gebhart/patrepeval huggingface dataset:
Metabotropic Glutamate Receptors: Potential Drug Targets for the Treatment of Schizophrenia (2002)

Schizophrenia is a debilitating chronic psychiatric illness affecting 1% of the population. The cardinal features of schizophrenia are positive symptoms (thought disorder, hallucinations, catatonic behavior), negative symptoms (social withdrawal, anhedonia, apathy) and cognitive impairment. Although progress in elucidating the aetiology of schizophrenia has been slow, new insights on the neurochemical and neurophysiological mechanisms underlying the pathophysiology of this illness are beginning to emerge. The glutamate/N-methyl-D-aspartate (NMDA) hypofunction hypothesis of schizophrenia is supported by observations that administration of NMDA glutamate receptor antagonists such as phencyclidine (PCP) or ketamine induces psychosis in humans; moreover, decreased levels of glutamate and changes in several markers of glutamatergic function occur in schizophrenic brain. Administration of PCP or ketamine to rodents elicits an increase in locomotion and stereotypy accompanied by an increase in glutamate efflux in several brain regions. Systemic administration of group II metabotropic glutamate (mGlu) receptor agonists suppresses PCP-induced behavioral effects and the increase in glutamate efflux. Activation of group II mGlu receptors (mGlu2 and mGlu3) decreases glutamate release from presynaptic nerve terminals, suggesting that group II mGlu receptor agonists may be beneficial in the treatment of schizophrenia. In addition, pharmacological manipulations that enhance NMDA function may be efficacious antipsychotics. Selective activation of mGlu5 receptors significantly potentiates NMDA-induced responses, supporting this novel approach for the treatment of schizophrenia. The glutamate hypothesis of schizophrenia predicts that agents that restore the balance in glutamatergic neurotransmission will ameliorate the symptomatology associated with this illness. Development of potent, efficacious, systemically active drugs will help to address the antipsychotic potential of these novel therapeutics. This review will discuss recent progress in elucidating the pharmacology and function of group II mGlu and mGlu5 receptors in the context of current hypotheses on the pathophysiology of schizophrenia and the need for new and better antipsychotics.
Prevention of HIV Infection by Passive Immunization with HIV Immunoglobulin (1991)

The use of a human immunodeficiency virus (HIV) immune globulin (HIVIG) in prevention of HIV infection in chimpanzees was investigated in the hope of ultimate application to interruption of vertical transmission. In previous experiments, no protection was observed when relatively high challenge doses were used. This study shows that HIVIG protected against a challenge dose (10 CID50) tenfold lower than that used previously. The protected animal remained free of HIV infection as determined by cocultivation and by polymerase chain reaction (PCR), and did not mount a primary immune response detectable by enzyme-linked immunosorbant assay (ELISA) and neutralization assays. These results imply that HIV vaccines should induce neutralizing antibody and may not need to induce cell-mediated immunity in order to be protective against exposure to HIV. They also provide an experimental basis for the conduct of clinical trials to evaluate prevention of maternal-infant transmission by HIVIG.
Peptidases released by necrotic cells control CD8+ T cell cross-priming (2013)

Cross-priming of CD8+ T cells and generation of effector immune responses is pivotal for tumor immunity as well as for successful anticancer vaccination and therapy. Dead and dying cells produce signals that can influence Ag processing and presentation; however, there is conflicting evidence regarding the immunogenicity of necrotic cell death. We used a mouse model of sterile necrosis, in which mice were injected with sterile primary necrotic cells, to investigate a role of these cells in priming of CD8+ T cells. We discovered a molecular mechanism operating in Ag donor cells that regulates cross-priming of CD8+ T cells during primary sterile necrosis and thereby controls adaptive immune responses. We found that the cellular peptidases dipeptidyl peptidase 3 (DPP-3) and thimet oligopeptidase 1 (TOP-1), both of which are present in nonimmunogenic necrotic cells, eliminated proteasomal degradation products and blocked Ag cross-presentation. While sterile necrotic tumor cells failed to induce CD8+ T cell responses, their nonimmunogenicity could be reversed in vitro and in vivo by inactivation of DPP-3 and TOP-1. These results indicate that control of cross-priming and thereby immunogenicity of primary sterile necrosis relies on proteasome-dependent oligopeptide generation and functional status of peptidases in Ag donor cells.
Dreams of the skull (1999)

