julilili42/papers huggingface dataset:
Targeting c-MET by LY2801653 for treatment of cholangiocarcinoma
2016-01-12

Palliative treatment options for human cholangiocarcinoma (CCC) are quite limited and new therapeutic strategies are of utmost need. c-MET has been shown to be deregulated in many cancers, but the role of c-MET in the carcinogenesis of CCC remains unclear. The main purpose of this study is to evaluate the expression and also to investigate the role of c-MET and its effective inhibition for the treatment of CCC. In this study we investigated the effects of LY2801653, a small-molecule inhibitor with potent activity against MET kinase, in human CCC cell lines and in vivo using a xenograft mouse model. We have investigated the role of c-MET and its inhibitory effects on migration, invasion, colony formation, MET downstream targets, and CCC tumor growth. We also analyzed the role of apoptosis and senescence as well as the influence of hypoxia in this context. c-MET and p-MET were expressed in 72% and 12.5% of human CCC tissues and in TFK-1, SZ-1 cell lines. MET inhibition was achieved by blocking phosphorylation of MET with LY2801653 and subsequent down regulation of c-MET downstream targets. Treatment showed in a xenograft model potent anti-tumor activity. LY2801653 is an effective inhibitor and suppress the proliferation of CCC cells as well as the growth of xenograft tumors. Therefore, inhibition of c-MET could be a possible alternative approach for the treatment of human CCC. © 2016 Wiley Periodicals, Inc.
Online Local Input Selection Through Evolving Heterogeneous Fuzzy Inference System
2016-01-12

Recently, online input selection has gained an increasing attention in evolving fuzzy models. In this paper, we proposed a new evolving fuzzy system referred to as evolving heterogeneous fuzzy inference system (eHFIS), which can simultaneously perform local input selection and system identification in an evolving and integrative manner. The introduced eHFIS is structured by some fuzzy rules with different effective input variables. This was achieved through inclusion of some parameters (local input selectors) in the structure of the Takagi-Sugeno system. An online learning algorithm is proposed to identify the eHFIS, where 1) the premise parameter learning and rule evolution take place with the usage of an incremental and evolving clustering for partitioning the data space; 2) a local input selection strategy based on switching to a neighboring model is adopted, and then, all fuzzy rules with the same input structure form a new category; and 3) for each category, the parameters of linear models, in consequent parts, are updated by weighted recursive fuzzily weighted least-squares estimator. The performance of the proposed eHFIS is evaluated and compared through several simulations on hand made as well as real-life datasets.
Eighteenth century Yersinia pestis genomes reveal the long-term persistence of an historical plague focus
2016-01-12

The 14th-18th century pandemic of Yersinia pestis caused devastating disease outbreaks in Europe for almost 400 years. The reasons for plague's persistence and abrupt disappearance in Europe are poorly understood, but could have been due to either the presence of now-extinct plague foci in Europe itself, or successive disease introductions from other locations. Here we present five Y. pestis genomes from one of the last European outbreaks of plague, from 1722 in Marseille, France. The lineage identified has not been found in any extant Y. pestis foci sampled to date, and has its ancestry in strains obtained from victims of the 14th century Black Death. These data suggest the existence of a previously uncharacterized historical plague focus that persisted for at least three centuries. We propose that this disease source may have been responsible for the many resurgences of plague in Europe following the Black Death.
Transfer Learning in Brain-Computer Interfaces Abstract\\uFFFDThe performance of brain-computer interfaces (BCIs) improves with the amount of avail
2016-01-13

The performance of brain-computer interfaces (BCIs) improves with the amount of available training data, the statistical distribution of this data, however, varies across subjects as well as across sessions within individual subjects, limiting the transferability of training data or trained models between them. In this article, we review current transfer learning techniques in BCIs that exploit shared structure between training data of multiple subjects and/or sessions to increase performance. We then present a framework for transfer learning in the context of BCIs that can be applied to any arbitrary feature space, as well as a novel regression estimation method that is specifically designed for the structure of a system based on the electroencephalogram (EEG). We demonstrate the utility of our framework and method on subject-to-subject transfer in a motor-imagery paradigm as well as on session-to-session transfer in one patient diagnosed with amyotrophic lateral sclerosis (ALS), showing that it is able to outperform other comparable methods on an identical dataset.
Ectonucleotidase activity and immunosuppression in astrocyte-CD4 T cell bidirectional signaling
2016-01-13

