bluuebunny/crossref_metadata_2025_split huggingface dataset:
FAK and Pyk2 activity promote TNF-α and IL-1β-mediated pro-inflammatory gene expression and vascular inflammation
Authors: Murphy James M. , Jeong Kyuho , Rodriguez Yelitza A. R. , Kim Jung-Hyun , Ahn Eun-Young Erin , Lim Ssang-Taek Steve 
Published: May 2019

AbstractProtein tyrosine kinase (PTK) activity has been implicated in pro-inflammatory gene expression following tumor necrosis factor-α (TNF-α) or interkeukin-1β (IL-1β) stimulation. However, the identity of responsible PTK(s) in cytokine signaling have not been elucidated. To evaluate which PTK is critical to promote the cytokine-induced inflammatory cell adhesion molecule (CAM) expression including VCAM-1, ICAM-1, and E-selectin in human aortic endothelial cells (HAoECs), we have tested pharmacological inhibitors of major PTKs: Src and the focal adhesion kinase (FAK) family kinases - FAK and proline-rich tyrosine kinase (Pyk2). We found that a dual inhibitor of FAK/Pyk2 (PF-271) most effectively reduced all three CAMs upon TNF-α or IL-1β stimulation compared to FAK or Src specific inhibitors (PF-228 or Dasatinib), which inhibited only VCAM-1 expression.In vitroinflammation assays showed PF-271 reduced monocyte attachment and transmigration on HAoECs. Furthermore, FAK/Pyk2 activity was not limited to CAM expression but was also required for expression of various pro-inflammatory molecules including MCP-1 and IP-10. Both TNF-α and IL-1β signaling requires FAK/Pyk2 activity to activate ERK and JNK MAPKs leading to inflammatory gene expression. Knockdown of either FAK or Pyk2 reduced TNF-α-stimulated ERK and JNK activation and CAM expression, suggesting that activation of ERK or JNK is specific through FAK and Pyk2. Finally, FAK/Pyk2 activity is required for VCAM-1 expression and macrophage recruitment to the vessel wall in a carotid ligation model inApoE−/− mice. Our findings define critical roles of FAK/Pyk2 in mediating inflammatory cytokine signaling and implicate FAK/Pyk2 inhibitors as potential therapeutic agents to treat vascular inflammatory disease such as atherosclerosis.
Social noise interferes with learning in a volatile environment
Authors: Shin Dong Woo , Kim Jaejoong , Jeong Bumseok , Kim Ko Woon , Shim Geumsook , Yoon Taekeun 
Published: May 2019

AbstractTo learn through feedback, feedback should be reliable. However, if feedback is blurred by irrelevant social information, learning in a volatile environment, which requires fast learning and adaptation, might be disturbed. In this study, we investigated how feedback with social noise interferes with learning in a volatile environment by designing a probabilistic associative learning task in which the association probability changes dynamically, and the outcome was randomly blurred by an emotional face with incongruent valence. Learning in this situation was modelled by HGF-S such that emotionally incongruent feedback induces perceptual uncertainty called social noise. The Bayesian model comparison showed that the HGF-S model explains the subjects’ behaviour well, and the simulation showed that social noise interrupts both learning the association probability and the volatility. Furthermore, the learning interruption influenced the subsequent decision. Finally, we found that the individual difference in how the same emotionally incongruent feedback induces social noise in varying degrees was related to the differences in event-related desynchronization induced by happy and sad faces in the right anterior insula, which encodes the degree of emotional feeling. These results advance our understanding of how feedback with emotional interference affects learning.
Ranking Regions, Edges and Classifying Tasks in Functional Brain Graphs by Sub-Graph Entropy
Authors: Sen Bhaskar , Chu Shu-Hsien , Parhi Keshab K. 
Published: May 2019

