Miracle-dz/UniFAR-FTUs huggingface dataset:
Anti-VEGFR2 driven nuclear translocation of VEGFR2 and acquired malignant hallmarks are mutation dependent in glioblastoma.

OBJECTIVE Anti-angiogenic therapies (AATs), targeting VEGF-VEGFR pathways, are being used as an adjuvant to normalize glioblastoma (GBM) vasculature. Unexpectedly, clinical trials have witnessed transient therapeutic effect followed by aggressive tumor recurrence. In pre-clinical studies, targeting VEGFR2 with vatalanib, increased GBM growth under hypoxic microenvironment. There is limited understanding of these unanticipated results. Here, we investigated tumor cell associated phenotypes in response to VEGFR2 blockade. METHODS Human U251 cells were orthotopically implanted in mice (day 0) and were treated with vehicle or vatalanib on day 8. Tumor specimens were collected for immunohistochemistry and protein array. Nuclear translocation of VEGFR2 was analyzed through IHC and western blot. In vitro studies were performed in U251 (p53 and EGFR mutated) and U87 (p53 and EGFR wildtype) cells following vehicle or vatalanib treatments under normoxia (21% O2) and hypoxia (1% O2). Proliferation, cell cycle and apoptosis assays were done to analyze tumor cell phenotypes after treatments. RESULTS Vatalanib treated animals displayed distinct patterns of VEGFR2 translocation into nuclear compartment of U251 tumor cells. In vitro studies suggest that vatalanib significantly induced nuclear translocation of VEGFR2, characterized in chromatin bound fraction, especially in U251 tumor cells grown under normoxia and hypoxia. Anti-VEGFR2 driven nuclear translocation of VEGFR2 was associated with increased cell cycle and proliferation, decreased apoptosis, and displayed increased invasiveness in U251 compared to U87 cells. CONCLUSIONS Study suggests that AAT- induced molecular and phenotypic alterations in tumor cells are associated with mutation status and are responsible for aggressive tumor growth. Therefore, mutation status of the tumor in GBM patients should be taken in to consideration before applying targeted therapy to overcome unwanted effects.
Review of Creep Cavitation and Rupture of Low Cr Alloy and its Weldment

This paper presents a review of creep cavitation and rupture of low Cr alloy and its weldment, particular in the heat-affected zone (HAZ). Creep damage is one of the serious problems for the high temperature industry. One of the computational approaches is continuum damage mechanics which has been developed and applied complementary to the experimental approach and assists in the safe operation. However, the existing creep damage constitutive equations are not developed specifically for low stress. Therefore, in order to form the physical bases for the development of creep damage constitutive equation, it is necessary to critically review the creep cavitation and rupture characteristics of low Cr alloy and its weldment.
PIC SIMULATIONS OF THE EFFECT OF VELOCITY SPACE INSTABILITIES ON ELECTRON VISCOSITY AND THERMAL CONDUCTION

In low-collisionality plasmas, velocity-space instabilities are a key mechanism providing an effective collisionality for the plasma. We use particle-in-cell (PIC) simulations to study the interplay between electron- and ion-scale velocity-space instabilities and their effect on electron pressure anisotropy, viscous heating, and thermal conduction. The adiabatic invariance of the magnetic moment in low-collisionality plasmas leads to pressure anisotropy, , if the magnetic field is amplified ( and denote the pressure of species j (electron, ion) perpendicular and parallel to ). If the resulting anisotropy is large enough, it can in turn trigger small-scale plasma instabilities. Our PIC simulations explore the nonlinear regime of the mirror, IC, and electron whistler instabilities, through continuous amplification of the magnetic field by an imposed shear in the plasma. In the regime ( ), the saturated electron pressure anisotropy, , is determined mainly by the (electron-lengthscale) whistler marginal stability condition, with a modest factor of ∼1.5–2 decrease due to the trapping of electrons into ion-lengthscale mirrors. We explicitly calculate the mean free path of the electrons and ions along the mean magnetic field and provide a simple physical prescription for the mean free path and thermal conductivity in low-collisionality βj ≳ 1 plasmas. Our results imply that velocity-space instabilities likely decrease the thermal conductivity of plasma in the outer parts of massive, hot, galaxy clusters. We also discuss the implications of our results for electron heating and thermal conduction in low-collisionality accretion flows onto black holes, including Sgr A* in the Galactic Center.
Formation of Deep-Subwavelength Structures on Organic Materials by Femtosecond Laser Ablation