Astrocytes play a crucial role in neuroinflammation as part of the glia limitans, which regulates infiltration of the brain parenchyma by leukocytes. The signaling pathways and molecular events, which result from the interaction of activated T cells with astrocytes are poorly defined. Here we show that astrocytes promote the expression and enzymatic activity of CD39 and CD73 ectonucleotidases in recently activated CD4 cells by a contact dependent mechanism that is independent of T cell receptor interaction with class II major histocompatibility complex (MHC). Transforming growth factor-β (TGF-β) is robustly upregulated and sufficient to promote ectonucleotidases expression. T cell adhesion to astrocyte results in differentiation to an immunosuppressive phenotype defined by expression of the transcription factor Rorγt, which characterizes the CD4 T helper 17 subset. CD39 activity in T cells in turn inhibits spontaneous calcium oscillations in astrocytes that correlated with enhanced and reduced transcription of CCL2 chemokine and Sonic hedgehog (Shh), respectively. We hypothesize this TCR-independent interaction promote an immunosuppressive program in T cells to control possible brain injury by deregulated T cell activation during neuroinflammation. On the other hand, the increased secretion of CCL2 with concomitant reduction of Shh might promote leukocytes extravasation into the brain parenchyma.
Early-onset familial hemiplegic migraine due to a novel SCN1A mutation
2016-01-14

Introduction Familial hemiplegic migraine (FHM) is a rare autosomal dominant subtype of migraine with aura. The FHM3 subtype is caused by mutations in SCN1A, which is also the most frequent epilepsy gene encoding the voltage-gated Na + channel Na V 1.1. The aim of this study was to explore the clinical, genetic and pathogenetic features of a pure FHM3 family. Methods A three-generation family was enrolled in this study for genetic testing and assessment of clinical features. Whole cell patch-clamp was performed to determine the functions of identified mutant Na V 1.1 channels, which were transiently expressed in human tsA201 cells together with β 1 and β 2 subunits. Results and conclusions We identified a novel SCN1A (p.Leu1624Pro) mutation in a pure FHM family with notably early-onset attacks at mean age of 7. L1624P locates in S3 of domain IV, the same domain as two of four known pure FHM3 mutations. Compared to WT channels, L1624P displayed an increased threshold-near persistent current in addition to other gain-of-function features such as: a slowing of fast inactivation, a positive shift in steady-state inactivation, a faster recovery and higher channel availability during repetitive stimulation. Similar to the known FHM3 mutations, this novel mutation predicts hyperexcitability of GABAergic inhibitory neurons.
Hypercoagulant Abdominal Swabs in Cardiac Surgery: Potential Problems and Background
2016-01-14

<b>Background</b> During cardiac surgery with heart-lung-machine support, abdominal swabs are routinely used to adsorb blood from the operation field. In part, abdominal swabs exhibit procoagulant activity, which is usually considered harmless. However, coagulation induction and abnormal clot formation on the surface of abdominal swabs in the operation field may, if the blood is retransfused into the extracorporeal circuit, lead to severe thromboembolic complications. The aim of the present study was to elucidate the origin of the unexpected blood clotting upon contact with hypercoagulant swabs. <b>Methods</b> The coagulant properties of three abdominal swabs were characterized using a simple clotting test and human whole blood, which was anticoagulated with different heparin concentrations. Eluates prepared from the abdominal swabs and the color stabilizer polydiallyamine (PDAA) were incubated with blood and blood clotting was investigated. Furthermore, the effects of the abdominal swabs on blood clotting time and on heparin were investigated. <b>Results</b> Our data show that the three abdominal swabs as well as the respective eluates exhibit distinctive coagulant properties. The abdominal swab with the highest hypercoagulant effect significantly reduced blood clotting time and also led to a reduction in free heparin. PDAA does not induce activation of the coagulation system. <b>Conclusion</b> The data indicate that the hypercoagulant swab reduces the clotting time and the concentration of free heparin. Abdominal swabs used during complex cardiac surgery with heart-lung-machine support should definitely be tested for their coagulant properties using appropriate tests before clinical applications, as it cannot be specified what leads to their hypercoagulant property.
Information Coding through Adaptive Gating of Synchronized Thalamic Bursting
2016-01-15

