Miracle-dz/UniFAR-FTUs huggingface dataset:
MiRTDL: A Deep Learning Approach for miRNA Target Prediction

MicroRNAs (miRNAs) regulate genes that are associated with various diseases. To better understand miRNAs, the miRNA regulatory mechanism needs to be investigated and the real targets identified. Here, we present miRTDL, a new miRNA target prediction algorithm based on convolutional neural network (CNN). The CNN automatically extracts essential information from the input data rather than completely relying on the input dataset generated artificially when the precise miRNA target mechanisms are poorly known. In this work, the constraint relaxing method is first used to construct a balanced training dataset to avoid inaccurate predictions caused by the existing unbalanced dataset. The miRTDL is then applied to 1,606 experimentally validated miRNA target pairs. Finally, the results show that our miRTDL outperforms the existing target prediction algorithms and achieves significantly higher sensitivity, specificity and accuracy of 88.43, 96.44, and 89.98 percent, respectively. We also investigate the miRNA target mechanism, and the results show that the complementation features are more important than the others.
Therapeutic Angiogenesis Using Vascular Endothelial Growth Factor

Therapeutic angiogenesis using vascular endothelial growth factor can reduce tissue ischemia by simulating the natural process of angiogenesis. Vascular endothelial growth factor not only stimulates endothelial cells to proliferate and migrate, but also mobilizes endothelial progenitor cells and achieves vascular protection. Besides direct administration of angiogenic proteins, plasmids and viral vectors carrying angiogenic genes have been used. Animal experiments have shown promise with evidence of neovascularization and improved perfusion in the target myocardium. Initial phase I and II clinical trials results are encouraging and reflect the potential success of therapeutic angiogenesis as a clinical modality for the treatment of ischemic heart disease. This review discusses the role of vascular endothelial growth factor in therapeutic angiogenesis, along with the problems and considerations of this approach as a treatment strategy.
Novel PEGylated Basal Insulin LY2605541 Has a Preferential Hepatic Effect on Glucose Metabolism

The impact of the novel basal insulin LY2605541 (LY) on hepatic and nonhepatic glucose uptake (non-HGU) was evaluated. Conscious dogs underwent euglycemic clamps with tracer and hepatic balance measurements. Clamp period infusions were peripheral venous regular insulin (0.1 nmol ⋅ kg−1 ⋅ h−1 [control], n = 6) or LY (bolus [nmol/kg], continuous [nmol ⋅ kg−1 ⋅ h−1]: 0.5, 0.5 [n = 6]; 0.375, 0.375 [n = 5]; 0.25, 0.25 [n = 4]), somatostatin, and glucose, as well as intraportal glucagon (basal). During the clamp, the dogs switched from net hepatic glucose output to uptake (rates reached 2.1 ± 1.2, 0.9 ± 2.1, 8.6 ± 2.3, and 6.0 ± 1.1 µmol ⋅ kg−1 ⋅ min−1 within 5 h in control, LY0.25, LY0.375, and LY0.5, respectively). Non-HGU in LY increased less than in control; the ratio of change from basal in non-HGU to change in net hepatic glucose balance, calculated when glucose infusion rates (GIRs) were ~20 µmol ⋅ kg-1 ⋅ min−1 in all groups, was higher in control (1.17 ± 0.38) versus LY0.25 (0.39 ± 0.33), LY0.375 (−0.01 ± 0.13), and LY0.5 (−0.09 ± 0.07). Likewise, the change from baseline in glucose Rd-to-Ra ratio was greatest in control (1.4 ± 0.3 vs. 0.6 ± 0.4, 0.5 ± 0.2, and 0.6 ± 0.2 in LY0.25, LY0.375, and LY0.5, respectively). In contrast to exogenously administered human insulin, LY demonstrated preferential hepatic effects, similar to endogenously secreted insulin. Therefore, the analog might reduce complications associated with current insulin therapy.
A Resolved Debris Disk around the G2 V Star HD 107146

