Miracle-dz/UniFAR-FTUs huggingface dataset:
Growth hormone resistance exacerbates cholestasis‐induced murine liver fibrosis

Growth hormone (GH) resistance has been associated with liver cirrhosis in humans but its contribution to the disease remains controversial. In order to elucidate whether GH resistance plays a causal role in the establishment and development of liver fibrosis, or rather represents a major consequence thereof, we challenged mice lacking the GH receptor gene (Ghr–/–, a model for GH resistance) by crossing them with Mdr2 knockout mice (Mdr2–/–), a mouse model of inflammatory cholestasis and liver fibrosis. Ghr–/–;Mdr2–/– mice showed elevated serum markers associated with liver damage and cholestasis, extensive bile duct proliferation, and increased collagen deposition relative to Mdr2–/– mice, thus suggesting a more severe liver fibrosis phenotype. Additionally, Ghr–/–;Mdr2–/– mice had a pronounced down‐regulation of hepatoprotective genes Hnf6, Egfr, and Igf‐1, and significantly increased levels of reactive oxygen species (ROS) and apoptosis in hepatocytes, compared to control mice. Moreover, single knockout mice (Ghr–/–) fed with a diet containing 1% cholic acid displayed an increase in hepatocyte ROS production, hepatocyte apoptosis, and bile infarcts compared to their wild‐type littermates, indicating that loss of Ghr renders hepatocytes more susceptible to toxic bile acid accumulation. Surprisingly, and despite their severe fibrotic phenotype, Ghr–/–;Mdr2–/– mice displayed a significant decrease in tumor incidence compared to Mdr2–/– mice, indicating that loss of Ghr signaling may slow the progression from fibrosis/cirrhosis to cancer in the liver. Conclusion: GH resistance dramatically exacerbates liver fibrosis in a mouse model of inflammatory cholestasis, therefore suggesting that GH resistance plays a causal role in the disease and provides a novel target for the development of liver fibrosis treatments. (Hepatology 2015;61:613‐626)
Semi-Supervised Learning of Attribute-Value Pairs from Product Descriptions

We describe an approach to extract attribute-value pairs from product descriptions. This allows us to represent products as sets of such attribute-value pairs to augment product databases. Such a representation is useful for a variety of tasks where treating a product as a set of attribute-value pairs is more useful than as an atomic entity. Examples of such applications include product recommendations, product comparison, and demand forecasting. We formulate the extraction as a classification problem and use a semi-supervised algorithm (co-EM) along with (Naive Bayes). The extraction system requires very little initial user supervision: using unlabeled data, we automatically extract an initial seed list that serves as training data for the supervised and semi-supervised classification algorithms. Finally, the extracted attributes and values are linked to form pairs using dependency information and co-location scores. We present promising results on product descriptions in two categories of sporting goods.
A Unified and Comprehensible View of Parametric and Kernel Methods for Genomic Prediction with Application to Rice

One objective of this study was to provide readers with a clear and unified understanding of parametric statistical and kernel methods, used for genomic prediction, and to compare some of these in the context of rice breeding for quantitative traits. Furthermore, another objective was to provide a simple and user-friendly R package, named KRMM, which allows users to perform RKHS regression with several kernels. After introducing the concept of regularized empirical risk minimization, the connections between well-known parametric and kernel methods such as Ridge regression [i.e., genomic best linear unbiased predictor (GBLUP)] and reproducing kernel Hilbert space (RKHS) regression were reviewed. Ridge regression was then reformulated so as to show and emphasize the advantage of the kernel “trick” concept, exploited by kernel methods in the context of epistatic genetic architectures, over parametric frameworks used by conventional methods. Some parametric and kernel methods; least absolute shrinkage and selection operator (LASSO), GBLUP, support vector machine regression (SVR) and RKHS regression were thereupon compared for their genomic predictive ability in the context of rice breeding using three real data sets. Among the compared methods, RKHS regression and SVR were often the most accurate methods for prediction followed by GBLUP and LASSO. An R function which allows users to perform RR-BLUP of marker effects, GBLUP and RKHS regression, with a Gaussian, Laplacian, polynomial or ANOVA kernel, in a reasonable computation time has been developed. Moreover, a modified version of this function, which allows users to tune kernels for RKHS regression, has also been developed and parallelized for HPC Linux clusters. The corresponding KRMM package and all scripts have been made publicly available.
On methods, methodologies and how they matter

