Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic time dependence of deletions affecting codons 557 and/or 558 of KIT gene for relapse-free survival (RFS) in localized GIST: a Spanish Group for Sarcoma Research (GEIS) Study.

BACKGROUND To assess whether deletions involving codons 557 and/or 558 (critical deletions) of exon 11 of KIT are relevant in the prognosis of relapse-free survival (RFS) in gastrointestinal stromal tumor (GIST) patients with a long follow-up. PATIENTS AND METHODS A univariate and multivariate analysis for RFS were carried out on 162 localized GIST patients over the entire follow-up period and over the intervals 0-4 years and >4 years. Factors assessed among others were Fletcher/National Institutes of Health and Miettinen-Lasota/Armed Forces Institute of Pathology (M-L/AFIP) risk categories, critical deletions and non-deletion-type mutation (NDTM) within exon 11 of KIT. RESULTS Multivariate analyses revealed that M-L/AFIP [relative risk (RR) 11.45, confidence interval (CI) 4.40-29.76, for the high-risk subgroup and RR 5.97, CI 2.09-17.06, for the intermediate subgroup] and critical deletions (RR 3.05, CI 1.59-5.85) were independent prognostic factors for RFS for the first 4 years and for the entire follow-up period. Beyond 4 years, the high-risk M-L/AFIP subgroup (RR 8.12, CI 1.48-44.4) and NDTM (RR 6.42, CI 1.17-35.12) were independent prognostic factors for RFS. The median follow-up was 84 months. CONCLUSION Critical deletions represent a time-dependent prognostic factor limited to the first 4 years after surgery, which could help identify a subset with higher and earlier risk for relapse in GIST patients.
A Crisis of Missed Opportunities? Foreclosure Costs and Mortgage Modification During the Great Recession

We investigate the impact of Great Recession policies in California that substantially increased lender pecuniary and time costs of foreclosure. We estimate that the California Foreclosure Prevention Laws (CFPLs) prevented 250,000 California foreclosures (a 20% reduction) and created $\$$300 billion in housing wealth. The CFPLs boosted mortgage modifications and reduced borrower transitions into default. They also mitigated foreclosure externalities via increased maintenance spending on homes that entered foreclosure. The CFPLs had minimal adverse side effects on the availability of mortgage credit for new borrowers. Altogether, findings suggest that policy interventions that keep borrowers in their homes may be broadly beneficial during times of widespread housing distress.
Corneal dystrophies and genetics in the International Committee for Classification of Corneal Dystrophies era: a review

Many of the corneal dystrophies have now been genetically characterized, and a system was established in 2008 by The International Committee for Classification of Corneal Dystrophies (IC3D) in an attempt to standardize the nomenclature. IC3D provided a classification system whereby all dystrophies can be categorized on the basis of the underlying genetic knowledge. Since that time, further work has established even more phenotypic and allelic heterogeneity than anticipated, particular for Fuchs endothelial corneal dystrophy and posterior polymorphous dystrophy. Using genome‐wide association studies, a number of genes are now implicated both in normal corneal quantitative traits, such as central corneal thickness, as well as in disease. There is also a trend towards functional characterization of the genetic variants involved to elucidate the pathophysiology of these entities. This review article will provide an overview of the knowledge to date, with an emphasis on findings since the IC3D classification was published in 2008.
Cost minimization by helpers in cooperative vertebrates

When parents invest heavily in reproduction they commonly suffer significant energetic costs. Parents reduce the long-term fitness implications of these costs through increased foraging and reduced reproductive investment in the future. Similar behavioral modifications might be expected among helpers in societies of cooperative vertebrates, in which helping is associated with energetic costs. By using multivariate analyses and experiments, we show that in cooperative meerkats, Suricata suricatta, helping is associated with substantial short-term growth costs but limited long-term fitness costs. This association forms because individual contributions to cooperation are initially condition dependent, and, because when helpers invest heavily in cooperation, they increase their foraging rate during the subsequent nonbreeding period and reduce their level of cooperative investment in the subsequent reproductive period. These results provide a unique demonstration that despite significant short-term costs, helpers, like breeders, are able to reduce the fitness consequences of these costs through behavioral modifications.
The link between sleep Bruxism, Sleep Disordered Breathing and Temporomandibular Disorders: An Evidence-Based Review