Femtosecond (fs-) laser induced subwavelength and deep-subwavelength periodic structures have attracted attention due to their sub-diffraction feature size and rich physics of laser-matter interaction. However, the formation mechanisms of fs-laser induced deep-subwavelength structures on organic materials have not been reported nor systematically studied. Herein, based on the degree of laser induced free-carrier excitation, the formation of deep-subwavelength structures by fs-laser ablation was systematically studied on popular materials: negative tone resists SU8 and conductive polymer poly-3, 4-ethylenedioxythiophene: poly-(styrenesulfonate) (PEDOT: PSS). A weak propensity to form deep-subwavelength structures was found on poly-methylmethacrylate and polyvinyl alcohol. The photo-excited electrons forming the surface plasmonic wave contributed to energy localization and absorption, which led to the imprinting of deep-subwavelength structures on polymers. It has been found that materials with $\pi $ -bonds and benzene rings were most susceptible to deep-subwavelength structure formation. Based on a laser-induced surface plasmonic model, the period of regular patterns was estimated and was in a good accordance with experimental results. The proposed formation mechanism of the deep-subwavelength structures on organic materials extends an application field of fs-laser micro/nanomachining of polymers.
An Unusual Accumulation of Ribosomal Multigene Families and Microsatellite DNAs in the XX/XY Sex Chromosome System in the Trans-Andean Catfish Pimelodella cf. chagresi (Siluriformes:Heptapteridae).

This work constitutes the first cytogenetic characterization of a trans-Andean species of Heptapteridae. The catfish Pimelodella cf. chagresi from the Upper Rio Magdalena was studied, applying standard cytogenetic techniques (Giemsa, C-banding, and argyrophilic nucleolar organizer region [Ag-NOR]) and fluorescence in situ hybridization techniques using repetitive DNA probes: microsatellites (CA15 and GA15) and ribosomal RNA (rRNA) multigene families (18S and 5S recombinant DNA [rDNA] probes). The species showed a unique diploid chromosome number 2n = 50 (32m [metacentrics] +14sm [submetacentrics] +4st [subtelocentrics]) and a XX/XY sex chromosomal system, where the heteromorphic Y-chromosome revealed a conspicuous accumulation of all the assayed domains of repetitive DNA. P. cf. chagresi karyotype shares common features with other Heptapteridae, such as the predominance of metacentric and submetacentric chromosomes, and one pair of subtelomeric nucleolar organizer regions (NORs). These results reflect an independent karyological identity of a trans-Andean species and the relevance of repetitive DNA sequences in the process of sex chromosome differentiation in fish; it is the first case of syntenic accumulation of rRNA multigene families (18S and 5S rDNA) and microsatellite sequences (CA15 and GA15) in a differentiated sex chromosome in Neotropical fish.
Six-year review of traumatic brain injury in a regional trauma unit: demographics, contributing factors and service provision in Ireland

ABSTRACT Background: Traumatic brain injury (TBI) represents a significant burden of care for acute surgical services, particularly in the absence of on-site neurosurgical cover or sufficient post-acute rehabilitation facilities. We examine factors contributing to TBI, prolonged lengths of stay (LoS) and implications for hospital resources. Long-term outcomes are assessed. Methods: This is a retrospective cohort study of patients admitted to a regional trauma unit with TBI from 2008 to 2013. Patients with LoS > 48 h were assessed. Demographic, clinical and longitudinal mortality data were collected using electronic clinical and radiological systems and chart review. Results: A total of 690 patients presented with TBI from 2008 to 2013; 213 patients with LoS > 48 h were assessed. One hundred and thirty (61%) were male. Mean age was 56 years (±SD 24). Mechanical fall was the most frequent injury mechanism (n = 120/213, 56%). Twenty-five per cent were associated with alcohol consumption; these were more likely to be male, involved in an Road Traffic Accident (RTA) or assault and necessitate transfer to a neurosurgical unit (p < 0.001, p = 0.029, p < 0.001, p = 0.05). A total of 112 patients(53%) had a prolonged LoS (>2 weeks). Mean LoS was 20 days (±SD 35), increasing to 39 days for patients requiring neurosurgical intervention. The 12-month all-cause mortality rate was 12%. Conclusions: TBIs result in significant utilisation of acute inpatient bed days. Improved rehabilitation services and strategies to reduce acute hospital LoS are warranted.
Sex differences in adult cell proliferation within the zebrafish (Danio rerio) cerebellum

