Miracle-dz/UniFAR-FTUs huggingface dataset:
Polyamines preserve connexin 43-mediated gap junctional communication during intracellular hypercalcemia and acidosis

Changes in the regulation, formation, and gating of connexin-based gap junction channels occur in various disorders. It has been shown that H+ and Ca2+ are involved in the regulation of gap junctional communication. Ischemia-induced intracellular acidification and Ca2+ overload lead to closure of gap junctions and inhibit an exchange by ions and small molecules throughout the network of cells in the heart, brain, and other tissues. In this study, we examined the role of the polyamines in the regulation of connexin 43 (Cx43)-based gap junction channels under elevated intracellular concentrations of hydrogen ([H+]i) and calcium ([Ca2+]i) ions. Experiments, conducted in Novikoff and A172 human glioblastoma cells, which endogenously express Cx43, showed that polyamines prevent downregulation of Cx43-mediated gap junctional communication caused by elevated [Ca2+]i and [H+]i, accompanying ischemic and other pathological conditions. siRNA knockdown of Cx43 significantly reduces gap junctional communication, indicating that Cx43 gap junctions are the targets for spermine regulation.
Activation of retinal glial (Müller) cells by extracellular ATP induces pronounced increases in extracellular H+ flux

Small alterations in extracellular acidity are potentially important modulators of neuronal signaling within the vertebrate retina. Here we report a novel extracellular acidification mechanism mediated by glial cells in the retina. Using self-referencing H+-selective microelectrodes to measure extracellular H+ fluxes, we show that activation of retinal Müller (glial) cells of the tiger salamander by micromolar concentrations of extracellular ATP induces a pronounced extracellular H+ flux independent of bicarbonate transport. ADP, UTP and the non-hydrolyzable analog ATPγs at micromolar concentrations were also potent stimulators of extracellular H+ fluxes, but adenosine was not. The extracellular H+ fluxes induced by ATP were mimicked by the P2Y1 agonist MRS 2365 and were significantly reduced by the P2 receptor blockers suramin and PPADS, suggesting activation of P2Y receptors. Bath-applied ATP induced an intracellular rise in calcium in Müller cells; both the calcium rise and the extracellular H+ fluxes were significantly attenuated when calcium re-loading into the endoplasmic reticulum was inhibited by thapsigargin and when the PLC-IP3 signaling pathway was disrupted with 2-APB and U73122. The anion transport inhibitor DIDS also markedly reduced the ATP-induced increase in H+ flux while SITS had no effect. ATP-induced H+ fluxes were also observed from Müller cells isolated from human, rat, monkey, skate and lamprey retinae, suggesting a highly evolutionarily conserved mechanism of potential general importance. Extracellular ATP also induced significant increases in extracellular H+ flux at the level of both the outer and inner plexiform layers in retinal slices of tiger salamander which was significantly reduced by suramin and PPADS. We suggest that the novel H+ flux mediated by ATP-activation of Müller cells and of other glia as well may be a key mechanism modulating neuronal signaling in the vertebrate retina and throughout the brain.
Top-down Proteomics: Technology Advancements and Applications to Heart Diseases

ABSTRACT Introduction: Heart diseases are a leading cause of morbidity and mortality for both men and women worldwide, and impose significant economic burdens on the healthcare systems. Despite substantial effort over the last several decades, the molecular mechanisms underlying diseases of the heart remain poorly understood. Areas covered: Altered protein post-translational modifications (PTMs) and protein isoform switching are increasingly recognized as important disease mechanisms. Top-down high-resolution mass spectrometry (MS)-based proteomics has emerged as the most powerful method for the comprehensive analysis of PTMs and protein isoforms. Here, we will review recent technology developments in the field of top-down proteomics, as well as highlight recent studies utilizing top-down proteomics to decipher the cardiac proteome for the understanding of the molecular mechanisms underlying diseases of the heart. Expert commentary: Top-down proteomics is a premier method for the global and comprehensive study of protein isoforms and their PTMs, enabling the identification of novel protein isoforms and PTMs, characterization of sequence variations, and quantification of disease-associated alterations. Despite significant challenges, continuous development of top-down proteomics technology will greatly aid the dissection of the molecular mechanisms underlying diseases of the hearts for the identification of novel biomarkers and therapeutic targets.
The role of the complement system in cancer

