Miracle-dz/UniFAR-FTUs huggingface dataset:
Gene therapy for cystic fibrosis using cationic liposome mediated gene transfer: a phase I trial of safety and efficacy in the nasal airway.

SCIENTIFIC ABSTRACT Cystic fibrosis (CF) is a common, lethal, inherited disease among Caucasian children and young adults. While the pathophysiology of CF includes many organ systems (e.g., gastrointestinal, reproductive, endocrine) the predominant cause of death is respiratory failure. Hyperviscous respiratory secretions and related chronic pulmonary infections lead to scarring and fibrosis of the lungs, deteriorating pulmonary function, and death, with an average CF life expectancy of approximately 29 years. The disease is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR functions, at least in part, as an epithelial chloride channel which resides in the apical membranes of exocrine gland epithelial cells. It has been suggested that the fluid and electrolyte content of normal respiratory mucus is dependent upon CFTR chloride channel activity, and that failure to secrete chloride by CF cells results in diminished hydration of mucous, sputum hyperviscosit.
Peripheral Interventions Enhancing Brain Glutamate Homeostasis Relieve Amyloid &bgr;- and TNF&agr;- Mediated Synaptic Plasticity Disruption in the Rat Hippocampus

Dysregulation of glutamate homeostasis in the interstitial fluid of the brain is strongly implicated in causing synaptic dysfunction in many neurological and psychiatric illnesses. In the case of Alzheimer's disease (AD), amyloid β (Aβ)-mediated disruption of synaptic plasticity and memory can be alleviated by interventions that directly remove glutamate or block certain glutamate receptors. An alternative strategy is to facilitate the removal of excess glutamate from the nervous system by activating peripheral glutamate clearance systems. One such blood-based system, glutamate oxaloacetate transaminase (GOT), is activated by oxaloacetate, which acts as a co-substrate. We report here that synthetic and AD brain-derived Aβ-mediated inhibition of synaptic long-term potentiation in the hippocampus is alleviated by oxaloacetate. Moreover the effect of oxaloacetate was GOT-dependent. The disruptive effects of a general inhibitor of excitatory amino acid transport or TNFα, a pro-inflammatory mediator of Aβ action, were also reversed by oxaloacetate. Furthermore, another intervention that increases peripheral glutamate clearance, peritoneal dialysis, mimicked the beneficial effect of oxaloacetate. These findings lend support to the promotion of the peripheral clearance of glutamate as a means to alleviate synaptic dysfunction that is caused by impaired glutamate homeostasis in the brain.
Road Traffic Forecasting through Simulation and Live GPS-Feed from Intervehicle Networks

Any disaster management requires sending emergency aids to the affected areas in an earliest possible time. In urban areas, high traffic volume is an impediment for efficient transportation of such goods and services. In this paper, we present a traffic flow forecasting model that may help emergency service delivery. In our approach, we used a microscopic traffic simulator with live vehicle statistics collected from intervehicle networks. The use of traffic simulator based technique enables repetitive exploration of different route planning options ahead of time. The simulator is also helpful for a comprehensive representation of urban road network. In this work, we have also designed and implemented necessary hardware and software tools for traffic data collection, which gives full control on the data collection mechanism. Our approach has been tested in a large university campus where all constraints of a modern city are present. The study shows promising results of our approach.
Flow control in packet-switched multistage interconnection networks

The authors present a threshold-based flow control procedure, based on feedback schemes for reducing the performance degradation of packet-switched multistage interconnection networks with binary routing, under a nonuniform hot spot traffic pattern. The use of the proposed feedback policies in such networks permits the discrimination between regular and hot packets, controls the tree saturation, and offers a significant network performance improvement. <<ETX>>
Inhibition of dynamin‐dependent endocytosis interferes with type III IFN expression in bacteria‐infected human monocyte‐derived DCs

