Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence of Stereoscopic Surface Disambiguation in the Responses of V1 Neurons

Abstract For the important task of binocular depth perception from complex natural‐image stimuli, the neurophysiological basis for disambiguating multiple matches between the eyes across similar features has remained a long‐standing problem. Recurrent interactions among binocular disparity‐tuned neurons in the primary visual cortex (V1) could play a role in stereoscopic computations by altering responses to favor the most likely depth interpretation for a given image pair. Psychophysical research has shown that binocular disparity stimuli displayed in 1 region of the visual field can be extrapolated into neighboring regions that contain ambiguous depth information. We tested whether neurons in macaque V1 interact in a similar manner and found that unambiguous binocular disparity stimuli displayed in the surrounding visual fields of disparity‐selective V1 neurons indeed modified their responses when either bistable stereoscopic or uniform featureless stimuli were presented within their receptive field centers. The delayed timing of the response behavior compared with the timing of classical surround suppression and multiple control experiments suggests that these modulations are carried out by slower disparity‐specific recurrent connections among V1 neurons. These results provide explicit evidence that the spatial interactions that are predicted by cooperative algorithms play an important role in solving the stereo correspondence problem.
Mesenchymal stem cells attenuate acute liver injury by altering ratio between interleukin 17 producing and regulatory natural killer T cells

Mesenchymal stem cells (MSCs) are, due to immunomodulatory characteristics, considered as novel agents in the treatment of immune‐mediated acute liver failure. Although it is known that MSCs can regulate activation of T lymphocytes, their capacity to modulate function of neutrophils and natural killer T (NKT) cells, major interleukin (IL) 17–producing cells in acute liver injury, is still unknown. By using 2 well‐established murine models of neutrophil and NKT cell–mediated acute liver failure (induced by carbon tetrachloride and α‐galactoceramide), we investigated molecular and cellular mechanisms involved in MSC‐mediated modulation of IL17 signaling during acute liver injury. Single intravenous injection of MSCs attenuate acute hepatitis and hepatotoxicity of NKT cells in a paracrine, indoleamine 2,3‐dioxygenase (IDO)–dependent manner. Decreased levels of inflammatory IL17 and increased levels of immunosuppressive IL10 in serum, reduced number of interleukin 17–producing natural killer T (NKT17) cells, and increased presence of forkhead box P3 + IL10–producing natural killer T regulatory cells (NKTregs) were noticed in the injured livers of MSC‐treated mice. MSCs did not significantly alter the total number of IL17‐producing neutrophils, CD4+, and CD8 + T lymphocytes in the injured livers. Injection of mesenchymal stem cell–conditioned medium (MSC‐CM) resulted with an increased NKTreg/NKT17 ratio in the liver and attenuated hepatitis in vivo and significantly reduced hepatotoxicity of NKT cells in vitro. This phenomenon was completely abrogated in the presence of IDO inhibitor, 1‐methyltryptophan. In conclusion, the capacity of MSCs to alter NKT17/NKTreg ratio and suppress hepatotoxicity of NKT cells in an IDO‐dependent manner may be used as a new therapeutic approach in IL17‐driven liver inflammation. Liver Transplantation 23 1040–1050 2017 AASLD.
Tenofovir Disoproxil Fumarate Is a New Substrate of ATP-Binding Cassette Subfamily C Member 11

ABSTRACT Tenofovir disoproxil fumarate (TDF), a nucleotide reverse transcriptase inhibitor, after conversion to tenofovir (TFV), is mainly eliminated by glomerular filtration and active tubular secretion. The major adverse effect of tenofovir is nephrotoxicity; however, the exact mechanism remains poorly understood. In this study, the ATP-binding cassette subfamily C member 11 (ABCC11; multidrug resistance protein 8 [MRP8]) transporter, which is abundant in proximal tubular cells, was demonstrated to act as an efflux transporter of tenofovir. Real-time PCR (RT-PCR) and indirect immunofluorescence assays were used to determine MRP8 overexpression in a continuous cell line. Tenofovir accumulations were assessed by cytotoxicity, cellular transport, and vesicular uptake assays. Substrate specificity was confirmed using MK-571, an MRP-specific inhibitor, and methotrexate, which served as a known substrate. Intracellular and intravesicular concentrations of tenofovir were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The 50% cytotoxic concentration (CC50) of TDF in MRP8-overexpressing cells was 4.78 times higher than that of parental cells. Transport assays also showed that the intracellular accumulation of tenofovir in MRP8-overexpressing cells was 55 times lower than that in parental cells and was partly reversed by MK-571. Similarly, an “inside-out” vesicular uptake assay, using Sf9 inverted membrane vesicles to allow measuring of accumulation of the substrates into the vesicles, demonstrated a higher intravesicular concentration of tenofovir in MRP8-overexpressing vesicles than in Sf9 insect control vesicles. These effects were effectively reversed by increasing concentrations of the specific inhibitor MK-571. In conclusion, tenofovir is a new substrate of the MRP8 transporter. An alteration in the activity of this efflux pump may increase the intracellular accumulation of tenofovir in proximal renal tubular cells.
Phosphorylation Regulates Functions of ZEB1 Transcription Factor