We present resolved scattered-light images of the debris disk around HD 107146, a G2 star 28.5 pc from the Sun. This is the first debris disk to be resolved in scattered light around a solar-type star. We observed it with the Hubble Space Telescope/Advanced Camera for Surveys coronagraph, using a 1. ″8 occulting spot and the F606W (broad V) and F814W (broad I) filters. Within 2'' from the star, the image is dominated by point-spread function subtraction residuals. Outside this limit, the disk looks featureless, except for a northeast-southwest brightness asymmetry that we attribute to forward scattering. The disk has scattered-light fractional luminosities of (Lsca/L*)F606W = × 10-5 and (Lsca/L*)F814W = × 10-5, and it is detected up to 6. ″5 away from the star. To map the surface density of the disk, we deproject it by 25° ± 5°, divide by the dust-scattering phase (gF606W = 0.3 ± 0.1, gF814W = 0.2 ± 0.1), and correct for the geometric dilution of starlight. Within the errors, the surface density has the same shape in each bandpass, and it appears to be a broad (85 AU) ring with most of the opacity concentrated at 130 AU. The ratio of the relative luminosity in F814W to that in F606W has the constant value of 1.3 ± 0.3, with the error dominated by uncertainties in the value of g in each filter. An examination of far-infrared and submillimeter measurements suggests the presence of small grains. The colors and the derived values of g are consistent with the presence of dust particles smaller than the radiation pressure limit. Possible scenarios that may explain the shape of the surface density profile are the creation of a small planet or the scattering and circularization of a large one.
Role of Pregnane X Receptor in Control of All-Trans Retinoic Acid (ATRA) Metabolism and Its Potential Contribution to ATRA Resistance

Although all-trans-retinoic acid (ATRA) is an effective treatment for acute promyelocytic leukemia and several solid tumors, its use is limited by resistance due to increased metabolism. The most studied mechanism for ATRA resistance is the autoinduced metabolism regulated by the retinoic acid receptor-CYP26 pathway. However, treatment of cancer is usually not done with a single antineoplastic agent, but with a variety of combined chemotherapy regimens, including several anticancer drugs, and other concomitantly administered supportive drugs. Pregnane X receptor (PXR), an orphan nuclear receptor that functions as a ligand-activated transcription factor, serves as an important xenobiotic sensor regulating metabolism and elimination. Many prescription drugs are PXR ligands, which can activate PXR target genes, including phase I enzyme, phase II enzyme, and transporter genes. The present study was designed to examine the role of PXR in ATRA metabolism. Due to the marked species differences in response to PXR ligands, Pxr-null, wild-type, and PXR-humanized transgenic mouse models were used. In addition to pregnenolone 16α-carbonitrile, several clinically relevant PXR ligands (rifampicin and dexamethasone) all increased ATRA metabolism both in vitro and in vivo, which was PXR-dependent, and up-regulation of Cyp3a was the major contributor. Furthermore, induction of the Mdr1a, Mrp3, and Oatp2 genes was also observed. This study suggested that coadministration of PXR ligands can increase ATRA metabolism through activation of the PXR-CYP3A pathway, which might be a mechanism for some form of ATRA resistance. Other PXR target transporters might also be involved.
Opening up the HIV epidemic: a review of HIV seropositive status disclosure among people who inject drugs

ABSTRACT HIV status disclosure plays a crucial role in reducing risk behaviors of drug and sexual partners and thereby limiting HIV transmission. As people who inject drugs (PWID) bear a significant HIV burden and disclosure research among PWID is relatively few, we reviewed the literature to highlight what is known about disclosure among HIV-positive PWID. Searches of articles published from 2000 to 2015 yielded 17 studies addressing different aspects of disclosure, and results are presented by major themes. Our results suggest that despite the difficulties, most PWID (64–86%) disclose their HIV-positive status to trusted individuals (family members and intimate sexual partners) and to those who are known to be HIV-positive. Disclosure to non-intimate sexual partners and fellow drug users is relatively lower. Disclosure decision-making is primarily driven by the perceived positive and negative consequences of disclosure. Subsequent risk reduction practices following disclosure are influenced by the feeling of responsibility, as well as partners’ willingness to accept risk. Cultural family values, ethnicity, and different localities were several contextual factors that affect patterns of disclosure and risk behaviors of PWID. Areas for future research are recommended.
Effects of high-dose ulinastatin on inflammatory response and pulmonary function in patients with type-A aortic dissection after cardiopulmonary bypass under deep hypothermic circulatory arrest.

