone, the efficacy and safety of ESBD remain controversial. This meta-analysis aimed to compare the efficacy and safety of ESBD vs. EST for the removal of large CBD stones.

Methods Electronic databases were searched up to 15 July 2018 for literature that compared ESBD with EST for the removal of CBD stones. Pooled odds ratios (ORs) of the stone clearance rate and the complication rate were used to compare the efficacy and safety of ESBD vs. EST.

Results A total of 18 studies with 2789 patients were included. The results showed that the stone removal rate was much higher in the ESBD group than in the EST group, both across all endoscopic retrograde cholangiopancreatography (ERCP) sessions (OR 2.68, 95 % confidence interval [CI] 1.79 to 4.01) and during the first ERCP session (OR 2.07, 95 %CI 1.37 to 3.12). The ESBD group had fewer complications than EST alone (OR 0.63, 95 %CI 0.47 to 0.85). Moreover, the ESBD group needed less mechanical lithotripsy (OR 0.38, 95 %CI 0.24 to 0.61) and had a shorter procedure time (mean difference – 4.05, 95 %CI – 7.02 to – 1.09) than EST alone.

Conclusion The efficacy and safety of ESBD were superior to those of EST for the removal of large CBD stones. Moreover, less mechanical lithotripsy and shorter procedure times were needed with ESBD to manage large stones.
Palladium-Catalyzed Decarboxylative [4+2] Cycloaddition of Vinyl Benzoxazinanones with Cyclic N-Sulfimines: Stereoselective Synthesis­ of Benzosulfamidate-Fused Tetrahydroquinazolines
Authors: Mun Dasom , Kim Eunjin , Kim Sung-Gon
Published: February 2019

Methods for the catalytic synthesis of highly functionalized benzosulfamidate-fused tetrahydroquinazolines are presented. The decarboxylative [4+2] cycloaddition of vinyl benzoxazinanones with benzoxathiazine 2,2-dioxides catalyzed by Pd(PPh3)4 affords fused-tetrahydroquinazolines with high diastereoselectivities. Alternatively, catalytic asymmetric [4+2] cycloaddition employing a chiral palladium-containing phosphoramidite ligand provides optically enriched benzosulfamidate-fused tetrahydroquinazolines in good yields and with excellent diastereoselectivities and enantioselectivities.
Total Synthesis of PF1163B
Authors: Hosokawa Seijiro , Sengupta Aakash
Published: February 2019

A total synthesis of PF1163B has been achieved. The vinylogous Mukaiyama aldol reaction of ketene silyl N,O-acetal 6 (ent-6) mediated by excess TiCl4 proceeded with saturated aldehydes to give adduct 10 in moderate yield with moderate stereoselectivity. The major isomer is the diastereomer that was provided by using one equivalent of TiCl4. The Birch reduction of α,β-unsaturated imide 4, possessing a less hindered side chain, gave 12 in good stereoselectivity by employing 2-isopropylbenzimidazole as a bulky proton source. After elongation of the carbon chain and connection with the amino acid part, we accomplished a total synthesis of PF1163B. These methods constitute a concise synthetic route to obtain polyketides as well as depsipeptides.
Regionale Weichteilrekonstruktion an der unteren Extremität
Authors: Schmidt Volker , Kneser Ulrich
Published: February 2019

Dieser Artikel beleuchtet den Stellenwert von gestielten Lappenplastiken an der unteren Extremität im Rahmen der regionalen Weichteilrekonstruktion nach Trauma. Die typischen Fallstricke dieser Verfahren sowie Tipps und Tricks zu 5 gängigen gestielten Lappenplastiken werden detailliert dargestellt.
Role of sheath dynamics in multiple double layer formations in expanding RF plasma
Authors: Paul Manash Kumar , Chakraborty Shamik , Bose Subhojit
Published: February 2019

Potential double layers are observed to form as nested cylindrical sheaths that energize charge particles in the absence of any externally applied magnetic field. These visibly glowing nested cylindrical sheaths are named as “Fire Tube” in the present work. Sheaths, in unmagnetized collisionless plasmas, have been observed to be functional in generating energetic charge particles. Two characteristically different plasma sources are compared in terms of the dependence of potential and density profiles on the plasma sheath formations near the source boundary. The sheath structures, complex fire tube formation, and space charge formations demarcate the two sources in terms of complex structure formations and motion of the charge particles. We present here the characteristic study of high pressure collisional boundary sheath formations through systematic experiments carried out during the transition from unmagnetized to magnetized charge particles, in the case of two different plasma sources designed. The cylindrical ambient plasma sheaths are observed to energize the charge particles, in the absence of any external magnetic field. The fire tube formations essentially represent a non-neutral region located radially away from the plasma source boundary, connecting the ion sheath with the electron sheath. The probe diagnostic results suggest a significant role of energetic electrons in the formation of multiple double layer structures in the present operational regime. Generation of nonthermal electrons during the formation of MDL in radio frequency capacitive discharges is subjected to interactions of the plasma with the electrodes as well as the confining wall material.
Stochastic simulation of anharmonic dissipation. II. Harmonic bath potentials with quadratic couplings
Authors: Yan Yun-An
Published: February 2019