Type I IFNs (IFN‐α/βs) and type III IFNs (IFN‐λ1–3) play an important role in host defense against viral infections. The induction of type I IFNs has recently been found to take place also in bacterial infections, and therefore, this study focuses on analyzing the regulation of type III IFNs in response to bacterial stimulation. We found by quantitative RT‐PCR that the expression of IFN‐λ1 and IFN‐λ2/3 mRNAs, as well as that of IFN‐β, was similarly up‐regulated in response to stimulation with live Salmonella typhimurium or TLR4 agonist LPS in human moDCs. The induction of IFN‐λ mRNAs did not require ongoing protein synthesis, and only IFN‐λ1 was detected at the protein level. The induction of IFN‐λ mRNAs was sensitive to SB202190, Ly294002, and PDTC, which inhibit p38 MAPK, PI3K, and NF‐κB activation, respectively. Furthermore, we observed that blocking dynamin‐dependent endocytosis pathways with dynasore led to decreased cell surface expression of CD86 and HLA class II molecules and reduced production of IFN‐λ1, CXCL10, and IL‐6 when the cells were infected with S. typhimurium. Cytokine production was also impaired in dynasore‐treated, Streptococcus thermophilus‐stimulated cells. Further, inhibition of dynamin prevented S. typhimurium‐induced phosphorylation of IRF3 and the internalization of the bacteria. In summary, induction of type III IFNs in bacteria‐infected human moDCs requires multiple signaling pathways and involves bacterial phagocytosis.
Small Molecule Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: An Overview

Abstract The epidermal growth factor receptor (EGFR) has been identified as a relevant target for treatment of solid tumors, as it is involved in regulating cellular functions important in the proliferation and survival of cancer cells, is commonly expressed in a range of tumors, and high expression is often related to poor prognosis. Some of the most advanced target based agents in clinical development are the EGFR tyrosine kinase inhibitors (EGFR-TKIs). This brief review summarizes the results of phase II monotherapy trials of EGFR TKIs in cancer patients. The molecular mechanisms involved in regulating the sensitivity/resistance of tumor cells to EGFR-TKIs are also discussed.
Applications and Analysis of Client Consumer Behavior Based on Big Data

Consumer behavior analysis is an important part of customer relationship management, the traditional means of analysis are carried out basic theory of economics, there is no quantitative research, the results of some limitations. In today's new technology development, data mining technology as a powerful data analysis technology, used in customer relationship management is gaining more and more attention. However, from the application layer perspective, the study of data mining and customer relationship management applications are a considerable part in the commercial area, the application in non-commercial areas have no major development. With the development of information technology, in many of the non-commercial sector we have established appropriate information systems, generating large amounts of data, such as the campus information system.
AUC Optimization Based Confidence Measure for Keyword Spotting

Conﬁdence measure plays an important role in keyword spot-ting. To enhance the effectiveness of the conﬁdence measure, we propose a novel method which improves the performance of keyword spotting by directly maximizing the area under the ROC curve (AUC). Firstly, we approximate the AUC as an ob-jective function with the weighted mean conﬁdence measure. Then, we optimize the objective function by training the weighting factors with the generalized probabilistic descent algorithm. Compared with the current method based on minimum classi-ﬁcation error (MCE) criterion, the proposed method makes a global enhancement of ROC curve and does not need to train any threshold. The experiments conducted on the King-ASR-023 database show that the proposed method outperforms both the method averaging phone-level conﬁdences and the method based on MCE.
Gene Regulation by Melatonin

Abstract: The physiological and neuroendocrine functions of the pineal gland hormone, melatonin, and its therapeutic potential critically depend on the understanding of its target sites and its mechanisms of action. This has progressed considerably in the last few years through the cloning of G protein‐coupled seven‐transmembrane melatonin receptors (Mel1a and Mel1b) as well as of nuclear receptors (RZR/RORα and RZRβ) that are associated with melatonin signaling. The transcription factor RZR/RORα appears to mediate a direct gene regulatory action of the hormone, and specific binding sites have been identified in promoter regions of a variety of genes, such as 5‐lipoxygenase (5‐LO), p21WAF1/CIP1, and bone sialoprotein (BSP). The membrane signaling pathway clearly shows higher ligand sensitivity than the nuclear signaling pathway, but details of its signal transduction cascade, and target genes are presently unknown. Membrane melatonin receptors are expressed mainly in the central nervous system, whereas RZR/RORα is prominently expressed both in the periphery and the brain. The action of membrane melatonin receptors and their specific agonists have been associated with circadian rhythmicity, whereas direct effects of melatonin in the periphery, such as immunomodulation, cellular growth, and bone differentiation, mainly appear to be mediated by RZR/RORα. It is hypothesized in this review that, in some cases, RZR/RORα may be a primary target of membrane melatonin receptors.
Joint Intensity and Spatial Metric Learning for Robust Gait Recognition