OBJECTIVES To investigate effects of high-dose ulinastatin on the release of proinflammatory cytokines and lung injury in patients with aortic dissection after cardiopulmonary bypass (CPB) under deep hypothermic circulatory arrest (DHCA). DESIGN A prospective, randomized and double-blinded study. SETTING A teaching hospital. PARTICIPANTS Thirty-six patients with acute type-A aortic dissection undergoing cardiac surgery using CPB under DHCA. INTERVENTIONS These patients randomly were selected to received total doses of 20,000 units/kg of ulinastatin (n = 18) or 0.9% saline (control, n = 18) at 3 time points (after anesthetic induction, before aortic cross-clamp, and after aortic cross-clamp release). MEASUREMENTS AND MAIN RESULTS Tumor necrosis factor-alpha, interleukin 6, interleukin 8 and polymorphonuclear neutrophil elastase (PMNE) were measured after anesthetic induction (T0), 30 minutes (T1) after aortic cross-clamp, 3 (T2), 6 (T3) and 9 (T4) hours after weaning from CPB. Except for T1, pulmonary data, such as alveolar-arterial oxygen pressure difference, physiologic deadspace, peak inspiratory pressure, plateau pressure, static compliance and dynamic compliance, were obtained at the same time points. Concentrations of cytokines and PMNE were significantly lower in the ulinastatin group than the control group from T1 to T4, and peaked at T2 between the 2 groups. Compared with the pulmonary data of the control group at T2~T4, postoperative alveolar-arterial oxygen pressure difference, physiologic deadspace, peak inspiratory pressure, and plateau pressure significantly were lower, and static compliance and dynamic compliance higher in the ulinastatin group. Significantly shorter intubation time and intensive care unit stay were found in the ulinastatin group. CONCLUSIONS High-dose ulinastatin attenuates the elevation of cytokines and PMNE, reduces the pulmonary injury and improves the pulmonary function after CPB under DHCA. Consequently, it shortens the time of intubation and intensive care unit stay.
Mimics That of Calreticulin and not Calnexin I Molecules Is Tapasin Dependent and Association of ERp57 with Mouse MHC Class

Before peptide binding in the endoplasmic reticulum, the class I heavy (H) chain- b 2 -microglobulin complexes are detected in association with TAP and two chaperones, TPN and CRT. Recent studies have shown that the thiol-dependent reductase, ERp57, is also present in this peptide-loading complex. However, it remains controversial whether the association of ERp57 with MHC class I molecules precedes their combined association with the peptide-loading complex or whether ERp57 only associates with class I molecules in the presence of TPN. Resolution of this controversy could help determine the role of ERp57 in class I folding and/or assembly. To deﬁne the mouse class I H chain structures involved in interaction with ERp57, we tested chaperone association of L d mutations at residues 134 and 227/229 (previously implicated in TAP association), residues 86/88 (which ablate an N -linked glycan), and residue 101 (which disrupts a disulﬁde bond). The association of ERp57 with each of these mutant H chains showed a complete concordance with CRT, TAP, and TPN but not with calnexin. Furthermore, ERp57 failed to associate with H chain in TPN-deﬁcient . 220 cells. These combined data demonstrate that, during the assembly of the peptide-loading complex, the association of ERp57 with mouse class I is TPN dependent and parallels that of CRT and not calnexin. The Journal of Immunology, 2001, 166: 6686–6692.
Psychometric Properties of the Revised Teachers' Attitude Toward Inclusion Scale

This paper presents the psychometric properties of a questionnaire measure that updates and extends Larrivee and Cook's (1979) Opinions Relative to Mainstreaming Scale in terms of structure, terminology, and language. The revised scale was tested using a sample of 106 teachers based in inclusive mainstream schools. Using Principal Component Analysis, a four-factor structure was found for the “attitudes toward inclusion” section of the revised scale: (a) problems of inclusion of special educational needs (SEN) children in mainstream classes; (b) social benefits for all of the inclusion of SEN pupils in mainstream classes; (c) implications of inclusion for teaching practice; and (d) implications for addressing the needs of children with SEN. Moderate to good reliability was found for these components (Cronbach's α: .76–.86). In conclusion, the updated and revised Teachers' Attitude to Inclusion Scale (TAIS) shows promise of being a reliable and valid measure for both research and applied purposes.
Surgical and Endovascular Treatment of Extracranial Carotid Stenosis.