It has been reported that neurons generated in the adult brain show sex‐specific differences in several brain regions of lower vertebrates and mammals. The present study questioned whether cell proliferation and survival in the adult zebrafish (Danio rerio) cerebellum, the most mitotically active area of adult teleost brain, is sexually differentiated. Adult zebrafish were treated with the thymidine analogue 5′‐bromo‐2′‐deoxyuridine (BrdU) and allowed to survive for 24 h (short‐term) and for 21 days (long‐term). BrdU immunohistochemistry allowed visualization of cells incorporating BrdU at the S phase of mitosis. At short‐term survival, male zebrafish had a higher number of labelled cells at proliferation sites of the molecular layer of corpus cerebelli (CCe) and the granular layer of the caudal lobe of the cerebellum (LCa) than did females. In long‐term survival, BrdU‐positive cells were found at their final destination, but only the granular layer of the medial division of the valvula cerebelli showed sex‐specific differences in the number of labelled cells. This higher mitotic activity in male cerebellum might be related to sex‐specific motor behaviour observed in male zebrafish. To investigate the role of programmed cell death, the terminal deoxynucleotidyl‐mediated dUTP nick‐end‐labelling (TUNEL) method was applied. The vast majority of apoptotic figures occurred in the granular cell layer of valvula and CCe, only in a few cases within the BrdU‐retaining cells. Apoptosis was found specifically at the sites of the final destination of proliferating cells, indicating that the close relation of cell birth and death might represent a possible plasticity mechanism in the adult zebrafish cerebellum.
IL-4–, TGF-β–, and IL-1–Dependent Expansion of Parasite Antigen-Specific Th9 Cells Is Associated with Clinical Pathology in Human Lymphatic Filariasis

Th9 cells are a subset of CD4+ T cells, shown to be important in allergy, autoimmunity, and antitumor responses; however, their role in human infectious diseases has not been explored in detail. We identified a population of IL-9 and IL-10 coexpressing cells (lacking IL-4 expression) in normal individuals. These cells respond to antigenic and mitogenic stimulation, but are distinct from IL-9+ Th2 cells. We also demonstrate that these Th9 cells exhibit Ag-specific expansion in a chronic helminth infection (lymphatic filariasis). Comparison of Th9 responses reveals that individuals with pathology associated with filarial infection exhibit significantly expanded frequencies of filarial Ag-induced Th9 cells, but not of IL9+Th2 cells in comparison with filarial-infected individuals without associated disease. Moreover, the per cell production of IL-9 is significantly higher in Th9 cells compared with IL9+Th2 cells, indicating that the Th9 cells are the predominant CD4+ T cell subset producing IL-9 in the context of human infection. This expansion was reflected in elevated Ag-stimulated IL-9 cytokine levels in whole blood culture supernatants. Finally, the frequencies of Th9 cells correlated positively with the severity of lymphedema (and presumed inflammation) in filarial-diseased individuals. This expansion of Th9 cells was dependent on IL-4, TGF-β, and IL-1 in vitro. We have therefore identified an important human CD4+ T cell subpopulation coexpressing IL-9 and IL-10, but not IL-4, the expansion of which is associated with disease in chronic lymphatic filariasis and could potentially have an important role in the pathogenesis of other inflammatory disorders.
Ecological controls on N 2 O emission in surface litter and near-surface soil of a managed grassland: modelling and measurements