In addition to being a component of innate immunity and an ancient defense mechanism against invading pathogens, complement activation also participates in the adaptive immune response, inflammation, hemostasis, embryogenesis, and organ repair and development. Activation of the complement system via classical, lectin, or alternative pathways generates anaphylatoxins (C3a and C5a) and membrane attack complex (C5b-9) and opsonizes targeted cells. Complement activation end products and their receptors mediate cell-cell interactions that regulate several biological functions in the extravascular tissue. Signaling of anaphylatoxin receptors or assembly of membrane attack complex promotes cell dedifferentiation, proliferation, and migration in addition to reducing apoptosis. As a result, complement activation in the tumor microenvironment enhances tumor growth and increases metastasis. In this Review, I discuss immune and nonimmune functions of complement proteins and the tumor-promoting effect of complement activation.
Universal alternative splicing of noncoding exons

The human transcriptome is so large, diverse and dynamic that, even after a decade of investigation by RNA sequencing (RNA-Seq), we are yet to resolve its true dimensions. RNA-Seq suffers from an expression-dependent bias that impedes characterization of low-abundance transcripts. We performed targeted single-molecule and short-read RNA-Seq to survey the transcriptional landscape of a single human chromosome (Hsa21) at unprecedented resolution. Our analysis reaches the lower limits of the transcriptome, identifying a fundamental distinction between protein-coding and noncoding gene content: almost every noncoding exon undergoes alternative splicing, producing a seemingly limitless variety of isoforms. Analysis of syntenic regions of the mouse genome shows that few noncoding exons are shared between human and mouse, yet human splicing profiles are recapitulated on Hsa21 in mouse cells, indicative of regulation by a deeply conserved splicing code. We propose that noncoding exons are functionally modular, with alternative splicing generating an enormous repertoire of potential regulatory RNAs and a rich transcriptional reservoir for gene evolution.
To Explore the Validity of Change Scores of the Children's Hand-use Experience Questionnaire (CHEQ) in Children with Unilateral Cerebral Palsy

ABSTRACT Aims: To explore the validity of change scores of the Children's Hand-use Experience Questionnaire (CHEQ). Methods: Analysis of the CHEQ included 44 children (15 girls) between 6–16 years (median 9.0; IQR 8–11) with unilateral cerebral palsy, with baseline and post- (two-week intensive) intervention assessments using the Goal Attainment Scale (GAS) as external anchor for change. Hypotheses on the magnitude of expected change were formulated and correlation coefficients and effect sizes calculated. Receiver operating curve analysis was performed and the area under the curve (AUC) calculated to investigate the ability of CHEQ to discriminate between improvement and non-improvement according to GAS. Results: All hypotheses about the magnitude of change were confirmed supporting longitudinal validity of CHEQ scales to measure change in the perception of bimanual performance. AUCs for the Grasp efficacy and the Time utilization were slightly below, and for the Feeling bothered slightly above the threshold. The latter one accurately discriminating between children that improved and did not improve according to the GAS. Conclusions: Evidence was found that CHEQ scales capture change in bimanual performance but with limited accuracy for two out of three scales. The validity of CHEQ change scores needs to be further explored in a wider population.
On the Security of Compressed Sensing-Based Signal Cryptosystem

With the development of the cyber-physical systems (CPS), the security analysis of the data therein becomes more and more important. Recently, due to the advantage of joint encryption and compression for data transmission in CPS, the emerging compressed sensing (CS)-based cryptosystem has attracted much attention, where security is of extreme importance. The existing methods only analyze the security of the plaintext under the assumption that the key is absolutely safe. However, for sparse plaintext, the prior sparsity knowledge of the plaintext could be exploited to partly retrieve the key, and then the plaintext, from the ciphertext. So, the existing methods do not provide a satisfactory security analysis. In this paper, it is conducted in the information theory frame, where the plaintext sparsity feature and the mutual information of the ciphertext, key, and plaintext are involved. In addition, the perfect secrecy criteria (Shannon-sense and Wyner-sense) are extended to measure the security. While the security level is given, the illegal access risk is also discussed. It is shown that the CS-based cryptosystem achieves the extended Wyner-sense perfect secrecy, but when the key is used repeatedly, both the plaintext and the key could be conditionally accessed.
Embedding of the personalized sentiment engine PERSEUS in an artificial companion