The workhorse simulating the dissipative dynamics is mainly based on the harmonic bath potentials together with linear system-bath couplings, but a realistic bath always assumes anharmonicity. In this work, we extend the linear dissipation model to include quadratic couplings and suggest a stochastic simulation scheme for the anharmonic dissipation. We show that the non-Gaussian noises induced by the anharmonic bath can be rigorously constructed, and the resulting stochastic Liouville equation has the same form as that for the linear dissipation model. As a preliminary application, we use this stochastic method to investigate the vibration-induced symmetry breaking in two-level electronic systems and find that the characteristic function of the non-Gaussian noises determines the absorption and fluorescence spectra.
Synchronization of Rulkov neuron networks coupled by excitatory and inhibitory chemical synapses
Authors: Ge Penghe , Cao Hongjun
Published: February 2019

This paper takes into account a neuron network model in which the excitatory and the inhibitory Rulkov neurons interact each other through excitatory and inhibitory chemical coupling, respectively. Firstly, for two or more identical or non-identical Rulkov neurons, the existence conditions of the synchronization manifold of the fixed points are investigated, which have received less attention over the past decades. Secondly, the master stability equation of the arbitrarily connected neuron network under the existence conditions of the synchronization manifold is discussed. Thirdly, taking three identical Rulkov neurons as an example, some new results are presented: (1) topological structures that can make the synchronization manifold exist are given, (2) the stability of synchronization when different parameters change is discussed, and (3) the roles of the control parameters, the ratio, as well as the size of the coupling strength and sigmoid function are analyzed. Finally, for the chemical coupling between two non-identical neurons, the transversal system is given and the effect of two coupling strengths on synchronization is analyzed.
Evolution of ultra-relativistic hollow electron beams during their propagation in plasmas
Authors: Jain Neeraj
Published: February 2019

Ultra-relativistic hollow electron beams can drive plasma wakefields (∼GV/m) suitable for positron acceleration. Stable propagation of hollow electron beams for long distances in plasmas is required to accelerate positrons to high energies by these plasma wakefields. In this work, we show by quasi-static kinetic simulations using the code WAKE that an ultra-relativistic azimuthally symmetric hollow electron beam with zero emittance propagates in a plasma by developing a fish-bone like structure and shifting its bulk, differentially along its length (rear part fastest), towards its axis due to the decrease in the betatron time period of beam electrons from the beam-front to beam-rear. Hollow electron beams with a small radius collapse into their axis due to the pull by the secondary wakefields generated by some of the beam electrons reaching the axis. Hollow beams with the radius equal to or larger than a minimum value, however, can propagate stably in plasmas for several meters. The minimum beam radius for the stable beam propagation in plasmas depends very weakly on the peak beam density with which the magnitude of the positron-accelerating electric field increases. Thus, the peak beam density can be used as a control parameter to achieve high acceleration gradients for positrons without affecting the minimum beam radius.
Femtosecond-laser-induced spin-polarized electron emission from a GaAs tip
Authors: Brunkow Evan , Jones Eric R. , Batelaan Herman , Gay T. J.
Published: February 2019

It is shown that focusing circularly polarized 800 nm light pulses of duration 100 fs on the tips of p-GaAs crystalline shards having no negative electron affinity (NEA) activation results in electron emission that is both fast and spin-polarized. The 400 fs duration of the emission process was determined by pump/probe measurements. The three samples we investigated produced electron polarizations of 13.1(0.9)%, 13.3(0.7)%, and 10.4(0.2)%. Emission currents ranged between 50 pA and 3 nA with a sample bias of −100 V and an average laser power of 100 mW. The electron emission exhibited linear dichroism and was obtained under moderate vacuum conditions, similar to that of metallic tips. This source of spin-polarized electron pulses is “fast” in the sense that the electron emission process is of comparable duration to the laser pulses that initiate it.
Back-focal-plane interferometric detection of nanoparticles in spatially confined microfluidic channels
Authors: Kotnala Abhay , Zheng Yi , Fu Jianping , Cheng Wei
Published: February 2019

Nanoparticles are important in several areas of modern biomedical research. However, detection and characterization of nanoparticles is challenging due to their small size. Back-focal-plane interferometry (BFPI) is a highly sensitive technique that has been used in laser tweezers for quantitative measurement of force and displacement. The utility of BFPI for detection and characterization of nanoparticles, however, has not yet been achieved. Here we show that BFPI can be used for rapid probing of a suspension of nanoparticles in a spatially confined microfluidic channel. We show that the Gaussian Root-mean-squared noise of the BFPI signal is highly sensitive to the nanoparticle size and can be used as a parameter for rapid detection of nanoparticles at a single-particle level and characterization of particle heterogeneities in a suspension. By precisely aligning the optical trap relative to the channel boundaries, individual polystyrene particles with a diameter as small as 63 nm can be detected using BFPI with a high signal-to-noise ratio.
Probing alkylsilane molecular structure on amorphous silica surfaces by sum frequency generation vibrational spectroscopy: First-principles calculations
Authors: Tetsassi Feugmo Conrard Giresse , Liégeois Vincent , Caudano Yves , Cecchet Francesca , Champagne Benoît
Published: February 2019