1School of Dentistry, University of Western Australia, Perth, Australia; 2School of Dentistry, Louisiana State University, New Orleans, LA; 3Centre for Sleep Health and Research, Department of Respiratory and Sleep Medicine, Royal North Shore Hospital, and University of Sydney, NSW, Australia; 4Department of Oral Health, Faculty of Dental Medicine, Universite de Montreal, Surgery and Trauma Department, Hopital du Sacre Coeur de Montreal, Montreal, Canada REVIEW ARTICLES
Towards Neural Network Model for Insulin/Glucose in Diabetics-II

In this work we extending our investigations for a general neural network model that resembles the interactions between glucose concentration levels and amount of insulin injected in the bodies of diabetics. We use real data for 70 different patients of diabetics and build on it our model. Two types of neural networks (NN’s) are experimented in building that model; the first type is called the LevenbergMarquardt (LM) training algorithm of multilayer feed forward neural network (NN), the other one is based on Polynomial Network (PN’s). We do comparisons between the two models based on their performance. The design stages mainly consist of training, testing, and validation. A linear regression between the output of the multi-layer feed forward neural network trained by LM algorithm (abbreviated by LM NN) and the actual outputs shows that the LM NN is a better model. The PN’s have proved to be good static “mappers”, but their performance is degraded when used in modelling a dynamical system. The LM NN based model still proved that it can potentially be used to build a theoretical general regulator controller for insulin injections and, hence, can reflect an idea about the types and amounts of insulin required for patients. Povzetek: Na osnovi podatkov o 70 pacientih je razvit nevronski model za razmerna med insulinom in glukozo.
Maximum Size of Reverse-Free Sets of Permutations

Two words have a reverse if they have the same pair of distinct letters on the same pair of positions, but in reversed order. A set of words no two of which have a reverse is said to be reverse-free. Let F(n,k) be the maximum size of a reverse-free set of words from [n]^k where no letter repeats within a word. We show the following lower and upper bounds in the case n >= k: F(n,k) \in n^k k^{-k/2 + O(k/log k)}. As a consequence of the lower bound, a set of n-permutations each two having a reverse has size at most n^{n/2 + O(n/log n)}.
Dopamine-Mediated Learning and Switching in Cortico-Striatal Circuit Explain Behavioral Changes in Reinforcement Learning

The basal ganglia are thought to play a crucial role in reinforcement learning. Central to the learning mechanism are dopamine (DA) D1 and D2 receptors located in the cortico-striatal synapses. However, it is still unclear how this DA-mediated synaptic plasticity is deployed and coordinated during reward-contingent behavioral changes. Here we propose a computational model of reinforcement learning that uses different thresholds of D1- and D2-mediated synaptic plasticity which are antagonized by DA-independent synaptic plasticity. A phasic increase in DA release caused by a larger-than-expected reward induces long-term potentiation (LTP) in the direct pathway, whereas a phasic decrease in DA release caused by a smaller-than-expected reward induces a cessation of long-term depression, leading to LTP in the indirect pathway. This learning mechanism can explain the robust behavioral adaptation observed in a location-reward-value-association task where the animal makes shorter latency saccades to reward locations. The changes in saccade latency become quicker as the monkey becomes more experienced. This behavior can be explained by a switching mechanism which activates the cortico-striatal circuit selectively. Our model also shows how D1- or D2-receptor blocking experiments affect selectively either reward or no-reward trials. The proposed mechanisms also explain the behavioral changes in Parkinson's disease.
Decentralized algorithms for vehicle routing in a stochastic time-varying environment