The field of Information Systems, it is argued, suffers from identity crisis and faces difficulties in achieving a disciplinary status (Galliers, 2006; Hassan, 2011). The IS research continues to be seen as lacking relevance and impact that negatively affects IS prospects for becoming a discipline. Key charges include the narrow research focus and a rigid application of research methods that constrain investigative possibilities, impede the relevance of IS research and also stifle creativity and the production of relevant knowledge. Given a historical privileging of the positivist research approach and associated methods (survey and experiments in particular) IS research has been slow in adopting other approaches and expanding research methods. While this is gradually happening and IS researchers are seen venturing into non-positivist territories, adopting a broader range of methods (such as ethnographies or action research), the emphasis on research methods and their ‘rigorous’ application remains. After critiquing the narrow focus on methods and drawing attention to limitations of all methods, the paper proposes a broader focus on research methodology that is concerned with the ontological, epistemological, and normative assumptions behind research methods and their inherent limitations. The paper argues for a (re)turn to methodology conceived as a theory of inquiry that is contextually sensitive and evolving within a research project. The return to methodology would involve a continuous interplay between assumptions about the phenomena studied and the practical questions of designing research strategies and selecting and adopting research methods underpinned by the assumptions. The broadening of focus and the questioning of both metatheoretical assumptions and methods might open up researchers’ perspectives and stimulate the discovery of new and innovative ways of conducting research and thereby facilitate progress in the IS field.
Implementing Content Constraints in Alpha-Stratified Adaptive Testing Using a Shadow Test Approach

The methods of alpha-stratified adaptive testing and constrained adaptive testing with shadow tests are combined. The advantages are twofold: First, application of the shadow test approach allows the implementation of any type of constraint on item selection in alpha-stratified adaptive testing. Second, the result yields a simple set of constraints that can be used in any application of the shadow test approach to reduce overexposure and underexposure of the items in the pool. An example from the Law School Admission Test is used to demonstrate the advantages.
Ascertainment of cause-specific mortality in COPD: operations of the TORCH Clinical Endpoint Committee

Background: TORCH (Towards a Revolution in COPD Health) is an international multicentre, randomised, placebo-controlled clinical trial of inhaled fluticasone propionate/salmeterol combination treatment and its monotherapy components for maintenance treatment of moderately to severely impaired patients with chronic obstructive pulmonary disease (COPD). The primary outcome is all-cause mortality. Cause-specific mortality and deaths related to COPD are additional outcome measures, but systematic methods for ascertainment of these outcomes have not previously been described. Methods: A Clinical Endpoint Committee (CEC) was tasked with categorising the cause of death and the relationship of deaths to COPD in a systematic, unbiased and independent manner. The key elements of the operation of the committee were the use of predefined principles of operation and definitions of cause of death and COPD-relatedness; the independent review of cases by all members with development of a consensus opinion; and a substantial infrastructure to collect medical information. Results: 911 deaths were reviewed and consensus was reached in all. Cause-specific mortality was: cardiovascular 27%, respiratory 35%, cancer 21%, other 10% and unknown 8%. 40% of deaths were definitely or probably related to COPD. Adjudications were identical in 83% of blindly re-adjudicated cases (κ = 0.80). COPD-relatedness was reproduced 84% of the time (κ = 0.73). The CEC adjudication was equivalent to the primary cause of death recorded by the site investigator in 52% of cases. Conclusion: A CEC can provide standardised, reliable and informative adjudication of COPD mortality that provides information which frequently differs from data collected from assessment by site investigators.
Frequency-Dependent Modes of Synaptic Vesicle Endocytosis and Exocytosis at Adult Mouse Neuromuscular Junctions