The sum frequency generation (SFG) signatures of octadecyl-trichlorosilane (OTS) and dodecyl-dimethyl-chlorosilane (DDCS) monolayers on silica were simulated in the C–H stretching region for three polarization combinations (ppp, sps, and ssp), showing the impact of the additional Si-linked methyl groups of DDCS on its SFG signatures. These simulations are based on a two-step procedure where (i) the molecular properties (vibrational frequencies, IR and Raman intensities) are evaluated using first principles methods and (ii) the three-layer model is employed to calculate the macroscopic responses using these molecular responses, the geometry of the experimental setup, and the optical properties of the layers. These first principles calculations adopt the own N-layered integrated orbital molecular mechanics (ONIOM) approach, which divides the system and enables different levels of approximation to be applied to its different parts. Here, the same ωB97X-D exchange-correlation functional is used for all parts, while the underlying silica layers are described with a smaller atomic basis set (STO-3G, 3-21G, or 6-31G) than the alkylsilane and the top silica layer (6-311G*). Calculations show that for describing the lower layer the minimal STO-3G basis set already provides reliable spectral profiles. For OTS, the results are compared to the experiment, demonstrating a good agreement for ppp and sps configurations, provided the refractive index of the layer nl is set to 1.1. To highlight the origin of the SFG signatures, two chemical models were used, one that includes explicitly the SiO2 surface in the first principles calculations (adsorbed-model) and the other that only considers the silane chain (isolated-model). Simulations show that OTS and DDCS display similar spectral patterns where, for ppp and sps configurations, the r− CH3 stretching vibrations are dominant in comparison to the r+ stretching ones. Still, in the case of DDCS, the r− peak presents a shoulder, which is assigned to the vibrations of the Si-linked methyl groups. This shoulder vanishes when these CH3 groups are frozen. Then, using the isolated-model, the rotation angle (ξ) is gradually changed, showing that in the ppp SFG spectrum the r−/r+ intensity ratio decreases from 73.4 at 0° to 1.7 at 180°.
Phase-frequency model of strongly pulse-coupled Belousov-Zhabotinsky oscillators
Authors: Horváth Viktor , Kutner Daniel Jackson , Zeng Manhao Danny , Epstein Irving R.
Published: February 2019

We demonstrate that the dynamical behavior of strongly pulse-coupled Belousov-Zhabotinsky oscillators can be reproduced and predicted using a model that treats both the phase and the instantaneous frequency of the oscillators. Model parameters are extracted from the experimental data obtained using a single pulse-perturbed oscillator and are used to simulate the temporal dynamics of a system of two coupled oscillators. Our model exhibits the out-of-phase and anti-phase synchronization and the 1:N and N:M temporal patterns as well as the oscillator suppression that are observed in experiments when the inhibitory coupling is asymmetric. This approach may be adapted to other systems, such as coupled neurons, where the oscillatory dynamics is affected by strong pulses.
Solid-phase reactive inter-diffusion of Mg/B multilayers
Authors: Bayu Aji L. B. , Baker A. A. , Jacob R. E. , Maich A. A. , Bae J. H. , Rodriguez J. A. , McCall S. K. , Kucheyev S. O.
Published: February 2019

A better understanding of the reaction of Mg and B in the solid-phase regime is needed for the low-temperature synthesis of MgB2 films. Here, we study the kinetics of reactive inter-diffusion of Mg and B multilayers on glassy carbon substrates in the temperature range of 400−650°C. Results show that, at these temperatures, inter-diffusion is characterized by a single activation energy of ∼0.45eV. The formation of the superconducting MgB2 phase with critical temperatures of 25–31 K occurs at reaction temperatures of 450°C and above, with the rate of inter-diffusion obeying a power law with a kinetic exponent of ∼0.3. This suggests that rate-limiting processes are the nucleation and growth of MgB2 grains rather than diffusion and interfacial reactions. Implications of these results to the low-temperature synthesis of MgB2 films are discussed.
Stability of SiC and SiN interfaces in titanium carbide and nitride based heterostructures
Authors: Ivashchenko V. I. , Turchi P. E. A. , Gorb Leonid , Leszczynski Jerzy , Medukh N. R. , Shevchenko R. V.
Published: February 2019

First-principles molecular dynamics simulations of the stability of the NaCl-type (B1) SiC and SiN interfaces in TiX/one multilayer SiY (X,Y=C,N) heterostructures were carried out as functions of temperature. It was previously shown that the SiX interfaces in the heterostructures based on transition metal compounds could be dynamically unstable owing to the elongated interfacial Si-X bonds compared to the Si-X bonds in the B1-SiX phases in equilibrium. However, this criterion is not satisfied for some SiX(111) interfaces. The aim of this work is to study the temperature-induced changes in the structure of the heterostructures under consideration and to clarify a possible origin of instability of the interfaces in them. It is shown that, at finite temperatures, the interfacial layer in the TiN(001)/SiC heterostructure transforms into the zinc blende-type (B3) SiC-like layer, whereas the interfaces in other (001) heterostructures transform into amorphous-like interfacial layers. The TiC(111)/SiC and TiN(111)/SiN heterostructures are stable up to 1400 K. The TiN(111)/B3-like SiC and TiC(111)/B3-like SiN systems form during static relaxation of the initial heterostructures. The phase transformations of the interfaces are explained in terms of dynamical and elastic stability criteria. In contrast to the (111) interfacial layers, all the B1-(001) interfaces are found to be dynamically unstable. The formation of the B3-(111) interfaces occurs due to the elastic instability of the corresponding B1-(111) interface.
Validation of ion temperature measurement using an ion sensitive probe technique in finite boundary RF plasma
Authors: Takahashi H. , Ogasawara K. , Boonyarittipong P. , Saikyo T. , Seino T. , Kitajima S. , Okamoto A. , Tobita K.
Published: February 2019