In this paper we present decentralized algorithms for motion coordination of a group of autonomous vehicles, aimed at minimizing the expected waiting time to service stochastically-generated targets. The vehicles move within a convex environment with bounded velocity, and target generation is modeled by a spatio-temporal Poisson process. The general problem is known as the m-vehicle dynamic traveling repairperson problem (m-DTRP); the best previously known control algorithms rely on centralized a-priori task assignment and locational optimization, and are of limited applicability in scenarios involving ad-hoc networks of autonomous vehicles. In this paper, we present a new class of algorithms for the m-DTRP problem that: (i) are spatially distributed, scalable to large networks, and adaptive to network changes, (ii) are provably locally optimal in the light load case, and (iii) achieve the same performance as the best known centralized algorithms in the heavy-load, single-vehicle case. Simulation results are presented and discussed.
Mechanisms underlying the neuropathological consequences of epileptic activity in the rat hippocampus in vitro

Blockade of γ‐aminobutyric acid (GABA)ergic synaptic transmission in mature hippocampal slice cultures for a period of 3 days with convulsants was shown previously to induce chronic epileptiform activity and to mimic many of the degenerative changes observed in the hippocampi of epileptic humans. The cellular mechanisms underlying the induction of this degeneration were examined in the present study by comparing the effects of GABA blockers with the effects produced by the K+ channel blocker tetraethylammonium (2 mM). Both types of convulsant caused a comparable decrease in the number of Nissl‐stained pyramidal cells in areas CA1 and CA3. No significant cell loss was induced by tetraethylammonium when epileptiform discharge was reduced by simultaneous exposure of cultures to tetrodotoxin (0.5 μM) or to the anticonvulsants pentobarbital (50 μM) or tiagabine (50 μM). We conclude that this degeneration was mediated by convulsant‐induced epileptiform discharge itself. The hypothesis that N‐methyl‐D‐aspartate (NMDA) receptor‐mediated excitotoxicity underlies cell death in this model was tested by applying convulsants together with specific antagonists of glutamate receptors. Whereas coapplication of antagonists of both non‐NMDA and NMDA receptors strongly reduced the degeneration induced by the convulsants, application of either class of antagonist alone did not. Application of exogenous NMDA produced potent cell death, and this degeneration was blocked by the NMDA receptor antagonist methyl‐10,11‐dihydro‐5‐H‐dibenzocyclohepten‐5,10‐imine (MK‐801). Convulsants also induced a loss of dendritic spines that could be partially prevented by NMDA or non‐NMDA receptor antagonists. We conclude that NMDA receptor activation is not solely responsible for the neuronal pathology resulting as a consequence of epileptiform discharge. © 1996 Wiley‐Liss, Inc.
Contrasting Synaptic Actions of the Inhalational General Anesthetics Isoflurane and Xenon

Background: The mechanisms by which the inhalational general anesthetics isoflurane and xenon exert their effects are unknown. Moreover, there have been surprisingly few quantitative studies of the effects of these agents on central synapses, with virtually no information available regarding the actions of xenon. Methods: The actions of isoflurane and xenon on &ggr;-aminobutyric acid–mediated (GABAergic) and glutamatergic synapses were investigated using voltage-clamp techniques on autaptic cultures of rat hippocampal neurons, a preparation that avoids the confounding effects of complex neuronal networks. Results: Isoflurane exerts its greatest effects on GABAergic synapses, causing a marked increase in total charge transfer (by approximately 70% at minimum alveolar concentration) through the inhibitory postsynaptic current. This effect is entirely mediated by an increase in the slow component of the inhibitory postsynaptic current. At glutamatergic synapses, isoflurane has smaller effects, but it nonetheless significantly reduces the total charge transfer (by approximately 30% at minimum alveolar concentration) through the excitatory postsynaptic current, with the N-methyl-D-aspartate (NMDA) and &agr;-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor–mediated components being roughly equally sensitive. Xenon has no measurable effect on GABAergic inhibitory postsynaptic currents or on currents evoked by exogenous application of GABA, but it substantially inhibits total charge transfer (by approximately 60% at minimum alveolar concentration) through the excitatory postsynaptic current. Xenon selectively inhibits the NMDA receptor–mediated component of the current but has little effect on the AMPA/kainate receptor–mediated component. Conclusions: For both isoflurane and xenon, the most important targets appear to be postsynaptic. The authors’ results show that isoflurane and xenon have very different effects on GABAergic and glutamatergic synaptic transmission, and this may account for their differing pharmacologic profiles.
P-Selectin Glycoprotein Ligand 1 (Psgl-1) Is Expressed on Platelets and Can Mediate Platelet–Endothelial Interactions in Vivo

