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By using the Ising model formulation for combinatorial optimization with 0-1 binary variables, we investigated the extent to which partisan gerrymandering is possible from a random but even distribution of supporters. Assuming that an electoral district consists of square subareas and that each subarea shares at least one edge with other subareas in the district, it was possible to find the most tilted assignment of seats in most cases. However, in cases where supporters' distribution included many enclaves, the maximum tilted assignment was usually found to fail. We also discussed the proposed algorithm is applicable to other fields such as the redistribution of delivery destinations.In a simple reaction time task, the presentation of a startling acoustic stimulus has been shown to trigger the prepared response at short latency, known as the StartReact effect. However, it is unclear under what conditions it can be assumed that the loud stimulus results in response triggering. The purpose of the present study was to examine how auditory stimulus intensity and preparation level affect the probability of involuntary response triggering and the incidence of activation in the startle reflex indicator of sternocleidomastoid (SCM). In two reaction time experiments, participants were presented with an irrelevant auditory stimulus of varying intensities at various time points prior to the visual go-signal. Responses were independently categorized as responding to either the auditory or visual stimulus and those with or without SCM activation (i.e., SCM+/-). Both the incidence of response triggering and proportion of SCM+ trials increased with stimulus intensity and presentation closer to the go-signal. Data also showed that participants reacted to the auditory stimulus at a much higher rate on trials where the auditory stimulus elicited SCM activity versus those that did not, and a logistic regression analysis confirmed that SCM activation is a reliable predictor of response triggering for all conditions.Endocannabinoids, particularly anandamide (AEA) and 2-arachidonoylglycerol (2-AG), are instrumental in regulating energy homeostasis and stress response. However, little is known about the endocannabinoid system (ECS) in ruminants, although EC could improve dairy health and productivity, at least by increasing feed intake. In this study, we report if intraperitoneal (i.p.) AEA and 2-AG administration affects feed intake, whole-body macronutrient metabolism, isolation and restraint stress, and whether diet composition modulates circulating endocannabinoid concentrations in cows. Twenty Simmental cows in late lactation were fed a grass silage and a corn silage based diet. On each diet, cows received daily i.p. injections with either AEA (5 µg/kg; n = 7), 2-AG (2.5 µg/kg; n = 6) or saline (n = 7) for 8 days. Endocannabinoid administration for 5 days under free-ranging (non-stressed) conditions had no effect on feed intake or energy balance, but attenuated the stress-induced suppression of feed intake when housing changed to individual tie-stalls without social or tactile interaction. Endocannabinoids increased whole-body carbohydrate oxidation, reduced fat oxidation, and affected plasma non-esterified fatty acid concentrations and fatty acid contents of total lipids. There was no effect of endocannabinoids on plasma triglyceride concentrations or hepatic lipogenesis. Plasma AEA concentrations were not affected by diet, however, plasma 2-AG concentrations tended to be lower on the corn silage based diet. In conclusion, endocannabinoids attenuate stress-induced hypophagia, increase short-term feed intake and whole-body carbohydrate oxidation and decrease whole-body fat oxidation in cows.Tumor necrosis factor (TNF)-α is a potent mediator of inflammation and is involved in the pathophysiology of chronic kidney disease (CKD). However, the effects of TNF-α inhibition on the progression of kidney fibrosis have not been fully elucidated. We examined the effects of TNF-α inhibition by etanercept (ETN) on kidney inflammation and fibrosis in mice with aristolochic acid (AA) nephropathy as a model of kidney fibrosis. C57BL/6 J mice were administered AA for 4 weeks, followed by a 4-week remodeling period. The mice exhibited kidney fibrosis, functional decline, and albuminuria concomitant with increases in renal mRNA expression of inflammation- and fibrosis-related genes. The 8-week ETN treatment partially but significantly attenuated kidney fibrosis and ameliorated albuminuria without affecting kidney function. selleck chemicals These findings were accompanied by significant suppression of interleukin (IL)-1β, IL-6, and collagen types I and III mRNA expression. Moreover, ETN tended to reduce the AA-induced increase in interstitial TUNEL-positive cells with a significant reduction in Bax mRNA expression. Renal phosphorylated p38 MAPK was significantly upregulated by AA but was normalized by ETN. These findings indicate a substantial role for the TNF-α pathway in the pathogenesis of kidney fibrosis and suggest that TNF-α inhibition could become an adjunct therapeutic strategy for CKD with fibrosis.Structural Maintenance of Chromosomes Hinge Domain Containing 1 (SMCHD1) is a chromatin repressor, which is mutated in > 95% of Facioscapulohumeral dystrophy (FSHD) type 2 cases. In FSHD2, SMCHD1 mutations ultimately result in the presence of the cleavage stage transcription factor DUX4 in muscle cells due to a failure in epigenetic repression of the D4Z4 macrosatellite repeat on chromosome 4q, which contains the DUX4 locus. While binding of SMCHD1 to D4Z4 and its necessity to maintain a repressive D4Z4 chromatin structure in somatic cells are well documented, it is unclear how SMCHD1 is recruited to D4Z4, and how it exerts its repressive properties on chromatin. Here, we employ a quantitative proteomics approach to identify and characterize novel SMCHD1 interacting proteins, and assess their