Miracle-dz/UniFAR-FTUs huggingface dataset:
The sarcoplasmic reticulum luminal thiol oxidase ERO1 regulates cardiomyocyte excitation‐coupled calcium release and response to hemodynamic load

Two related ER oxidation 1 (ERO1) proteins, ERO1α and ERO1β, dynamically regulate the redox environment in the mammalian endoplasmic reticulum (ER). Redox changes in cysteine residues on intralumenal loops of calcium release and reuptake channels have been implicated in altered calcium release and reuptake. These findings led us to hypothesize that altered ERO1 activity may affect cardiac functions that are dependent on intracellular calcium flux. We established mouse lines with loss of function insertion mutations in Ero1l and Ero1lb encoding ERO1α and ERO1β. The peak amplitude of calcium transients in homozygous Ero1α, mutant adult cardiomyocytes was reduced to 42.0 ± 2.2% (n=10, P≤0.01) of values recorded in wild‐type cardiomyocytes. Decreased ERO1 activity blunted cardiomyocyte inotropic response to adrenergic stimulation and sensitized mice to adrenergic blockade. Whereas all 12 wild‐type mice survived challenge with 4 mg/kg esmolol, 6 of 8 compound Ero1l and Ero1lb mutant mice succumbed to this level of β adrenergic blockade (P≤0.01). In addition, mice lacking ERO1α were partially protected against progressive heart failure in a transaortic constriction model [at 10 wk postprocedure, fractional shortening was 0.31 ±0.02 in the mutant (n=20) vs. 0.23±0.03 in the wild type (n=18); P≤0.01]. These findings establish a role for ERO1 in calcium homeostasis and suggest that modifying the lumenal redox environment may affect the progression of heart failure. —Chin, K. T. , Kang, G. , Qu, J., Gardner, L. B. , Coetzee, W. A. , Zito, E. , Fishman, G. I. , Ron, R. The sarcoplasmic reticulum luminal thiol oxidase ERO1 regulates cardiomyocyte excitation‐coupled calcium release and response to hemodynamic load. FASEB J. 25, 2583–2591 (2011). www.fasebj. org
Managing the Planned Cessation of a Global Supply Market: Lessons Learned From the Global Cessation of the Trivalent Oral Poliovirus Vaccine Market

Abstract The Polio Eradication and Endgame Strategic Plan 2013-2018 calls for the phased withdrawal of OPV, beginning with the globally synchronized cessation of tOPV by mid 2016. From a global vaccine supply management perspective, the strategy provided two key challenges; (1) the planned cessation of a high volume vaccine market; and (2) the uncertainty of demand leading and timeline as total vaccine requirements were contingent on epidemiology. The withdrawal of trivalent OPV provided a number of useful lessons that could be applied for the final OPV cessation. If carefully planned for and based on a close collaboration between programme partners and manufacturers, the cessation of a supply market can be undertaken with a successful outcome for both parties. As financial risks to manufacturers increase even further with OPV cessation, early engagement from the cessation planning phase and consideration of production lead times will be critical to ensure sufficient supply throughout to achieve programmatic objectives. As the GPEI will need to rely on residual stocks including with manufacturers through to the last campaign to achieve its objectives, the GPEI should consider to decide on and communicate a suitable mechanism for co-sharing of financial risks or other financial arrangement for the outer years.
Selected heat conduction problems in thermomechanical treatment of steel

This thesis considers two related problems where heat conduction is accompanied by phase transformation during the cooling of carbon steels – phenomena which are fundamental to modern thermomechanical treatment processes. In the first problem, a non-linear heat equation formulation is described which includes linkage between irreversible diffusive and diffusionless phase transformation processes and thermophysical properties. A family of numerical schemes using finite difference methods with diagonally implicit Runge-Kutta method integrators for solving this formulation is present. Sample calculations using these schemes are presented for a mild steel cooled under range of industrially relevant heat transfer conditions. These calculations illustrate the need for careful scheme design and solver selection when coupled heat conduction and microstructure evolution equations become non-linear and stiff. The second section of the thesis extends this heat conduction formulation into the realm of inverse analysis. The problem of temperature reconstruction and boundary condition estimation using temperature measurements obtained thermocouples embedded into laboratory samples undergoing phase transformation is considered. A solution method based on iterative regularization is described for solving the resulting ill-posed problem. An analysis of extremely high rate cooling experiments made on a pilot-plant descaling unit using the inverse method is presented. This analysis highlights some of the practical issues associated with embedded thermocouple temperature measurements made in this fashion.
Controller Design for Nonlinear Systems with Stochastic Time Delays Using Neural Networks and Information Entropy