The platelet plays a pivotal role in maintaining vascular integrity. In a manner similar to leukocytes, platelets interact with selectins expressed on activated endothelium. P-selectin glycoprotein ligand 1 (PSGL-1) is the main P-selectin ligand expressed on leukocytes. Searching for platelet ligand(s), we used a P-selectin–immunoglobulin G (IgG) chimera to affinity purify surface-biotinylated proteins from platelet lysates. P-selectin–bound ligands were eluted with ethylenediaminetetraacetic acid. An ∼210-kD biotinylated protein was isolated from both human neutrophil and platelet preparations. A band of the same size was also immunopurified from human platelets using a monoclonal anti–human PSGL-1 antibody and could be blotted with P-selectin–IgG. Under reducing conditions, both the predicted PSGL-1 ∼210-kD dimer and the ∼120-kD monomer were isolated from platelets. Comparative immunoelectron microscopy and Western blotting experiments suggested that platelet PSGL-1 expression is 25–100-fold lower than that of leukocytes. However, patients with chronic idiopathic thrombocytopenic purpura who harbor predominantly young platelets displayed greater expression, indicating that PSGL-1 expression may be decreased during platelet aging. By flow cytometry, thrombin-activated platelets from normal individuals exhibited greater expression than those unstimulated. An inhibitory anti–PSGL-1 antibody significantly reduced platelet rolling in mesenteric venules, as observed by intravital microscopy. Our results indicate that functional PSGL-1 is expressed on platelets, and suggest an additional mechanism by which selectins and their ligands participate in inflammatory and/or hemostatic responses.
Electronic sensitivity of a single-walled carbon nanotube to internal electrolyte composition

Carbon nanotubes (CNTs) are well known as materials for nanoelectronics and show great potential to be used as the sensing elements in chemical and biological sensors. Recently, CNTs have been shown to be effective nanofluidic channels and the transport of substances through small diameter CNTs is intrinsically fast, selective, and operates at the single molecule level. It has been shown that the transport characteristics of semiconducting single-walled CNT (SWCNT) field effect transistors (FETs) are sensitive to internal water wetting. We report here that the characteristics of semiconducting SWCNT FETs are also sensitive to the concentration, pH and ion type of the ionic solution when the electrolyte is inside the CNT. Such sensitivity is not observed at the outside surface of a semiconducting SWCNT. This opens a new avenue for building new types of CNT sensor devices in which the SWCNT concurrently functions as a nanochannel and an electronic detector.
The operative treatment of pressure wounds: a 10‐year experience in flap selection