Cells producing human antibodies to synthetic viral peptides MH-24 (corresponding to 302-325 residues of HIV-1 gp120) and p107 (main peptide of EBV antigen EBNA-1) were fused with human x mouse heteromyeloma B6B11. The efficacy of specific hybridization was 40%. Hybrid cells H1F2 (MN-specific) and HF4 (p107-specific) were cloned by the limiting dilutions method. Monoclonal antibodies (MAb) were tested in enzyme immunoassay on a panel of synthetic peptides. All resultant MAbs were polyspecific for tested synthetic peptides. The data permit a conclusion that previously detected polyspecificity of human cultural antibodies to virus peptides is due to the true polyspecificity of antigen-binding centers of MAb, but not to the presence of strange cells in the culture.
Damping of flexural vibrations in turbofan blades using the acoustic black hole effect (2013)

The results of the experimental study into the damping of flexural vibrations in turbofan blades with trailing edges tapered according to a power-law profile are reported. Trailing edges of power-law profile (wedges), with small pieces of attached absorbing layers, materialise one-dimensional acoustic black holes for flexural waves that can absorb a large proportion of the incident flexural wave energy. The experiments were carried out on four model blades made of aluminium. Two of them were twisted, so that a more realistic fan blade could be considered. All model blades, the ones with tapered trailing edges and the ones of traditional form, were excited by an electromagnetic shaker, and the corresponding frequency response functions have been measured. The results show that the resonant peaks are reduced substantially once a power-law tapering is introduced to the blade. An initial study into the aerodynamic implications of this method has been carried out as well, using measurements in a closed circuit wind tunnel. In particular, the effects of the trailing edge of power-law profile on the airflow-excited vibrations of the fan blades have been investigated. It has been demonstrated that trailing edges of power-law profile with appropriate damping layers are efficient in reduction of the airflow-excited vibrations of the fan blades. The obtained results demonstrate that power-law tapering of trailing edges of turbofan blades can be a viable method of reduction of blade vibrations.
The Language of Actions: Recovering the Syntax and Semantics of Goal-Directed Human Activities (2014)

This paper describes a framework for modeling human activities as temporally structured processes. Our approach is motivated by the inherently hierarchical nature of human activities and the close correspondence between human actions and speech: We model action units using Hidden Markov Models, much like words in speech. These action units then form the building blocks to model complex human activities as sentences using an action grammar. To evaluate our approach, we collected a large dataset of daily cooking activities: The dataset includes a total of 52 participants, each performing a total of 10 cooking activities in multiple real-life kitchens, resulting in over 77 hours of video footage. We evaluate the HTK toolkit, a state-of-the-art speech recognition engine, in combination with multiple video feature descriptors, for both the recognition of cooking activities (e.g., making pancakes) as well as the semantic parsing of videos into action units (e.g., cracking eggs). Our results demonstrate the benefits of structured temporal generative approaches over existing discriminative approaches in coping with the complexity of human daily life activities.
Inflight modifications of content: who are the culprits? (2011)

When a user requests content from a cloud service provider, sometimes the content sent by the provider is modified inflight by third-party entities. To our knowledge, there is no comprehensive study that examines the extent and primary root causes of the content modification problem. We design a lightweight experiment and instrument a vast number of clients in the wild to make two additional DNS queries every day. We identify candidate rogue servers and develop a measurement methodology to determine, for each candidate rogue server, whether the server is performing inflight modifications or not. In total, we discover 349 servers as malicious, that is, as modifying content inflight, and more than 1.9% of all US clients are affected by these malicious servers. We investigate the root causes of the problem. We identify 9 ISPs, whose clients are predominately affected. We find that the root cause is not sophisticated transparent in-network services, but instead local DNS servers in the problematic ISPs. 1
Structure-Activity Relationship of .alpha.-Galactosylceramides against B16-Bearing Mice (1995)