During locomotion, adult rodent lumbar motoneurons fire in high-frequency (80–100 Hz) 1–2 s bursts every several seconds, releasing between 10,000 and 20,000 vesicles per burst. The estimated total vesicle pool size indicates that all vesicles would be used within 30 s; thus, a mechanism for rapid endocytosis and vesicle recycling is necessary to maintain effective transmission and motor behavior. However, whether such rapid recycling exists at mouse neuromuscular junctions (NMJs) or how it is regulated has been unclear. Here, we show that much less FM1-43 dye is lost per stimulus with 100 Hz stimulation than with 10 Hz stimulation even when the same number of vesicles undergo exocytosis. Electrophysiological data using folimycin show this lesser amount of dye loss is caused in part by the rapid reuse of vesicles. We showed previously that a myosin light chain kinase (MLCK)–myosin II pathway was required for effective transmission at 100 Hz. Here, we confirm the activation of MLCK, based on increased nerve terminal phospho-MLC immunostaining, with 100 Hz but not with 10 Hz stimulation. We further demonstrate that activation of MLCK, by increased extracellular Ca2+, by PKC (protein kinase C) activation, or by a MLCK agonist peptide, reduces the amount of dye lost even with 10 Hz stimulation. MLCK activation at 10 Hz also resulted in more vesicles being rapidly reused. Thus, MLCK activation by 100 Hz stimulation switches the mechanism of vesicle cycling to a rapid-reuse mode and is required to sustain effective transmission in adult mouse NMJs.
Virtual Environments for Motor Rehabilitation: Review

In this paper, the current "state of the art" for virtual reality (VR) applications in the field of motor rehabilitation is reviewed. The paper begins with a brief overview of available equipment options. Next, a discussion of the scientific rationale for use of VR in motor rehabilitation is provided. Finally, the major portion of the paper describes the various VR systems that have been developed for use with patients, and the results of clinical studies reported to date in the literature. Areas covered include stroke rehabilitation (upper and lower extremity training, spatial and perceptual-motor training), acquired brain injury, Parkinson's disease, orthopedic rehabilitation, balance training, wheelchair mobility and functional activities of daily living training, and the newly developing field of telerehabilitation. Four major findings emerge from these studies: (1) people with disabilities appear capable of motor learning within virtual environments; (2) movements learned by people with disabilities in VR transfer to real world equivalent motor tasks in most cases, and in some cases even generalize to other untrained tasks; (3) in the few studies (n = 5) that have compared motor learning in real versus virtual environments, some advantage for VR training has been found in all cases; and (4) no occurrences of cybersickness in impaired populations have been reported to date in experiments where VR has been used to train motor abilities.
AP site structural determinants for Fpg specific recognition.

The binding of Escherichia coli and Lactococcus lactis Fapy-DNA glyosylase (Fpg) proteins to DNA containing either cyclic or non-cyclic abasic (AP) site analogs was investigated by electrophoretic mobility shift assay (EMSA) and by footprinting experiments. We showed that the reduced AP site is the best substrate analog for the E.coli and L.lactis enzymes ( K Dapp = 0.26 and 0.5 nM, respectively) as compared with the other analogs tested in this study ( K Dapp >2.8 nM). The 1,3-propanediol (Pr) residue-containing DNA seems to be the minimal AP site structure allowing a Fpg specific DNA binding, since the ethyleneglycol residue is not specifically bound by these enzymes. The newly described cyclopentanol residue is better recognized than tetrahydrofuran (for the E.coli Fpg, K Dapp = 2.9 and 25 nM, respectively). These results suggest that the hemiacetal form of the AP site is negatively discriminated by the Fpg protein suggesting a hydrogen bond between the C4'-hydroxyl group of the sugar and a Fpg residue. High-resolution hydroxyl radical footprinting using a duplex containing Pr shows that Fpg binds to six nucleotides on the strand containing the AP site and only the base opposite the lesion on the undamaged complementary strand. This comparative study provides new information about the molecular mechanism involved in the Fpg AP lyase activity.
UC Irvine Recent Work Title Interference Cancellation at the Relay for Multi-User Wireless Cooperative Networks