Abstract. Large variability in N2O emissions from managed grasslands may occur because most emissions originate in surface litter or near-surface soil where variability in soil water content (θ) and temperature (Ts) is greatest. To determine whether temporal variability in θ and Ts of surface litter and near-surface soil could explain this in N2O emissions, a simulation experiment was conducted with ecosys, a comprehensive mathematical model of terrestrial ecosystems in which processes governing N2O emissions were represented at high temporal and spatial resolution. Model performance was verified by comparing N2O emissions, CO2 and energy exchange, and θ and Ts modelled by ecosys with those measured by automated chambers, eddy covariance (EC) and soil sensors on an hourly timescale during several emission events from 2004 to 2009 in an intensively managed pasture at Oensingen, Switzerland. Both modelled and measured events were induced by precipitation following harvesting and subsequent fertilizing or manuring. These events were brief (2–5 days) with maximum N2O effluxes that varied from N m−2 h−1 in early spring and autumn to > 3 mg N m−2 h−1 in summer. Only very small emissions were modelled or measured outside these events. In the model, emissions were generated almost entirely in surface litter or near-surface (0–2 cm) soil, at rates driven by N availability with fertilization vs. N uptake with grassland regrowth and by O2 supply controlled by litter and soil wetting relative to O2 demand from microbial respiration. In the model, NOx availability relative to O2 limitation governed both the reduction of more oxidized electron acceptors to N2O and the reduction of N2O to N2, so that the magnitude of N2O emissions was not simply related to surface and near-surface θ and Ts. Modelled N2O emissions were found to be sensitive to defoliation intensity and timing which controlled plant N uptake and soil θ and Ts prior to and during emission events. Reducing leaf area index (LAI) remaining after defoliation to half that under current practice and delaying harvesting by 5 days raised modelled N2O emissions by as much as 80 % during subsequent events and by an average of 43 % annually. Modelled N2O emissions were also found to be sensitive to surface soil properties. Increasing near-surface bulk density by 10 % raised N2O emissions by as much as 100 % during emission events and by an average of 23 % annually. Relatively small spatial variation in management practices and soil surface properties could therefore cause the large spatial variation in N2O emissions commonly found in field studies. The global warming potential from annual N2O emissions in this intensively managed grassland largely offset those from net C uptake in both modelled and field experiments. However, model results indicated that this offset could be adversely affected by suboptimal land management and soil properties.
Bitterness and astringency of grape and wine polyphenols

Extracts containing anthocyanins (ACN), and skin tannins (SKIN) and seed tannins (SEED) were prepared from Vitis vinifera cv. Cabernet Franc grapes grown in the Loire Valley, and characterised. Phenolic fractions from Cabernet Franc wines made from three Loire Valley locations were also isolated and characterised. Bitterness and astringency of ACN, SEED and SKIN as well as the wine extracts were evaluated by time intensity procedures in citric acid solution and in a base white wine. SEED and SKIN were equally astringent when tasted at the same concentration in spite of differences in tannin composition. The lower molecular weight (MW) of SEED was equal in astringency to larger MW SKIN which had a lower percentage of galloylation. The SEED fraction was slightly more bitter than the SKIN fraction in the citric acid solution, although no difference could be detected between samples in base white wine. Astringency of ACN alone was much lower than either SKIN or SEED. Addition of ACN to either tannin fraction produced very small sensory effects in citric acid. In wine, addition of ACN to either SEED or SKIN increased astringency significantly over either fraction alone, but had no effect on bitterness. The wine fractions differed only in astringency, which was correlated with tannin units as determined by thiolysis.
Future Generation Computer Systems ( ) – Future Generation Computer Systems towards Secure Mobile Cloud Computing: a Survey