In this paper, a novel controller is proposed for discrete-time nonlinear systems with uncertain output-channel time delays using RBF neural networks and information entropy. The controller is designed by minimizing the quadratic Renyi entropy. The probability density function (PDF) of tracking error is estimated by Parzen windowing technique. The Jacobian information is estimated by an RBF neural network. The convergent condition of the proposed control algorithm is given. A simulation example is given to show the effectiveness of the proposed algorithm.
Population Genetic Analyses of GlobalfilerTM Loci for Indian Population

Copyright: © 2015 Razdan A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. GlobalFilerTM Express PCR Amplification Kit is a highly discriminative STR kit developed by Life Technologies to meet the requirements of FBI recommendations [1,2], including 21 autosomal STR loci (i.e., D3S1358, vWA, D16S539, CSF1PO, TPOX, D8S1179, D21S11, D18S51, D2S441, D19S433, TH01, FGA, D22S1045, D5S818, D13S317, D7S820, SE33, D10S1248, D1S1656, D12S391, and D2S1338), 1 Y STR locus (i.e., DYS391), 1 Y-indel locus, and Amelogenin. In this study, we did population genetic analyses with the GlobalFilerTM Express Kit for Indian population. 201 samples were collected, with consent, from unrelated individuals from different geographic regions of India. The samples were anonymized prior to analysis.
Special Section on the Architectures , Protocols , and Applications for the Future Internet Simulation Study of Low Latency Network Architecture Using Mobile Edge Computing ∗

Attaining extremely low latency service in 5G cellular networks is an important challenge in the communication research field. A higher QoS in the next-generation network could enable several unprecedented services, such as Tactile Internet, Augmented Reality, and Virtual Reality. However, these services will all need support from powerful computational resources provided through cloud computing. Unfortunately, the geolocation of cloud data centers could be insufficient to satisfy the latency aimed for in 5G networks. The physical distance between servers and users will sometimes be too great to enable quick reaction within the service time boundary. The problem of long latency resulting from long communication distances can be solved by Mobile Edge Computing (MEC), though, which places many servers along the edges of networks. MEC can provide shorter communication latency, but total latency consists of both the transmission and the processing times. Always selecting the closest edge server will lead to a longer computing latency in many cases, especially when there is a mass of users around particular edge servers. Therefore, the research studies the effects of both latencies. The communication latency is represented by hop count, and the computation latency is modeled by processor sharing (PS). An optimization model and selection policies are also proposed. Quantitative evaluations using simulations show that selecting a server according to the lowest total latency leads to the best performance, and permitting an over-latency barrier would further improve results. key words: mobile edge computing, 5G, low latency, network architecture, processor sharing, and performance evaluation
Graph pattern matching

Graph pattern matching is typically defined in terms of subgraph isomorphism, which makes it an np-complete problem. Moreover, it requires bijective functions, which are often too restrictive to characterize patterns in emerging applications. We propose a class of graph patterns, in which an edge denotes the connectivity in a data graph within a predefined number of hops. In addition, we define matching based on a notion of bounded simulation, an extension of graph simulation. We show that with this revision, graph pattern matching can be performed in cubic-time, by providing such an algorithm. We also develop algorithms for incrementally finding matches when data graphs are updated, with performance guarantees for dag patterns. We experimentally verify that these algorithms scale well, and that the revised notion of graph pattern matching allows us to identify communities commonly found in real-world networks.
Is Pre-K Classroom Quality Associated With Kindergarten and Middle-School Academic Skills?

