bluuebunny/crossref_metadata_2025 huggingface dataset:
Harmine suppresses bladder tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis
Authors: Hai-rong Cai , Xiang Huang , Xiao-rong Zhang
Published: March 2019

Angiogenesis is a vital step during the process of oncogenesis of a lot of tumors, with no exception in bladder cancer. One of the useful strategies for the development of new drugs against cancer is targeting angiogenesis. In the present study, we found that a small-molecule natural product, which belonged to the β-carboline alkaloid, named harmine, could strongly inhibit tumor angiogenesis thus exhibiting its ideal treatment efficacy in bladder cancer. In vivo study verified that harmine had the effect of inhibition on human bladder tumor xenograft growth. The inhibitory effect of harmine to bladder cancer growth was coordinated by the effects shown on angiogenesis. To further explore the pharmacological activities of harmine, we tested harmine’s influence on blood vessel formation and found that harmine effectively blocked the microvessel sprouting in rat aortic ring assay when stimulated by vascular endothelial growth factor (VEGF). Furthermore, harmine inhibited human umbilical vein endothelial cell (HUVEC) proliferation as well as chemotactic motility, and when we treated HUVEC cell with harmine, the formation of capillary-like structures was also restrained. Moreover, harmine induced bladder cancer cell apoptosis through triggering the caspase-dependent apoptotic pathway and the downstream vascular endothelial growth factor receptor 2 (VEGFR2) kinase pathway was down-regulated, thus suppressing tumor development signals. Herein, our study demonstrated that natural product harmine might have potential in curing human bladder tumor because of its pharmacological function on tumor angiogenesis, trigged by VEGFR2 signaling pathways.
Machine Learning Approaches to Analyze Speech-Evoked Neurophysiological Responses
Authors: Xie Zilong , Reetzke Rachel , Chandrasekaran Bharath
Published: March 2019

Purpose

Speech-evoked neurophysiological responses are often collected to answer clinically and theoretically driven questions concerning speech and language processing. Here, we highlight the practical application of machine learning (ML)–based approaches to analyzing speech-evoked neurophysiological responses.

Method

Two categories of ML-based approaches are introduced: decoding models, which generate a speech stimulus output using the features from the neurophysiological responses, and encoding models, which use speech stimulus features to predict neurophysiological responses. In this review, we focus on (a) a decoding model classification approach, wherein speech-evoked neurophysiological responses are classified as belonging to 1 of a finite set of possible speech events (e.g., phonological categories), and (b) an encoding model temporal response function approach, which quantifies the transformation of a speech stimulus feature to continuous neural activity.

Results

We illustrate the utility of the classification approach to analyze early electroencephalographic (EEG) responses to Mandarin lexical tone categories from a traditional experimental design, and to classify EEG responses to English phonemes evoked by natural continuous speech (i.e., an audiobook) into phonological categories (plosive, fricative, nasal, and vowel). We also demonstrate the utility of temporal response function to predict EEG responses to natural continuous speech from acoustic features. Neural metrics from the 3 examples all exhibit statistically significant effects at the individual level.

Conclusion

We propose that ML-based approaches can complement traditional analysis approaches to analyze neurophysiological responses to speech signals and provide a deeper understanding of natural speech and language processing using ecologically valid paradigms in both typical and clinical populations.
Functional Logistic Mixed-Effects Models for Learning Curves From Longitudinal Binary Data
Authors: Paulon Giorgio , Reetzke Rachel , Chandrasekaran Bharath , Sarkar Abhra
Published: March 2019

Purpose

We present functional logistic mixed-effects models (FLMEMs) for estimating population and individual-level learning curves in longitudinal experiments.

Method

Using functional analysis tools in a Bayesian hierarchical framework, the FLMEM captures nonlinear, smoothly varying learning curves, appropriately accommodating uncertainty in various aspects of the analysis while also borrowing information across different model layers. An R package implementing our method is available as part of theSupplemental Materials.

Results

Application to speech learning data fromReetzke, Xie, Llanos, and Chandrasekaran (2018)and a simulation study demonstrate the utility of FLMEM and its many advantages over linear and logistic mixed-effects models.

Conclusion

The FLMEM is highly flexible and efficient in improving upon the practical limitations of linear models and logistic linear mixed-effects models. We expect the FLMEM to be a useful addition to the speech, language, and hearing scientist's toolkit.

Supplemental Material

https://doi.org/10.23641/asha.7822568
The Heterogeneity of Word Learning Biases in Late-Talking Children
Authors: Perry Lynn K. , Kucker Sarah C.
Published: March 2019

Purpose

The particular statistical approach researchers choose is intimately connected to the way they conceptualize their questions, which, in turn, can influence the conclusions they draw. One particularly salient area in which statistics influence our conclusions is in the context of atypical development. Traditional statistical approaches such as
t
tests or analysis of variance lend themselves to a focus on group differences, downplaying the heterogeneity that exists within so many atypically developing populations. Understanding such variability is important—classification of what a disorder is, an individual's diagnosis, and whether or not a child receives intervention all directly relate to an accurate classification of the disorder and individual's abilities compared to their typically developing peers.

Method

Here, we use word learning biases (i.e., shape and material biases) in late-talking children as a sample case and employ a variety of statistical approaches to compare the conclusions those approaches might warrant.

