Miracle-dz/UniFAR-FTUs huggingface dataset:
SpliceVec: distributed feature representations for splice junction prediction

Background Identification of intron boundaries, called splice junctions, is an important part of delineating gene structure and functions. This also provides valuable insights into the role of alternative splicing (AS) in increasing functional diversity of genes. Identification of splice junctions through RNA-seq is by mapping short reads to the reference genome which is prone to errors due to random sequence matches. This encourages identification of splicing junctions through computational methods based on machine learning. Existing models are dependent on feature extraction and selection for capturing splicing signals lying in vicinity of splice junctions. But such manually extracted features are not exhaustive. Methods We introduce distributed feature representation, SpliceVec, to avoid explicit and biased feature extraction generally adopted for such tasks. SpliceVec is based on two widely used distributed representation models in natural language processing. Learned feature representation in form of SpliceVec is fed to multilayer perceptron for splice junction classification task. Results An intrinsic evaluation of SpliceVec indicates that it is able to group true and false sites distinctly. Our study on optimal context to be considered for feature extraction indicates inclusion of entire intronic sequence is better than flanking upstream and downstream region around splice junctions. Further, SpliceVec is invariant to canonical and non-canonical splice junction detection. The proposed model is consistent in its performance even with reduced dataset and class-imbalanced dataset. Conclusions SpliceVec is computationally efficient and can be trained with user defined data as well. Keywords: Splice junction; Feature representation; Alternative splicing; Distributed representation
Guinea pig pancreatic neurons: morphology, neurochemistry, electrical properties, and response to 5-HT.

The morphology, neurochemistry, and electrical properties of guinea pig pancreatic neurons were determined. The majority of neurons expressed choline acetyltransferase (ChAT) immunoreactivity; however, ChAT-negative neurons were also found. Both cholinergic and noncholinergic neurons expressed nitric oxide synthase (NOS) immunoreactivity. Three types of pancreatic neurons were distinguished. Phasic neurons fired action potentials (APs) at the onset of depolarizing current pulse, tonic neurons spiked throughout the duration of a suprathreshold depolarizing pulse, and APs could not be generated in nonspiking neurons, even though they did receive synaptic input. APs were tetrodotoxin sensitive, and all types of neurons received fast and slow excitatory postsynaptic potentials (EPSPs). Fast EPSPs had cholinergic and noncholinergic components. The majority of pancreatic neurons appeared to innervate the acini. NOS- and/or neuropeptide Y-immunoreactive phasic and tonic neurons were found. Microejection of 5-hydroxytryptamine (5-HT) caused a slow depolarization that was inhibited by the 5-HT1P antagonist N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide and mimicked by the 5-HT1Pagonist 6-hydroxyindalpine. A pancreatic 5-HT transporter was located, and inhibition of 5-HT uptake by fluoxetine blocked slow EPSPs in 5-HT-responsive neurons by receptor desensitization.
Network-based integration of systems genetics data reveals pathways associated with lignocellulosic biomass accumulation and processing

Significance Carbon fixation and accumulation as lignocellulosic biomass is of global ecological and industrial importance and most significantly occurs in the form of wood development in trees. Traits of importance in biomass accumulation are highly complex and, aside from environmental factors, are affected by many pathways and thousands of genes. We have applied a network-based data integration method for a systems genetics analysis of genes, processes, and pathways underlying biomass and bioenergy-related traits using segregating Eucalyptus hybrid tree populations. We could link biologically meaningful sets of genes to complex traits and at the same time reveal the molecular basis of trait variation. Such a holistic view of the biology of wood formation will contribute to genetic improvement and engineering of plant biomass. As a consequence of their remarkable adaptability, fast growth, and superior wood properties, eucalypt tree plantations have emerged as key renewable feedstocks (over 20 million ha globally) for the production of pulp, paper, bioenergy, and other lignocellulosic products. However, most biomass properties such as growth, wood density, and wood chemistry are complex traits that are hard to improve in long-lived perennials. Systems genetics, a process of harnessing multiple levels of component trait information (e.g., transcript, protein, and metabolite variation) in populations that vary in complex traits, has proven effective for dissecting the genetics and biology of such traits. We have applied a network-based data integration (NBDI) method for a systems-level analysis of genes, processes and pathways underlying biomass and bioenergy-related traits using a segregating Eucalyptus hybrid population. We show that the integrative approach can link biologically meaningful sets of genes to complex traits and at the same time reveal the molecular basis of trait variation. Gene sets identified for related woody biomass traits were found to share regulatory loci, cluster in network neighborhoods, and exhibit enrichment for molecular functions such as xylan metabolism and cell wall development. These findings offer a framework for identifying the molecular underpinnings of complex biomass and bioprocessing-related traits. A more thorough understanding of the molecular basis of plant biomass traits should provide additional opportunities for the establishment of a sustainable bio-based economy.
A systematic review of the effectiveness of flipped classrooms in medical education