We employed data from a longitudinal investigation of over 1,000 children who participated in Tulsa’s universal school-based pre-K program in 2005, and path modeling techniques, to examine the contribution of pre-K classroom quality to both kindergarten- and middle-school academic skills. We also examined gender and income-related differences in quality-outcome associations. Both Instructional and Emotional Support in pre-K classrooms, but not Classroom Management, assessed with the Classroom Assessment Scoring System (CLASS), were associated with kindergarten academic skills and, modestly indirectly associated through these immediate impacts, to middle-school test scores. Linear associations were found for Instructional Support whereas nonlinear patterns of association were evident for Emotional Support. Gender and income differences characterized Instructional Support-outcome associations. Results are discussed in terms of implications for improving pre-K quality as one avenue for supporting the ongoing development of academic skills.
DNA Methylation Status of the Estrogen Receptor α Gene in Canine Mammary Tumors

Estrogen receptor α (ERα) has an important role in mammary carcinogenesis, prognosis, and treatment. In human and canine mammary cancer, the most aggressive tumors show loss of ERα expression, which in human breast cancer has been attributed to methylation of the cytosine followed by guanine (CpG) island within the estrogen receptor α gene (ESR1) promoter. This study aimed to investigate the role of ESR1 CpG island (CGI) methylation in ERα expression in canine mammary tumors. Twenty-one canine mammary samples were sorted into three groups: malignant tumor (n = 9), benign tumor (n = 8), and normal gland (n = 4). Immunohistochemical analysis and reverse-transcription quantitative real-time PCR were performed to assess ERα expression and ESR1 mRNA levels. The methylation status was determined using sodium-bisulfite-treated DNA sequencing. All normal mammary glands and benign tumors showed high ERα expression (score range, 5–8). Six of the nine malignant tumors did not show ERα expression (score 0), two had score 2, and one had score 4. Lower ERα (P < .005) and ESR1 mRNA levels (P < .005) were found in malignant mammary tumors than in the other two groups. Canine ESR1 has an intragenic and non-promoter-associated CGI, different from humans. No significant variation in methylation percentage was observed among the groups, suggesting that ESR1 is not regulated by DNA methylation, unlike that in humans. This difference should be considered in further research using ERα as a biomarker for mammary tumors in canine studies on ERα-targeting therapy.
A novel assay for the quantification of internalized nanoparticles in macrophages

One of the most urgent requirements in nanotoxicology is a quantitative assessment of internalized nanomaterials in cells. We present an in vitro assay called ‘max-flat’ for the measurement of internalized particles in macrophages. Fluorescent polystyrene (PS) beads of diameters 1 µm, 500 nm, 200 nm, 100 nm and 20 nm were employed. Different concentrations of fibronectin (FN) coated substrates were tested to achieve a maximal cell spreading area and minimal nucleus height, hence ‘max-flat’. We found this cell spreading area depends on FN concentration, and it is independent of particle concentration. An optimal condition of FN was found at 2.5×10−3 mg/ml, and it was selected for the max-flat assay to assess the internalization of PS beads. Cells under these conditions neither generate reactive oxygen species nor show noticeable differences in pro-survival/pro-apoptotic signals. Confocal images were employed for the max-flat assay and we set the interval scanning for a Z-stack as nucleus height divided by particle diameter. The max-flat assay provided a significantly higher number of internalized particles and the saturation is reached faster for nano-scale PS beads. We show how the proposed max-flat assay clearly outperform existing techniques by providing easier, more precise and far more reliable access to the number of internalized nanoparticles in macrophages.
New Psychoactive Substances 3-Methoxyphencyclidine (3-MeO-PCP) and 3-Methoxyrolicyclidine (3-MeO-PCPy): Metabolic Fate Elucidated with Rat Urine and Human Liver Preparations and their Detectability in Urine by GC-MS, “LC-(High Resolution)-MSn” and “LC-(High Resolution)-MS/MS”