Results

We argue that advanced statistical approaches, such as mixed-effects regression, can help us make sense of heterogeneity and are more consistent with a modern dimensional view of language disorders.

Conclusions

Accurate characterization of late-talking children (and others at risk for delays) and their prognoses is necessary for accurate diagnosis and implementation of appropriate target interventions. It therefore requires rigorous statistical analyses that can capture and allow for interpretation of the heterogeneity inherent in populations with language delays and disorders.
Solar activity: periodicities beyond 11 years are consistent with random forcing
Authors: Cameron R. H. , Schüssler M.
Published: March 2019

Power spectra of solar activity based on historical records of sunspot numbers and on cosmogenic isotopes show peaks with enhanced power apart from the dominant 11-year solar cycle, such as the 90-year Gleissberg cycle or the 210-year de Vries cycle. In a previous paper we have shown that the overall shape of the power spectrum is well represented by the results of the generic normal form model for a noisy and weakly nonlinear limit cycle, with parameters all determined by observations. Using this model as a null case, we show here that all local peaks with enhanced power, apart from the 11-year band, are consistent with realization noise. Even a 3σ peak is expected to occur with a probability of about 0.25 at least once among the 216 period bins resolved by the cosmogenic isotope data. This casts doubt upon interpretations of such peaks in terms of intrinsic periodicities of the solar dynamo process.
Fast magnetoacoustic wave trains with time-dependent drivers
Authors: Goddard C. R. , Nakariakov V. M. , Pascoe D. J.
Published: March 2019

Context. Frequent observations of quasi-periodic rapidly-propagating wave trains in coronal structures have been made in the last decade. The dispersive evolution of fast magnetohydrodynamic waves propagating in coronal waveguides can provide a physical interpretation for many of these observations.

Aims. Previous studies have considered the generation of fast wave trains by impulsive drivers which deposit energy instantaneously. The signatures of dispersively formed wave trains must depend on the temporal nature of the driver. We investigate the effect of varying the temporal width of the driving perturbation.

Methods. 2D magnetohydrodynamic numerical simulations of impulsively generated wave trains in a guiding field-aligned density enhancement were performed with the novel addition of a time-dependant driver.

Results. The final spatial and spectral signatures of the guided wave trains are found to depend strongly on the temporal duration of the initial perturbation. In particular, the wavelength (or frequency) of highest spectral amplitude is found to increase (decrease) with increasing temporal duration, whereas the spectral width decreases. Additionally, the efficiency of generation of fast wave trains is found to decrease strongly with increasing temporal width of the driver, with a cut-off at twice the internal Alfvén crossing time.
Study of off-axis current drive using EC top-launch in KSTAR
Authors: Bae Young-soon
Published: March 2019

The off-axis current drive using electron cyclotron (EC) wave is typically very low due to the low density and temperature and electron trapping effect when it is launched from outside midplane. However, the heating and current drive by EC wave is being regarded as a essential element as an off-axis current drive source together with lower hybrid current drive (LHCD) for advanced tokamak operation research in KSTAR in future. Therefore, the reliable and high efficient ECCD using top launch has been studied for two different launch schemes of down-shift and up-shift resonance with various EC frequencies which will be available in the future KSTAR ECRH system. The ray tracing (GENRAY) simulation studies show that a broad ECCD profile peaked off axis is obtained with a high current drive efficiency for both schemes. It is almost twice as high as that of the outside midplane launch for the fundamental O-mode EC wave.
Design and development of the ITER CTS diagnostic
Authors: Korsholm Søren B. , Gonçalves Bruno , Gutierrez Heidi E. , Henriques Elsa , Infante Virginia , Jensen Thomas , Jessen Martin , Klinkby Esben B. , Larsen Axel W. , Leipold Frank , Lopes André , Luis Raul , Naulin Volker , Nielsen Stefan K. , Nonbøl Erik , Rasmussen Jesper , Salewski Mirko , Stejner Morten , Taormina Arianna , Vale Alberto , Vidal Catarina , Sanchez Laura , Ballester Raul M. , Udintsev Victor
Published: March 2019

The Collective Thomson Scattering (CTS) diagnostic will be a primary diagnostic for measuring the dynamics of the confined fusion born alpha particles in ITER and will be the only diagnostic for alphas below 1.7 MeV [1]. The probe beam of the CTS diagnostic comes from a 60 GHz 1 MW gyrotron operated in a ~100 Hz modulation sequence. In the plasma, the probing beam will be scattered off fluctuations primarily due to the dynamics of the ions. Seven fixed receiver mirrors will pick up scattered radiation (the CTS signal) from seven measurement volumes along the probe beam covering the cross section of the plasma. The diagnostic is planned to provide a temporal resolution of ~100 ms and a spatial resolution of ~a/4 in the core and ~a/20 near the plasma edge where a = 2.0 m is the nominal minor radius of ITER. The front-end quasi-optics will be installed in an equatorial port plug (EPP#12). A particular challenge will be to pass the probing beam through the fundamental electron cyclotron resonance, which is located in the port plug (R=10.3 m) for the nominal magnetic field Bt = 5.3 T. Hence, particular mitigation actions against arcing have to be applied. The status of the design and specific challenges will be discussed.
Development of ECE/ECEI diagnostics and MHD-related studies on HL-2A tokamak
Authors: Yang Z.C. , Jiang M. , Shi Z.B. , Ding X.T. , Luhmann N.C. , Zhong W.L. , Chen W. , Shi P.W. , Xu Y. , Wen J. , Liang A.S. , Liu Y. , Yang Q.W. ,   HL-2A team
Published: March 2019

