Miracle-dz/UniFAR-FTUs huggingface dataset:
Retinal ischemia and reperfusion causes capillary degeneration: similarities to diabetes.

PURPOSE Retinal neurons and vasculature interact with each other under normal conditions, and occlusion of the retinal vasculature can result in damage to retinal neurons. Whether damage to the neural retina will damage the vasculature, however, is less clear. This study was conducted to explore the relationship between vascular and nonvascular cells of the retina. The response of the retinal vasculature to an injury (ischemia and reperfusion; I/R) that is known to cause neuronal degeneration was studied. METHODS I/R injury to the retinas was induced in Lewis rats and C57BL/6J mice by elevating intraocular pressure (IOP), and reperfusion was established immediately afterward. Some rats were pretreated with aminoguanidine (AMG, 50 mg/Kg BW in drinking water) before the procedure. Poly(ADP-ribose) polymerase (PARP) activity and expression of inducible nitric oxide synthase (iNOS), and cycloxygenase-2 (COX-2) were measured by Western blot analysis, and levels of TNF-alpha and intercellular adhesion molecule (ICAM)-1 mRNA were measured by qPCR at 2 and 7 days after the procedure. Also at 2 and 7 days after the I/R injury, apoptosis of retinal neural cells (demonstrated by TUNEL assay), density of cells in the ganglion cell layer, and thickness of retinas were quantitated, and the number of TUNEL-positive capillary cells and degenerated capillaries were assessed. Retinal neurodegeneration and capillary degeneration were also examined in C57BL/6J mice 2, 5, 8, and 14 days after I/R injury. RESULTS As expected, loss of cells in the retinal ganglion cell layer was apparent 2 days after I/R injury in the rat and mouse models. In contrast, the retinal vasculature had essentially no pathology at this time in either model. Surprisingly, the number of degenerated capillaries increased greatly by 7 to 8 days after the injury. Administration of aminoguanidine significantly inhibited the I/R-induced capillary degeneration as well as neurodegeneration in the rat model. Retinal I/R caused increased PARP activity (detected by poly(ADP-ribosy)lated proteins), as well as upregulation of iNOS, COX-2, TNF-alpha, and ICAM-1 levels in rats, consistent with an inflammatory process. CONCLUSIONS Capillary degeneration is an unrecognized component of acutely elevated IOP and develops only after neurodegeneration is severe. Thus, this finding raises the possibility that damage to the neural retina contributes to capillary degeneration. Aminoguanidine, a nonspecific inhibitor of iNOS, inhibited I/R-induced degeneration of both neuronal and vascular cells of the retina. The model of retinal ischemia and reperfusion will be a useful tool for investigating the relationship between neuronal damage and vascular damage in glaucoma and other diseases such as diabetic retinopathy.
Thresholds of skin sensitivity are partially influenced by mechanical properties of the skin on the foot sole

Across the foot sole, there are vibration and monofilament sensory differences despite an alleged even distribution of cutaneous afferents. Mechanical property differences across foot sole sites have been proposed to account for these differences. Vibration (VPT; 3 Hz, 40 Hz, 250 Hz), and monofilament (MF) perception threshold measurements were compared with skin hardness, epidermal thickness, and stretch response across five foot sole locations in young healthy adults (n = 22). Perceptual thresholds were expected to correlate with all mechanical property measurements to help address sensitivity differences between sites. Following this hypothesis, the MedArch was consistently found to be the thinnest and softest site and demonstrated the greatest sensitivity. Conversely, the Heel was found to be the thickest and hardest site, and was relatively insensitive across perceptual tests. Site differences were not observed for epidermal stretch response measures. Despite an apparent trend of elevated sensory threshold at harder and thicker sites, significant correlations between sensitivity measures and skin mechanical properties were not observed. Skin hardness and epidermal thickness appeared to have a negligible influence on VPT and minor influence on MF within this young healthy population. When normalized (% greater or smaller than subject mean) to the subject mean for each variable, significant positive correlations were observed between MF and skin hardness (R2 = 0.422, P < 0.0001) and epidermal thickness (R2 = 0.433, P < 0.0001) providing evidence that skin mechanics can influence MF threshold. In young healthy adults, differences in sensitivity are present across the foot sole, but cannot solely be accounted for by differences in the mechanical properties of the skin.
Unexpected but Incidental Positive Outcomes Predict Real-World Gambling