Validation of ion sensitive probe (ISP) measurements in radio-frequency plasma was investigated using Doppler spectroscopy. Ion temperature Ti obtained by an ISP was consistent with that obtained by Doppler spectroscopy when the recessed distance between two electrodes h satisfied 10ρe<h<10(ρe+λD). However, ISP yielded a larger ion temperature than that obtained by Doppler spectroscopy when the above relation was not fulfilled. The effective ion temperature calculated based on the ion kinetic motion matched well with the ISP measurement result, which indicates that the ISP could overestimate Ti owing to the ion Larmor motion when h is not optimized. The availability of the ISP technique for measuring the radial Ti profile was also investigated. Ti showed a rapid increase in the edge region of a cylindrical plasma and finally became larger than the electron temperature even though there was no direct ion heating power source. Calculations considering the ion kinetic effect well reproduced both the magnitude and the radial trend of ion temperature and ion density near the plasma edge. This result postulates that Ti evaluation could also be inadequate due to the ion kinetic effect when an ISP is placed at the edge and outside a finite boundary plasma.
Structural phase transition in Al-substituted Fe2MnGa Heusler alloy
Authors: Guimarães C. E. A. , Krohling A. C. , Larica C. , Scopel W. L. , Passamani E. C.
Published: February 2019

In this work, we have systematically investigated the face centered cubic (FCC) to body centered cubic (BCC) transition and its influence on hyperfine and magnetic properties of Al-substituted Fe2MnGa laminated metallic ribbons (non-annealed and annealed) prepared by arc-melting. X-ray diffraction results of non-annealed ribbons show the formation of the atomically disordered FCC (A1) phase in low Al-content (<30 at. %), while a full atomically disordered BCC phase (A2) is found for high Al-content (≥50 at. %). An ordered cubic phase (L21-structure) is established in plastically deformed Al-substituted alloys annealed at 573 K for a few hours. In the L21 state, the Al content increase induces a linear reduction of the cubic cell volume, which influence s and d-electron charge and spin densities at Fe atoms. These changes are responsible for the modifications in hyperfine and magnetic properties of the studied alloys, as confirmed by first principles calculation. We have also demonstrated that the L21 state can be obtained when small percentages (5 at. %) of Al replace Ga atoms and the structural transition is basically explained by an enhancement of chemical pressure in the Al isoelectronically substituted Fe2MnGa system.
The evolution process of nonlinear cold-electron-plasma oscillations against fixed periodic ion density cavities
Authors: Xu Hui , Su Fu-fang , Kong Xiang-mu , Sun Yu , Jin Rui-ning , Huang Guo-xin , Du Shao-jie
Published: February 2019

Using the one-dimensional Vlasov-Poisson simulation method, the nonlinear cold-electron-plasma oscillations against a fixed periodic ion background are studied. It is shown that a gradual loss of the phase coherence in the excited Langmuir wave dynamics occurs in such plasmas leading to wave-breaking at arbitrary low wave amplitudes. Not only the salient features of a steepening of the electric field gradient and large electron density peaks caused by the presence of the ion cavities have been found but also the change of phase-mixing and burst time with the initial ion density perturbation and electron temperature has been studied. The evolution processes of the electron distributions in phase space, especially the electron distribution at the phase-mixing and burst time, have been studied.
LHCSR3 is a nonphotochemical quencher of both photosystems in
Chlamydomonas reinhardtii
Authors: Girolomoni Laura , Cazzaniga Stefano , Pinnola Alberta , Perozeni Federico , Ballottari Matteo , Bassi Roberto
Published: February 2019

Significance

Photosystems catalyze photosynthetic light absorption and energy conversion, and yet require photoprotection mechanisms for avoiding oxidative damage from excess light absorption. The major short-term mechanism is thermal dissipation of the excitation energy absorbed in excess, called nonphotochemical quenching (NPQ). Although NPQ of photosystem II (PSII) excitons has been extensively investigated, we focus here on NPQ of PSI in the model organism for green algae:
Chlamydomonas reinhardtii
. By analyzing several NPQ and state transition mutants, we show that NPQ occurs within antenna proteins excitonically connected to PSI and is catalyzed by LHCSR (Light Harvesting Complex Stress Related) subunits, with a major role observed for LHCSR3. State transitions have a limited effect in quenching by redistributing Light Harvesting Complexes II, the major target of quenching by LHCSR, between photosystems.
Self-regulation and the
foraging
gene (
PRKG1
) in humans
Authors: Struk Andriy A. , Mugon Jhotisha , Huston Andrea , Scholer Abigail A. , Stadler Gertraud , Higgins E. Tory , Sokolowski Marla B. , Danckert James
Published: February 2019