Mobile cloud computing is gaining popularity among mobile users. The ABI Research predicts that the number of mobile cloud computing subscribers is expected to grow from 42.8 million (1.1% of total mobile users) in 2008 to 998 million (19% of total mobile users) in 2014. Despite the hype achieved by mobile cloud computing, the growth of mobile cloud computing subscribers is still below expectations. According to the recent survey conducted by the International Data Corporation, most IT Executives and CEOs are not interested in adopting such services due to the risks associated with security and privacy. The security threats have become a hurdle in the rapid adaptability of the mobile cloud computing paradigm. Significant efforts have been devoted in research organizations and academia to build secure mobile cloud computing environments and infrastructures. In spite of the efforts, there are a number of loopholes and challenges that still exist in the security policies of mobile cloud computing. This literature review: (a) highlights the current state of the art work proposed to secure mobile cloud computing infrastructures, (b) identifies the potential problems, and (c) provides a taxonomy of the state of the art.
P-Glycoprotein Function at the Blood–Brain Barrier in Humans Can Be Quantified with the Substrate Radiotracer 11C-N-Desmethyl-Loperamide

Permeability-glycoprotein (P-gp), an efflux transporter in several organs, acts at the blood–brain barrier to protect the brain from exogenous toxins. P-gp almost completely blocks brain entry of the PET radiotracer 11C-N-desmethyl-loperamide (11C-dLop). We examined the ability of 11C-dLop to quantify P-gp function in humans after increasing doses of tariquidar, an inhibitor of P-gp. Methods: Seventeen healthy volunteers had a total of 23 PET scans with 11C-dLop at baseline and after increasing doses of tariquidar (2, 4, and 6 mg/kg intravenously). A subset of subjects received PET with 15O-H2O to measure cerebral blood flow. Brain uptake of 11C-dLop was quantified in 2 ways. Without blood data, uptake was measured as area under the time–activity curve in the brain from 10 to 30 min (AUC10–30). With arterial blood data, brain uptake was quantified with compartmental modeling to estimate the rates of entry into (K1) and efflux from (k2) the brain. Results: Brain uptake of radioactivity was negligible at baseline and increased only slightly (∼30%) after 2 mg of tariquidar per kilogram. In contrast, 4 and 6 mg of tariquidar per kilogram increased brain uptake 2- and 4-fold, respectively. Greater brain uptake reflected greater brain entry (K1), because efflux (k2) and cerebral blood flow did not differ between tariquidar-treated and untreated subjects. In the subjects who received the highest dose of tariquidar (and had the highest brain uptake), regional values of K1 correlated linearly with absolute cerebral blood flow, consistent with high single-pass extraction of 11C-dLop. AUC10–30 correlated linearly with K1. Conclusion: P-gp function at the blood–brain barrier in humans can be quantified using PET and 11C-dLop. A simple measure of brain uptake (AUC10–30) may be used as a surrogate of the fully quantified rate constant for brain entry (K1) and thereby avoid arterial sampling. However, to dissect the function of P-gp itself, both brain uptake and the influx rate constant must be corrected for radiotracer delivery (blood flow).
Place-Historical Narratives: Road—or Roadblock—to Sustainability?

Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content.
Human vulnerability to stress depends on amygdala's predisposition and hippocampal plasticity

Variations in people's vulnerability to stressful life events may rise from a predated neural sensitivity as well as from differential neural modifications in response to the event. Because the occurrence of a stressful life event cannot be foreseen, characterizing the temporal trajectory of its neural manifestations in humans has been a real challenge. The current prospective study examined the emotional experience and brain responses of 50 a priori healthy new recruits to the Israeli Defense Forces at 2 time points: before they entered their mandatory military service and after their subsequent exposure to stressful events while deployed in combat units. Over time, soldiers reported on increase in stress symptoms that was correlated with greater amygdala and hippocampus responsiveness to stress-related content. However, these closely situated core limbic regions exhibited different temporal trajectories with regard to the stress effect; whereas amygdala's reactivity before stress predicted the increase in stress symptoms, the hippocampal change in activation over time correlated with the increase in such symptoms. Hippocampal plasticity was also reflected by a modification over time of its functional coupling with the ventromedial prefrontal cortex, and this coupling magnitude was again predicted by predated amygdala reactivity. Together, these findings suggest that variations in human's likelihood to develop symptomatic phenomena following stressful life events may depend on a balanced interplay between their amygdala's predisposing reactivity and hippocampal posteriori intra- and interregional plasticity. Accordingly, an individually tailored therapeutic approach for trauma survivors should target these 2 neural probes while considering their unique temporal prints.