The term Artificial Companion has originally been introduced by Y. Wilks [1] as “…an intelligent and helpful cognitive agent, which appears to know its owner and their habits, chats to them and diverts them, assists them with simple tasks…”. To serve the users' interests by considering a personal knowledge is, furthermore, demanded. The following position paper takes this request as motivation for the embedding of the PERSEUS1 system, which is a personalized sentiment framework based on a Deep Learning approach. We discuss how such an embedding with a group of users should be realized and why the utilization of PERSEUS is beneficial.
Tenascin-C promotes chronic pressure overload-induced cardiac dysfunction, hypertrophy and myocardial fibrosis

Aims: Left ventricular (LV) hypertrophy is characterized by cardiomyocyte hypertrophy and interstitial fibrosis ultimately leading to increased myocardial stiffness and reduced contractility. There is substantial evidence that the altered expression of matrix metalloproteinases (MMP) and Tenascin-C (TN-C) are associated with the progression of adverse LV remodeling. However, the role of TN-C in the development of LV hypertrophy because of chronic pressure overload as well as the regulatory role of TN-C on MMPs remains unknown. Methods and results: In a knockout mouse model of TN-C, we investigated the effect of 10 weeks of pressure overload using transverse aortic constriction (TAC). Cardiac function was determined by magnetic resonance imaging. The expression of MMP-2 and MMP-9, CD147 as well as myocardial fibrosis were assessed by immunohistochemistry. The expression of TN-C was assessed by RT-qPCR and ELISA. TN-C knockout mice showed marked reduction in fibrosis (P < 0.001) and individual cardiomyocytes size (P < 0.01), in expression of MMP-2 (P < 0.05) and MMP-9 (P < 0.001) as well as preserved cardiac function (P < 0.01) in comparison with wild-type mice after 10 weeks of TAC. In addition, CD147 expression was markedly increased under pressure overload (P < 0.01), irrespectively of genotype. TN-C significantly increased the expression of the markers of hypertrophy such as ANP and BNP as well as MMP-2 in H9c2 cells (P < 0.05, respectively). Conclusion: Our results are pointed toward a novel signaling mechanism that contributes to LV remodeling via MMPs upregulation, cardiomyocyte hypertrophy as well as myocardial fibrosis by TN-C under chronic pressure overload.
Parallel Branch and Bound Algorithms on Semi-supervised SVMs

Branch and bound for semi-supervised support vector machines as an exact, globally optimal solution is useful for benchmarking different practical S3VM implementation. But, global optimization can be computationally very demanding. Parallel implementation of the algorithm enables us to reduce computational time significantly and to solve larger problems. Focusing on the time consuming problem of BBS3VM, a novel parallel branch and bound semi-supervised support vector machines (PBBS3VM) is proposed. Experimental results on server dataset show that the proposed algorithm outperforms the classical sequential algorithm in terms of accuracy and greatly reduce the running time using the Linux PCs.
Peekaboo-Where are the Objects? Structure Adjusting Superpixels

This paper addresses the search for a fast and meaningful image segmentation in the context of k-means clustering. The proposed method builds on a widely-used local version of Lloyd's algorithm, called Simple Linear Iterative Clustering (SLIC). We propose an algorithm which extends SLIC to dynamically adjust the local search, adopting superpixel resolution dynamically to structure existent in the image, and thus provides for more meaningful superpixels in the same linear runtime as standard SLIC. The proposed method is evaluated against state-of-the-art techniques and improved boundary adherence and undersegmentation error are observed, whilst still remaining among the fastest algorithms which are tested.
Automated Measurement of Blood Vessels in Tissues from Microscopy Images

