bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnetic-Field-Induced Suppression of Jahn-Teller Phonon Bands in (La0.6Pr0.4)0.7Ca0.3MnO3: the Mechanism of Colossal Magnetoresistance shown by Raman Spectroscopy
Authors: Merten S. , Shapoval O. , Damaschke B. , Samwer K. , Moshnyaga V. 
Published: February 2019

AbstractA long-standing issue in the physics of the colossal magnetoresistance is the role of electron-phonon coupling, which manifests itself as Jahn-Teller polarons. The origin and architecture of polarons makes it possible to study their behavior by Raman spectroscopy, which allows to analyze the polaronic behavior in an applied magnetic field. We performed magnetic-field-dependent Raman spectroscopy on thin films of (La0.6Pr0.4)0.7Ca0.3MnO3 in a range of H = 0–50 kOe and compared the obtained Raman spectra with the magnetic field behavior of the electrical resistivity. In the vicinity of the Curie temperature, TC = 197 K, the intensity of the Jahn-Teller stretching mode at 614 cm−1 and of the bending mode at 443 cm−1 was found to be suppressed and enhanced, respectively. This observed behavior has a remarkable similarity with the field and temperature dependence of the colossal magnetoresistance in (La0.6Pr0.4)0.7Ca0.3MnO3. Our work provides direct evidence that the reduction of the amount of Jahn-Teller polarons at the phase transition is the main mechanism underlying the colossal magnetoresistance.
The impact of proliferation-migration tradeoffs on phenotypic evolution in cancer
Authors: Gallaher Jill A. , Brown Joel S. , Anderson Alexander R. A. 
Published: February 2019

AbstractTumors are not static masses of cells but dynamic ecosystems where cancer cells experience constant turnover and evolve fitness-enhancing phenotypes. Selection for different phenotypes may vary with (1) the tumor niche (edge or core), (2) cell turnover rates, (3) the nature of the tradeoff between traits, and (4) whether deaths occur in response to demographic or environmental stochasticity. Using a spatially-explicit agent-based model, we observe how two traits (proliferation rate and migration speed) evolve under different tradeoff conditions with different turnover rates. Migration rate is favored over proliferation at the tumor’s edge and vice-versa for the interior. Increasing cell turnover rates slightly slows tumor growth but accelerates the rate of evolution for both proliferation and migration. The absence of a tradeoff favors ever higher values for proliferation and migration, while a convex tradeoff tends to favor proliferation, often promoting the coexistence of a generalist and specialist phenotype. A concave tradeoff favors migration at low death rates, but switches to proliferation at higher death rates. Mortality via demographic stochasticity favors proliferation, and environmental stochasticity favors migration. While all of these diverse factors contribute to the ecology, heterogeneity, and evolution of a tumor, their effects may be predictable and empirically accessible.
Natural ligand-nonmimetic inhibitors of the lipid-transfer protein CERT
Authors: Nakao Naoki , Ueno Masaharu , Sakai Shota , Egawa Daichi , Hanzawa Hiroyuki , Kawasaki Shohei , Kumagai Keigo , Suzuki Makoto , Kobayashi Shu , Hanada Kentaro 
Published: February 2019

AbstractLipid transfer proteins mediate inter-organelle transport of membrane lipids at organelle contact sites in cells, playing fundamental roles in the lipidome and membrane biogenesis in eukaryotes. We previously developed a ceramide-mimetic compound as a potent inhibitor of the ceramide transport protein CERT. Here we develop CERT inhibitors with structures unrelated to ceramide. To this aim, we identify a seed compound with no ceramide-like structure but with the capability of forming a hydrogen-bonding network in the ceramide-binding START domain, by virtual screening of ~3 × 106 compounds. We also establish a surface plasmon resonance-based system to directly determine the affinity of compounds for the START domain. Then, we subject the seed compound to a series of in silico docking simulations, efficient chemical synthesis, affinity analysis, protein-ligand co-crystallography, and various in vivo assays. This strategy allows us to obtain ceramide-unrelated compounds that potently inhibited the function of CERT in human cultured cells.
Bone morphogenetic protein-7 retards cell subculture-induced senescence of human nucleus pulposus cells through activating the PI3K/Akt pathway
Authors: Gong Chen , Pan Wei , Hu Wei , Chen Liang 
Published: February 2019