functionality in D4Z4 repression. We identify 28 robust SMCHD1 nuclear interactors, of which 12 are present in D4Z4 chromatin of myocytes. We demonstrate that loss of one of these SMCHD1 interacting proteins, RuvB-like 1 (RUVBL1), further derepresses DUX4 in FSHD myocytes. We also confirm the interaction of SMCHD1 with EZH inhibitory protein (EZHIP), a protein which prevents global H3K27me3 deposition by the Polycomb repressive complex PRC2, providing novel insights into the potential function of SMCHD1 in the repression of DUX4 in the early stages of embryogenesis. The SMCHD1 interactome outlined herein can thus provide further direction into research on the potential function of SMCHD1 at genomic loci where SMCHD1 is known to act, such as D4Z4 repeats, the inactive X chromosome, autosomal gene clusters, imprinted loci and telomeres.Acute cold induces beige adipocyte protein marker expression in human subcutaneous white adipose tissue (SC WAT) from both the cold treated and contralateral leg, and the immune system regulates SC WAT beiging in mice. Cold treatment significantly increased the gene expression of the macrophage markers CD68 and 86 in SC WAT. Therefore, we comprehensively investigated the involvement of macrophages in SC WAT beiging in lean and obese humans by immunohistochemistry. Cold treatment significantly increased CD163/CD68 macrophages in SC WAT from the cold treated and contralateral legs of lean and obese subjects, and had similar effects on CD206/CD68 macrophages, whereas the effects on CD86/CD68 macrophages were inconsistent between lean and obese. However, linear regression analysis did not find significant relationships between the change in macrophage numbers and the change in UCP1 protein abundance. A high percentage of CD163 macrophages in SC WAT expressed UCP1, and these UCP1 expressing CD163 macrophages were significantly increased by cold treatment in SC WAT of lean subjects. In conclusion, our results suggest that CD163 macrophages are involved in some aspect of the tissue remodeling that occurs during SC WAT beiging in humans after cold treatment, but they are likely not direct mediators of the beiging process.Degeneration of brainstem serotonin neurons has been demonstrated in ALS patients and mouse models and was found responsible for the development of spasticity. Consistent with involvement of central serotonin pathways, 5-HT2B receptor (5-HT2BR) was upregulated in microglia of ALS mice. Its deletion worsened disease outcome in the Sod1G86R mouse model and led to microglial degeneration. In ALS patients, a polymorphism in HTR2B gene leading to higher receptor expression in CNS, was associated with increased survival in patients as well as prevention of microglial degeneration. Thus, the aim of our study was to determine the effect of a 5-HT2BR agonist BW723C86 (BW), in the Sod1G86R mouse model. Despite good pharmacokinetic and pharmacological profiles, BW did not ameliorate disease outcome or motor neuron degeneration in a fast progressing mouse model of ALS despite evidence of modulation of microglial gene expression.Vision loss happens due to diabetic retinopathy (DR) in severe stages. Thus, an automatic detection method applied to diagnose DR in an earlier phase may help medical doctors to make better decisions. DR is considered one of the main risks, leading to blindness. Computer-Aided Diagnosis systems play an essential role in detecting features in fundus images. Fundus images may include blood vessels, exudates, micro-aneurysm, hemorrhages, and neovascularization. In this paper, our model combines automatic detection for the diabetic retinopathy classification with localization methods depending on weakly-supervised learning. The model has four stages; in stage one, various preprocessing techniques are applied to smooth the data set. In stage two, the network had gotten deeply to the optic disk segment for eliminating any exudate's false prediction because the exudates had the same color pixel as the optic disk. In stage three, the network is fed through training data to classify each label. Finally, the layers of the convolution neural network are re-edited, and used to localize the impact of DR on the patient's eye. The framework tackles the matching technique between two essential concepts where the classification problem depends on the supervised learning method. While the localization problem was obtained by the weakly supervised method. An additional layer known as weakly supervised sensitive heat map (WSSH) was added to detect the ROI of the lesion at a test accuracy of 98.65%, while comparing with Class Activation Map that involved weakly supervised technology achieved 0.954. The main purpose is to learn a representation that collect the central localization of discriminative features in a retina image. CNN-WSSH model is able to highlight decisive features in a single forward pass for getting the best detection of lesions.In ectotherms, adult body size commonly declines with increasing environmental temperature, a pattern known as the temperature-size rule. One influential hypothesis explaining this observation is that the challenge of obtaining sufficient oxygen to support metabolism becomes greater with increasing body size, and more so at high temperatures. Yet, previous models based on this hypothesis do not account for phenotypic plasticity in the physiology of organisms that counteracts oxygen limitation at high temperature. Here, we model the predicted strength of the temperature-size response using estimates of how both the oxygen supply and demand is affected by temperature when allowing for phenotypic plasticity in the aquatic ectotherm Daphnia magna. Our predictions remain highly inconsistent with empirical temperature-size responses, with the prior being close to one order of magnitude stronger than the latter. These results fail to provide quantitative support for the hypothesis that oxygen limitation drives temperature-size clines in aquatic ectotherms.