A novel 60-channel electron cyclotron emission (ECE) radiometer has been designed and tested for the measurement of electron temperature profiles on the HL-2A tokamak. This system is based on the intermediate frequency division technique, and has the features of wide working frequency range (60−90 GHz) and high temporal-spatial resolution (3 µs, 1 cm), which covers almost the entire plasma region. Also, an electron cyclotron emission imaging (ECEI) system has been developed for studying two dimensional electron temperature fluctuations. It is comprised of several front-end quasi-optical lenses, a 24 channel heterodyne imaging array with a tunable RF frequency range spanning 60−135 GHz, and a set of back-end ECEI electronics that together generate two 24×8 array images of the 2nd harmonic X-mode electron cyclotron emission from the HL-2A plasma. The measurement region can be flexibly shifted due to two independent local oscillator sources, and the field of view can be adjusted easily by changing the position of the zoom lenses as well. The temporal resolution is about 2.5 µs and the achievable spatial resolution is 1 cm. The ECE/ECEI diagnostics have been demonstrated to be powerful tools to study MHD-related physics including the multi-scale interaction between macro-scale MHD and micro-scale turbulence on the HL-2A tokamak.
Developments towards 1MW Gyrotron Test Facility at ITER-India
Authors: Rathod Vipal , Dilip E. Sharan , Shah Ronak , Mandge Deepak , Yadav Amit , Sharma Anjali , Parmar Rajvi , Singh N.P. , Rao S.L.
Published: March 2019

ITER-India, the Indian domestic agency for the ITER project, has the responsibility to supply a set of two high power Gyrotron sources (1 MW, 170 GHz, 3600 s) along with the auxiliary systems for Electron Cyclotron Heating & Current Drive applications. For such high power Gyrotron systems, one of the challenging areas is the system integration and establishment of reliable integrated system performance. ITER-India plans to establish the integrated Gyrotron system performance that essentially meets the ITER requirements in a Gyrotron Test Facility which is specifically being developed at ITER-India. This paper discusses about the recent updates towards the Test Facility development which includes, development of cost effective & modular Body Power Supply (BPS), Industrial grade prototype interlock & protection modules, a Gyrotron field simulator and cooling water distribution system.
Schematherapie
Authors: Schupp Tobias
Published: March 2019

Bei der Zusammenarbeit mit Borderline-Patienten kann die Schematherapie eine
große Hilfe sein. Mit der empathischen Unterstützung der Pflegenden soll der
Patient eine gute Eltern-Kind-Beziehung erleben. Wir stellen die Therapieform
vor und erläutern, wie damit die gesunden Anteile des Patienten gestärkt werden
können.
Wound Healing Potential of the Standardized Extract of Boswellia serrata on Experimental Diabetic Foot Ulcer via Inhibition of Inflammatory, Angiogenetic and Apoptotic Markers
Authors: Pengzong Zhang , Yuanmin Li , Xiaoming Xiong , Shang Deng , Wei Xiong , Zhigang Lang , Dongzhou Du , Wenjing Yu , Jianbiao Yue , Yang Xiang , Xia Li
Published: March 2019

The aim of the present study was to evaluate the wound healing potential and possible mechanism of action of the standardized extract of Boswellia serrata against the experimental model of diabetic foot ulcer. α-Boswellic acid was isolated from the standardized extract of B. serrata and characterized (HPLC, 1H-NMR, 13C-NMR, ESI-MS). Diabetes was induced in Sprague-Dawley rats by streptozotocin (55 mg/kg, i. p.), and wounds were created on the dorsal surface of the hind paw. B. serrata (100, 200, and 400 mg/kg, p. o.) was administered to the rats for 16 days. The HPLC analysis showed a single peak with a retention time of 12.51 min. The compound was identified with ESI-MS [M + Na]+ = 455.37 as α-boswellic acid. Treatment with B. serrata (200 and 400 mg/kg) significantly increased the rate of wound contraction via modulation of oxido-nitrosative stress and elevated the hydroxyproline level at the wound area. reverse transcription-PCR analysis revealed that streptozotocin-induced increases in TNF-α, interleukin-1β, interleukin-6, nuclear factor-kappa-light-chain-enhancer of activated B cells, and Bcl-2-associated X protein, and decreases in angiopoietin-1, Tie2, transforming growth factor beta 1, vascular endothelial growth factor, and collagen-1 mRNA expression were significantly inhibited by B. serrata. It also significantly reduced wound cellular necrosis as evaluated by flow cytometry using propidium iodide fluorescence intensity. Streptozotocin-induced histopathological alterations were also significantly ameliorated by B. serrata. In conclusion, standardized extracts of B. serrata exert its wound healing potential via orchestrating mechanisms, which include the inhibition of oxido-inflammatory markers (oxido-nitrosative stress, TNF-α, interleukins, and nuclear factor-kappa-light-chain-enhancer of activated B cells), increased collagen synthesis (hydroxyproline and collagen-1) and angiogenesis (Ang-1/Tie2), promoting growth factors (transforming growth factor beta 1 and vascular endothelial growth factor), and inhibition of apoptosis (Bcl-2-associated X protein) to accelerate wound healing in experimental delayed diabetic foot ulcer.
Novel Targets in the Immune Microenvironment of the Hepatic Sinusoids for Treating Liver Diseases
Authors: Patten Daniel , Shepherd Emma , Weston Christopher , Shetty Shishir
Published: March 2019