This paper describes a joint intensity metric learning method to improve the robustness of gait recognition with silhouette-based descriptors such as gait energy images. Because existing methods often use the difference of image intensities between a matching pair (e.g., the absolute difference of gait energies for the l1-norm) to measure a dissimilarity, large intrasubject differences derived from covariate conditions (e.g., large gait energies caused by carried objects vs. small gait energies caused by the background), may wash out subtle intersubject differences (e.g., the difference of middle-level gait energies derived from motion differences). We therefore introduce a metric on joint intensity to mitigate the large intrasubject differences as well as leverage the subtle intersubject differences. More specifically, we formulate the joint intensity and spatial metric learning in a unified framework and alternately optimize it by linear or ranking support vector machines. Experiments using the OU-ISIR treadmill data set B with the largest clothing variation and large population data set with bag, &#x03B2; version containing carrying status in the wild demonstrate the effectiveness of the proposed method.
Pain management in patients who undergo outpatient arthroscopic surgery of the knee.

→Arthroscopy of the knee joint produces an initial afferent barrage of pain signals that have the capacity to initiate prolonged changes in the nervous system leading to the amplification and prolongation of postoperative pain. →Preemptive analgesia involves the administration of analgesics prior to painful stimuli to prevent the amplification of postoperative pain. →It is currently recommended that multimodal analgesic regimens be utilized in the management of postoperative pain. →Intra-articular bupivacaine and morphine are effective analgesics for arthroscopic knee surgery. →Intra-articular ketorolac, corticosteroids, and clonidine may also have a role in reducing pain following arthroscopic knee surgery. →Nonsteroidal anti-inflammatory drugs play an important role in the management of postoperative orthopaedic pain, and the newer cyclooxygenase-2-specific nonsteroidal anti-inflammatory drugs may have additional advantages with respect to safety. →Preemptive and multimodal analgesic techniques should be utilized in the management of patients undergoing anterior cruciate reconstruction. Arthroscopy of the knee joint, including reconstruction of the anterior cruciate ligament, is a common procedure that is routinely performed on an outpatient basis. Traditionally, oral analgesics are prescribed for the management of postoperative pain. The routine prescription of oral opioid analgesics administered on an as-needed basis, however, frequently results in inadequate pain relief112. Unrelieved postoperative pain may delay the patient's eligibility for discharge, resulting in a prolonged hospital stay, inability to participate in rehabilitation programs, delayed recovery, poor outcome, and greater use of health-care resources112. At present, several techniques are available to treat pain following arthroscopic knee surgery; these include the use of opioids (providing either peripherally or centrally mediated analgesia), local anesthetics, nonsteroidal anti-inflammatory drugs, corticosteroids, clonidine, and cryotherapy (Fig. 1). In this paper, we will present a review of the current knowledge of the principles of acute pain physiology as well as current techniques for the control of pain associated with …
Catecholamines and Aggression: The Role of COMT and MAO Polymorphisms