Agelasphin-9b, (2S,3S,4R)-1-O-(alpha-D-galactopyranosyl)-16-methyl-2- [N-((R)-2- hydroxytetracosanoyl)-amino]- 1,3,4-heptadecanetriol, is a potent antitumor agent isolated from the marine sponge Agelas mauritianus. Various analogues of agelasphin-9b (a lead compound) were synthesized, and the relationship between their structures and biological activities was examined using several assay systems. From the results, KRN7000, (2S,3S,4R)-1-O-(alpha-D- galactopyranosyl)-2-(N-hexacosanoylamino)-1,3,4-octadecanetriol , was selected as a candidate for clinical application.
Efficient selection of access control systems through multi criteria analytical hierarchy process (2012)

Access control is the process by which the system grants or denies a request made to it, by the user, for the data it maintains. Often the systems providing the services are open ended and face the access control dilemma. If the beneficiaries of the system are too restricted, then the servicing nature of the system loses flexibility. Otherwise the system with lenient access control policy posses threats to the existence of the system itself. As a remedy several access control models like ACL, DAC, MAC, RBAC and other have been proposed and each of which comes with its own baggage of pros and cons. These models protect only the data against unauthorized access until some access decision is made. On the other hand as the computer systems advance, they present new challenges and the traditional access models do not respond to them effectively. In this paper we have analyzed the existing access control models, compared them and finally provided the statistical criteria for selecting the best model depending upon the users' needs and requirements.
Large-Scale Copy Number Polymorphism in the Human Genome (2004)

The extent to which large duplications and deletions contribute to human genetic variation and diversity is unknown. Here, we show that large-scale copy number polymorphisms (CNPs) (about 100 kilobases and greater) contribute substantially to genomic variation between normal humans. Representational oligonucleotide microarray analysis of 20 individuals revealed a total of 221 copy number differences representing 76 unique CNPs. On average, individuals differed by 11 CNPs, and the average length of a CNP interval was 465 kilobases. We observed copy number variation of 70 different genes within CNP intervals, including genes involved in neurological function, regulation of cell growth, regulation of metabolism, and several genes known to be associated with disease.
Identification of a potent adipocyte-specific enhancer: involvement of an NF-1-like factor. (1991)

The molecular basis for adipocyte-specific gene expression is not known. We have demonstrated that while short (-168) segments of the 5'-flanking sequence of the adipocyte P2 gene containing AP-1- and C/EBP-binding sites can direct expression of a heterologous gene in cultured adipocytes, they cannot support tissue-specific expression in a transgenic mouse. We have therefore analyzed larger segments of the aP2 5'-flanking region by transfection into adipocytes and have found an enhancer at -5.4 kb. This 500-bp enhancer directs expression of the bacterial chloramphenicol acetyltransferase (CAT) gene in a differentiation-dependent fashion when linked to its own minimal promoter or to an enhancerless SV40 promoter. Moreover, this enhancer stimulates very strong and highly specific expression from the CAT gene in the adipose tissues of transgenic mice. A smaller fragment (190 bp) having enhancer activity in adipocytes was defined and demonstrated to contain a binding site for an abundant nuclear protein. This factor has the binding specificity and several other properties characteristic of the nuclear factor 1 (NF-1) transcription/replication factor family, and mutation of this NF-1-binding site greatly reduces the function of the 500-bp enhancer. These results identify and characterize the first functional enhancer with specificity for adipose cells and also demonstrate that a member(s) of the NF-1 family is involved in adipocyte-specific gene expression.
Activity maps for location-aware computing (2003)

Location-based context is important for many applications. Previous systems offered only coarse room-level features or used manually specified room regions to determine fine-scale features. We propose a location context mechanism based on activity maps, which define regions of similar context based on observations of 3-D patterns of location and motion in an environment. We describe an algorithm for obtaining activity maps using the spatio-temporal clustering of visual tracking data. We show how the recovered maps correspond to regions for common tasks in the environment and describe their use in some applications.
Integrated platform for detection of DNA sequence variants using capillary array electrophoresis (2002)