Immune dysregulation and accumulation of leukocytes is a hallmark of adult chronic liver diseases. Progressive hepatic inflammation can lead to fibrosis and cirrhosis with a high risk of liver failure or hepatocellular cancer (HCC). Recent advances have been made in the treatment of liver disease including the development of highly effective antiviral therapy for hepatitis C and the potential of immunotherapy for HCC. Despite this, the majority of other chronic liver diseases including alcoholic liver disease, fatty liver disease, and cholestatic diseases do not respond to conventional anti-inflammatory therapies. Recent studies defining the organ-specific properties that contribute to resident immune activation and immune cell recruitment from the circulation in these conditions have identified novel hepatic inflammatory pathways, which are now being targeted in clinical trials. Further understanding of how the immune microenvironment is regulated within the liver and how disease-specific mechanisms alter this process will hopefully lead to combination therapies to prevent aberrant inflammation and also promote fibrosis resolution. In this review, we focus on the advances that have been made in identifying key components of the inflammatory pathway including the recognition of danger signals, the recruitment and retention of lymphocytes from the circulation, and the pathways that promote resolution.
Detection and analysis of laser driven proton beams by calibrated Gafchromic HD-V2 and MD-V3 radiochromic films
Authors: Xu X. H. , Liao Q. , Wu M. J. , Geng Y. X. , Li D. Y. , Zhu J. G. , Li C. C. , Hu R. H. , Shou Y. R. , Chen Y. H. , Lu H. Y. , Ma W. J. , Zhao Y. Y. , Zhu K. , Lin C. , Yan X. Q.
Published: March 2019

The radiochromic film (RCF) is a high-dose, high-dynamic range dosimetry detection medium. A stack of RCFs can be used to detect both spatial and energetic distribution of laser driven ion beams with a large divergence angle and continuous energy spectrum. Two types of RCFs (HD-V2 and MD-V3, from Radiation Products Design, Inc.) have been calibrated using MeV energy protons and carbon ions produced by using a 2 × 6 MV tandem electrostatic accelerator. The proportional relationship is obtained between the optical density and the irradiation dose. For protons, the responses are consistent at all energies with a variation of about 15%. For carbon ions, the responses are energy related, which should be noted for heavy ion detection. Based on the calibration, the broad energy spectrum and charge distribution of laser accelerated proton beam with energy from 3 to 8 MeV and pC charge were detected and reconstructed at the Compact LAser Plasma Accelerator at Peking University.
Performance analysis and optimization of a hybrid renewable energy system for sustainable NEOM city in Saudi Arabia
Authors: Awan Ahmed Bilal
Published: March 2019

This work aims to design and evaluate the performance of a Hybrid Renewable Energy System (HRES) for the newly proposed grand city NEOM in Saudi Arabia. The average value of wind speed and Global Horizontal Irradiance at the proposed location are 4.86 m/s and 6.43 kWh/m2 per day, respectively. The various mixtures and sizes of photovoltaic (PV) arrays, wind turbines, power converters, diesel generators, and batteries are evaluated to find out the optimal system configuration to meet the required peak load of 1353 kW. The recommended HRES is optimized for the minimum net present cost (NPC). The electrical power, economic, and greenhouse gas emission analyses of the optimized HRES architecture are performed. Finally, a detailed sensitivity analysis is carried out to determine the impact of uncertainties in diesel cost and renewable resource variations on various system architectures, NPC, and CO2 emissions. The optimal system consists of two generators 500 kW and 1 MW, one V82 wind turbine (1.65 MW), a 100 kW PV, a 200 kW converter, and 100 batteries. The NPC of the optimal HRES is US$8.13 million, which is US$0.6 million less than the NPC of the diesel-only system. The cost of energy of the proposed HRES is found to be 0.164 US$/kWh as compared to 0.176 US$/kWh from the diesel-only system. Emission analysis shows a 46.5% reduction in CO2 emissions.
Critical behavior and magnetocaloric effect in La0.7Ba0.25Nd0.05Mn1-xCuxO3
Authors: Manh T. V. , Shinde K. P. , Nanto D. , Lin H. , Pham Y. , Razaq D. S. , Munazat D. R. , Kurniawan Budhy , Yu S. C. , Chung K. C. , Kim D. H.
Published: March 2019

In this work, the magnetic and magnetocaloric properties of La0.7Ba0.25Nd0.05Mn1-xCuxO3 samples (x = 0 - 0.07) synthesized by the sol-gel method are presented. The compounds exhibited a second-order phase transition (SOPT) of ferromagnetic-paramagnetic (FM-PM) phase transition following Banerjee’s criterion. Curie temperature TC decreased with increasing doping concentration. The critical behavior analysis using modified Arrott plots (MAP) showed a short-range FM ordering. Significant entropy change of samples was observed near the TC, which decreased with Cu content. The SOPT nature of compounds was confirmed by both the universal curves and scaling hypothesis.
Integration of a rapid scanning technique into THz time-domain spectrometers for nonlinear THz spectroscopy measurements
Authors: Hoberg C. , Balzerowski P. , Havenith M.
Published: March 2019