We study multi-user transmission and detection schemes for a multi-access relay network (MARN) with linear constraints at all nodes. In a (J, Ja, Ra, M) MARN, J sources, each equipped with Ja antennas, communicate to one M -antenna destination through one Ra-antenna relay. A new protocol called IC-RelayTDMA is proposed which takes two phases. During the first phase, symbols of different sources are transmitted concurrently to the relay. At the relay, interference cancellation (IC) techniques, previously proposed for systems with direct transmission, are applied to decouple the information of different sources without decoding. During the second phase, symbols of different sources are forwarded to the destination in a time division multi-access (TDMA) fashion. At the destination, the maximum-likelihood (ML) decoding is performed source-by-source. The protocol of IC-Relay-TDMA requires the number of relay antennas no less than the number of sources, i.e., Ra ≥ J . Through outage analysis, the achievable diversity gain of the proposed scheme is shown to be min{Ja(Ra − J + 1), RaM}. When M ≤ Ja ( 1 − J−1 Ra ) , the proposed scheme achieves the maximum interference-free (int-free) diversity gain RaM . Since concurrent transmission is allowed during the first phase, compared to full TDMA transmission, the proposed scheme achieves the same diversity, but with a higher symbol rate.
The IBM 2015 English conversational telephone speech recognition system

We describe the latest improvements to the IBM English conversational telephone speech recognition system. Some of the techniques that were found beneficial are: maxout networks with annealed dropout rates; networks with a very large number of outputs trained on 2000 hours of data; joint modeling of partially unfolded recurrent neural networks and convolutional nets by combining the bottleneck and output layers and retraining the resulting model; and lastly, sophisticated language model rescoring with exponential and neural network LMs. These techniques result in an 8.0% word error rate on the Switchboard part of the Hub5-2000 evaluation test set which is 23% relative better than our previous best published result.
Voltage-gated sodium channel (NaV) protein dissection creates a set of functional pore-only proteins

Many voltage-gated ion channel (VGIC) superfamily members contain six-transmembrane segments in which the first four form a voltage-sensing domain (VSD) and the last two form the pore domain (PD). Studies of potassium channels from the VGIC superfamily together with identification of voltage-sensor only proteins have suggested that the VSD and the PD can fold independently. Whether such transmembrane modularity is common to other VGIC superfamily members has remained untested. Here we show, using protein dissection, that the Silicibacter pomeroyi voltage-gated sodium channel (NaVSp1) PD forms a stand-alone, ion selective pore (NaVSp1p) that is tetrameric, α-helical, and that forms functional, sodium-selective channels when reconstituted into lipid bilayers. Mutation of the NaVSp1p selectivity filter from LESWSM to LDDWSD, a change similar to that previously shown to alter ion selectivity of the bacterial sodium channel NaVBh1 (NaChBac), creates a calcium-selective pore-only channel, CaVSp1p. We further show that production of PDs can be generalized by making pore-only proteins from two other extremophile NaVs: one from the hydrocarbon degrader Alcanivorax borkumensis (NaVAb1p), and one from the arsenite oxidizer Alkalilimnicola ehrlichei (NaVAe1p). Together, our data establish a family of active pore-only ion channels that should be excellent model systems for study of the factors that govern both sodium and calcium selectivity and permeability. Further, our findings suggest that similar dissection approaches may be applicable to a wide range of VGICs and, thus, serve as a means to simplify and accelerate biophysical, structural, and drug development efforts.
Increased connective tissue growth factor associated with cardiac fibrosis in the mdx mouse model of dystrophic cardiomyopathy