Abstract: Catecholaminergic systems are involved in the regulation of aggressive behavior; this regulation is implemented in interactions with other neurobiological mechanisms. Most of the available evidence indicates that norepinephrine and dopamine lower the threshold for an aggressive response to environmental stimuli. Two major enzymes are responsible for catecholamine catabolism in the brain: catechol‐O‐methyltransferase (COMT) and monoamine oxidase A (MAOA). The transcriptional activity of the genes coding for these enzymes is governed by common functional polymorphisms. If aggressive behavior is enhanced by catecholaminergic activity, then the lower activity of COMT and MAOA (resulting in a slower inactivation of catecholamines) should indirectly enhance aggression. This prediction has been supported by most (but not all) observations in rodents and humans. Male mice that have either the COMT or the MAOA gene knocked out show elevated aggression. The allele that codes for the lower enzymatic activity of COMT has been associated with elevated aggressive behavior in several samples of psychiatric patients. Similarly, the alleles that code for the lower activity of MAOA were associated with the development of aggressive behavior in maltreated male children in a large birth cohort study. Collectively, these results suggest that COMT and MAOA polymorphisms represent a basic neurobiological mechanism that contributes to the regulation of aggressive behavior.
Cardiology patient page. Tetralogy of Fallot.

Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease, occurring in 1 in 3,600 live births [1]. Complete repair of TOF was devised over 50 years ago (first reported by Lillehei in 1954) and can result in complete intra-cardiac repair in early infancy [2]. However, despite excellent short- and medium-term survival rates, the 30 year actuarial survival for patients repaired before their 5th birthday is 90 % of the expected survival rate and the annualized risk of death triples in the third postoperative decade [2, 3]. Late morbidity and mortality, in particular related to pulmonary incompetence, has been observed in many patients long after total repair.
Artifacts in design: representation, ideation, and process

Artifacts-representations that express properties or captured information-can serve to inspire, represent, and manage the decisions made throughout the design process. This workshop will explore how these artifacts are created, used, and reused during design projects, toward understanding the overall impact on the larger discipline of design. Through active engagement with novel design artifacts and methods, workshop participants will examine, categorize, and evaluate various design artifacts.
A Procedure of an Automatic Grapheme-to-Phoneme Transfornation of German

The automatic transformation of texts graphemically stored to the corresponding phonemic symbols will enable the speech synthesizer Rosy 4000 (.developed by VEB Robotron Dres~ den) to extend its field of application (application in information systems, development of reading machines for the blind). The texts for this kind of application cannot be limi~ ted in any way a fact which had to be taken into account concerning the methods suitable for such a procedure. The use of the d_%ctionary method, that means storing the whole vocabulary needed together with the corresponding phonemic strings was impossible for this purpose.
Customized growth charts for twin gestations to optimize identification of small‐for‐gestational age fetuses at risk of intrauterine fetal death

Customized growth charts developed for singleton pregnancies have been shown to be more effective than population‐based ones at identifying small‐for‐gestational age (SGA) fetuses at risk for intrauterine fetal death (IUFD). We sought to compare the association between SGA and IUFD in twins using customized growth charts designed for twin gestations compared to those designed for singletons.
Measuring quality of life in prosthetic practice: benefits and challenges

There is an increasing awareness that the inclusion of quality of life as an outcome measure is important in ensuring a client-centred and holistic assessment. This review outlines the benefits of quality of life as an outcome measurement in the field of prosthetics. It introduces the key concepts and challenges in the definition and assessment of quality of life post-amputation, including the relative advantages and disadvantages of adopting generic, disease/condition specific, dimension specific and individualized measures of quality of life. In conclusion, the review delineates and recommends issues and guidelines for consideration when undertaking quality of life research and assessment. A co-ordinated approach by practitioners in the field of prosthetics is necessary to ensure the inclusion of quality of life as an outcome measure and to ensure its measurement in a standardized and rigorous manner.
Effect of continuous antistaphylococcal therapy on the rate of P. aeruginosa acquisition in patients with cystic fibrosis

Summary. Continuous therapy with antistaphylococcal antibiotics is advocated by some cystic fibrosis (CF) centers, but it is unclear whether this strategy favors early colonization with P. aeruginosa. We used the data base for the German Centers of the European Registry for Cystic Fibrosis (ERCF) to assess the effect of continuous antistaphyloccocal therapy on the rate of P. aeruginosa acquisition in CF patients. Patients included in this analysis had to be < 18 years of age, P. aeruginosa‐negative prior to entry in the ERCF, and to have had at least 2 additional P. aeruginosa‐negative respiratory cultures while followed in the ERCF.
Prediction of the remaining useful life: An integrated framework for model estimation and failure prognostics