There are inconsistent claims made about the effectiveness of the flipped classroom (FC) in medical education; however, the quality of the empirical evidence used to back up these claims is not evident. The aims of this review are to examine the scope and quality of studies on the FC teaching approach in medical education and to assess the effects of FCs on medical learning.
Near-infrared hyperspectral reflective confocal microscopy

A Near-Infrared HyperSpectral Reflective Confocal Microscopy (NIHS-RCM) is proposed in order to get high resolution images of deep biological tissues such as skin. The microscopy system uses a super-continuum laser for illumination, an acousto-optic tunable filter (AOTF) for rapid selection of near-infrared spectrum, a resonant galvanometer scanner for high speed imaging (15f/s) and near-infrared avalanche diode as detector. Porcine skin and other experiments show that the microscopy system could get deep tissue images (180 μm), and show the different ingredients of tissue with different wavelength of illumination. The system has the ability of selectively imaging of multiple ingredients at deep tissue which can be used in skin diseases diagnosis and other fields.
Heterogeneity of MYCN amplification in neuroblastoma at diagnosis, treatment, relapse, and metastasis

Amplification of the MYCN gene in neuroblastoma is associated with a poor prognosis and is considered to remain unchanged in post‐treatment specimens and metastases. While heterogeneity of MYCN copy number in tumor cells has been reported, serial samples have only been studied in a limited way, and the biologic relevance of this finding is not well understood. We used in situ hybridization on paraffin sections of 102 specimens from 30 patients with MYCN‐amplified neuroblastoma to determine MYCN copy number in the primary tumor, pre‐ and post‐treatment, and in metastatic samples. Nineteen cases (63%) showed diffuse MYCN amplification in all samples tested. Nine cases (30%) showed a reduction in MYCN copy number: five cases with diffuse amplification subsequently showed focal amplification, one case with diffuse MYCN amplification showed MYCN gain after treatment, and three focally amplified cases were non‐amplified in later specimens. In two cases (7%), focal amplification became diffuse in subsequent samples. Histology was not predictive of the temporal or spatial pattern of MYCN amplification for a particular tumor. If extent of amplification (focal vs. diffuse) is not considered, 26/30 (87%) of cases were consistently MYCN‐amplified. However, our data suggest that MYCN status can be heterogeneous between tumor sites, during tumor progression or following treatment, challenging the notion that MYCN copy number does not change for a particular neuroblastoma. Assessing the biologic significance of MYCN heterogeneity will require larger studies of clinically annotated tumor samples, and will depend on interpreting heterogeneity in MYCN status in combination with other genetic changes. © 2016 Wiley Periodicals, Inc.
Herpes Simplex Virus Type 1 Infects Enteric Neurons and Triggers Gut Dysfunction via Macrophage Recruitment

Herpes Simplex Virus type 1 (HSV-1), a neurotropic pathogen widespread in human population, infects the enteric nervous system (ENS) in humans and rodents and causes intestinal neuromuscular dysfunction in rats. Although infiltration of inflammatory cells in the myenteric plexus and neurodegeneration of enteric nerves are common features of patients suffering from functional intestinal disorders, the proof of a pathogenic link with HSV-1 is still unsettled mainly because the underlying mechanisms are largely unknown. In this study we demonstrated that following intragastrical administration HSV-1 infects neurons within the myenteric plexus resulting in functional and structural alterations of the ENS. By infecting mice with HSV-1 replication-defective strain we revealed that gastrointestinal neuromuscular anomalies were however independent of viral replication. Indeed, enteric neurons exposed to UV-inactivated HSV-1 produced monocyte chemoattractant protein-1 (MCP-1/CCL2) to recruit activated macrophages in the longitudinal muscle myenteric plexus. Infiltrating macrophages produced reactive oxygen and nitrogen species and directly harmed enteric neurons resulting in gastrointestinal dysmotility. In HSV-1 infected mice intestinal neuromuscular dysfunctions were ameliorated by in vivo administration of (i) liposomes containing dichloromethylene bisphosphonic acid (clodronate) to deplete tissue macrophages, (ii) CCR2 chemokine receptor antagonist RS504393 to block the CCL2/CCR2 pathway, (iii) Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and AR-C 102222 to quench production of nitrogen reactive species produced via iNOS. Overall these data demonstrate that HSV-1 infection makes enteric neurons recruit macrophages via production of a specific chemoattractant factor. The resulting inflammatory reaction is mandatory for intestinal dysmotility. These findings provide insights into the neuro-immune communication that occurs in the ENS following HSV-1 infection and allow recognition of an original pathophysiologic mechanism underlying gastrointestinal diseases as well as identification of novel therapeutic targets.
Quantification of nitrogen in the liquid fraction and in vitro assessment of lysine bioavailability in the solid fraction of soybean meal hydrolysates