We have implemented a rapid scanning technique into THz time-domain spectrometers using an oscillating frictionless delay line, especially adapted for nonlinear THz experiments. Thereby we were able to increase the dynamic range of THz measurements in the frequency range from 40 to 200 cm-1 by up to 24 dB and reduce the scanning time by up to a factor of 200. We report here test measurements on TDS-setups at repetition rates of 80 MHz and 5 kHz. The dynamic range exceeds 64 dB, which allows to record even small changes in the THz absorption upon optical excitation by a THz probe, covering the frequency range of the intermolecular modes and the phonon bands. We demonstrate the potential of this technique for optical-pump THz-probe experiments using a 70 μm thick high-resistivity silicon, excited by 400 nm, ∼50 fs pulses as a sample.
Transferability of the SRP32-vdW specific reaction parameter functional to CHD3 dissociation on Pt(110)-(2 × 1)
Authors: Chadwick Helen , Gutiérrez-González Ana , Beck Rainer D. , Kroes Geert-Jan
Published: March 2019

Stepped transition metal surfaces, including the reconstructed Pt(110)-(2 × 1) surface, can be used to model the effect of line defects on catalysts. We present a combined experimental and theoretical study of CHD3 dissociation on this surface. Theoretical predictions for the initial sticking coefficients, S0, are obtained from ab initio molecular dynamics calculations using the specific reaction parameter (SRP) approach to density functional (DF) theory, while the measured sticking coefficients were obtained using the King and Wells method. The SRP DF used here had been previously derived for methane dissociation on Pt(111) so that the experiments test the transferability of this SRP DF to methane + Pt(110)-(2 × 1). The agreement between the experimental and calculated S0 is poor, with the average energy shift between the theoretical and measured reactivities being 20 kJ/mol. There are two factors which may contribute to this difference, the first of which is that there is a large uncertainty in the calculated sticking coefficients due to a large number of molecules being trapped on the surface at the end of the 1 ps propagation time. The second is that the SRP32-vdW functional may not accurately describe the Pt(110)-(2 × 1) surface. At the lowest incident energies considered here, Pt(110)-(2 × 1) is more reactive than the flat Pt(111) surface, but the situation is reversed at incident energies above 100 kJ/mol.
Enhanced on-chip terahertz sensing with hybrid metasurface/lithium niobate structures
Authors: Wang Ride , Wu Qiang , Zhang Yaqing , Xu Xitan , Zhang Qi , Zhao Wenjuan , Zhang Bin , Cai Wei , Yao Jianghong , Xu Jingjun
Published: March 2019

Recognizing special molecules is crucial in many biochemical processes, and thus, highly enhanced sensing methods are in high demand. In this work, we designed a microrod array metasurface with a SiO2-loaded subwavelength lithium niobate waveguide as a unique platform for enhanced experimental fingerprint detection of lactose. The metasurface could lead to strong surface wave modes due to the near-field coupling of the spoof localized surface plasmon, which also could provide a stronger interaction length between light and matter. The selectivity was remarkable in the transmission spectrum at an intrinsic characteristic frequency of 0.529 THz with a thin layer of lactose, while it was faint while transmitting terahertz (THz) waves normally through a lactose layer of the same thickness. Together with the ability to freely design the shape of the metasurface and the electromagnetic properties, we believe that this platform can function as an elegant on-chip-scale enhanced THz sensing platform.
Structural and mutational analyses of psychrophilic and mesophilic adenylate kinases highlight the role of hydrophobic interactions in protein thermal stability
Authors: Moon Sojin , Kim Junhyung , Koo Jasung , Bae Euiyoung
Published: March 2019

Protein thermal stability is an important field since thermally stable proteins are desirable in many academic and industrial settings. Information on protein thermal stabilization can be obtained by comparing homologous proteins from organisms living at distinct temperatures. Here, we report structural and mutational analyses of adenylate kinases (AKs) from psychrophilic Bacillus globisporus (AKp) and mesophilic Bacillus subtilis (AKm). Sequence and structural comparison showed suboptimal hydrophobic packing around Thr26 in the CORE domain of AKp, which was replaced with an Ile residue in AKm. Mutations that improved hydrophobicity of the Thr residue increased the thermal stability of the psychrophilic AKp, and the largest stabilization was observed for a Thr-to-Ile substitution. Furthermore, a reverse Ile-to-Thr mutation in the mesophilic AKm significantly decreased thermal stability. We determined the crystal structures of mutant AKs to confirm the impact of the residue substitutions on the overall stability. Taken together, our results provide a structural basis for the stability difference between psychrophilic and mesophilic AK homologues and highlight the role of hydrophobic interactions in protein thermal stability.
Cu-Zn disorder in stoichiometric and non-stoichiometric Cu2ZnSnS4/Cu2ZnSnSe4
Authors: Zheng Yi-Feng , Yang Ji-Hui , Gong Xin-Gao
Published: March 2019