The quantification of tunica media thickness in histological cross sections is a ubiquitous exercise in cardiopulmonary research, yet the methods for quantifying medial wall thickness have never been rigorously examined with modern image analysis tools. As a result, inaccurate and cumbersome manual measurements of discrete wall regions along the vessel periphery have become common practice for wall thickness quantification. The aim of this study is to introduce, validate, and facilitate the use of an improved method for medial wall thickness quantification. We describe a novel method of wall thickness calculation based on image skeletonization and compare its results to those of common techniques. Using both theoretical and empirical approaches, we demonstrate the accuracy and superiority of the skeleton‐based method for measuring wall thickness while discussing its interpretation and limitations. Finally, we present a new freely available software tool, the VMI Calculator, to facilitate wall thickness measurements using our novel method. © 2016 by John Wiley & Sons, Inc.
Antibiotics for uncomplicated skin abscesses: systematic review and network meta-analysis

Objective To assess the impact of adjunctive antibiotic therapy on uncomplicated skin abscesses. Design Systematic review and network meta-analysis. Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov. Study selection A BMJ Rapid Recommendation panel provided input on design, important outcomes and the interpretation of the results. Eligible randomised controlled trials (RCTs) included a comparison of antibiotics against no antibiotics or a comparison of different antibiotics in patients with uncomplicated skin abscesses, and reported outcomes prespecified by the linked guideline panel. Review methods Reviewers independently screened abstracts and full texts for eligibility, assessed risk of bias and extracted data. We performed random-effects meta-analyses that compared antibiotics with no antibiotics, along with a limited number of prespecified subgroup hypotheses. We also performed network meta-analysis with a Bayesian framework to compare effects of different antibiotics. Quality of evidence was assessed with The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results Fourteen RCTs including 4198 patients proved eligible. Compared with no antibiotics, antibiotics probably lower the risk of treatment failure (OR 0.58, 95% CI 0.37 to 0.90; low quality), recurrence within 1 month (OR 0.48, 95% CI 0.30 to 0.77; moderate quality), hospitalisation (OR 0.55, 95% CI 0.32 to 0.94; moderate quality) and late recurrence (OR 0.64, 95% CI 0.48 to 0.85; moderate quality). However, relative to no use, antibiotics probably increase the risk of gastrointestinal side effects (trimethoprim and sulfamethoxazole (TMP-SMX): OR 1.28, 95% CI 1.04 to 1.58; moderate quality; clindamycin: OR 2.29, 95% CI 1.35 to 3.88; high quality) and diarrhoea (clindamycin: OR 2.71, 95% CI 1.50 to 4.89; high quality). Cephalosporins did not reduce the risk of treatment failure compared with placebo (moderate quality). Conclusions In patients with uncomplicated skin abscesses, moderate-to-high quality evidence suggests TMP-SMX or clindamycin confer a modest benefit for several important outcomes, but this is offset by a similar risk of adverse effects. Clindamycin has a substantially higher risk of diarrhoea than TMP-SMX. Cephalosporins are probably not effective.
A Drosophila model for LRRK2-linked parkinsonism

Mutations in the leucine-rich repeat kinase (LRRK2) gene cause late-onset autosomal dominant Parkinson's disease (PD) with pleiomorphic pathology. Previously, we and others found that expression of mutant LRRK2 causes neuronal degeneration in cell culture. Here we used the GAL4/UAS system to generate transgenic Drosophila expressing either wild-type human LRRK2 or LRRK2-G2019S, the most common mutation associated with PD. Expression of either wild-type human LRRK2 or LRRK2-G2019S in the photoreceptor cells caused retinal degeneration. Expression of LRRK2 or LRRK2-G2019S in neurons produced adult-onset selective loss of dopaminergic neurons, locomotor dysfunction, and early mortality. Expression of mutant G2019S-LRRK2 caused a more severe parkinsonism-like phenotype than expression of equivalent levels of wild-type LRRK2. Treatment with l-DOPA improved mutant LRRK2-induced locomotor impairment but did not prevent the loss of tyrosine hydroxylase-positive neurons. To our knowledge, this is the first in vivo“gain-of-function” model which recapitulates several key features of LRRK2-linked human parkinsonism. These flies may provide a useful model for studying LRRK2-linked pathogenesis and for future therapeutic screens for PD intervention.
Focused Ultrasound Enhances Central Nervous System Delivery of Bevacizumab for Malignant Glioma Treatment.