BACKGROUND Carotid endarterectomy (CEA) and carotid artery stenting (CAS) can be used to prevent stroke due to arteriosclerotic lesions of the carotid artery. In Germany, legally mandated quality assurance (QA) enables the evaluation of outcome quality after CEA and CAS performed under routine conditions. METHODS We analyzed data on all elective CEA and CAS procedures performed over the periods 2009-2014 and 2012-2014, respectively. The endpoints of the study were the combined in-hospital stroke and death rate, stroke rate and mortality separately, local complications, and other complications. We analyzed the raw data with descriptive statistics and carried out a risk-adjusted analysis of the association of clinically unalterable variables with the risk of stroke and death. All analyses were performed separately for CEA and CAS. RESULTS Data were analyzed from 142 074 CEA procedures (67.8% of them in men) and 13 086 CAS procedures (69.7% in men). The median age was 72 years (CEA) and 71 years (CAS). The periprocedural rate of stroke and death after CEA was 1.4% for asymptomatic and 2.5% for symptomatic stenoses; the corresponding rates for CAS were 1.7% and 3.7%. Variables associated with increased risk included older age, higher ASA class (ASA = American Society of Anesthesiologists), symptomatic vs. asymptomatic stenosis, 50-69% stenosis, and contralateral carotid occlusion (for CEA only). CONCLUSION These data reveal a low periprocedural rate of stroke or death for both CEA and CAS. This study does however not permit any conclusions as to the superiority or inferiority of CEA and CAS.
Algorithmic Composition of Melodies with Deep Recurrent Neural Networks

A big challenge in algorithmic composition is to devise a model that is both easily trainable and able to reproduce the long-range temporal dependencies typical of music. Here we investigate how artificial neural networks can be trained on a large corpus of melodies and turned into automated mu- sic composers able to generate new melodies coherent with the style they have been trained on. We employ gated-recurrent unit (GRU) networks that have been shown to be particularly efficient in learning complex sequential activations with arbitrary long time lags. Our model processes rhythm and melody in parallel while modeling the relation between these two properties. Using such an approach, we were able to generate interesting complete melodies or suggest possible continuations of a melody fragment that is coherent with the characteristics of the fragment itself.
Electroconvulsive therapy for depression.

n engl j med 358;6 www.nejm. org february 7, 2008 645 To the Editor: Lisanby (Nov. 8 issue)1 reports, in her Clinical Therapeutics article, on the use of electroconvulsive therapy (ECT) in patients with depression. ECT is rarely recommended in patients with schizophrenia (except for those with acute catatonia). In the guidelines of the German Medical Association, ECT is restricted as a treatment for patients with depression who have psychotic and suicidal symptoms.2 Modern ECT protocols for investigating the use of ECT in patients with schizophrenia are limited. To date, data are available from only 26 studies with a total of 798 such patients.3 However, it is noteworthy that short-term responses are promising, and common predictors of a response to ECT in both schizophrenic and affective disorders, such as delusions and hallucinations, have been reported. Although these observations have led to recommendations to preferentially use ECT in certain subtypes of depression, such a syndromal approach is lacking in schizophrenia. Future investigations may lead to a broadening of ECT indications to include specific subtypes of schizophrenia.
An Enhancer Element Harboring Variants Associated with Systemic Lupus Erythematosus Engages the TNFAIP3 Promoter to Influence A20 Expression

Functional characterization of causal variants present on risk haplotypes identified through genome-wide association studies (GWAS) is a primary objective of human genetics. In this report, we evaluate the function of a pair of tandem polymorphic dinucleotides, 42 kb downstream of the promoter of TNFAIP3, (rs148314165, rs200820567, collectively referred to as TT>A) recently nominated as causal variants responsible for genetic association of systemic lupus erythematosus (SLE) with tumor necrosis factor alpha inducible protein 3 (TNFAIP3). TNFAIP3 encodes the ubiquitin-editing enzyme, A20, a key negative regulator of NF-κB signaling. A20 expression is reduced in subjects carrying the TT>A risk alleles; however, the underlying functional mechanism by which this occurs is unclear. We used a combination of electrophoretic mobility shift assays (EMSA), mass spectrometry (MS), reporter assays, chromatin immunoprecipitation-PCR (ChIP-PCR) and chromosome conformation capture (3C) EBV transformed lymphoblastoid cell lines (LCL) from individuals carrying risk and non-risk TNFAIP3 haplotypes to characterize the effect of TT>A on A20 expression. Our results demonstrate that the TT>A variants reside in an enhancer element that binds NF-κB and SATB1 enabling physical interaction of the enhancer with the TNFAIP3 promoter through long-range DNA looping. Impaired binding of NF-κB to the TT>A risk alleles or knockdown of SATB1 expression by shRNA, inhibits the looping interaction resulting in reduced A20 expression. Together, these data reveal a novel mechanism of TNFAIP3 transcriptional regulation and establish the functional basis by which the TT>A risk variants attenuate A20 expression through inefficient delivery of NF-κB to the TNFAIP3 promoter. These results provide critical functional evidence supporting a direct causal role for TT>A in the genetic predisposition to SLE.
International Journal of Organ Transplantation Medicine Isolation and Characterization of Human Mesenchymal Stem Cells Derived from Human Umbilical Cord Wharton's Jelly and Amniotic Membrane