Cardiomyopathy contributes to morbidity and mortality in Duchenne muscular dystrophy (DMD), a progressive muscle‐wasting disorder. A major feature of the hearts of DMD patients and the mdx mouse model of the disease is cardiac fibrosis. Connective tissue growth factor (CTGF) is involved in the fibrotic process in many organs. This study utilized the mdx mouse model to assess the role of CTGF and other extracellular matrix components during the development of fibrosis in the dystrophic heart. Left ventricular function of mdx and control mice at 6, 29 and 43 weeks was measured by echocardiography. Young (6 weeks old) mdx hearts had normal function and histology. At 29 weeks of age, mdx mice developed cardiac fibrosis and increased collagen expression. The onset of fibrosis was associated with increased CTGF transcript and protein expression. Increased intensity of CTGF immunostaining was localized to fibrotic areas in mdx hearts. The upregulation of CTGF was also concurrent with increased expression of tissue inhibitor of matrix metalloproteinases (TIMP‐1). These changes persisted in 43 week old mdx hearts and were combined with impaired cardiac function and increased gene expression of transforming growth factor (TGF)‐β1 and matrix metalloproteinases (MMP‐2, MMP‐9). In summary, an association was observed between cardiac fibrosis and increased CTGF expression in the mdx mouse heart. CTGF may be a key mediator of early and persistent fibrosis in dystrophic cardiomyopathy.
The laryngeal mask and high-frequency jet ventilation for resection of high tracheal stenosis.

A useful consequence of the low pressure seal formed by the laryngeal mask airway (LMA) cuff around the laryngeal inlet is that it enables access to the larynx and tracheobronchial tree while avoiding impairment of airflow, tracheal stimulation, and/or trauma and interference with tracheal mucosal blood flow (1). The LMA tube also forms a conduit for passing instruments into the trachea and has been used for preand postthoracotomy airway evaluation (2,3), diagnostic bronchoscopy (4,5), fiberoptic-guided percutaneous tracheostomy (6,7), tracheobronchial laser surgery (8,9), vocal cord biopsy (lo), and nonairway surgery in patients with coincidental tracheobronchial pathology, such as tracheal stenosis (11-13). We describe the use of the LMA and high-frequency jet ventilation for airway management during resection of a high tracheal stenosis.
Visible Light Induced Green Transformation of Primary Amines to Imines Using a Silicate Supported Anatase Photocatalyst

Catalytic oxidation of amine to imine is of intense present interest since imines are important intermediates for the synthesis of fine chemicals, pharmaceuticals, and agricultural chemicals. However, considerable efforts have been made to develop efficient methods for the oxidation of secondary amines to imines, while little attention has until recently been given to the oxidation of primary amines, presumably owing to the high reactivity of generated imines of primary amines that are easily dehydrogenated to nitriles. Herein, we report the oxidative coupling of a series of primary benzylic amines into corresponding imines with dioxygen as the benign oxidant over composite catalysts of TiO2 (anatase)-silicate under visible light irradiation of λ > 460 nm. Visible light response of this system is believed to be as a result of high population of defects and contacts between silicate and anatase crystals in the composite and the strong interaction between benzylic amine and the catalyst. It is found that tuning the intensity and wavelength of the light irradiation and the reaction temperature can remarkably enhance the reaction activity. Water can also act as a green medium for the reaction with an excellent selectivity. This report contributes to the use of readily synthesized, environmentally benign, TiO2 based composite photocatalyst and solar energy to realize the transformation of primary amines to imine compounds.
A Probabilistic Formula for a Poisson Equation with Neumann Boundary Condition

Abstract In this work we extend Brosamler's formula (see “A probabalistic solution to the Neumann problem,” Math. Scand. 1976, 38:137–147) and give a probabilistic solution of a non degenerate Poisson type equation with Neumann boundary condition in a bounded domain of the Euclidean space.