Machine failure prognostic is concerned with the generation of long term predictions and the estimation of the probability density function of the remaining useful life. Nowadays, a commonly used approach for this task is to make the prediction using a dynamical state-space model of the fault evolution. However, the main limitation of this approach is that it requires the values of the model parameters to be known. This work aims to alleviate the need for extensive prior efforts related to finding the exact model. For this we propose a framework for data-driven prediction of RUL with on-line model estimation. This is achieved by combining the state estimation algorithm with Maximum-Likelihood parameter estimation in the form of the Expectation-Maximization algorithm. We show that the proposed algorithm can be used with different classes of both black-box and grey-box models. First, a detailed solution for linear black-box models with the Kalman filter is presented followed by the extension to nonlinear models using either the Unscented Kalman filter or the particle filter. The performance of the algorithms is demonstrated using the experimental data from a single stage gearbox.
Phosphorylation of the 19S regulatory particle ATPase subunit, Rpt6, modifies susceptibility to proteotoxic stress and protein aggregation

The ubiquitin proteasome system (UPS) is a highly conserved and tightly regulated biochemical pathway that degrades the majority of proteins in eukaryotic cells. Importantly, the UPS is responsible for counteracting altered protein homeostasis induced by a variety of proteotoxic stresses. We previously reported that Rpt6, the ATPase subunit of the 19S regulatory particle (RP) of the 26S proteasome, is phosphorylated in mammalian neurons at serine 120 in response to neuronal activity. Furthermore, we found that Rpt6 S120 phosphorylation, which regulates the activity and distribution of proteasomes in neurons, is relevant for proteasome-dependent synaptic remodeling and function. To better understand the role of proteasome phosphorylation, we have constructed models of altered Rpt6 phosphorylation in S. cerevisiae by introducing chromosomal point mutations that prevent or mimic phosphorylation at the conserved serine (S119). We find that mutants which prevent Rpt6 phosphorylation at this site (rpt6-S119A), had increased susceptibility to proteotoxic stress, displayed abnormal morphology and had reduced proteasome activity. Since impaired proteasome function has been linked to the aggregation of toxic proteins including the Huntington’s disease (HD) related huntingtin (Htt) protein with expanded polyglutamine repeats, we evaluated the extent of Htt aggregation in our phospho-dead (rpt6-S119A) and phospho-mimetic (rpt6-S119D) mutants. We showed Htt103Q aggregate size to be significantly larger in rpt6-S119A mutants compared to wild-type or rpt6-S119D strains. Furthermore, we observed that phosphorylation of endogenous Rpt6 at S119 is increased in response to various stress conditions. Together, these data suggest that Rpt6 phosphorylation at S119 may play an important function in proteasome-dependent relief of proteotoxic stress that can be critical in protein aggregation pathologies.
Drug interactions in the management of HIV infection

The availability of antiretroviral therapy has significantly reduced the morbidity and mortality of HIV infection. In addition, improved treatment of opportunistic infections and comorbidities common to patients with HIV is further prolonging the lives of patients. Improvement in the treatment of HIV has led to a significant increase in the number of medications which caregivers are able to utilise to manage HIV/AIDS. Antiretroviral medications, as well as many of the drugs used in the management of opportunistic infections and primary care (e.g., macrolide antibiotics, azole antifungals, cholesterol-lowering medications), are particularly prone to drug interactions. The interpretation of clinically significant interactions is complicated by the rate at which new information on drug metabolism and transport is becoming available. Management of drug interactions in HIV is further confounded by conflicting study results and differences between documented and theoretical inter-actions. The mechanisms and significance of interactions involving antiretro-virals, drugs used for opportunistic infections, and other medications commonly used in HIV patients will be reviewed.