Positive mood can affect a person’s tendency to gamble, possibly because positive mood fosters unrealistic optimism. At the same time, unexpected positive outcomes, often called prediction errors, influence mood. However, a linkage between positive prediction errors—the difference between expected and obtained outcomes—and consequent risk taking has yet to be demonstrated. Using a large data set of New York City lottery gambling and a model inspired by computational accounts of reward learning, we found that people gamble more when incidental outcomes in the environment (e.g., local sporting events and sunshine) are better than expected. When local sports teams performed better than expected, or a sunny day followed a streak of cloudy days, residents gambled more. The observed relationship between prediction errors and gambling was ubiquitous across the city’s socioeconomically diverse neighborhoods and was specific to sports and weather events occurring locally in New York City. Our results suggest that unexpected but incidental positive outcomes influence risk taking.
A Comparative Analysis of Scheduling Policies in a Distributed System using Simulation

In this paper we study scheduling in a distributed system. A simulation model is used to address performance issues associated with scheduling. Three policies which combine processor and I/O scheduling are used to schedule parallel jobs for a variety of workloads. Fairness is required among competing jobs. Simulated results reveal that all scheduling methods have merit, but one method significantly improves the overall performance and also provides a guarantee for fairness in individual job execution.
A Novel Method for Measurement of Submembrane ATP Concentration*

There has been considerable debate as to whether adenosine triphosphate (ATP) is compartmentalized within cells and, in particular, whether the ATP concentration directly beneath the plasma membrane, experienced by membrane proteins, is the same as that of the bulk cytoplasm. This issue has been difficult to address because there is no indicator of cytosolic ATP, such as those available for Ca2+, capable of resolving the submembrane ATP concentration ([ATP]sm) in real time within a single cell. We show here that mutant ATP-sensitive K+ channels can be used to measure [ATP]sm by comparing the increase in current amplitude on patch excision with the ATP dose-response curve. In Xenopus oocytes, [ATP]sm was 4.6 ± 0.3 mm (n = 29) under resting conditions, slightly higher than that measured for the bulk cytoplasm (2.3 mm). In mammalian (COSm6) cells, [ATP]smwas slightly lower and averaged 1.4 ± 0.1 mm(n = 66). Metabolic poisoning (10 min of 3 mm azide) produced a significant fall in [ATP]sm in both types of cells: to 1.2 ± 0.1 mm (n = 24) in oocytes and 0.8 ± 0.11 mm for COSm6 cells. We conclude that [ATP]sm lies in the low millimolar range and that there is no gradient between bulk cytosolic and submembrane [ATP].
Clinical and histopathologic factors related to prognosis in primary squamous cell carcinoma of the vagina

The goal of this retrospective study concerning primary carcinoma of the vagina (PCV) was to analyze clinical and histopathologic prognostic factors in one of the largest known material, which comprised 314 patients. PCV is a rare disease, and the majority of published studies are based on small materials; therefore, the established knowledge concerning prognostic factors is insufficient. Routine treatment is based on irradiation with risk for undertreatment or overtreatment, which leads to unnecessary complications in the absence of prognostic factors. The overall 5-year disease-specific survival rate in this study was 45% and in stage I 75%. In the univariate statistical analysis, several factors correlated significantly with disease-specific survival. However, in the multivariate analysis, there were only three factors that independently could predict poor survival—high age at diagnosis, large tumors (≥4 cm), and advanced stage. Common background factors with no prognostic significance were prior hysterectomy, other gynecological malignancies, and pelvic irradiation. In conclusion, this study has elucidated three strong prognostic factors that might be considered in the choice of therapy and also for modification of the FIGO guidelines. Increased knowledge concerning complementary biologic markers to discriminate between low- and high malignant tumors is however of great importance.
Prognostic factors and survival of colorectal cancer in Kurdistan province, Iran