Significance

We show that different genotypes of the human ortholog of the
foraging
gene,
PRKG1
, were associated with unique patterns of self-regulation. On a virtual foraging task, we show that these self-regulatory profiles also engaged distinct search strategies. One of the genotypes looks remarkably similar, in terms of foraging behavior, to a phenotype described in adult
Drosophila melanogaster
, the fruit fly. This phenotype, known as the sitter, tends to restrict exploration of the environment to local resources, a pattern we replicated in humans.
The changing career trajectories of new parents in STEM
Authors: Cech Erin A. , Blair-Loy Mary
Published: February 2019

Significance

Why are women still underrepresented in science, technology, engineering, and math (STEM) jobs? Social processes beyond individual preferences may shape the STEM employment trajectories of new mothers and new fathers differently. Using representative US longitudinal survey data, we followed full-time STEM professionals after the birth or adoption of their first child. We found substantial attrition of new parents; nearly one-half of new mothers and nearly one-quarter of new fathers leave full-time STEM employment after having children. Thus, parenthood is an important driver of gender imbalance in STEM employment, and both mothers and fathers appear to encounter difficulties reconciling caregiving with STEM careers. These findings have implications for the vitality of the US science and engineering workforce.
Paper-based microfluidics for DNA diagnostics of malaria in low resource underserved rural communities
Authors: Reboud Julien , Xu Gaolian , Garrett Alice , Adriko Moses , Yang Zhugen , Tukahebwa Edridah M. , Rowell Candia , Cooper Jonathan M.
Published: February 2019

Rapid, low-cost, species-specific diagnosis, based upon DNA testing, is becoming important in the treatment of patients with infectious diseases. Here, we demonstrate an innovation that uses origami to enable multiplexed, sensitive assays that rival polymerase chain reactions (PCR) laboratory assays and provide high-quality, fast precision diagnostics for malaria. The paper-based microfluidic technology proposed here combines vertical flow sample-processing steps, including paper folding for whole-blood sample preparation, with an isothermal amplification and a lateral flow detection, incorporating a simple visualization system. Studies were performed in village schools in Uganda with individual diagnoses being completed in <50 min (faster than the standard laboratory-based PCR). The tests, which enabled the diagnosis of malaria species in patients from a finger prick of whole blood, were both highly sensitive and specific, detecting malaria in 98% of infected individuals in a double-blind first-in-human study. Our method was more sensitive than other field-based, benchmark techniques, including optical microscopy and industry standard rapid immunodiagnostic tests, both performed by experienced local healthcare teams (which detected malaria in 86% and 83% of cases, respectively). All assays were independently validated using a real-time double-blinded reference PCR assay. We not only demonstrate that advanced, low-cost DNA-based sensors can be implemented in underserved communities at the point of need but also highlight the challenges associated with developing and implementing new diagnostic technologies in the field, without access to laboratories or infrastructure.
Exceptionally high δ
15
N values in collagen single amino acids confirm Neandertals as high-trophic level carnivores
Authors: Jaouen Klervia , Richards Michael P. , Le Cabec Adeline , Welker Frido , Rendu William , Hublin Jean-Jacques , Soressi Marie , Talamo Sahra
Published: February 2019

Significance

Identifying past hominin diets is a key to understanding adaptation and biological evolution. Bone collagen isotope studies have added much to the discussion of Neandertal subsistence strategies, providing direct measures of diet. Neandertals consistently show very elevated nitrogen isotope values. These values have been seen as the signature of a top-level carnivore diet, but this interpretation was recently challenged by a number of additional theories. We here apply compound-specific isotope analysis of carbon and nitrogen in bone collagen single amino acids of two Neandertals. These Neandertals had the highest nitrogen isotope ratios of bulk collagen measured so far, and our study confirms that these values can be most parsimoniously explained by a carnivorous diet.
Solving matrix equations in one step with cross-point resistive arrays
Authors: Sun Zhong , Pedretti Giacomo , Ambrosi Elia , Bricalli Alessandro , Wang Wei , Ielmini Daniele
Published: February 2019

Significance

Linear algebra is involved in virtually all scientific and engineering disciplines, e.g., physics, statistics, machine learning, and signal processing. Solving matrix equations such as a linear system or an eigenvector equation is accomplished by matrix factorizations or iterative matrix multiplications in conventional computers, which is computationally expensive. In-memory computing with analog resistive memories has shown high efficiencies of time and energy, through realizing matrix-vector multiplication in one step with Ohm’s law and Kirchhoff’s law. However, solving matrix equations in a single operation remains an open challenge. Here, we show that a feedback circuit with cross-point resistive memories can solve algebraic problems such as systems of linear equations, matrix eigenvectors, and differential equations in just one step.
Narrow safety margin in the phyllosphere during thermal extremes
Authors: Pincebourde Sylvain , Casas Jérôme
Published: February 2019

Significance

The thermal limits of terrestrial ectotherms vary more locally than globally. Local microclimatic variations can explain this pattern, but the underlying mechanisms remain unclear. We show that cryptic microclimatic variations at the scale of a single leaf determine the thermal limit in a community of arthropod herbivores living on the same host plant. Herbivores triggering an increase in transpiration, thereby cooling the leaf, had a lower thermal limit than those decreasing leaf transpiration and causing the leaf to warm up. These subtle mechanisms have major consequences for the safety margin of these herbivores during thermal extremes. Our findings suggest that temperate species may be more vulnerable to heat waves than previously thought.
A bacteria-based genetic assay detects prion formation
Authors: Fleming Eleanor , Yuan Andy H. , Heller Danielle M. , Hochschild Ann
Published: February 2019