ZEB1 transcription factor is important in both development and disease, including many TGFβ‐induced responses, and the epithelial‐to‐mesenchymal transition (EMT) by which many tumors undergo metastasis. ZEB1 is differentially phosphorylated in different cell types; however the role of phosphorylation in ZEB1 activity is unknown. Luciferase reporter studies and electrophoresis mobility shift assays (EMSA) show that a decrease in phosphorylation of ZEB1 increases both DNA‐binding and transcriptional repression of ZEB1 target genes. Functional analysis of ZEB1 phosphorylation site mutants near the second zinc finger domain (termed ZD2) show that increased phosphorylation (due to either PMA plus ionomycin, or IGF‐1) can inhibit transcriptional repression by either a ZEB1‐ZD2 domain clone, or full‐length ZEB1. This approach identifies phosphosites that have a substantial effect regulating the transcriptional and DNA‐binding activity of ZEB1. Immunoprecipitation with anti‐ZEB1 antibodies followed by western analysis with a phospho‐Threonine‐Proline‐specific antibody indicates that the ERK consensus site at Thr‐867 is phosphorylated in ZEB1. In addition to disrupting in vitro DNA‐binding measured by EMSA, IGF‐1‐induced MEK/ERK phosphorylation is sufficient to disrupt nuclear localization of GFP‐ZEB1 fusion clones. These data suggest that phosphorylation of ZEB1 integrates TGFβ signaling with other signaling pathways such as IGF‐1. J. Cell. Physiol. 231: 2205–2217, 2016. © 2016 Wiley Periodicals, Inc.
Attention and Regional Gray Matter Development in Very Preterm Children at Age 12 Years

Abstract Objectives: This study examines the selective, sustained, and executive attention abilities of very preterm (VPT) born children in relation to concurrent structural magnetic resonance imaging (MRI) measures of regional gray matter development at age 12 years. Methods: A regional cohort of 110 VPT (≤32 weeks gestation) and 113 full term (FT) born children were assessed at corrected age 12 years on the Test of Everyday Attention-Children. They also had a structural MRI scan that was subsequently analyzed using voxel-based morphometry to quantify regional between-group differences in cerebral gray matter development, which were then related to attention measures using multivariate methods. Results: VPT children obtained similar selective (p=.85), but poorer sustained (p=.02) and executive attention (p=.01) scores than FT children. VPT children were also characterized by reduced gray matter in the bilateral parietal, temporal, prefrontal and posterior cingulate cortices, bilateral thalami, and left hippocampus; and increased gray matter in the occipital and anterior cingulate cortices (family-wise error–corrected p<.05). Poorer sustained auditory attention was associated with increased gray matter in the anterior cingulate cortex (p=.04). Poor executive shifting attention was associated with reduced gray matter in the right superior temporal cortex (p=.04) and bilateral thalami (p=.05). Poorer executive divided attention was associated with reduced gray matter in the occipital (p=.001), posterior cingulate (p=.02), and left temporal (p=.01) cortices; and increased gray matter in the anterior cingulate cortex (p=.001). Conclusions: Disturbances in regional gray matter development appear to contribute, at least in part, to the poorer attentional performance of VPT children at school age. (JINS, 2017, 23, 539–550)
Hybrid Rugosity Mesostructures (HRMs) for fast and accurate rendering of fine haptic detail