Abstract Colorectal cancer (CRC) survival varies at individual and geographically level. This population-based study aimed to evaluating various factors affecting the survival rate of CRC patients in Kurdistan province. In a retrospective cohort study, patients diagnosed as CRC were collected through a population-based study from March 1, 2009 to 2014. The data were collected from Kurdistan's Cancer Registry database. Additional information and missing data were collected reference to patients’ homes, medical records, and pathology reports. The CRC survival was calculated from the date of diagnosis to the date of cancer-specific death or the end of follow-up (cutoff date: October 2015). Kaplan–Meier method and log-rank test were used for the univariate analysis of survival in various subgroups. The proportional-hazard model Cox was also used in order to consider the effects of different factors on survival including age at diagnosis, place of residence, marital status, occupation, level of education, smoking, economic status, comorbidity, tumor stage, and tumor grade. A total number of 335 patients affected by CRC were assessed and the results showed that 1- and 5-year survival rate were 87% and 33%, respectively. According to the results of Cox's multivariate analysis, the following factors were significantly related to CRC survival: age at diagnosis (≥65 years old) (HR 2.08, 95% CI: 1.17–3.71), single patients (HR 1.62, 95% CI: 1.10–2.40), job (worker) (HR 2.09, 95% CI: 1.22–3.58), educational level: diploma or below (HR 0.61, 95% CI: 0.39–0.92), wealthy economic status (HR 0.51, 95% CI: 0.31–0.82), tumor grade in poorly differentiated (HR 2.25, 95% CI: 1.37–3.69), and undifferentiated/anaplastic grade (HR 2.90, 95% CI: 1.67–4.98). We found that factors such as low education, inappropriate socioeconomic status, and high tumor grade at the time of disease diagnosis were effective in the poor survival of CRC patients in Kurdistan province; this, which need more attention.
Synaptic Interactions of Late-Spiking Neocortical Neurons in Layer 1

Layer 1 of the neocortex is an important zone in which synaptic integration of inputs originating from a variety of cerebral regions is thought to take place. Layer 1 does not contain pyramidal cells, and several histochemical studies have suggested that most layer 1 neurons are GABAergic. However, although layer 1 neurons could be an important source of inhibition in this layer, the synaptic action of these neurons and the identity of their postsynaptic targets are unknown. We studied the physiological properties and synaptic interactions of a class of cells within layer 1 called late-spiking (LS) cells. The dendrites and axons of layer 1 LS cells were confined primarily to layer 1. Using paired recording, we showed that LS cells formed GABAergic connections with other LS cells as well as with non-LS cells in layer 1 and with pyramidal cells in layer 2/3. We also found that layer 2/3 pyramidal neurons provide excitatory inputs to LS cells. It has been suggested previously that GABAergic neurons belonging to the same class in the cortex are electrically coupled. In agreement with that hypothesis, we found that LS cells were interconnected by electrical coupling (83%), whereas electrical coupling between LS cells and non-LS cells was infrequent (2%). Thus, we provide evidence showing that a group of GABAergic neurons within layer 1 are specifically interconnected by electrical coupling and can provide significant inhibitory inputs to neurons in layer 1 and to distal dendrites of pyramidal cells.
A Probabilistic Model of Lexical and Access and Disambiguation

The problems of access-retrieving linguistic structure from some mental grammor-and disomblguatlon-choosing among these structures to correctly parse ambiguous linguistic input-are fundamental to language understanding. The literature abounds with psychological results on lexical access, the access of idioms, syntactic rule access, parsing preferences, syntactic disombiguation, and the processing of garden-path sentences. Unfortunately, it has been difficult to combine models which account for these results to build a general, uniform model of access and disombiguation at the lexical, idiomatic, and syntactic levels. For example, psycholinguistic theories of lexical access and idiom access and parsing theories of syntactic rule access hove almost no commonality in methodology or coverage of psycholinguistic data. This article presents o single probabilistic algorithm which models both the access and disambiguation of linguistic knowledge. The algorithm is based on a parallel porser which ranks constructions for access, and interpretations for disambiguation, by their conditional probability. Low-ranked constructions and interpretations ore pruned through beam-search; this pruning accounts, among other things, for the garden-path effect. I show that this motivated probabilistic treatment accounts for a wide variety of psycholinguistic results, arguing for a more uniform representation of linguistic knowledge and for the use of probabilistically-enriched grammars and interpreters as models of human knowledge of ond processing of language. 1 INTRODUCTION The problems of access-retrieving linguistic structure from some mental grammar-and disambiguation-choosing among combinations of these structures to correctly parse ambiguous linguistic input-are fundamental to language understanding. Recently, a number of computational cognitive models of these tasks have appeared, including models of lexical access, Many thanks to Jerry Feldman and Robert Wilensky for their significant contributions to and support of this work, and thanks to and two anonymous reviewers for their contributions to this article and earlier versions.
Role of H- and D- MATE-Type Transporters from Multidrug Resistant Clinical Isolates of Vibrio fluvialis in Conferring Fluoroquinolone Resistance