Significance

Prions are infectious, self-propagating protein aggregates that are best known as the cause of the fatal transmissible spongiform encephalopathies in mammals. Unique among infectious agents because they lack nucleic acid, prions also exist in fungi, where they function as protein-based genetic elements. The recent identification of a bacterial prion-forming protein suggests that bacteria also harbor prions, but genetic tools for detecting prion-like behavior in bacteria are lacking. We describe the development of a bacteria-based genetic assay that reports on prion formation, and we use this assay to present evidence for a second bacterial prion protein, a DNA-binding protein from
Campylobacter hominis
. This genetic assay has the potential to facilitate the investigation of prion-like phenomena in all domains of life.
The social networks and structural variation of Mississippian sociopolitics in the southeastern United States
Authors: Lulewicz Jacob
Published: February 2019

Significance

An alternative approach to the use of sociotypological models in interpreting sociopolitical organization is presented. The development of analytical and conceptual strategies to compare and describe sociopolitical organizations is a cornerstone of anthropological inquiry. This study contributes to such disciplinary foci by presenting a formal, comparative approach to the study of sociopolitics, particularly contributing to discussions of the evolution and development of organizational complexity in small-scale, nonstate societies. Beyond archaeology however, this study demonstrates the value of a deep, historical perspective on the evolution of human networks more broadly and highlights the value of a productive relationship between contemporary social, economic, and political theory and the historical sciences for the investigation of both past and present societies.
Egg-based influenza split virus vaccine with monoglycosylation induces cross-strain protection against influenza virus infections
Authors: Tseng Yung-Chieh , Wu Chia-Yu , Liu Ming-Liang , Chen Ting-Hua , Chiang Wan-Ling , Yu Yueh-Hsiang , Jan Jia-Tsrong , Lin Kuo-I , Wong Chi-Huey , Ma Che
Published: February 2019

Significance

Glycosylation is important for the proper folding and function of glycoproteins. However, glycosylation on viral surface protein may mask the conserved epitopes and causes poor host immune responses and protection against viral infection. To expose more antigenic sites shielded by glycans, we developed a strategy to remove the glycans on the viral surface by modification of the traditional egg-based influenza vaccine production procedure. By means of immunization with the monoglycosylated split virus vaccine, mice were induced with broader immune responses, and thus better protection against cross-strain H1N1 virus infections. The results showed that the monoglycosylated split virus vaccine is a broadly protective vaccine and can be produced through simple modifications of the current vaccine manufacturing process.
Amyloid fibril-directed synthesis of silica core–shell nanofilaments, gels, and aerogels
Authors: Cao Yiping , Bolisetty Sreenath , Wolfisberg Gianna , Adamcik Jozef , Mezzenga Raffaele
Published: February 2019

Significance

Proteinaceous fibrils networks are ubiquitous in nature and span most domains of living matter. Among these, amyloid networks bear a twofold significance, due to their implication in the formation of amyloid plaques and tangles in vivo, but also the remarkable width of applications in which they start to emerge when synthesized in vitro. This work provides a solid strategy to improve the mechanical properties of amyloid networks by biosilicification and demonstrates how the resulting hydrogels can be used for further material design, such as in the fabrication of ultra-high porous aerogels. This contribution also advances our fundamental understanding of complex dynamic networks by introducing a general theoretical model capable of quantitatively capturing the effects of filament bundling on gel rigidity.
AGLF
provides C-function in floral organ identity through transcriptional regulation of
AGAMOUS
in
Medicago truncatula
Authors: Zhao Yang , Liu Rong , Xu Yiteng , Wang Minmin , Zhang Jing , Bai Mingyi , Han Chao , Xiang Fengning , Wang Zeng-Yu , Mysore Kirankumar S. , Wen Jiangqi , Zhou Chuanen
Published: February 2019

Significance

Organogenesis is of great importance in both plant and animal development. Flowers have been studied exclusively to illustrate the mechanism underlying floral organ differentiation, which is controlled by the well-known ABC model. In this study, we identified a MYB-like gene in
Medicago truncatula
,
AGAMOUS-LIKE FLOWER
(
AGLF
), the null mutants of which developed homeotic transformation of stamens and carpel into petals and sepals. The relationships of
AGLF
with conventional ABC genes illustrated by the genetic and expression assays indicate that
AGLF
plays a C-function role in floral organ identity. Our work not only identifies a regulator of C-function genes, but also demonstrates the necessity of exploring the ABC models in other plant species with derived flower patterns.
Synaptic retinoic acid receptor signaling mediates mTOR-dependent metaplasticity that controls hippocampal learning
Authors: Hsu Yu-Tien , Li Jie , Wu Dick , Südhof Thomas C. , Chen Lu
Published: February 2019