ABSTRACT Soybean meal (SBM) is a product generated from the manufacture of soybean oil and has the potential for use as a source of fermentable sugars for ethanol production or as a protein source for animal feeds. Knowing the levels of nitrogen available from ammonium is a necessary element of the ethanolic fermentation process while identifying the levels of essential amino acids such as lysine is important in determining usage as a feed source. As such the purpose of this study was to quantify total nitrogen and ammonium in the liquid fraction of hydrolyzed SBM and to evaluate total and bioavailable lysine in the solid fraction of the hydrolyzed SBM. The effects of acid concentration, cellulase and β-glucosidase on total and ammonium nitrogen were studied with analysis indicating that higher acid concentrations increased nitrogen compounds with ammonium concentrations ranging from 0.20 to 1.24 g L−1 while enzymatic treatments did not significantly increase nitrogen levels. Total and bioavailable lysine was quantified by use of an auxotrophic gfpmut3 E.coli whole-cell bioassay organism incapable of lysine biosynthesis. Acid and enzymatic treatments were applied with lysine bioavailability increasing from a base of 82% for untreated SBM to up to 97%. Our results demonstrated that SBM has the potential to serve in ethanolic fermentation and as an optimal source essential amino acid lysine.
Endogenous markers for kidney function in children: a review

Abstract Although glomerular filtration rate (GFR) in children can be measured using a gold-standard technique following injection of an exogenous marker, this invasive and cumbersome technique is not widely available and GFR is commonly estimated using serum levels of endogenous markers. Creatinine, urea, cystatin C, beta-trace protein, and beta-2 microglobulin are well-established endogenous markers of kidney function. These markers differ in site of production and effects of diet and medication, as well as renal-tubular handling and extra-renal elimination. For each marker, different methods are available for measurement. Importantly, the measurements of creatinine and cystatin C have recently been standardized with the introduction of international reference standards. In order to allow estimation of GFR from serum marker concentrations, different equations for estimated GFR (eGFR) have been developed in children, using simple or more complex regression strategies with gold standard GFR measurements as a dependent variable. As a rule, estimation strategies relying on more than one marker – either by calculating the average of single parameter equations or by using more complex equations incorporating several parameters – outperform eGFR estimations using only a single marker. This in-depth review will discuss the physiology, measurement and clinical use of creatinine, urea, cystatin C, beta-trace protein, and beta-2 microglobulin in children. It will also address the generation of eGFR equations in children and provide an overview of currently available eGFR equations for the pediatric age group.
A Rapid and Semi-Quantitative Gold Nanoparticles Based Strip Sensor for Polymyxin B Sulfate Residues

Increasing attention is now being directed to the utilization of polymyxin B (PMB) as a last-line treatment for life-threatening infections caused by multidrug resistant Gram-negative bacteria. Unfortunately, polymyxins resistance is also increasingly reported, leaving a serious threat to human health. Therefore, the establishment of rapid detection methods for PMB residues is highly essential to ensure public health. In this study, two monoclonal antibodies (mAb; 2A2 and 3C6) were obtained using PMB-bovine serum albumin as the immunogen and PMB-ovalbumin as the coating antigen, which were prepared with N-(γ-maleimidobutyryloxy) succinimide ester and glutaraldehyde as cross-linking agents, respectively. Through an indirect competitive enzyme-linked immunosorbent assay, resultant two mAbs were compared and the results indicated that 3C6 showed higher sensitivity with a half maximum inhibition concentration of 13.13 ng/mL. Based on 3C6, a gold nanoparticles (AuNPs)-based immunochromatographic test (ICT) strip was then established, the mechanism of which is that free PMB competes with the fixed coating antigen to combine with mAb labeled by AuNPs. Using ICT strip to detect milk and animal feed samples revealed the visible detection limits were 25 ng/mL and 500 μg/kg, respectively and the cutoff limits were 100 ng/mL and 1000 μg/kg, respectively. The ICT strip provides results within 15 min, facilitating rapid and semi-quantitative analysis of PMB residues in milk and animal feed.
Plasma augmented laser welding and its applications

Abstract The present paper is concerned with hybrid laser-arc welding processes. Previous work is reviewed, and attention is then focused on plasma augmented laser welding. Features, application parameters, and mechanisms of the process are discussed, followed by a summary of the research and development work undertaken by the present authors, concentrating on application areas where the process can offer distinct advantages, such as tailor welded blanks, lap welding of coated steels, welding using additional filler material, and high speed welding of thin sheet metals.
Performance Visualization for TAU Instrumented Scientific Workflows