AbstractThis paper considers analysis of human brain networks or graphs constructed from time-series collected from functional magnetic resonance imaging (fMRI). In the network of time-series, the nodes describe the regions and the edge weights correspond to the absolute values of correlation coefficients of the time-series of the two nodes associated with the edges. The paper introduces a novel information-theoretic metric, referred assub-graphentropy, to measure uncertainty associated with asub-graph. Nodes and edges constitute two special cases ofsub-graphstructures. Node and edge entropies are used in this paper to rank regions and edges in a functional brain network. The paper analyzes task-fMRI data collected from 475 subjects in the Human Connectome Project (HCP) study for gambling and emotion tasks. The proposed approach is used to rank regions and edges associated with these tasks. Thedifferentialnode (edge) entropy metric is defined as the difference of the node (edge) entropy corresponding to two different networks belonging to two different classes. Differential entropy of nodes and edges are used to rank top regions and edges associated with the two classes of data. Using top node and edge entropy features separately, two-class classifiers are designed using support vector machine (SVM) with radial basis function (RBF) kernel and leave-one-out method to classify time-series for emotion taskvs.no-task, gambling taskvs.no-task and emotion taskvs. gambling task. Using node entropies, the SVM classifier achieves classification accuracies of 0.96, 0.97 and 0.98, respectively. Using edge entropies, the classifier achieves classification accuracies of 0.91, 0.96 and 0.94, respectively.
FABP1 controls hepatic transport and biotransformation of Δ9-THC
Authors: Elmes Matthew W. , Prentis Lauren E. , McGoldrick Luke L. , Giuliano Christopher J. , Sweeney Joseph M. , Joseph Olivia M. , Che Joyce , Carbonetti Gregory S. , Studholme Keith , Deutsch Dale G. , Rizzo Robert C. , Glynn Steven E. , Kaczocha Martin 
Published: May 2019

AbstractThe increasing use of medical marijuana highlights the importance of developing a better understanding of cannabinoid metabolism. Phytocannabinoids, including ∆9-tetrahydrocannabinol (THC), are metabolized and inactivated by cytochrome P450 enzymes primarily within the liver. The lipophilic nature of cannabinoids necessitates mechanism(s) to facilitate their intracellular transport to metabolic enzymes. Here, we test the central hypothesis that liver-type fatty acid binding protein (FABP1) mediates phytocannabinoid transport and subsequent inactivation. Using X-ray crystallography, molecular modeling, and in vitro binding approaches we demonstrate that FABP1 accommodates one molecule of THC within its ligand binding pocket. Consistent with its role as a THC carrier, biotransformation of THC was reduced in primary hepatocytes obtained from FABP1-knockout (FABP1-KO) mice. Compared to their wild-type littermates, administration of THC to male and female FABP1-KO mice potentiated the physiological and behavioral effects of THC. The stark pharmacodynamic differences were confirmed upon pharmacokinetic analyses which revealed that FABP1-KO mice exhibit reduced rates of THC biotransformation. Collectively, these data position FABP1 as a hepatic THC transport protein and a critical mediator of cannabinoid inactivation. Since commonly used medications bind to FABP1 with comparable affinities to THC, our results further suggest that FABP1 could serve a previously unrecognized site of drug-drug interactions.
Surface ocean carbon dioxide variability in South Pacific boundary currents and Subantarctic waters
Authors: C. Pardo Paula , Tilbrook Bronte , van Ooijen Erik , Passmore Abraham , Neill Craig , Jansen Peter , Sutton Adrienne J. , Trull Thomas W. 
Published: May 2019

AbstractTo improve estimates of the long-term response of the marine carbon system to climate change a better understanding of the seasonal and interannual variability is needed. We use high-frequency multi-year data at three locations identified as climate change hotspots: two sites located close to South Pacific boundary currents and one in the Subantarctic Zone (SAZ). We investigate and identify the main drivers involved in the seasonal an interannual (2012–2016) variability of the carbon system. The seasonal variability at boundary current sites is temporally different and highly controlled by sea surface temperature. Advection processes also play a significant role on the monthly changes of the carbon system at the western boundary current site. The interannual variability at these sites most likely responds to long-term variability in oceanic circulation ultimately related to climatic indices such as the El Niño Southern Oscillation, the Pacific Decadal Oscillation and the Southern Annular Mode (SAM). In the SAZ, advection and entrainment processes drive most of the seasonality, augmented by the action of biological processes in spring. Given the relevance of advection and entrainment processes at SAZ, the interannual variability is most probably modulated by changes in the regional winds linked to the variability of the SAM.
Two-Dimensional-Like Amorphous Indium Tungsten Oxide Nano-Sheet Junctionless Transistors with Low Operation Voltage
Authors: Kuo Po-Yi , Chang Chien-Min , Liu I-Han , Liu Po-Tsun 
Published: May 2019