Purpose To demonstrate that magnetic resonance (MR) imaging-monitored transcranial focused ultrasound can enhance the delivery of the antiangiogenic monoclonal antibody bevacizumab into the central nervous system (CNS) for glioblastoma multiforme (GBM) treatment. Materials and Methods All animal experiments were approved by the animal committee and adhered to experimental animal care guidelines. Transcranial focused ultrasound exposure in the presence of microbubbles was used to open the blood-brain barrier (BBB) to enhance bevacizumab penetration into the CNS in healthy and glioma-bearing mice. Bevacizumab concentration was quantitated with high-performance liquid chromatography, and Western blot testing was performed to confirm the specific biologic form in the CNS. Penetration of bevacizumab into brain tissue was estimated in vivo by means of contrast material-enhanced MR imaging and quantitative gallium 68 ((68)Ga)-bevacizumab micro-positron emission tomography, and glioma progression was longitudinally followed with T2-weighted MR imaging. Hematoxylin-eosin staining and cluster of differentiation 31 immunostaining were used to assess morphologic changes and vascular inhibition at histologic examination. The two-tailed Student t test and the Mantel-Cox log-rank test were used for statistical analyses, with a significance level of . 05. Results Focused ultrasound significantly enhanced bevacizumab penetration into the CNS by 5.7- to 56.7-fold compared with that in nonexposed brain (both P < .0001). Contrast-enhanced MR imaging indexes correlated with bevacizumab concentration (r = 0.748-0.857) in vivo. Focused ultrasound-enhanced bevacizumab delivery significantly retarded glioma progression, with a significantly increased median survival (median increase in survival time = 135% in the group treated with bevacizumab and focused ultrasound, P < .0001; as compared with 48% in the group treated with bevacizumab alone, P = .0002). Conclusion Focused ultrasound-enhanced bevacizumab delivery can provide an antivascularization normalization effect to suppress glioma. (©) RSNA, 2016 Online supplemental material is available for this article.
Multiconstraint Static Scheduling of Synchronous Dataflow Graphs Via Retiming and Unfolding

Synchronous dataflow graphs (SDFGs) are widely used to represent digital signal processing algorithms and streaming media applications. This paper presents several methods for binding and scheduling SDFGs on a multiprocessor platform. Exploring the state space generated by a self-timed execution (STE) of an SDFG, we present an exact method for static rate-optimal scheduling of SDFGs via implicit retiming and unfolding. By modeling a constraint as an extra enabling condition for the STE, we get a constrained STE which implies a schedule under the constraint. We present a general framework for scheduling SDFGs under constraints on the number of processors, buffer sizes, auto-concurrency, or combinations of them. Exploring the state space generated by the constrained STE, we can check whether a retiming, which leads to a rate-optimal schedule under the processor (or memory) constraint, exists. Combining this with a binary search strategy, we present heuristic methods to find a proper retiming and a static scheduling that schedules the retimed SDFG with optimal rate and with as few processors (or as little storage space) as possible. None of the methods explicitly converts an SDFG to its equivalent homogenous SDFG, the size of which may be tremendously larger than the original SDFG. We perform experiments on several models of real applications and hundreds of synthetic SDFGs. The results show that the exact method outperforms existing methods significantly; our heuristics reduce the resources used and are computationally efficient.
Tree Cover Based Geographic Routing with Guaranteed Delivery

For wireless ad hoc or sensor networks, non-flooding, guaranteed delivery routing protocols are preferred because of limited energy. In this paper we introduce TCGR, a tree cover based geographic routing protocol for wireless networks. We assign to each node a set of short labels such that nodes are embedded in a metric space induced by one or multiple trees. Based on the embedding, we use only greedy routing to deliver packets, i.e., packets are always forwarded to the neighbor closest to the destination. Unlike many previous geographic routing protocols, we guarantee a full success ratio in finding a route to the destination, if such a route exists in the network. Moreover, each node only needs to maintain a small amount of information, which is almost surely bounded by O((logn)^2) bits, and the label size and packet header size are also bounded by O((logn)^2) bits. Simulations show TCGR can achieve remarkable performance in both path stretch and node load.