Background The study seeks to understand the role of efflux pumps in multidrug resistance displayed by the clinical isolates of Vibrio fluvialis, a pathogen known to cause cholera-like diarrhoea. Methodology Two putative MATE family efflux pumps (H- and D-type) were PCR amplified from clinical isolates of V. fluvialis obtained from Kolkata, India, in 2006 and sequenced. Bioinformatic analysis of these proteins was done to predict protein structures. Subsequently, the genes were cloned and expressed in a drug hypersusceptible Escherichia coli strain KAM32 using the vector pBR322. The recombinant clones were tested for the functionality of the efflux pump proteins by MIC determination and drug transport assays using fluorimeter. Results The sequences of the genes were found to be around 99% identical to their counterparts in V. cholerae. Protein structure predicting servers TMHMM and I-TASSER depicted ten-twelve membrane helical structures for both type of pumps. Real time PCR showed that these genes were expressed in the native V. fluvialis isolates. In the drug transport assays, the V. fluvialis clinical isolates as well as recombinant E. coli harbouring the efflux pump genes showed the energy-dependent and sodium ion-dependent drug transport activity. KAM32 cells harbouring the recombinant plasmids showed elevated MIC to the fluoroquinolones, norfloxacin and ciprofloxacin but H-type pumps VCH and VFH from V. cholerae and V. fluvialis respectively, showed decreased MIC to aminoglycosides like gentamicin, kanamycin and streptomycin. Decrease in MIC was also observed for acriflavin, ethidium bromide, safranin and nalidixic acid. Significance Increased resistance towards fluoroquinolones exhibited due to these efflux pumps from multidrug resistant clinical isolates of V. fluvialis implies that treatment procedure may become more elaborate for this simple but highly infectious disease. To the best of our knowledge, this is the first report of cloning and characterization of efflux pumps from multidrug resistant clinical isolates of V. fluvialis.
Sulfhydryl Modification Induces Calcium Entry through IP3-Sensitive Store-Operated Pathway in Activation-Dependent Human Neutrophils

As the first line of host defense, neutrophils are stimulated by pro-inflammatory cytokines from resting state, facilitating the execution of immunomodulatory functions in activation state. Sulfhydryl modification has a regulatory role in a wide variety of physiological functions through mediation of signaling transductions in various cell types. Recent research suggested that two kinds of sulfhydryl modification, S-nitrosylation by exogenous nitric oxide (NO) and alkylation by N-ethylmaleimide (NEM), could induce calcium entry through a non-store-operated pathway in resting rat neutrophils and DDT1MF-2 cells, while in active human neutrophils a different process has been observed by us. In the present work, data showed that NEM induced a sharp rising of cytosolic calcium concentration ([Ca2+]c) without external calcium, followed by a second [Ca2+]c increase with readdition of external calcium in phorbol 12-myristate 13-acetate (PMA)-activated human neutrophils. Meanwhile, addition of external calcium did not cause [Ca2+]c change of Ca2+-free PMA-activated neutrophils before application of NEM. These data indicated that NEM could induce believable store-operated calcium entry (SOCE) in PMA-activated neutrophils. Besides, we found that sodium nitroprusside (SNP), a donor of exogenous NO, resulted in believable SOCE in PMA-activated human neutrophils via S-nitrosylation modification. In contrast, NEM and SNP have no effect on [Ca2+]c of resting neutrophils which were performed in suspension. Furthermore, 2-Aminoethoxydiphenyl borate, a reliable blocker of SOCE and an inhibitor of inositol 1,4,5-trisphosphate (IP3) receptor, evidently abolished SNP and NEM-induced calcium entry at 75 µM, while preventing calcium release in a concentration-dependent manner. Considered together, these results demonstrated that NEM and SNP induced calcium entry through an IP3-sensitive store-operated pathway of human neutrophils via sulfhydryl modification in a PMA-induced activation-dependent manner.
Building Meaningful Parasocial Relationships Between Toddlers and Media Characters to Teach Early Mathematical Skills