Background: 3-Methoxyphencyclidine (3-MeO-PCP) and 3-methoxyrolicyclidine (3-MeO-PCPy) are two new psychoactive substances (NPS). The aims of the present study were the elucidation of their metabolic fate in rat and pooled human liver microsomes (pHLM) the identification of the cytochrome P450 (CYP) isoenzymes involved and the detectability using standard urine screening approaches (SUSA) after intake of common users’ doses using gas chromatography-mass spectrometry (GC-MS) liquid chromatography-multi-stage mass spectrometry (LC-MSn) and liquid chromatography-high-resolution tandem mass spectrometry (LC-HR-MS/MS) Methods: For metabolism studies rat urine samples were treated by solid phase extraction or simple precipitation with or without previous enzymatic conjugate cleavage. After analyses via LC-HR-MSn the phase I and II metabolites were identified Results: Both drugs showed multiple aliphatic hydroxylations at the cyclohexyl ring and the heterocyclic ring single aromatic hydroxylation carboxylation after ring opening O-demethylation and glucuronidation. The transferability from rat to human was investigated by pHLM incubations where O-demethylation and hydroxylation were observed. The involvement of the individual CYP enzymes in the initial metabolic steps was investigated after single CYP incubations. For 3-MeO-PCP CYP 2B6 was responsible for aliphatic hydroxylations and CYP 2C19 and CYP 2D6 for O-demethylation. For 3-MeO-PCPy aliphatic hydroxylation was again catalyzed by CYP 2B6 and O-demethylation by CYP 2C9 and CYP 2D6 Conclusions: As only polymorphically expressed enzymes were involved pharmacogenomic variations might occur but clinical data are needed to confirm the relevance. The detectability studies showed that the authors’ SUSAs were suitable for monitoring the intake of both drugs using the identified metabolites
Robust Kernelized Multi-View Self-Representations for Clustering by Tensor Multi-Rank Minimization

Most recently, tensor-SVD is implemented on multi-view self-representation clustering and has achieved the promising results in many real-world applications such as face clustering, scene clustering and generic object clustering. However, tensor-SVD based multi-view self-representation clustering is proposed originally to solve the clustering problem in the multiple linear subspaces, leading to unsatisfactory results when dealing with the case of non-linear subspaces. To handle data clustering from the non-linear subspaces, a kernelization method is designed by mapping the data from the original input space to a new feature space in which the transformed data can be clustered by a multiple linear clustering method. In this paper, we make an optimization model for the kernelized multi-view self-representation clustering problem. We also develop a new efficient algorithm based on the alternation direction method and infer a closed-form solution. Since all the subproblems can be solved exactly, the proposed optimization algorithm is guaranteed to obtain the optimal solution. In particular, the original tensor-based multi-view self-representation clustering problem is a special case of our approach and can be solved by our algorithm. Experimental results on several popular real-world clustering datasets demonstrate that our approach achieves the state-of-the-art performance.
Scene semantic classification based on scale invariance convolutional neural networks

Convolutional neural networks (CNNs) has been introduced into remote sensing scene classification, achieving outstanding performance. However, the scale change of objects contained in remote sensing scene image make it difficult to extract feature robust to scale, limiting the further improvement of classification accuracy. In this paper, a scene classification method named Scale Invariance Convolutional Neural Networks (SICNNs) is proposed for remote sensing scene classification. In the proposed method, two images with different scales generated by randomly stretching one image are fed into CNNs simultaneously for training at intervals of several iterations. Then a similarity measure layer was added in SICNN to make the distance of the two feature vectors extracted from the two images as close as possible, leading extracted feature to be robust to scale. Experimental results using two datasets, i.e. the UC Merced dataset, Google dataset of SIRI-WHU, demonstrated the effectiveness of the proposed method.
Overexpression of miR169o, an Overlapping MicroRNA in Response to Both Nitrogen Limitation and Bacterial Infection, Promotes Nitrogen Use Efficiency and Susceptibility to Bacterial Blight in Rice