In exascale scientific computing, it is essential to efficiently monitor, evaluate and improve performance. Visualization and especially visual analytics are useful and inevitable techniques in the exascale computing era to enable such a human-centered experience. In this ongoing work, we present a visual analytics framework for performance evaluation of scientific workflows. Ultimately, we aim to solve two current challenges: the capability to deal with workflows, and the scalability toward exascale scenario. On the way to achieve these goals, in this work, we first incorporate TAU (Tuning and Analysis Utilities) instrumentation tool and improve it to accommodate workflow measurements. Then we establish a web-based visualization framework, whose back end handles data storage, query and aggregation, while front end presents the visualization and takes user interaction. In order to support the scalability, a few level-of-detail mechanisms are developed. Finally, a chemistry workflow use case is adopted to verify our methods.
Treatment of selective serotonin reuptake inhibitor-resistant depression in adolescents: predictors and moderators of treatment response.

OBJECTIVE To advance knowledge regarding strategies for treating selective serotonin reuptake inhibitor (SSRI)-resistant depression in adolescents, we conducted a randomized controlled trial evaluating alternative treatment strategies. In primary analyses, cognitive-behavioral therapy (CBT) combined with medication change was associated with higher rates of positive response to short-term (12-week) treatment than medication alone. This study examines predictors and moderators of treatment response, with the goal of informing efforts to match youths to optimal treatment strategies. METHOD Youths who had not improved during an adequate SSRI trial (N = 334) were randomized to an alternative SSRI, an alternative SSRI plus CBT, venlafaxine, or venlafaxine plus CBT. Analyses examined predictors and moderators of treatment response. RESULTS Less severe depression, less family conflict, and absence of nonsuicidal self-injurious behavior predicted better treatment response status. Significant moderators of response to CBT + medication (combined) treatment were number of comorbid disorders and abuse history; hopelessness was marginally significant. The CBT/combined treatment superiority over medication alone was more evident among youths who had more comorbid disorders (particularly attention-deficit/hyperactivity disorder and anxiety disorders), no abuse history, and lower hopelessness. Further analyses revealed a stronger effect of combined CBT + medication treatment among youths who were older and white and had no nonsuicidal self-injurious behavior and longer prestudy pharmacotherapy. CONCLUSIONS Combined treatment with CBT and antidepressant medication may be more advantageous for adolescents whose depression is comorbid with other disorders. Given the additional costs of adding CBT to medication, consideration of moderators in clinical decision making can contribute to a more personalized and effective approach to treatment.
Exploration and Optimization of User Experience in Viewing Videos on a Mobile Phone

Compared with viewing videos on PCs or TVs, mobile users have different experiences in viewing videos on a mobile phone due to different device features such as screen size and distinct usage contexts. To understand how mobile user's viewing experience is impacted, we conducted a field user study with 42 participants in two typical usage contexts using a custom-designed iPhone application. With user's acceptance of mobile video quality as the index, the study addresses four influence aspects of user experiences, including context, content type, encoding parameters and user profiles. Accompanying the quantitative method (acceptance assessment), we used a qualitative interview method to obtain a deeper understanding of a user's assessment criteria and to support the quantitative results from a user's perspective. Based on the results from data analysis, we advocate two user-driven strategies to adaptively provide an acceptable quality and to predict a good user experience, respectively. There are two main c.
Bystander Effect Fuels Human Induced Pluripotent Stem Cell‐Derived Neural Stem Cells to Quickly Attenuate Early Stage Neurological Deficits After Stroke

Present therapies for stroke rest with tissue plasminogen activator (tPA), the sole licensed antithrombotic on the market; however, tPA's effectiveness is limited in that the drug not only must be administered less than 3–5 hours after stroke but often exacerbates blood‐brain barrier (BBB) leakage and increases hemorrhagic incidence. A potentially promising therapy for stroke is transplantation of human induced pluripotent stem cell‐derived neural stem cells (hiPSC‐NSCs). To date, the effects of iPSCs on injuries that take place during early stage ischemic stroke have not been well studied. Consequently, we engrafted iPSC‐NSCs into the ipsilesional hippocampus, a natural niche of NSCs, at 24 hours after stroke (prior to secondary BBB opening and when inflammatory signature is abundant). At 48 hours after stroke (24 hours after transplant), hiPSC‐NSCs had migrated to the stroke lesion and quickly improved neurological function. Transplanted mice showed reduced expression of proinflammatory factors (tumor necrosis factor‐α, interleukin 6 [IL‐6], IL‐1β, monocyte chemotactic protein 1, macrophage inflammatory protein 1α), microglial activation, and adhesion molecules (intercellular adhesion molecule 1, vascular cell adhesion molecule 1) and attenuated BBB damage. We are the first to report that engrafted hiPSC‐NSCs rapidly improved neurological function (less than 24 hours after transplant). Rapid hiPSC‐NSC therapeutic activity is mainly due to a bystander effect that elicits reduced inflammation and BBB damage.