AbstractIn this work, we have successfully demonstrated the junctionless (JL) transistors with two-dimensional-like (2D-like) nano-sheet (NS) material, amorphous indium tungsten oxide (a-IWO), as an active channel layer. The influences of the different gate insulator (GI) materials and the scalings of GI thickness, a-IWO channel thickness, and channel lengths on the a-IWO NS JL transistors (a-IWO NS-JLTs) have been studied for the purposes of low operation voltage (gate voltage ≤2V) and high performance. The 2D-like a-IWO NS-JLTs exhibit low operation voltage, low source/drain (S/D) contact resistance (RC) and other key electrical characteristics, such as high field-effect mobility (μFE), near ideal subthreshold swing (S.S.), and large ON/OFF currents ratio (ION/IOFF). The remarkable device characteristics also make the proposed 2D-like a-IWO NS-JLTs promising for system-on-panel (SoP) and vertically stacked (VS) hybrid CMOS applications.
Genetic Polymorphisms in the Open Reading Frame of the CCR5 gene From HIV-1 Seronegative and Seropositive Individuals From National Capital Regions of India
Authors: Ronsard Larance , Sood Vikas , Yousif Ashraf S. , Ramesh Janani , Shankar Vijay , Das Jishnu , Sumi N. , Rai Tripti , Mohankumar Kumaravel , Sridharan Subhashree , Dorschel Arianna , Ramachandran Vishnampettai G. , Banerjea Akhil C. 
Published: May 2019

AbstractC-C chemokine receptor type 5 (CCR5) serves as a co-receptor for Human immunodeficiency virus (HIV), enabling the virus to enter human CD4 T cells and macrophages. In the absence of CCR5, HIV strains that require CCR5 (R5 or M-tropic HIV) fail to successfully initiate infection. Various natural mutations of the CCR5 gene have been reported to interfere with the HIV-CCR5 interaction, which influences the rate of AIDS progression. Genetic characterization of the CCR5 gene in individuals from the National Capital Regions (NCRs) of India revealed several natural point mutations in HIV seropositive/negative individuals. Furthermore, we identified novel frame-shifts mutations in the CCR5 gene in HIV seronegative individuals, as well as the well reported CCR5Δ32 mutation. Additionally, we observed a number of mutations present only in HIV seropositive individuals. This is the first report to describe the genetic variations of CCR5 in individuals from the NCRs of India and demonstrates the utility of investigating understudied populations to identify novel CCR5 polymorphisms.
Molecular mechanisms of heterogeneous oligomerization of huntingtin proteins
Authors: Bonfanti Silvia , Lionetti Maria Chiara , Fumagalli Maria Rita , Chirasani Venkat R. , Tiana Guido , Dokholyan Nikolay V. , Zapperi Stefano , La Porta Caterina A. M. 
Published: May 2019

AbstractThere is still no successful strategy to treat Huntington’s disease, an inherited autosomal disorder associated with the aggregation of mutated forms of the huntingtin protein containing polyglutamine tracts with more than 36 repeats. Recent experimental evidence is challenging the conventional view of the disease by revealing transcellular transfer of mutated huntingtin proteins which are able to seed oligomers involving wild type forms of the protein. Here we decipher the molecular mechanism of this unconventional heterogeneous oligomerization by performing discrete molecular dynamics simulations. We identify the most probable oligomer conformations and the molecular regions that can be targeted to destabilize them. Our computational findings are complemented experimentally by fluorescence-lifetime imaging microscopy/fluorescence resonance energy transfer (FLIM-FRET) of cells co-transfected with huntingtin proteins containing short and large polyglutamine tracts. Our work clarifies the structural features responsible for heterogeneous huntingtin aggregation with possible implications to contrast the prion-like spreading of Huntington’s disease.
Human cortical folding across regions within individual brains follows universal scaling law
Authors: Wang Yujiang , Necus Joe , Rodriguez Luis Peraza , Taylor Peter Neal , Mota Bruno 
Published: May 2019

AbstractDifferent cortical regions vary systematically in their morphology. Here we investigate if the scaling law of cortical morphology, which was previously demonstrated across both human subjects and mammalian species, still holds within a single cortex across different brain regions. By topologically correcting for regional curvature, we could analyse how different morphological parameters co-vary within single cortices. We show in over 1500 healthy individuals that, despite their morphological diversity, regions of the same cortex obey the same universal scaling law, and age morphologically at similar rates. In Alzheimer’s disease, we observe a premature ageing in the morphological parameters that was nevertheless consistent with the scaling law. The premature ageing effect was most dramatic in the temporal lobe. Thus, while morphology can vary substantially across cortical regions, subjects, and species, it always does so in accordance with a common scaling law, suggesting that the underlying processes driving cortical gyrification are universal.
Three‐coil structure‐based WPT system design for electric bike CC and CV charging without communication
Authors: Liu Sheng , Li Xiaoming , Yang Lin 
Published: May 2019