Significance

Homeostatic synaptic plasticity has long been considered an anti-Hebbian mechanism that maintains the brain’s network stability, prevents aberrant Hebbian plasticity, and sustains normal cognitive functions. However, evidence supporting this hypothesis is largely lacking. Using region-specific deletions of the retinoic acid receptor RARα, a key mediator of homeostatic synaptic plasticity, we show that experience of an enriched environment (EE) engages homeostatic synaptic plasticity in hippocampal neurons in an RARα-dependent manner. EE experience in mice with deletion of RARα in the hippocampus caused runaway long-term potentiation (LTP), enhanced contextual memory, and reduced cognitive flexibility by hyperactivating mammalian target of rapamycin (mTOR) signaling. Treatment with the mTOR inhibitor rapamycin during an EE experience reversed both runaway LTP and enhanced learning, demonstrating a close functional interaction between Hebbian and homeostatic plasticity.
Anti-BCMA immunotoxins produce durable complete remissions in two mouse myeloma models
Authors: Shancer Zoë , Liu Xiu-fen , Nagata Satoshi , Zhou Qi , Bera Tapan K. , Pastan Ira
Published: February 2019

Significance

Multiple myeloma is a deadly disease for which new therapies are urgently needed. B cell maturation antigen (BCMA) is an excellent target for therapy of myeloma because it is a lineage restricted differentiation protein that is expressed on myeloma cells and plasma cells but not on essential organs. We have produced recombinant immunotoxins that target and kill myeloma cells expressing BCMA. We have examined two mouse models of myeloma and show that the anti-BCMA immunotoxins produce long-term complete regressions in both models. These data support further preclinical development of these agents.
Calcium‐dependent, non‐apoptotic, large plasma membrane bleb formation in physiologically stimulated mast cells and basophils
Authors: Jansen C. , Tobita C , Umemoto E. U. , Starkus J. , Rysavy N. M. , Shimoda L. M. N. , Sung C. , Stokes A.J. , Turner H
Published: February 2019

Large membrane derangements in the form of non‐detaching blebs or membrane protrusions occur in a variety of cell stress and physiological situations and do not always reflect apoptotic processes. They have been studied in model mast cells under conditions of cell stress, but their potential physiological relevance to mast cell function and formation in primary mast cells or basophils have not been addressed. In the current study, we examine the large, non‐detaching, non‐apoptotic, membrane structures that form in model and primary mast cells under conditions of stimulation that are relevant to allergy, atopy and Type IV delayed hypersensitivity reactions. We characterized the inflation kinetics, dependency of formation upon external free calcium and striking geometric consistency of formation for large plasma membrane blebs (LPMBs). We describe that immunologically stimulated LPMBs in mast cells are constrained to form in locations where dissociation of the membrane‐associated cytoskeleton occurs. Mast cell LPMBs decorate with wheat germ agglutinin, suggesting that they contain plasma membrane (PM) lectins. Electrophysiological capacitance measurements support a model where LPMBs are not being formed from internal membranes newly fused into the PM, but rather arise from stretching of the existing membrane, or inflation and smoothing of a micro‐ruffled PM. This study provides new insights into the physiological manifestations of LPMB in response to immunologically relevant stimuli and in the absence of cell stress, death or apoptotic pathways.
Pitfalls associated with lipophilic fluorophore staining of extracellular vesicles for uptake studies
Authors: Simonsen Jens B.
Published: February 2019

Post‐staining of extracellular vesicles (EVs) with lipid‐anchored fluorophores (LAFs) such as PKH67 is a widely used strategy for studying EVs but it is associated with several pitfalls. The pitfalls discussed in this commentary are related to LAF labelling of non‐EV species due to (1) lipoprotein contamination in EV samples, (2) desorption of the LAF reporters from vesicles into proteins and lipoproteins in blood and serum, and (3) the capability of the amphiphilic LAF compounds to form EV‐like particles. Awareness of these challenges and developing solutions to overcome these are important to ensure that we make relevant interpretations when using LAFs to track EVs.
COPII vesicles contribute to autophagosomal membranes
Authors: Shima Takayuki , Kirisako Hiromi , Nakatogawa Hitoshi
Published: February 2019

A hallmark of autophagy is the de novo formation of double-membrane vesicles called autophagosomes, which sequester various cellular constituents for degradation in lysosomes or vacuoles. The membrane dynamics underlying the biogenesis of autophagosomes, including the origin of the autophagosomal membrane, are still elusive. Although previous studies suggested that COPII vesicles are closely associated with autophagosome biogenesis, it remains unclear whether these vesicles serve as a source of the autophagosomal membrane. Using a recently developed COPII vesicle–labeling system in fluorescence and immunoelectron microscopy in the budding yeast Saccharomyces cerevisiae, we show that the transmembrane cargo Axl2 is loaded into COPII vesicles in the ER. Axl2 is then transferred to autophagosome intermediates, ultimately becoming part of autophagosomal membranes. This study provides a definitive answer to a long-standing, fundamental question regarding the mechanisms of autophagosome formation by implicating COPII vesicles as a membrane source for autophagosomes.
A major role for ferroptosis in Mycobacterium tuberculosis–induced cell death and tissue necrosis
Authors: Amaral Eduardo P. , Costa Diego L. , Namasivayam Sivaranjani , Riteau Nicolas , Kamenyeva Olena , Mittereder Lara , Mayer-Barber Katrin D. , Andrade Bruno B. , Sher Alan
Published: February 2019