The haptic rendering of surface mesostructure (fine relief features) in dense triangle meshes requires special structures, equipment, and high sampling rates for detailed perception of rugged models. Low cost approaches render haptic texture at the expense of fidelity of perception. We propose a faster method for sur- face haptic rendering using image-based Hybrid Rugosity Mesostructures (HRMs), paired maps with per-face heightfield displacements and normal maps, which are layered on top of a much decimated mesh, effectively adding greater surface detail than actually present in the geometry. The haptic probe's force response algorithm is modulated using the blended HRM coat to render dense surface features at much lower costs. The proposed method solves typical problems at edge crossings, concave foldings and texture transitions. To prove the well- ness of the approach, a usability testbed framework was built to measure and compare experimental results of haptic rendering approaches in a common set of specially devised meshes, HRMs, and performance tests. Trial results of user testing evaluations show the goodness of the proposed HRM technique, rendering accurate 3D surface detail at high sampling rates, deriving useful modeling and perception thresholds for this technique.
Western long-term accuracy of serum pepsinogen-based gastric cancer screening

Background Even though mass gastric cancer screening is controversial in Western countries, diverse strategies have been proposed in intermediate-risk to high-risk areas. Aim The aim of this study was to determine the long-term accuracy of the pepsinogen test (PG) for early diagnosis of gastric cancer. Participants and methods A cohort of inhabitants from the Northern part of Portugal, aged between 40 and 74 years (n=5913), subjected to the PG test (PGI⩽70 ng/ml and PGI/PGII⩽3), were followed up between November 2006 and December 2015. The diagnosis of gastric cancer was determined through linkage to the population-based registry of cancer [North Region Cancer Registry of Portugal (RORENO)]. Results Twenty-six gastric cancers were diagnosed (0.4%): nine (4%) among individuals ‘positive’ for the PG test (n=225) and 15 (0.3%) among those who were ‘negative’ (n=5688) [hazard ratio=12.7; 95% confidence interval (CI): 5.6–28.6]. Individuals with a ‘negative PG test’ had a 3-year risk of gastric cancer of 0.1%, representing a sensitivity of 35% (95% CI: 17–56%), globally, and of 58% (95% CI: 28–85%) at 3 years follow-up. The median survival rate in both groups was over 24 months. Conclusion The PG test was found to be suboptimal as a screening test and, if used (before upper gastrointestinal endoscopy), it is mandatory to repeat it after 3 years.
Efficacy and safety outcomes of recanalisation procedures in patients with acute symptomatic pulmonary embolism: systematic review and network meta-analysis

Background We aimed to review the efficacy and safety of recanalisation procedures for the treatment of PE. Methods We searched PubMed, the Cochrane Library, EMBASE, EBSCO, Web of Science and CINAHL databases from inception through 31 July 2015 and included randomised clinical trials that compared the effect of a recanalisation procedure versus each other or anticoagulant therapy in patients diagnosed with PE. We used network meta-analysis and multivariate random-effects meta-regression to estimate pooled differences between each intervention and meta-regression to assess the association between trial characteristics and the reported effects of recanalisation procedures versus anticoagulation. Results For all-cause mortality, there were no significant differences in event rates between any of the recanalisation procedures and anticoagulant treatment (full-dose thrombolysis: OR 0.60; 95% CI0.36 to 1.01; low-dose thrombolysis: 0.47; 95% CI 0.14 to 1.59; and catheter-associated thrombolysis: 0.31; 95% CI 0.01 to 7.96). Full-dose thrombolysis increased the risk of major bleeding (2.00; 95% CI 1.06 to 3.78) compared with anticoagulation. Catheter-directed thrombolysis was associated with the lowest probability of dying (surface under the cumulative ranking curve (SUCRA), 0.67), followed by low-dose thrombolysis (SUCRA, 0.66) and full-dose thrombolysis (SUCRA, 0.55). Similarly, low-dose thrombolysis was associated with the lowest probability of major bleeding (SUCRA, 0.61), followed by catheter-directed thrombolysis (SUCRA, 0.54) and full-dose thrombolysis (SUCRA, 0.17). The results were similar in sensitivity analyses based on restricting only to studies in haemodynamically stable patients with PE. Conclusions In the treatment of PE, recanalisation procedures do not seem to offer a clear advantage compared with standard anticoagulation. Low-dose thrombolysis was associated with the lowest probability of dying and bleeding. Trial registration number PROSPERO CRD42015024670.
A Qualitative Study of a Maintenance Support Program for Women at Risk of Homelessness: Part 2: Situational Factors