Cu-Zn disorder is unavoidable but plays an important role in high-efficiency Cu2ZnSnS4 and Cu2ZnSnSe4 solar cells. Using the cluster expansion method along with Monte Carlo (MC) simulations, we study the Cu-Zn disorder, considering cases both with and without vacancies. We find that the 2a, 2c, and 2d Wyckoff sites all show order-disorder transitions for both cases, in agreement with recent experiments supporting disorder at all 2a, 2c and 2d sites, but, in contrast to early experiments, supporting Cu-Zn disorder only at 2c and 2d sites. Below the transition temperature in non-stoichiometric cases, we find that excess Zn prefers to occupy 2c over 2a sites due to the greater similarity of 2c sites to 2d sites. Such site preferences indicate that Cu-Zn occupations exhibit some new kind of ordering rather than randomly distributed at 2a and 2c sites. We find that while Cu-Zn disorder reduces the band gap, the site preferences in non-stoichiometric samples increase the band gaps by suppressing Cu-Zn disorder. Generally, lowering annealing temperatures, while increasing Zn and vacancies, will lead to larger band gaps.
Scattering of charged particles in quantum plasmas: Zero energy resonances
Authors: Karmakar Akashdip , Ghoshal Arijit
Published: March 2019

The scattering of charged particles in quantum plasmas (QPs) has been investigated by employing a fully quantum mechanical treatment within the framework of the Schwinger variational principle in the momentum space. The effective potential in QP has been described by a modified Debye-Huckel potential. Scattering phase shifts for various plasma screening strengths have been obtained accurately by a convergent scheme of the Schwinger variational method. The accuracy of the results has been corroborated by solving the corresponding Schrodinger equation with accurate numerical techniques. The nature of scattering for a wide range of plasma screening has been studied. The role of quantum mechanical effects in plasma is examined by comparing the results in QP with the corresponding results in classical weakly coupled plasma for which effective potential has been described by Debye-Huckel potential. Special emphasis has been made to study the dynamics at low energies. In particular, a detailed investigation has been made on the zero-energy resonance phenomenon.
Long-range magnetic ordering in rocksalt-type high-entropy oxides
Authors: Jimenez-Segura Marco Polo , Takayama Tomohiro , Bérardan David , Hoser Andreas , Reehuis Manfred , Takagi Hidenori , Dragoe Nita
Published: March 2019

We report the magnetic properties of Mg0.2Co0.2Ni0.2Cu0.2Zn0.2O, a high-entropy oxide with a rocksalt structure, and the influence of substitutions on these properties. From the magnetic susceptibility and neutron diffraction measurements, we found that this compound exhibits long-range magnetic order below 120 K despite the substantial structural disorder. Other rocksalt-type high-entropy oxides with various chemical substitutions were found to host either an antiferromagnetic order or spin-glass state depending on the amount of magnetic ions. The presence of magnetic order for such a disordered material potentially provides a route to explore exotic magnetic properties and functions.
Mitigating a global expansion of toxic cyanobacterial blooms: confounding effects and challenges posed by climate change
Authors: Paerl Hans W. , Havens Karl. E. , Hall Nathan. S , Otten Timothy G. , Zhu Mengyuan , Xu Hai , Zhu Guangwei , Qin Boqiang
Published: March 2019

Managing and mitigating the global expansion of toxic cyanobacterial harmful algal blooms (CyanoHABs) is a major challenge facing researchers and water resource managers. Various approaches, including nutrient load reduction, artificial mixing and flushing, omnivorous fish removal, algaecide applications and sediment dredging, have been used to reduce bloom occurrences. However, managers now face the additional challenge of having to address the effects of climate change on watershed hydrological and nutrient load dynamics, water temperature, mixing regime and internal nutrient cycling. Rising temperatures and increasing frequencies and magnitudes of extreme weather events, including tropical cyclones, extratropical storms, floods and droughts, all promote CyanoHABs and affect the efficacy of ecosystem remediation measures. These climatic changes will likely require setting stricter nutrient (including both nitrogen and phosphorus) reduction targets for bloom control in affected waters. In addition, the efficacy of currently used methods to reduce CyanoHABs will need to be re-evaluated in light of the synergistic effects of climate change with nutrient enrichment.
Improved sperm motility after 4 h of ejaculatory abstinence: role of accessory sex gland secretions
Authors: Goss Dale , Ayad Bashir , van der Horst Gerhard , Skosana Bongekile , du Plessis Stefan S.
Published: March 2019

Various studies have sought to determine the typical v. optimal abstinence period after which semen samples should be collected, with many contradictory results reported. Several factors influence the semen microenvironment, and thus sperm parameters. In this study we focused on the secretions of the prostate, seminal vesicles and the epididymis. Semen samples were obtained from healthy normozoospermic males (n=16) after 4-day and 4-h periods of ejaculatory abstinence, and standard semen analysis was performed using computer-aided sperm analysis, whereas seminal plasma citric acid, neutral α-glucosidase and fructose concentrations were measured using assay kits. There were significant decreases in total sperm count (P<0.001), sperm concentration (P<0.05) and semen volume (P<0.05) after 4h compared with 4 days ejaculatory abstinence. Furthermore, increases were observed in total sperm motility (P<0.05) and sperm progressive motility (P<0.01) after a 4-h abstinence period, accompanied by significant reductions in citric acid (P<0.05), α-glucosidase (P<0.01) and fructose (P<0.01) concentrations. In addition, due to the decreased number of spermatozoa, these concentrations translated to a significant decrease in fructose (P<0.05) per spermatozoon, indicating an intrinsic mechanism capitalising on alternative sources of energy for increased metabolic function and subsequent sperm motility.
Assessing health reform: studying tool appropriateness & critical capacities
Authors: Bali Azad Singh , Ramesh M
Published: March 2019