Limiting nitrogen (N) supply contributes to improved resistance to bacterial blight (BB) caused by Xanthomonas oryzae pv. oryzae (Xoo) in susceptible rice (Oryza sativa). To understand the regulatory roles of microRNAs (miRNAs) in this phenomenon, 63 differentially expressed overlapping miRNAs in response to Xoo infection and N limitation stress in rice were identified through deep RNA sequencing and stem-loop quantitative real-time PCR. Among these, miR169o was further assessed as a typical overlapping miRNA through the overexpression of the miR169o primary gene. Osa-miR169o-OX plants were taller, and had more biomass accumulation with significantly increased nitrate and total amino acid contents in roots than the wild type (WT). Transcript level assays showed that under different N supply conditions, miR169o oppositely regulated NRT2, and this is reduced under normal N supply conditions but remarkably induced under N-limiting stress. On the other hand, osa-miR169o-OX plants also displayed increased disease lesion lengths and reduced transcriptional levels of defense gene (PR1b, PR10a, PR10b and PAL) compared with the WT after inoculation with Xoo. In addition, miR169o impeded Xoo-mediated NRT transcription. Therefore, the overlapping miR169o contributes to increase N use efficiency and negatively regulates the resistance to BB in rice. Consistently, transient expression of NF-YA genes in rice protoplasts promoted the transcripts of PR genes and NRT2 genes, while it reduced the transcripts of NRT1 genes. Our results provide novel and additional insights into the co ordinated regulatory mechanisms of cross-talk between Xoo infection and N deficiency responses in rice.
Risks and Benefits of Ceasing or Continuing Anticoagulant Medication for Image-Guided Procedures for Spine Pain: A Systematic Review

Objective To determine the risks of continuing or ceasing anticoagulant or antiplatelet medications prior to image-guided procedures for spine pain. Design Systematic review of the literature with comprehensive analysis of the published data. Interventions Following a search of the literature for studies pertaining to spine pain interventions in patients on anticoagulant medication, seven reviewers appraised the studies identified and assessed the quality of evidence presented. Outcome Measures Evidence was sought regarding risks associated with either continuing or ceasing anticoagulant and antiplatelet medication in patients having image-guided interventional spine procedures. The evidence was evaluated in accordance with the Grades of Recommendation, Assessment, Development, and Evaluation system. Results From a source of 120 potentially relevant articles, 14 provided applicable evidence. Procedures involving interlaminar access carry a nonzero risk of hemorrhagic complications, regardless of whether anticoagulants are ceased or continued. For other procedures, hemorrhagic complications have not been reported, and case series indicate that they are safe when performed in patients who continue anticoagulants. Three articles reported the adverse effects of ceasing anticoagulants, with serious consequences, including death. Conclusions Other than for interlaminar procedures, the evidence does not support the view that anticoagulant and antiplatelet medication must be ceased before image-guided spine pain procedures. Meanwhile, the evidence shows that ceasing anticoagulants carries a risk of serious consequences, including death. Guidelines on the use of anticoagulants should reflect these opposing bodies of evidence.
Importance of propionate for the repression of hepatic lipogenesis and improvement of insulin sensitivity in high‐fat diet‐induced obesity

1 Scope The SCFA acetate (Ac) and propionate (Pr) are major fermentation products of dietary fibers and provide additional energy to the host. We investigated short‐ and long‐term effects of dietary Ac and Pr supplementation on diet‐induced obesity and hepatic lipid metabolism.2 Methods and results C3H/HeOuJ mice received high‐fat (HF) diets supplemented with 5% SCFA in different Ac:Pr ratios, a high acetate (HF‐HAc; 2.5:1 Ac:Pr) or high Pr ratio (HF‐HPr; 1:2.5 Ac:Pr) for 6 or 22 weeks. Control diets (low‐fat (LF), HF) contained no SCFA. SCFA did not affect body composition but reduced hepatic gene and protein expression of lipogenic enzymes leading to a reduced hepatic triglyceride concentration after 22 weeks in HF‐HPr mice. Analysis of long‐chain fatty acid composition (liver and plasma phospholipids) showed that supplementation of both ratios led to a lower ω6:ω3 ratio. Pr directly led to increased odd‐chain fatty acid (C15:0, C17:0) formation as confirmed in vitro using HepG2 cells. Remarkably, plasma C15:0 was correlated with the attenuation of HF diet‐induced insulin resistance.3 Conclusion Dependent on the Ac:Pr ratio, especially odd‐chain fatty acid formation and insulin sensitivity are differentially affected, indicating the importance of Pr.