ABSTRACT People who are homeless tend to have a number of complex needs. A housing maintenance support program (MSP) for women from the perspectives of clients, case managers and health professionals within the program was explored in this qualitative descriptive study. Interviews were conducted, and data were analysed using thematic analysis. The overarching theme that emerged from the data was “A life-changing event: I have the power to change. ” This theme was supported by three sub-themes: personal, situational and societal dimensions. In this article, the sub-theme – situational factors, is presented and refers to poverty, resources and services, as well as social support systems. These aspects all impinged on the client's ability to face life changes with optimism towards a better future. Their experiences of disconnection with the community changed for the clients after being part of the MSP. The MSP enabled the clients to feel part of society again, and empowered them to participate in the world around them. Key aspects of inclusion in the world are relationships based on acceptance, connecting with others, being involved and creating a sense of home/community.
A heuristic method to identify runs of homozygosity associated with reduced performance in livestock

While for the most part genome-wide metrics are currently employed in managing livestock inbreeding, genomic data offer, in principle, the ability to identify functional inbreeding. Here we present a heuristic method to identify haplotypes contained within a run of homozygosity (ROH) associated with reduced performance. Results are presented for simulated and swine data. The algorithm comprises 3 steps. Step 1 scans the genome based on marker windows of decreasing size and identifies ROH genotypes associated with an unfavorable phenotype. Within this stage, multiple aggregation steps reduce the haplotype to the smallest possible length. In step 2, the resulting regions are formally tested for significance with the use of a linear mixed model. Lastly, step 3 removes nested windows. The effect of the unfavorable haplotypes identified and their associated haplotype probabilities for a progeny of a given mating pair or an individual can be used to generate an inbreeding load matrix (ILM). Diagonals of ILM characterize the functional inbreeding load of individual (IIL). We estimated the accuracy of predicting the phenotype based on ILL. We further compared the significance of the regression coefficient for IIL on phenotypes to genome-wide inbreeding metrics. We tested the algorithm using simulated scenarios (n =12) combining different levels of linkage disequilibrium (LD) and number of loci impacting a quantitative trait. Additionally, we investigated 9 traits from two maternal purebred swine lines. In simulated data, as the LD in the population increased the algorithm identified a greater proportion of the true unfavorable ROH effects. For example, the proportion of highly unfavorable true ROH effects identified raised from 32 to 41 % for the low to the high LD scenario. In both simulated and real data the haplotypes identified were contained within a much larger ROH (9.12-12.1 Mb). The IIL prediction accuracy was greater than zero across all scenarios for simulated data (high LD scenario mean (95% confidence interval): 0.49 (0.47-0.52)) and for nearly all swine traits (mean ± SD: 0.17±0.10). On average across simulated and swine datasets the IIL regression coefficient was more closely related to progeny performance than any genome-wide inbreeding metric. A heuristic method was developed that identified ROH genotypes with reduced performance and characterized the combined effects of ROH genotypes within and across individuals.
Genome‐wide discovery of tissue‐specific miRNAs in clusterbean (Cyamopsis tetragonoloba) indicates their association with galactomannan biosynthesis

Summary Owing to the presence of 80% soluble dietary fibre, high protein content and high value gum, clusterbean (Cyamopsis tetragonoloba) has recently emerged as an economically important legume. The developing clusterbean seeds accumulate 90% galactomannans in the endosperm and, therefore, can be used as a model crop to understand galactomannan biosynthesis and its regulation. miRNAs are tiny master regulators of their corresponding target genes, resulting in variations in the amounts of their metabolic end products. To understand the role of these regulators in galactomannan biosynthesis regulation, small RNA libraries were prepared and sequenced from five tissues of clusterbean genotype RGC‐936, and miRanalyzer and DSAP programs were used to identify conserved miRNAs and novel small RNAs. A total of 187 known and 171 novel miRNAs were found to be differentially expressed, of which 10 miRNAs were validated. A complicated network topology and 35% sharing of the target mRNAs between known and novel miRNAs suggest random evolution of novel miRNAs. The gene ontology (GO) annotation of potential target genes revealed the genes coding for signalling and carbohydrate metabolism (50.10%), kinases and other enzymes (20.75%), transcription factors (10.20%), transporters (8.35%) and other targets (10.6%). Two novel unigenes were annotated as ManS (mannosyltransferase/mannan synthase) and UGE (UDP‐ D‐glucose 4‐epimerase) and validated as targets for three novel miRNAs, that is Ct‐miR3130, Ct‐miR3135 and Ct‐miR3157. Our findings reveal that these novel miRNAs could play an important role in the regulation of the galactomannan pathway in C. tetragonoloba and possibly other galactomannan‐producing species.
The angiotensin II receptor type 1b is the primary sensor of intraluminal pressure in cerebral artery smooth muscle cells