Very young children have difficulty transferring what they view onscreen to their offscreen worlds. This study examined whether familiarizing toddlers with a character would improve toddlers' performance on a subsequent seriation task. Toddlers were randomly assigned to one of three conditions: (1) a familiarized character condition where toddlers viewed character-based videos and engaged in character-based play over a 3-month period before viewing the seriation video demonstration; (2) an unfamiliarized character condition where the toddler only saw the seriation video demonstration; and (3) a no-exposure control group where the toddler did not see the seriation video demonstration or have any involvement with the character. All toddlers were tested on the same seriation task at age 21 months, with the familiarized character group beginning the study at age 18 months and the other groups participating only at age 21 months. Toddlers in the familiarized character condition, but not the unfamiliarized character condition, completed the seriation task significantly better than the no-exposure control group. Within the familiarized character condition, toddlers who nurtured the character during play subsequently had higher seriation scores. The results suggest that meaningful relationships with media characters can help toddlers learn early mathematical skills.
Dynamical and Thermodynamical Causes of Large-Scale Changes in the Hydrological Cycle over North America in Response to Global Warming *

The mechanisms of model-projected atmospheric moisture budget change across North America are examined in simulations conducted with 22 models from phase 5 of the Coupled Model Intercomparison Project. Modern-day model budgets are validated against the European Centre for Medium-Range Weather Forecasts Interim Re-Analysis. In the winter half year transient eddies converge moisture across the continent while the mean flow wets the west from central California northward and dries the southwest. In the summer half year there is widespreadmean flowmoisture divergence across thewest and convergence over theGreat Plains that is offset by transient eddy divergence. In the winter half year the models project drying for the southwest and wetting to the north. Changes in the mean flowmoisture convergence are largely responsible across the west but intensified transient eddymoisture convergence wets the northeast. In the summer half year widespread declines in precipitationminus evaporation (P2E) are supported bymean flowmoisture divergence across the west and transient eddy divergence in the Great Plains. The changes in mean flow convergence are related to increases in specific humidity but also depend on changes in the mean flow including increased low-level divergence in the U.S. Southwest and a zonally varying wave that wets theNorthAmerican west and east coasts inwinter and dries the U.S. Southwest. Increased transient eddy fluxes occur even as low-level eddy activity weakens and arise from strengthened humidity gradients. A full explanation of North American hydroclimate changes will require explanation ofmean and transient circulation changes and the coupling between themoisture and circulation fields.
Maternal Betaine Supplementation throughout Gestation and Lactation Modifies Hepatic Cholesterol Metabolic Genes in Weaning Piglets via AMPK/LXR-Mediated Pathway and Histone Modification

Betaine serves as an animal and human nutrient which has been heavily investigated in glucose and lipid metabolic regulation, yet the underlying mechanisms are still elusive. In this study, feeding sows with betaine-supplemented diets during pregnancy and lactation increased cholesterol content and low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SR-BI) gene expression, but decreasing bile acids content and cholesterol-7a-hydroxylase (CYP7a1) expression in the liver of weaning piglets. This was associated with the significantly elevated serum betaine and methionine levels and hepatic S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) content. Concurrently, the hepatic nuclear transcription factor liver X receptor LXR was downregulated along with activated signal protein AMP-activated protein kinase (AMPK). Moreover, a chromatin immunoprecipitation assay showed lower LXR binding on CYP7a1 gene promoter and more enriched activation histone marker H3K4me3 on LDLR and SR-BI promoters. These results suggest that gestational and lactational betaine supplementation modulates hepatic gene expression involved in cholesterol metabolism via an AMPK/LXR pathway and histone modification in the weaning offspring.