In comparison with the traditional plug‐in charging systems for the electric bike (EB), wireless power transfer (WPT) systems have superior advantages of convenience and safety. Combining the application requirement range of the EB, this study proposes a three‐coil structure‐based WPT system in order to achieve ideal and reliable constant current (CC) output and constant voltage (CV) output without the need for a sophisticated control strategy and the real‐time communication links between the transmitter and receiver sides. Two ac switches are utilised at the transmitter side to implement the change of charging mode from CC to CV. By correctly selecting the parameters of compensation components, the required load‐independent CC and CV characteristics with zero phase angle in the CC and CV modes can be achieved. Besides this, a load identification method based on the active power calculation used to estimate the equivalent resistance of the battery in the whole charging process, is utilised to judge the switching point from CC to CV mode. Finally, the feasibility of the method is verified through the construction of a laboratory platform with a 3.3 A charging current and a 57 V charging voltage.
Cardiorespiratory and Autonomic Nervous System Responses to Prolonged Eccentric Cycling
Authors: Ritter Ophélie , Isacco Laurie , Rakobowchuk Mark , Tordi Nicolas , Laroche Davy , Bouhaddi Malika , Degano Bruno , Mourot Laurent 
Published: May 2019

AbstractOffering large muscle benefits despite low metabolic demand, continuous eccentric exercise appears to be an interesting alternative to concentric exercise. Nevertheless, further knowledge is needed about prolonged eccentric exercise. This work sought to investigate the cardiovascular responses to prolonged constant-load eccentric compared to concentric cycling. Ten healthy males performed two 45-min exercise sessions of either concentric or eccentric cycling separated by a month and matched for heart rate during the first 5 min of exercise. Cardiorespiratory, autonomic nervous system and vascular responses were assessed at rest, and during exercise and recovery. During cycling, oxygen uptake, cardiac output and systolic blood pressure were similar but heart rate and diastolic blood pressure were greater whereas stroke volume was lower during eccentric than concentric cycling (118±21 vs. 104±10 bpm; 77±9 vs. 65±8 mmHg; 122±12 vs. 135±13 mL). Baroreflex and noradrenaline concentration were altered during eccentric cycling, and after eccentric exercise, vascular tone was greater than after concentric cycling. We observed increased cardiovascular strain and altered baroreflex activity during eccentric compared with concentric exercise, suggesting eccentric cycling triggers greater sympathetic activity.
Update Breast Cancer 2019 Part 1 – Implementation of Study Results of Novel Study Designs in Clinical Practice in Patients with Early Breast Cancer
Authors: Hartkopf Andreas , Müller Volkmar , Wöckel Achim , Lux Michael , Janni Wolfgang , Nabieva Naiba , Taran Florin-Andrei , Ettl Johannes , Lüftner Diana , Belleville Erik , Schütz Florian , Fasching Peter , Fehm Tanja , Kolberg Hans-Christian , Overkamp Friedrich , Schneeweiss Andreas , Tesch Hans 
Published: May 2019

AbstractFor many years, small but significant advancements have been made time and again in the prevention and treatment of early breast cancer. The so-called panel gene analyses are becoming more and more important in prevention, since the risk due to the tested genes is better understood and as a result, concepts for integration in health care can be developed. In the adjuvant situation, the first study in the so-called post-neoadjuvant situation was able to demonstrate a clear improvement in the prognosis with an absent pathological complete remission following trastuzumab or pertuzumab + trastuzumab. Additional studies with this post-neoadjuvant therapeutic concept are still being conducted at present. The CDK4/6 inhibitors which had shown a significant improvement in progression-free survival in a metastatic situation are currently being tested in the adjuvant situation in large therapeutic studies. These and other new data for the treatment or prevention of primary breast cancer are presented in this review against the backdrop of current studies.
Perioperative antientzündliche Therapie im Rahmen der Glaukomchirurgie
Authors: Dietlein Thomas S. , Erb Carl , Hoffmann Esther 
Published: May 2019