We have developed a highly versatile platform that performs temperature gradient capillary electrophoresis (TGCE) for mutation/single-nucleotide polymorphism (SNP) detection, sequencing and mutation/SNP genotyping for identification of sequence variants on an automated 24-, 96- or 192-capillary array instrument. In the first mode, multiple DNA samples consisting of homoduplexes and heteroduplexes are separated by CE, during which a temperature gradient is applied that covers all possible temperatures of 50% melting equilibrium (Tms) for the samples. The differences in Tms result in separation of homoduplexes from heteroduplexes, thereby identifying the presence of DNA variants. The sequencing mode is then used to determine the exact location of the mutation/SNPs in the DNA variants. The first two modes allow the rapid identification of variants from the screening of a large number of samples. Only the variants need to be sequenced. The third mode utilizes multiplexed single-base extensions (SBEs) to survey mutations and SNPs at the known sites of DNA sequence. The TGCE approach combined with sequencing and SBE is fast and cost-effective for high-throughput mutation/SNP detection.
Ultra thin (&amp;gt;20 Å) CVD Si/sub 3/N/sub 4/ gate dielectric for deep-sub-micron CMOS devices (2002)

In this paper, we report the first sub-micron n- and p-MOSFETs with ultra thin (<20 /spl Aring/) Si/sub 3/N/sub 4/ gate dielectric fabricated by in-situ rapid thermal CVD (RTCVD) process, and compare their performance and reliability with control SiO/sub 2/ devices of identical equivalent oxide thickness (T/sub eq/). Both n- and p-MOSFETs with CVD Si/sub 3/N/sub 4/ gate dielectric show higher drain current and peak transconductance, enhanced immunity to hot carrier stress, and significant reduction of tunneling leakage current.
Design of MATLAB simulation tool box for rough set data analysis system (2007)

The two kernel concepts,indiscernibility relation and relative positive region, are focused on.An algorithm is proposed to analyze the rough set data analysis system,according to the mutual dependency between different kinds of knowledge.The numbers of reduced attributes are compared to pick out a reduction result involving the minimum number of attributes.Taking the advantage of MATLAB in dealing with set functions,the program realizations of many algorithms are given to solve relative core,upper approximation,lower approximation,equivalence relation,relative significance level,relative reduction of attributes,relative reduction of domain and minimal decision rules,thus designing the MATLAB simulation tool.By way of graphical user interface(GUI),the favorable main interface of man-machine interaction system is designed.An example resulting from running is given,which shows the practical significance to the applications of rough set theory.
Heregulin is sufficient for the promotion of tumorigenicity and metastasis of breast cancer cells in vivo. (2003)

Resistance of breast carcinomas to hormonal therapy is a clinical obstacle for the treatment of breast cancer. The molecular mechanisms and the factors involved in the progression of tumors from an estrogen (E2)-dependent to an E2-independent phenotype are not entirely understood. Heregulin (HRG) is a pleiotropic growth factor that binds to the erbB family of receptors, which are correlated with breast cancer progression and an aggressive phenotype in the breast carcinomas overexpressing the receptors. Previous studies in transgenic mice have shown that HRG is sufficient to induce mammary gland transformation and proliferation in the presence of hormonal stimulation. However, these studies did not address the important issue of the E2 independence that is part of the progression of breast cancer. In this study, we investigated the role of HRG in E2 independence. We were able to determine that HRG up-regulation was sufficient for the development of mammary tumors in the absence of E2 stimulation, a situation that mimics the progression of the human disease. We demonstrated that in ovariectomized nude mice, HRG induced E2 independence and antiestrogen resistance and promoted metastasis and preneoplastic transformation of the adjacent mouse mammary tissue. We show that one of the mechanisms by which HRG achieves the aggressive phenotype may be mediated via an increase in activated mitogen-activated protein kinase, an increase in a matrix-degrading enzyme, MMP-9, and the overexpression of vascular endothelial growth factors. The up-regulation of these genes occurred in the absence of any additional stimulation, in an autocrine manner. Our data provide new insights into the mechanisms of breast cancer progression in vivo, and reinforce the important role that HRG plays in this process.
CpG Oligodeoxynucleotides: A Novel Therapeutic Approach For Atopic Disorders (2003)