Abstract
Background: Allogeneic disc cell is the main cellular resource in tissue engineering (TE)-based strategy to retard disc degeneration. However, the accessible disc cells often exhibit senescent phenotype when they are subcultured in vitro. Hence, alleviating senescence of human disc cells during cell subculture is important for TE-based strategy to regenerate degenerative disc tissue. Objective: The present study was aimed to investigate whether bone morphogenetic protein-7 (BMP-7) can alleviate subculture-induced senescence of human nucleus pulposus (NP) cells in vitro. Methods: NP cells from human disc tissue were subcultured in vitro for six passages. Exogenous BMP-7 was added along with the culture medium to investigate its effects on senescence of NP cells. The inhibitor LY294002 was used to investigate the role of the PI3K/Akt pathway. Results: Compared with the human disc NP cells cultured in the baseline culture medium, addition of BMP-7 increased cell proliferation potency and telomerase activity, decreased senescence-associated β-galactosidase (SA-β-Gal) activity and G0/G1 phase fraction, and down-regulated the expression of p16 and p53. Moreover, these positive effects of BMP-7 against senescence of human disc NP cells coincided with activation of the PI3K/Akt pathway. Further analysis showed that inhibitor LY294002 partly inhibited these protective effects of BMP-7 against senescence of human disc NP cells. Conclusion: BMP-7 alleviates subculture-induced senescence of human disc NP cells through activating the PI3K/Akt pathway. The present study provides new knowledge on allogeneic disc NP cell-based TE strategy to regenerate degenerative human disc tissue.
Providing Services to Individuals With Complex Communication Needs in the Inpatient Rehabilitation Setting: The Experiences and Perspectives of Speech-Language Pathologists
Authors: Gormley Jessica , Light Janice 
Published: February 2019

Purpose
To guide the development of future trainings in the inpatient rehabilitation setting, this study aimed to expand the current understanding of (a) the experiences of speech-language pathologists (SLPs) who work in inpatient rehabilitation settings when providing augmentative and alternative communication (AAC) services to individuals with complex communication needs and (b) the challenges and facilitating factors related to AAC services within this context.

Method
An online focus group was used to explore experiences of 11 SLPs who work within the inpatient rehabilitation setting. Information was gathered about (a) the role of the inpatient SLP in AAC service delivery, (b) rehabilitation team service delivery, (c) successes and challenges to supporting individuals with complex communication needs within this setting, and (d) communication training opportunities.

Results
Themes that emerged related to (a) the complicated logistics of rehabilitation; (b) the centrality of the rehabilitation team; (c) the limited AAC tools, knowledge, and trainings for rehabilitation providers; and (d) SLPs’ attitudes. Participants reported navigating complicated logistics unique to the inpatient rehabilitation related to time constraints, limited AAC funding, the continuum of rehabilitation care, and limited AAC policies in attempting to meet patient needs. Generally, participants suggested successful team collaboration, yet limited time, expertise, tools, and training opportunities challenged attempts to support individuals with complex communication needs.

Conclusions
Increased access to AAC tools and the development of AAC trainings are recommended to equip rehabilitation professionals with skills to build interprofessional and AAC skills so patients with complex communication needs can maximally participate in the rehabilitation experience.

Supplemental Material

https://doi.org/10.23641/asha.7728710
Künstliche Intelligenz und Maschinelles
Lernen
Authors: Hahn Peter 
Published: February 2019

ZusammenfassungMaschinelles Lernen (ML), ein Teilbereich der Künstlichen Intelligenz, ist die
Fähigkeit von Computer-Algorithmen, Wissen aus Beispielen zu lernen, ohne dafür
explizit programmiert zu sein und dieses Wissen dann auf unbekannte Fälle
anzuwenden. Die Anwendung von ML in der Medizin wird in den nächsten Jahren
exponentiell zunehmen. Ärzte sollten daher über die prinzipiellen Arten von ML
sowie den Prozess des ML grundlegende Kenntnisse haben. Denn nur so ist es
möglich, ML optimal zu nutzen und die Grenzen und Probleme des Verfahrens zu
erkennen.
Priming of microglia with IFN-γ slows neuronal gamma oscillations in situ
Authors: Ta Thuy-Truc , Dikmen Hasan Onur , Schilling Simone , Chausse Bruno , Lewen Andrea , Hollnagel Jan-Oliver , Kann Oliver 
Published: February 2019