ZusammenfassungViele klinische Studien belegen, dass der funktionelle Ausgang der Glaukomchirurgie, insbesondere der Filtrationschirurgie, durch eine topische antientzündliche Vor- und Nachbehandlung signifikant beeinflusst werden kann. Die topischen Steroide erweisen sich sowohl in der Vor- als auch in der Nachbehandlung nach Trabekulektomie als günstig, wobei die Dauer der postoperativen Behandlung vom individuellen Befund abhängig gemacht werden soll. Eine systemische Steroidtherapie oder Immunmodulation ist beim uveitischen Sekundärglaukom für den Erfolg der Glaukomchirurgie signifikant von Bedeutung, bei anderen Glaukomformen ist ein Nutzen der systemischen Therapie nicht belegt. Eine zusätzliche topische Therapie mit nicht steroidalen Antiphlogistika ist bei einer kombinierten Katarakt-Glaukom-Chirurgie zu erwägen. Eine topische antientzündliche Therapie nach selektiver Lasertrabekuloplastik ist nicht notwendig, bei Argonlasertrabekuloplastik und Zyklophotokoagulation wirkt diese sich schmerzlindernd aus. Die intravitreale Gabe von Steroiden im Rahmen der Glaukomchirurgie muss aufgrund der Induktion von Augendruckspitzen immer kritisch abgewogen werden.
SIOP-E-BTG and GPOH Guidelines for Diagnosis and Treatment of Children and Adolescents with Low Grade Glioma
Authors: Gnekow Astrid K. , Kandels Daniela , Tilburg Cornelis van , Azizi Amedeo A. , Opocher Enrico , Stokland Tore , Driever Pablo Hernaiz , Meeteren A. Y. N. Schouten-van , Thomale Ulrich W. , Schuhmann Martin U. , Czech Thomas , Goodden John Robert , Warmuth-Metz Monika , Bison Brigitte , Avula Shivaram , Kortmann Rolf-D. , Timmermann Beate , Pietsch Torsten , Witt Olaf 
Published: May 2019

AbstractLow grade gliomas (LGGs) constitute the largest, yet clinically and (molecular-) histologically heterogeneous group of pediatric brain tumors of WHO grades I and II occurring throughout all pediatric age groups and at all central nervous system (CNS) sites. The tumors are characterized by a slow growth rate and may show periods of growth arrest. Around 40% of all LGG patients can be cured by complete neurosurgical resection and are followed by close observation. In case of relapse, second resection often is possible. Following incomplete resection observation is recommended, as long as there is no radiologic tumor growth and the patient does not suffer from significant, tumor-related symptoms. This also applies to patients with a diagnosis of LGG on the basis of radiological criteria. By contrast, clinical worsening and / or radiologic progression are an indication to treatment with either chemo- or radiotherapy. Overall survival is around 90%, and many patients survive with residual tumor, i. e. they suffer from chronic disease. All patients need comprehensive neuro-oncological care, the principles and details of which are summarized in the current guidelines. These represent standard of care for diagnostic work-up (including neuroimaging and neuropathology), and for therapeutic decisions (including the indications to non-surgical treatment) as well as concepts for neurosurgical intervention, chemotherapy and radiotherapy as well as surveillance and rehabilitation. The current treatment algorithm was compiled by members of the LGG working group of the SIOP-E brain tumor group (SIOP-E-BTG) and is based upon the results of previous European LGG studies and international reports.
Anoxic Brain Injury: The Abominable Malady
Authors: Hrishi Ajay P. , Prathapadas Unnikrishnan , Lionel Karen R. , Puthanveedu Divya K. , Sethuraman Manikandan 
Published: May 2019

AbstractAnoxic brain injury (ABI) is an important cause of prolonged hospital stay and morbidity across the globe. It is a sequel of major systemic insults resulting from various etiologies, such as reduced oxygen availability, insufficient cerebral blood flow, reduced oxygen carriage, or any metabolic condition that can interfere with the utilization of oxygen. A varying combination of pathophysiologic mechanisms leads to a spectrum of clinical manifestations, the understanding of which will significantly help in prognostication of patients. Neuroprognostication helps both the clinician and the patient's family in planning future course and is further aided by various neuromonitoring modalities, biomarkers, and imaging. Targeted temperature management still remains a therapeutic tool in ABI and along with other neuroprotective measures may improve the survival. Continuing research in ABI may uncover more promising treatment strategies.