It has been posited that the regulation of burst/tonic firing in the thalamus could function as a mechanism for controlling not only how much but what kind of information is conveyed to downstream cortical targets. Yet how this gating mechanism is adaptively modulated on fast timescales by ongoing sensory inputs in rich sensory environments remains unknown. Using single-unit recordings in the rat vibrissa thalamus (VPm), we found that the degree of bottom-up adaptation modulated thalamic burst/tonic firing as well as the synchronization of bursting across the thalamic population along a continuum for which the extremes facilitate detection or discrimination of sensory inputs. Optogenetic control of baseline membrane potential in thalamus further suggests that this regulation may result from an interplay between adaptive changes in thalamic membrane potential and synaptic drive from inputs to thalamus, setting the stage for an intricate control strategy upon which cortical computation is built.
Defect‐Related Luminescence in Nitridoborate Nitride, Mg3Ga(BN2)N2
2016-01-15

Abstract The new nitridoborate nitride Mg 3 Ga(BN 2 )N 2 was prepared by multilateral solid‐state metathesis reaction from MgCl 2 , GaN, Li 3 N, and Li 3 BN 2 at high temperature. The crystal structure of Mg 3 Ga(BN 2 )N 2 was refined from X‐ray powder diffraction patterns isotypically to Mg 3 Al(BN 2 )N 2 with the space group R m no.166 [ Z = 3, a = b = 3.4560(0) Å, c = 31.7924(2) Å]. The undoped and Eu 2+ ‐doped Mg 3 Ga(BN 2 )N 2 show orange‐red luminescence under UV excitation.
The Dyckia sordida complex (Bromeliaceae, Pitcairnioideae) and a new species from Minas Gerais, Brazil
2016-01-15

Dyckia nobilis, a new species of Bromeliaceae (Pitcairnioideae) from the Espinhaço Mountain Range (Minas Gerais, Brazil), is hereby described and illustrated. A summary of information on the species of the Dyckia sordida complex (i.e. D. inflexifolia, D. sordida and D. ursina), to which this new species belongs, is provided, including data on habitat, morphology, etymology as well as a key to the species of this complex. The species are evaluated for their conservation status according to the IUCN criteria.
Multi-omics enrichment analysis using the GeneTrail2 web service
2016-01-18

Abstract Motivation: Gene set analysis has revolutionized the interpretation of high-throughput transcriptomic data. Nowadays, with comprehensive studies that measure multiple -omics from the same sample, powerful tools for the integrative analysis of multi-omics datasets are required. Results: Here, we present GeneTrail2, a web service allowing the integrated analysis of transcriptomic, miRNomic, genomic and proteomic datasets. It offers multiple statistical tests, a large number of predefined reference sets, as well as a comprehensive collection of biological categories and enables direct comparisons between the computed results. We used GeneTrail2 to explore pathogenic mechanisms of Wilms tumors. We not only succeeded in revealing signaling cascades that may contribute to the malignancy of blastemal subtype tumors but also identified potential biomarkers for nephroblastoma with adverse prognosis. The presented use-case demonstrates that GeneTrail2 is well equipped for the integrative analysis of comprehensive -omics data and may help to shed light on complex pathogenic mechanisms in cancer and other diseases. Availability and implementation: GeneTrail2 can be freely accessed under https://genetrail2.bioinf.uni-sb.de. Contact: dstoeckel@bioinf.uni-sb.de Supplementary information: Supplementary data are available at Bioinformatics online.
Economic Hardship and Well-Being: Examining the Relative Role of Individual Resources and Welfare State Effort in Resilience Against Economic Hardship
2016-01-18