SignificancePriming with classic lymphocyte cytokine, interferon-gamma (IFN-γ) is crucial during the complex activation process of tissue macrophages, such as microglia in the CNS, under pathological conditions. According to current biological concepts, priming permits an exaggerated macrophage immune response given a secondary inflammatory stimulus like bacterial components occurs. Here, we demonstrate that priming with IFN-γ itself induces proliferation and moderate activation of microglia, including up-regulation of inducible nitric oxide synthase (iNOS). Importantly, the concomitant moderate release of nitric oxide (NO) is sufficient to disturb fast neuronal network oscillations (30–70 Hz) that underlie higher brain functions, such as perception, attention, and memory. This mechanism might contribute to early cognitive impairment in chronic brain disorders, such as multiple sclerosis and Alzheimer’s disease.
School English, literature and the knowledge‐base question
Authors: Yates Lyn , Davies Larissa McLean , Buzacott Lucy , Doecke Brenton , Mead Philip , Sawyer Wayne 
Published: February 2019

AbstractThis article takes up questions about knowledge and the school curriculum with respect to literary studies within subject English. Its intention is to focus on literary studies in English from the context of current waves of curriculum reform, rather than as part of the conversations primarily within the field of English, to raise questions about the knowledge agenda, and the knowledge‐base agenda for teaching and teacher education. The selection of texts and form of study of literature within the English curriculum has long been an area of controversy. Without assuming a particular position on knowledge in this area, this article shows that important questions of what knowledge‐base teachers are expected to bring to their work are elided both in current regulations and debates, and in research on ‘good teaching’ in this area. If ‘literary studies’ (as a discipline or university major) is itself an unstable and changing field, what kind of knowledge does a good English teacher bring to their work? This paper takes up these questions in the context of the Australian Curriculum and standards for teacher registration, but it also points to the way these issues about knowledge are of broader relevance for researchers and teacher education.
The TMCrys server for supporting crystallization of transmembrane proteins
Authors: Varga Julia K , Tusnády Gábor E 
Published: February 2019

Abstract

Motivation
Due to their special properties, the structures of transmembrane proteins are extremely hard to determine. Several methods exist to predict the propensity of successful completion of the structure determination process. However, available predictors incorporate data of any kind of proteins, hence they can hardly differentiate between crystallizable and non-crystallizable membrane proteins.

Results
We implemented a web server to simplify running TMCrys prediction method that was developed specifically to separate crystallizable and non-crystallizable membrane proteins.

Availability and implementation
http://tmcrys.enzim.ttk.mta.hu

Supplementary information
Supplementary data are available at Bioinformatics online.
Brain annotation toolbox: exploring the functional and genetic associations of neuroimaging results
Authors: Liu Zhaowen , Rolls Edmund T , Liu Zhi , Zhang Kai , Yang Ming , Du Jingnan , Gong Weikang , Cheng Wei , Dai Fei , Wang He , Ugurbil Kamil , Zhang Jie , Feng Jianfeng 
Published: February 2019

Abstract

Motivation
Advances in neuroimaging and sequencing techniques provide an unprecedented opportunity to map the function of brain regions and identify the roots of psychiatric diseases. However, the results from most neuroimaging studies, i.e. activated clusters/regions or functional connectivities between brain regions, frequently cannot be conveniently and systematically interpreted, rendering the biological meaning unclear.