The past two decades have witnessed unprecedented policy effort to improve access to medical services and strengthen financial protection from catastrophic healthcare expenditure. Despite billions of dollars in health spending, many – especially across the developing world – continue to remain vulnerable to financial impoverishment. What accounts for this poor performance? To respond to this question, we turn to the design literature in public policy, which emphasises the role of policy tools or combination of tools in addressing a social problem. In this paper, we focus on two inter-related aspects of the design orientation to explain outcomes: a) the appropriateness of the policy tool and b) the capacity of government agencies. We apply a framework, which integrates vital questions on both these aspects along three common dimensions (analytical, operational and political) to assess healthcare reforms in India and Thailand. The case studies illustrate the importance of both these aspects of the design orientation in explaining outcomes, and show how they are commonly overlooked in the health and social policy literatures, and in reforms underway.
Artificial versus Substantial Gauge Symmetries: A Criterion and an Application to the Electroweak Model
Authors: François Jordan
Published: March 2019

To systematically answer the generalized Kretschmann objection, I propose a mean to make operational a criterion widely recognized as allowing one to decide whether the gauge symmetry of a theory is artificial or substantial. My proposition is based on the dressing field method of gauge symmetry reduction, a new simple tool from mathematical physics. This general scheme allows one in particular to straightforwardly argue that the notion of spontaneous symmetry breaking is superfluous to the empirical success of the electroweak theory. Important questions regarding the context of justification of the theory then arise.
Natural Selection and Contrastive Explanation
Authors: Witteveen Joeri
Published: March 2019

This article defends the Negative View of natural selection explanation, according to which natural selection cannot explain of any given individual why it has the traits it does. Over the years, this view has been criticized on empirical, metaphysical, and explanatory grounds. I review the debate and offer additional reasons for rejecting the empirical and metaphysical objections. The explanatory objection, which holds that the Negative View is rooted in a flawed account of contrastive explanation, initially seems plausible. However, I argue that a closer consideration of the desiderata of contrastive explanation shows that this objection fails as well.
Stochastic Stability and Disagreements between Dynamics
Authors: Mohseni Aydin
Published: March 2019

The replicator dynamics and Moran process are the main deterministic and stochastic models of evolutionary game theory. The models are connected by a mean-field relationship—the former describes the expected behavior of the latter. However, there are conditions under which their predictions diverge. I demonstrate that the divergence between their predictions is a function of standard techniques used in their analysis and of differences in the idealizations involved in each. My analysis reveals problems for stochastic stability analysis in a broad class of games, demonstrates a novel domain of agreement between the dynamics, and indicates a broader moral for evolutionary modeling.
Thermal block of action potentials is primarily due to voltage-dependent potassium currents: a modeling study
Authors: Ganguly Mohit , Jenkins Michael W , Jansen E Duco , Chiel Hillel J
Published: March 2019

Objective. Thermal block of action potential conduction using infrared lasers is a new modality for manipulating neural activity. It could be used for analysis of the nervous system and for therapeutic applications. We sought to understand the mechanisms of thermal block. Approach. To analyze the mechanisms of thermal block, we studied both the original Hodgkin/Huxley model, and a version modified to more accurately match experimental data on thermal responses in the squid giant axon. Main results. Both the original and modified models suggested that thermal block, especially at higher temperatures, is primarily due to a depolarization-activated hyperpolarization as increased temperature leads to faster activation of voltage-gated potassium ion channels. The minimum length needed to block an axon scaled with the square root of the axon’s diameter. Significance. The results suggest that voltage-dependent potassium ion channels play a major role in thermal block, and that relatively short lengths of axon could be thermally manipulated to selectively block fine, unmyelinated axons, such as C fibers, that carry pain and other sensory information.
Slumped posture on chest X-ray—association with mortality and length of hospital stay in older hospitalised patients
Authors: Lloyd Aled , Thomas Elin , Haboubi Hasan
Published: March 2019

Introduction

frail, older patients are occasionally incapable of keeping their head out of the field of view of a chest radiograph (CXR) resulting in a ‘slumpogram’. This study aims to explore a possible link between a slumped appearance on a CXR; mortality and length of hospital stay.

Methods

the CXRs of patients aged over 65 admitted to a Health Board with a catchment area of approximately 300,000 were investigated in a retrospective analysis of all CXRs taken during the first week of January 2015. Slumped patients were compared to age matched controls. The degree of slumping was measured by the number of ribs covered and the MA/C factor (the shortest distance between the angle of the mandible and a line drawn between the heads of both acromion divided by the length of the patient’s clavicle). Outcomes investigated included length of hospital stay and 18-month mortality.

Results

806 CXRs were viewed with 53 slumped patients and 53 matched controls identified. In all patients aged over 65 there was a statistically significant correlation between the length of stay and the number of ribs covered by the patients’ head (P = 0.038). The MA/C factor was also associated with length of stay (P = 0.025). In patients over 80 there was a significant association between the number of ribs covered and death (P = 0.015).