Abstract With the aftermath of the economic crisis starting to fold out, the extent and the conditions under which the experience of economic hardship thwarts subjective well-being spark academic interest. In this paper, we examine the cushioning impact of three immaterial buffers embedded within civil society—namely social networks, religiosity, and confidence in politics—in combination with the cushioning role of the welfare state. Analyzing the 2010 wave of the European Social Survey, the results confirm that the experience of economic hardship is inversely related to happiness. All three proposed protective measures cushion the negative impact of economic strain on happiness, whereby the positive effect of social networks and confidence in politics is stronger in countries with lower levels of social expenditure. The latter finding provides some evidence for the crowding out-thesis but mainly suggests that a strong welfare state can take over the role of protective buffers in civil society, which is helpful as such buffers are less present among the most vulnerable social groups. The results of the analysis are discussed in relation to social science research and public policy.
Rule-based analysis of throughfall kinetic energy to evaluate biotic and abiotic factor thresholds to mitigate erosive power
2016-01-18

Below vegetation, throughfall kinetic energy (TKE) is an important factor to express the potential of rainfall to detach soil particles and thus for predicting soil erosion rates. TKE is affected by many biotic (e.g. tree height, leaf area index) and abiotic (e.g. throughfall amount) factors because of changes in rain drop size and velocity. However, studies modelling TKE with a high number of those factors are lacking. This study presents a new approach to model TKE. We used 20 biotic and abiotic factors to evaluate thresholds of those factors that can mitigate TKE and thus decrease soil erosion. Using these thresholds, an optimal set of biotic and abiotic factors was identified to minimize TKE. The model approach combined recursive feature elimination, random forest (RF) variable importance and classification and regression trees (CARTs). TKE was determined using 1405 splash cup measurements during five rainfall events in a subtropical Chinese tree plantation with five-year-old trees in 2013. Our results showed that leaf area, tree height, leaf area index and crown area are the most prominent vegetation traits to model TKE. To reduce TKE, the optimal set of biotic and abiotic factors was a leaf area lower than 6700 mm 2 , a tree height lower than 290 cm combined with a crown base height lower than 60 cm, a leaf area index smaller than 1, more than 47 branches per tree and using single tree species neighbourhoods. Rainfall characteristics, such as amount and duration, further classified high or low TKE. These findings are important for the establishment of forest plantations that aim to minimize soil erosion in young succession stages using TKE modelling.
Freezing of Swallowing
2016-01-18

Abstract View Supplementary Video 1 Background Swallowing deficits and freezing phenomena represent severe parkinsonian features. Freezing as a symptom occurring during swallowing has not been reported on yet. Methods We report on 3 patients with probable PSP ‐parkinsonism ( PSP ‐P) who manifested freezing of swallowing ( FOS ). Results All 3 patients experienced severe weight loss in recent months. At examination, 1 patient had freezing of gait. Video fluoroscopy showed nonfunctional trembling movements of the tongue and palate during chewing and volitional swallowing, with a 6‐ to 8‐Hz frequency that is typical for freezing episodes during walking and finger tapping. These freezing episodes were accompanied by impaired oral bolus transportation. The pharyngeal phase was not relevantly affected. Conclusions FOS represents a novel disease feature of PSP ‐P. The feature may have fundamental, but potentially treatable, consequences for patients' health and quality of life and may be considered in patients with degenerative parkinsonism who experience severe and unexplained weight loss.
Rule-based analysis of throughfall kinetic energy to evaluate biotic and abiotic factor thresholds to mitigate erosive power:
2016-01-18

Below vegetation, throughfall kinetic energy (TKE) is an important factor to express the potential of rainfall to detach soil particles and thus for predicting soil erosion rates. TKE is affected b...
Imaging-based characterization of cardiometabolic phenotypes focusing on whole-body MRI—an approach to disease prevention and personalized treatment
2016-01-18