Results
We describe a brain annotation toolbox that generates functional and genetic annotations for neuroimaging results. The voxel-level functional description from the Neurosynth database and gene expression profile from the Allen Human Brain Atlas are used to generate functional/genetic information for region-level neuroimaging results. The validity of the approach is demonstrated by showing that the functional and genetic annotations for specific brain regions are consistent with each other; and further the region by region functional similarity network and genetic similarity network are highly correlated for major brain atlases. One application of brain annotation toolbox is to help provide functional/genetic annotations for newly discovered regions with unknown functions, e.g. the 97 new regions identified in the Human Connectome Project. Importantly, this toolbox can help understand differences between psychiatric patients and controls, and this is demonstrated using schizophrenia and autism data, for which the functional and genetic annotations for the neuroimaging changes in patients are consistent with each other and help interpret the results.

Availability and implementation
BAT is implemented as a free and open-source MATLAB toolbox and is publicly available at http://123.56.224.61:1313/post/bat.

Supplementary information
Supplementary data are available at Bioinformatics online.
Use of avoidance behaviours to reduce the economic impacts of the EU Landing Obligation: the case study of a mixed trawl fishery
Authors: Pointin Fabien , Daurès Fabienne , Rochet Marie-Joëlle 
Published: February 2019

Abstract
The EU Landing Obligation (LO) is designed to reduce bycatch (i.e. unwanted catch) through more selective fishing practices, such as avoidance behaviours which consist in allocating fishing effort to other species, fishing grounds or seasons. Incentives for fishers to change their behaviours depend on their economic performances as well as their ability to avoid bycatch. Changes in economic performances under the LO are evaluated based on cost and revenue equations. The nested grid method is then used to explore the spatial and temporal distribution of landings and discards, and to suggest alternative effort allocation to avoid bycatch. This article is focussed specifically on the French otter trawl fishery in the eastern English Channel and southern North Sea. Results suggest that under the LO the choke species problem will curtail fishing activities earlier in the year, leading to significant economic losses. In the absence of significant quota top-ups (at least 75%), a change in fishing practices consisting in reducing overall bycatch by 30% is insufficient to reduce losses. With a particular attention to choke species, more economically efficient avoidance strategies can be found thanks to the nested grid method.
Mechanistic Interplay Between Autophagy and Apoptotic Signaling in Endosulfan-Induced Dopaminergic Neurotoxicity: Relevance to the Adverse Outcome Pathway in Pesticide Neurotoxicity
Authors: Song Chunjuan , Charli Adhithiya , Luo Jie , Riaz Zainab , Jin Huajun , Anantharam Vellareddy , Kanthasamy Arthi , Kanthasamy Anumantha G 
Published: February 2019

AbstractChronic exposure to pesticides is implicated in the etiopathogenesis of Parkinson’s disease (PD). Previously, we showed that dieldrin induces dopaminergic neurotoxicity by activating a cascade of apoptotic signaling pathways in experimental models of PD. Here, we systematically investigated endosulfan’s effect on the interplay between apoptosis and autophagy in dopaminergic neuronal cell models of PD. Exposing N27 dopaminergic neuronal cells to endosulfan rapidly induced autophagy, indicated by an increased number of autophagosomes and LC3-II accumulation. Prolonged endosulfan exposure (>9 h) triggered apoptotic signaling, including caspase-2 and -3 activation and protein kinase C delta (PKCδ) proteolytic activation, ultimately leading to cell death, thus demonstrating that autophagy precedes apoptosis during endosulfan neurotoxicity. Furthermore, inhibiting autophagy with wortmannin, a phosphoinositide 3-kinase inhibitor, potentiated endosulfan-induced apoptosis, suggesting that autophagy is an early protective response against endosulfan. Additionally, Beclin-1, a major regulator of autophagy, was cleaved during the initiation of apoptotic cell death, and the cleavage was predominantly mediated by caspase-2. Also, caspase-2 and caspase-3 inhibitors effectively blocked endosulfan-induced apoptotic cell death. CRISPR/Cas9-based stable knockdown of PKCδ significantly attenuated endosulfan-induced caspase-3 activation, indicating that the kinase serves as a regulatory switch for apoptosis. Additional studies in primary mesencephalic neuronal cultures confirmed endosulfan’s effect on autophagy and neuronal degeneration. Collectively, our results demonstrate that a functional interplay between autophagy and apoptosis dictate pesticide-induced neurodegenerative processes in dopaminergic neuronal cells. Our study provides insight into cell death mechanisms in environmentally linked neurodegenerative diseases.
SANTA-SIM: simulating viral sequence evolution dynamics under selection and recombination
Authors: Jariani Abbas , Warth Christopher , Deforche Koen , Libin Pieter , Drummond Alexei J , Rambaut Andrew , Matsen IV Frederick A , Theys Kristof 
Published: February 2019