This study sought to both assist in the selection of flaps for ischial pressure wound reconstruction and evaluate the overall complication rates associated with reconstruction. A retrospective medical record review was conducted for 78 patients following the surgical reconstruction of an ischial pressure sore. Records were reviewed for demographics, location of sores, methods of reconstruction and flap selection, as well as any complications and recurrences. A total of 72 wounds were reconstructed with an average of 1·4 flaps used per wound. An ischial flap complication rate of 16% was observed in flap follow‐up, with a recurrence rate of 7% recorded. The vast majority of complications went on to heal with 15% of patients requiring a second reconstruction. Our relatively large sample of ischial flaps allowed for a close comparison with previously published work. Both flap selection and site of reconstruction significantly affected the success rates for pressure sore coverage. The overall complication rates by flap and reconstructive site in this review are lower than previously published reports. Our experience with ischial reconstruction was extensive enough to suggest a posterior medial thigh fasciocutaneous flap combined with a biceps femoris muscle flap as a first choice in ischial pressure wound reconstruction.
Assessing reliability of precipitation data over the Mekong River Basin: A comparison of ground‐based, satellite, and reanalysis datasets

Accurate precipitation data are the basis for hydro‐climatological studies. As a highly populated river basin, with the biggest inland fishery in Southeast Asia, freshwater dynamics is extremely important for the Mekong River Basin (MB). This study focuses on evaluating the reliability of existing gridded precipitation datasets both from satellite and reanalysis, with a ground observations‐based gridded precipitation dataset as the reference. Two satellite products (Tropical Rainfall Measuring Mission [TRMM] and the Precipitation Estimation from Remote Sensing Information using an Artificial Neural Network—Climate Data Record [PERSIANN‐CDR]), as well as three reanalysis products (Modern‐Era Retrospective analysis for Research and Applications [MERRA2], the European Centre for Medium‐Range Weather Forecasts interim reanalysis [ERA‐Interim], and the Climate Forecast System Reanalysis [CFSR]) were compared with the Asian Precipitation—Highly Resolved Observational Data Integration Towards Evaluation of Water Resources (APHRODITE) over the MB. The APHRODITE was chosen as the reference for the comparison because it was developed based on ground observations and has also been selected as reference data in previous studies. Results show that most of the assessed datasets are able to capture the major climatological characteristics of precipitation in the MB for the 10‐year study period (1998–2007). Generally, both satellite data (TRMM and PERSIANN‐CDR) show higher reliability than reanalysis products at both spatial and temporal scales across the MB, with the TRMM outperforming when compared to the PERSIANN‐CDR. For the reanalysis products, MERRA2 is more reliable in terms of temporal variability, but with some underestimation of precipitation. The other two reanalysis products CFSR and ERA‐Interim are relatively unreliable due to large overestimations. CFSR is better positioned to capture the spatial variability of precipitation, while ERA‐Interim shows inconsistent spatial patterns but more realistically resembles the daily precipitation probability. These findings have practical implications for future hydro‐climatological studies.
Interplay between FGF2 and BMP controls the self-renewal, dormancy and differentiation of rat neural stem cells

Mouse and human central nervous system progenitor cells can be propagated extensively ex vivo as stem cell lines. For the rat, however, in vitro expansion has proven to be problematic owing to proliferation arrest and differentiation. Here, we analyse the establishment, in adherent culture, of undifferentiated tripotent neural stem (NS) cell lines derived from rat foetal brain and spinal cord. Rat NS cells invariably undergo growth arrest and apparent differentiation after several passages; however, conditioned medium from proliferating cultures can overcome this block, enabling continuous propagation of undifferentiated rat NS cells. We found that dormancy is induced by autocrine production of bone morphogenetic proteins (BMPs). Accordingly, the BMP antagonist noggin can replace conditioned medium to sustain continuous self-renewal. Noggin can also induce dormant cells to re-enter the cell cycle, upon which they reacquire neurogenic potential. We further show that fibroblast growth factor 2 (FGF2) is required to suppress terminal astrocytic differentiation and maintain stem cell potency during dormancy. These findings highlight an extrinsic regulatory network, comprising BMPs, BMP antagonists and FGF2 signals, that governs the proliferation, dormancy and differentiation of rat NS cells and which can be manipulated to enable long-term clonogenic self-renewal.