Necrotic cell death during Mycobacterium tuberculosis (Mtb) infection is considered host detrimental since it facilitates mycobacterial spread. Ferroptosis is a type of regulated necrosis induced by accumulation of free iron and toxic lipid peroxides. We observed that Mtb-induced macrophage necrosis is associated with reduced levels of glutathione and glutathione peroxidase-4 (Gpx4), along with increased free iron, mitochondrial superoxide, and lipid peroxidation, all of which are important hallmarks of ferroptosis. Moreover, necrotic cell death in Mtb-infected macrophage cultures was suppressed by ferrostatin-1 (Fer-1), a well-characterized ferroptosis inhibitor, as well as by iron chelation. Additional experiments in vivo revealed that pulmonary necrosis in acutely infected mice is associated with reduced Gpx4 expression as well as increased lipid peroxidation and is likewise suppressed by Fer-1 treatment. Importantly, Fer-1–treated infected animals also exhibited marked reductions in bacterial load. Together, these findings implicate ferroptosis as a major mechanism of necrosis in Mtb infection and as a target for host-directed therapy of tuberculosis.
On definite lattices bounded by integer surgeries along knots with slice genus at most 2
Authors: Golla Marco , Scaduto Christopher
Published: February 2019

We classify the positive definite intersection forms that arise from smooth 4-manifolds with torsion-free homology bounded by positive integer surgeries on the right-handed trefoil. A similar, slightly less complete classification is given for the

(
2
,
5
)

(2,5)

-torus knot, and analogous results are obtained for integer surgeries on knots of slice genus at most 2. The proofs use input from Yang–Mills instanton gauge theory, Heegaard Floer correction terms, and the topology of singular complex plane curves.
A new class of bell-shaped functions
Authors: Kwaśnicki Mateusz
Published: February 2019

We provide a large class of functions

f
f

that are bell-shaped: the

n
n

th derivative of

f
f

changes its sign exactly

n
n

times. This class is described by means of Stieltjes-type representation of the logarithm of the Fourier transform of

f
f

, and it contains all previously known examples of bell-shaped functions, as well as all extended generalised gamma convolutions, including all density functions of stable distributions. The proof involves representation of

f
f

as the convolution of a Pólya frequency function and a function which is absolutely monotone on

(
−
∞
,
0
)

(-\infty , 0)

and completely monotone on

(
0
,
∞
)

(0, \infty )

. In the final part we disprove three plausible generalisations of our result.
Self-improvement of pointwise Hardy inequality
Authors: Eriksson-Bique Sylvester , Vähäkangas Antti
Published: February 2019

We prove the self-improvement of a pointwise

p
p

-Hardy inequality. The proof relies on maximal function techniques and a characterization of the inequality by curves.
Isoform-specific Ras signaling is growth factor dependent
Authors: Hood Fiona E. , Klinger Bertram , Newlaczyl Anna U. , Sieber Anja , Dorel Mathurin , Oliver Simon P. , Coulson Judy M. , Blüthgen Nils , Prior Ian A.
Published: February 2019

HRAS, NRAS, and KRAS isoforms are almost identical proteins that are ubiquitously expressed and activate a common set of effectors. In vivo studies have revealed that they are not biologically redundant; however, the isoform specificity of Ras signaling remains poorly understood. Using a novel panel of isogenic SW48 cell lines endogenously expressing wild-type or G12V-mutated activated Ras isoforms, we have performed a detailed characterization of endogenous isoform-specific mutant Ras signaling. We find that despite displaying significant Ras activation, the downstream outputs of oncogenic Ras mutants are minimal in the absence of growth factor inputs. The lack of mutant KRAS-induced effector activation observed in SW48 cells appears to be representative of a broad panel of colon cancer cell lines harboring mutant KRAS. For MAP kinase pathway activation in KRAS-mutant cells, the requirement for coincident growth factor stimulation occurs at an early point in the Raf activation cycle. Finally, we find that Ras isoform-specific signaling was highly context dependent and did not conform to the dogma derived from ectopic expression studies.
Outcome-Based Critical Result Thresholds in the Adult Patient Population
Authors: Tan Eng Hooi , Yang Zhutian , Li Yingda , Metz Michael P , Loh Tze Ping
Published: February 2019

Objectives

To derive outcome-based critical result thresholds in the adult patient population.

Methods

We extracted deidentified laboratory results and outcomes (death or discharged) of patients 18 years and older from the Medical Information Mart for Intensive Care database. The lower and upper critical result thresholds were obtained from the nearest minimum and maximum laboratory values, which corresponded to predicted probability of death at 90%.

Results

The critical value thresholds were sodium (<123, >153 mmol/L), potassium (<2.2, >6.6 mmol/L), bicarbonate (<15, >49 mmol/L), chloride (<82, >121 mmol/L), urea (>20 mmol/L), creatinine (>1,052 μmol/L), glucose (<1.5, >23.8 mmol/L), total calcium (<1.62, >2.95 mmol/L), magnesium (<0.37, >1.48 mmol/L), phosphate (<0.19, >2.52 mmol/L), pH (<7.22, >7.57), lactate (>5.0 mmol/L), hemoglobin (<4.6 g/dL), WBCs (>32 × 103/μL), prothrombin time (>90 seconds), and international normalized ratio (>10).

Conclusions

The indirect approach described in this study is a pragmatic way to obtain threshold values that are clinically and operationally meaningful.