Metabolic syndrome and cardiovascular disorders pose a challenge to global healthcare systems. Too often, patients with metabolic syndrome are diagnosed in advanced disease stages, where disease-associated damage is irreversible and treatment options are limited. Thus, prevention plays an increasingly important role in the management of cardiometabolic disorders. The main challenge of prevention is to identify patient groups who are at risk for developing overt disease and who might benefit from early therapeutic intervention. In this context, imaging-based phenotyping can add significant information to clinical evaluations, revealing anatomical and physiological changes that reflect intrinsic and extrinsic risk factors. The purpose of this review article was to provide an overview of the current state of imaging-based phenotyping of metabolic syndrome and cardiovascular disorders and to discuss current and potential developments in this field.
Three‐layered radio frequency coil arrangement for sodium MRI of the human brain at 9.4 Tesla
2016-01-18

Purpose A multinuclei imaging setup with the capability to acquire both sodium ( 23 Na) and proton ( 1 H) signals at 9.4 Tesla is presented. The main objective was to optimize coil performance at the 23 Na frequency while still having the ability to acquire satisfactory 1 H images. Methods The setup consisted of a combination of three radio frequency (RF) coils arranged in three layers: the innermost layer was a 27‐channel 23 Na receive helmet which was surrounded by a four‐channel 23 Na transceiver array. The outer layer consisted of a four‐channel 1 H dipole array for B 0 shimming and anatomical localization. Transmit and receive performance of the 23 Na arrays was compared to a single‐tuned 23 Na birdcage resonator. Results While the transmit efficiency of the 23 Na transceiver array was comparable to the birdcage, the 23 Na receive array provided substantial signal‐to‐noise ratio (SNR) gain near the surface and comparable SNR in the center. The utility of this customized setup was demonstrated by 23 Na images of excellent quality. Conclusion High SNR, efficient transmit excitation and B 0 shimming capability can be achieved for 23 Na MRI at 9.4T using novel coil combination. This RF configuration is easily adaptable to other multinuclei applications at ultra high field (≥ 7T). Magn Reson Med 75:906–916, 2016. © 2015 Wiley Periodicals, Inc.
ImmunoPET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo
2016-01-19

Significance Invasive pulmonary aspergillosis (IPA) is a frequently fatal lung disease of immunocompromised patients, and is being increasingly reported in individuals with underlying respiratory diseases. Proven diagnosis of IPA currently relies on lung biopsy and detection of diagnostic biomarkers in serum, or in bronchoalveolar lavage fluids. This study supports the use of immunoPET/MR imaging for the diagnosis of IPA, which is so far not used for diagnosis. The antibody-guided imaging technique allows accurate, noninvasive and rapid detection of fungal lung infection and discrimination of IPA from bacterial lung infections and general inflammatory responses. This work demonstrates the applicability of molecular imaging for IPA detection and its potential for aiding clinical diagnosis and management of the disease in the neutropenic host.
Simulated magnetic field expulsion in neutron star cores
2016-01-19

The study of long-term evolution of neutron star (NS) magnetic fields is key to understanding the rich diversity of NS observations, and to unifying their nature despite the different emission mechanisms and observed properties. Such studies in principle permit a deeper understanding of the most important parameters driving their apparent variety, e.g. radio pulsars, magnetars, X-ray dim isolated NSs, gamma-ray pulsars. We describe, for the first time, the results from self-consistent magnetothermal simulations considering not only the effects of the Hall-driven field dissipation in the crust, but also adding a complete set of proposed driving forces in a superconducting core. We emphasize how each of these core-field processes drive magnetic evolution and affect observables, and show that when all forces are considered together in vectorial form, the net expulsion of core magnetic flux is negligible, and will have no observable effect in the crust (consequently in the observed surface emission) on megayear time-scales. Our new simulations suggest that strong magnetic fields in NS cores (and the signatures on the NS surface) will persist long after the crustal magnetic field has evolved and decayed, due to the weak combined effects of dissipation and expulsion in the stellar core.