Background: Mesenchymal stem cells (MSCs) have a capacity for self-renewal and multi-potential differentiations. These cells are considered powerful sources for cell therapy in regenerative medicine and tissue engineering. The cells can be isolated from various tissues; however, harvesting from human umbilical cord and amniotic membrane is easy and accessible source.
PavA of Streptococcus pneumoniae Modulates Adherence, Invasion, and Meningeal Inflammation

ABSTRACT Pneumococcal adherence and virulence factor A (PavA) is displayed to the cell outer surface of Streptococcus pneumoniae and mediates pneumococcal binding to immobilized fibronectin. PavA, which lacks a typical gram-positive signal sequence and cell surface anchorage motif, is essential for pneumococcal virulence in a mouse infection model of septicemia. In this report the impact of PavA on pneumococcal adhesion to and invasion of eukaryotic cells and on experimental pneumococcal meningitis was investigated. In the experimental mouse meningitis model, the virulence of the pavA knockout mutant of S. pneumoniae D39, which did not show alterations of subcellular structures as indicated by electron microscopic studies, was strongly decreased. Pneumococcal strains deficient in PavA showed substantially reduced adherence to and internalization of epithelial cell lines A549 and HEp-2. Similar results were obtained with human brain-derived microvascular endothelial cells and human umbilical vein-derived endothelial cells. Attachment and internalization of pneumococci were not significantly affected by preincubation or cocultivations of pneumococci with anti-PavA antisera. Pneumococcal adherence was also not significantly affected by the addition of PavA protein. Complementation of the pavA knockout strain with exogenously added PavA polypeptide did not restore adherence of the mutant. These data suggest that PavA affects pneumococcal colonization by modulating expression or function of important virulence determinants of S. pneumoniae.
Towards automated testing and fixing of re-engineered Feature Models

Mass customization of software products requires their efficient tailoring performed through combination of features. Such features and the constraints linking them can be represented by Feature Models (FMs), allowing formal analysis, derivation of specific variants and interactive configuration. Since they are seldom present in existing systems, techniques to re-engineer FMs have been proposed. There are nevertheless error-prone and require human intervention. This paper introduces an automated search-based process to test and fix FMs so that they adequately represent actual products. Preliminary evaluation on the Linux kernel FM exhibit erroneous FM constraints and significant reduction of the inconsistencies.
SENSORY PLASTICITY

A prosthetic challenge is offered by the possibility of using the tactile sensory system to carry optical information from an artificial receptor to the brain. After a training period, sensory plasticity may enable such information to be perceived as three-dimensional “visual” information. Sensory plasticity is defined here as the ability of one sensory system (receptors, afferent pathways, and the central nervous system representation) to assume the functions of another system. Sensory information reaches the brain in the form of nerve impulses (Rushton 1961). There is no doubt that the temporal and spatial patterns of nerve impulses provide the basis of our sensory perception; the coding of information in the form of nerve impulse patterns is a fundamental concept in ncurophysiology and psychology (MeZzack & W a l l 1962). For example, visual information is sent along the optic nerves in the form of patterns of nerve action potentials. The optical images, per se, reach no farther than the retinal receptors. The brain must interpret the nerve impulses as a visual image, after decoding the patterns of afferent impulses. A large body of evidence indicates that the brain demonstrates both motor and sensory plasticity. The aim of this paper is to examine the evidence for plasticity as a fundamental basis for the development of a high resolution vision substitution system.