The angiotensin II receptor type 1b (AT1Rb) is the primary sensor of intraluminal pressure in cerebral arteries. Pressure or membrane‐stretch induced stimulation of AT1Rb activates the TRPM4 channel and results in inward transient cation currents that depolarize smooth muscle cells, leading to vasoconstriction. Activation of either AT1Ra or AT1Rb with angiotensin II stimulates TRPM4 currents in cerebral artery myocytes and vasoconstriction of cerebral arteries. The expression of AT1Rb mRNA is ∼30‐fold higher than AT1Ra in whole cerebral arteries and ∼45‐fold higher in isolated cerebral artery smooth muscle cells. Higher levels of expression are likely to account for the obligatory role of AT1Rb for pressure‐induced vasoconstriction.
The postrhinal cortex is not necessary for landmark control in rat head direction cells

The rodent postrhinal cortex (POR), homologous to primate areas TH/TF and the human 'parahippocampal place area', has been implicated in processing visual landmark and contextual information about the environment. Head direction (HD) cells are neurons that encode allocentric head direction, independent of the animal's location or behavior, and are influenced by manipulations of visual landmarks. The present study determined whether the POR plays a role in processing environmental information within the HD circuit. Experiment 1 tested the role of the POR in processing visual landmark cues in the HD system during manipulation of a visual cue. HD cells from POR lesioned animals had similar firing properties, shifted their preferred firing direction following rotation of a salient visual cue, and in darkness had preferred firing directions that drifted at the same rate as controls. Experiment 2 tested the PORs involvement in contextual fear conditioning, where the animal learns to associate a shock with both a tone and a context in which the shock was given. In agreement with previous studies, POR lesioned animals were able to learn the tone–shock pairing, but displayed less freezing relative to controls when reintroduced into the environment previously paired with a shock. Therefore, HD cells from POR lesioned animals, with demonstrated impairments in contextual fear conditioning, were able to use a visual landmark to control their preferred direction. Thus, despite its importance in processing visual landmark information in primates, the POR in rats does not appear to play a pivotal role in controlling visual landmark information in the HD system. © 2016 Wiley Periodicals, Inc.
Detecting and Localizing End-to-End Performance Degradation for Cellular Data Services Based on TCP Loss Ratio and Round Trip Time

Providing high end-to-end (E2E) performance experienced by users is critical for cellular service providers to best serve their customers. This paper focuses on the detection and localization of E2E performance degradation (such as slow webpage page loading and unsmooth video playing) at cellular service providers. Detecting and localizing E2E performance degradation is crucial for cellular service providers, content providers, device manufactures, and application developers to jointly troubleshoot root causes. To the best of our knowledge, the detection and localization of E2E performance degradation at cellular service providers has not been previously studied. In this paper, we propose a holistic approach to detecting and localizing E2E performance degradation at cellular service providers across the four dimensions of user locations, content providers, device types, and application types. Our approach consists of three steps: modeling, detection, and localization. First, we use training data to build models that can capture the normal performance of every E2E instance, which means the flows corresponding to a specific location, content provider, device type, and application type. Second, we use our models to detect performance degradation for each E2E instance on an hourly basis. Third, after each E2E instance has been labeled as non-degrading or degrading, we use association rule mining techniques to localize the source of performance degradation. Our system detected performance degradation instances over a period of one week. In 80% of the detected degraded instances, content providers, device types, and application types were the only factors of performance degradation.