Abstract
Simulations are widely used to provide expectations and predictive distributions under known conditions against which to compare empirical data. Such simulations are also invaluable for testing and comparing the behaviour and power of inference methods. We describe SANTA-SIM, a software package to simulate the evolution of a population of gene sequences forwards through time. It models the underlying biological processes as discrete components: replication, recombination, point mutations, insertion–deletions, and selection under various fitness models and population size dynamics. The software is designed to be intuitive to work with for a wide range of users and executable in a cross-platform manner.
Recombinant production and purification of the human protein Tau
Authors: Ferrari Luca , Rüdiger Stefan G.D. 
Published: February 2019

ABSTRACTTau protein is a microtubule-stabilizing protein whose aggregation is linked to Alzheimer’s Disease and other forms of dementia. Tau biology is at the heart of cytoskeletal dynamics and neurodegenerative mechanisms, making it a crucial protein to study. Tau purification, however, is challenging as Tau is disordered, which makes it difficult to produce in recombinant system and is degradation-prone. It is thus challenging to obtain pure and stable preparations of Tau. Here, we present a fast and robust protocol to purify Tau recombinantly in Escherichia coli. Our protocol allows purifyig Tau either tag-less free or FLAG-tagged at its N-terminus. By exploiting a cleavable affinity tag and two anion exchange columns, we obtained Tau is of high purity, stable and suitable for in vitro studies, including aggregation experiments that resemble neurodegenerative processes.
Computational tool to study perturbations in muscle regulation and its application to heart disease
Authors: Barrick Samantha K. , Clippinger Sarah R. , Greenberg Lina , Greenberg Michael J. 
Published: February 2019

AbstractStriated muscle contraction occurs when myosin thick filaments bind to thin filaments in the sarcomere and generate pulling forces. This process is regulated by calcium, and it can be perturbed by pathological conditions (e.g., myopathies), physiological adaptations (e.g., β-adrenergic stimulation), and pharmacological interventions. Therefore, it is important to have a methodology to robustly determine the mechanism of these perturbations and statistically evaluate their effects. Here, we present an approach to measure the equilibrium constants that govern muscle activation, estimate uncertainty in these parameters, and statistically test the effects of perturbations. We provide a MATLAB-based computational tool for these analyses, along with easy-to-follow tutorials that make this approach accessible. The hypothesis testing and error estimation approaches described here are broadly applicable, and the provided tools work with other types of data, including cellular measurements. To demonstrate the utility of the approach, we apply it to determine the biophysical mechanism of a mutation that causes familial hypertrophic cardiomyopathy. This approach is generally useful for studying the mechanisms of muscle diseases and therapeutic interventions that target muscle contraction.
Nonlinear diversification rates of linguistic phylogenies over the Holocene
Authors: Hamilton Marcus J , Walker Robert S. 
Published: February 2019

AbstractThe expansion of the human species out of Africa in the Pleistocene, and the subsequent development of agriculture in the Holocene resulted in waves of linguistic diversification and replacement across the planet. Analogous to the growth of populations or the speciation of biological organisms, languages diversify over time to form phylogenies of language families. However, the dynamics of this diversification process are unclear. Bayesian methods applied to lexical and phonetic data have created dated linguistic phylogenies for 18 language families encompassing ∼3,000 of the world’s ∼7,000 extant languages. In this paper we use these phylogenies to quantify how fast languages expand and diversify through time both within and across language families. The overall diversification rate of languages in our sample is ∼0.001 yr-1(or a doubling time of ∼700 yr) over the last 6,000 years with evidence for nonlinear dynamics in language diversification rates over time, where both within and across language families, diversity initially increases rapidly and then slows. The large-scale replacement of the world’s hunter-gatherer languages by agricultural languages over the Holocene was a non-constant process.