Atopic disorders such as allergic rhinitis, asthma and atopic dermatitis are associated with skewing of immune responses towards a TH2 phenotype, resulting in eosinophilic inflammation. TH2 cytokines promote eosinophil growth, migration and activation, mast cell differentiation, and IgE production, and are candidate mediators of pathologic abnormalities in asthma and other atopic diseases. There has been a significant increase in the prevalence of allergic disorders over the past several decades. Recent epidemiological studies suggest that reduced early-life exposure to strong TH1 stimuli in industrialized counties has skewed the TH1/TH2 balance towards TH2 responses. Improved hygiene, vaccination, and use of antibiotics may contribute to this imbalance. In the last half of the twentieth century we have seen the use of multiple agents to treat atopic disorders, ranging from antihistamines, steroids and leukotriene modifiers to anti-IgE antibodies. All these agents can block symptoms but do not significantly modify the course of the disease. Recent attempts to restore TH1/TH2 balance by blocking TH2 cytokines or inducing TH1 cytokines, have not only failed to alter the outcome of atopic diseases but, in some cases, have caused significant adverse effects. An alternate method of suppressing TH2 responses takes advantage of the innate immune response to bacterial DNA. Oligodeoxynucleotides (ODN) containing sequence motifs centered on unmethylated CG dinucleotides (CpG ODN) resemble bacterial DNA, and like bacterial DNA are immunostimulatory; we and others have shown that CpG ODN can suppress TH2-mediated atopic inflammation without requiring the induction of TH1-type cytokines. These agents may represent a novel therapeutic approach toward restoring immune tolerance in atopic individuals.
2,3-Dihydro-5-benzofuranols as antioxidant-based inhibitors of leukotriene biosynthesis (1989)

The enzymes that catalyze the oxidative metabolism of arachidonic acid have provided fertile ground for the development of useful therapeutic agents for nearly a quarter century. Inhibitors of the enzyme cyclooxygenase prevent the formation of the prostaglandins and thromboxanes and are clinically useful antiinflammatories and peripheral analgesics. More recently it has been discovered that the enzyme 5-lipoxygenase is the first step in the formation of a series of biologically important metabolites of arachidonic acid, the leukotrienes. Evidence suggests that an inhibitor of 5-lipoxygenase may be a useful therapeutic agent in the treatment of asthma, immediate hypersensitivity, and inflammation. Various antioxidants have been examined as inhibitors of 5-lipoxygenase in vitro. We were intrigued by recent reports that the 2,3-dihydro-5-benzofuranol ring system maximizes the stereoelectronic effects necessary for efficient hydrogen atom abstraction by peroxyl radicals. In this study we describe the synthesis of over 50 new 2,3-dihydro-5-benzofuranols and their biological evaluation as inhibitors of leukotriene biosynthesis in isolated human polymorphonuclear leukocytes. We show that the 2,3-dihydro-5-benzofuranol ring system, although not a potent inhibitor of leukotriene biosynthesis in itself, can provide a useful template for the design of antioxidant-based inhibitors of leukotriene biosynthesis. Furthermore, within a structural class the potency of a given analogue can be predicted on the basis of its overall calculated lipophilicity (log P). The data are interpreted in terms of a model in which the observed inhibition by this class of inhibitors is dependent on the intrinsic ability of the antioxidant to reduce the enzyme and on the fraction of the inhibitor that is partitioned into the membrane.
The Algorithmic Aspects of Network Slicing (2017)

Network slicing is a technique for flexible resource provisioning in future wireless networks. With the powerful SDN and NFV technologies available, network slices can be quickly deployed and centrally managed, leading to simplified management, better resource utilization, and cost efficiency by commoditization of resources. Departing from the one-type-fits-all design philosophy, future wireless networks will employ the network slicing methodology in order to accommodate applications with widely diverse requirements over the same physical network. On the other hand, deciding how to efficiently allocate, manage, and control the slice resources in real time is very challenging. This article focuses on the algorithmic challenges that emerge in efficient network slicing, necessitating novel techniques from the communities of operation research, networking, and computer science.