Conclusion

a slumped CXR may be associated with longer hospitalisation or death. The results of this small study require further revalidation but if true could help inform clinical decision making.
Developing a Spatial Navigation Screening Tool Sensitive to the Preclinical Alzheimer Disease Continuum
Authors: Allison Samantha L , Rodebaugh Thomas L , Johnston Chiharu , Fagan Anne M , Morris John C , Head Denise
Published: March 2019

Objective

There remains a need for a non-invasive and cost-effective screening measure that could be administered prior to the provision of a lumbar puncture or positron emission tomography scan for the detection of preclinical Alzheimer disease (AD). Previous findings suggest that a hippocampally-based spatial navigation task may be effective for screening individuals for the preclinical AD continuum (i.e., low cerebrospinal fluid (CSF) Aβ42). Unfortunately, this task took 1.5–2 hours to administer, which would be time-prohibitive in a clinical setting. Therefore, the goal of this study was to compare psychometric properties of six spatial navigation-related tasks in order to take the next steps in developing a clinically appropriate screening measure.

Methods

Psychometric properties (i.e., reliability, diagnostic accuracy, validity) of a modified version of the cognitive mapping task, two binding tasks, a visual perspective taking task, and self- and informant report versions of a questionnaire were examined in a sample of 91 clinically normal (CN) individuals. CSF Aβ42 and ptau181 were available for 30 individuals.

Results

The learning phase of the cognitive mapping task and the self-report questionnaire were sensitive to identifying individuals in the preclinical AD continuum (93% and 87% sensitivity, 60% and 67% specificity, respectively). These two measures also demonstrated good test-retest stability (intraclass correlation coefficients = .719 and .838, respectively) and internal consistency (Cronbach’s αs = .825 and .965, respectively).

Conclusions

These findings suggest that a self-report questionnaire and aspects of a cognitive mapping task may be particularly appropriate for development as screening tools for identifying individuals in the preclinical AD continuum.
Permutation-based simultaneous confidence bounds for the false discovery proportion
Authors: Hemerik J , Solari A , Goeman J J
Published: March 2019

When multiple hypotheses are tested, interest is often in ensuring that the proportion of false discoveries is small with high confidence. In this paper, confidence upper bounds for the false discovery proportion are constructed, which are simultaneous over all rejection cut-offs. In particular, this allows the user to select a set of hypotheses post hoc such that the false discovery proportion lies below some constant with high confidence. Our method uses permutations to account for the dependence structure in the data. So far only Meinshausen (2006) has developed an exact, permutation-based and computationally feasible method for obtaining simultaneous false discovery proportion bounds. We propose an exact method which uniformly improves that procedure. Further, we provide a generalization of the method that lets the user select the shape of the simultaneous confidence bounds; this gives the user more freedom in determining the power properties of the method. Interestingly, several existing permutation methods, such as significance analysis of microarrays and the maxT method of Westfall & Young (1993), are obtained as special cases.
A Brief Overview of HPLC–MS Analysis of Alkyl Methylphosphonic Acid Degradation Products of Nerve Agents
Authors: B’Hymer Clayton
Published: March 2019

The analysis of degradation products from the classic chemical warfare nerve agents by high-performance liquid chromatography–mass spectrometry has been of much interest in recent years owing to the possible use as a terrorist weapon, and the incidents of chemical weapon usage in recent years in war torn countries. The alkyl methylphosphonic acid degradation products are of a particular interest, and they represent a specific chromatographic technical challenge for use in typical separation systems. Various published methods are summarized in this review and some of the problems associated with the analysis of these compounds are discussed. Future trends of the analysis in this area of research are also considered.
2019 EACTS Expert Consensus on long-term mechanical circulatory support
Authors: Potapov Evgenij V , Antonides Christiaan , Crespo-Leiro Maria G , Combes Alain , Färber Gloria , Hannan Margaret M , Kukucka Marian , de Jonge Nicolaas , Loforte Antonio , Lund Lars H , Mohacsi Paul , Morshuis Michiel , Netuka Ivan , Özbaran Mustafa , Pappalardo Federico , Scandroglio Anna Mara , Schweiger Martin , Tsui Steven , Zimpfer Daniel , Gustafsson Finn
Published: March 2019

Long-term mechanical circulatory support (LT-MCS) is an important treatment modality for patients with severe heart failure. Different devices are available, and many—sometimes contradictory—observations regarding patient selection, surgical techniques, perioperative management and follow-up have been published. With the growing expertise in this field, the European Association for Cardio-Thoracic Surgery (EACTS) recognized a need for a structured multidisciplinary consensus about the approach to patients with LT-MCS. However, the evidence published so far is insufficient to allow for generation of meaningful guidelines complying with EACTS requirements. Instead, the EACTS presents an expert opinion in the LT-MCS field. This expert opinion addresses patient evaluation and preoperative optimization as well as management of cardiac and non-cardiac comorbidities. Further, extensive operative implantation techniques are summarized and evaluated by leading experts, depending on both patient characteristics and device selection. The faculty recognized that postoperative management is multidisciplinary and includes aspects of intensive care unit stay, rehabilitation, ambulatory care, myocardial recovery and end-of-life care and mirrored this fact in this paper. Additionally, the opinions of experts on diagnosis and management of adverse events including bleeding, cerebrovascular accidents and device malfunction are presented. In this expert consensus, the evidence for the complete management from patient selection to end-of-life care is carefully reviewed with the aim of guiding clinicians in optimizing management of patients considered for or supported by an LT-MCS device.