gebhart/patrepeval huggingface dataset:
Potassium channels as therapeutic targets for autoimmune disorders. (2003)

In human T-lymphocytes, the voltage-gated Kv1.3 channel and the Ca(2+)-activated IKCa1 channel play an important role in Ca2+ signaling, activation, adhesion and migration and have, therefore, long been regarded as attractive targets for immunotherapy. Here, we review the pharmacology of the two channels, their expression pattern in naïve and memory T-cells and their functional roles during T-cell activation, and explain the rationale for the use of Kv1.3 blockers for the therapy of T-cell mediated autoimmune diseases.
Secretion of Yop proteins by Yersiniae (1990)

Upon incubation at 37 degrees C in the absence of Ca2+ ions, pathogenic strains of the genus Yersinia cease growing and produce large amounts of a series of plasmid-encoded proteins involved in pathogenicity. These proteins, called Yops (for Yersinia outer membrane proteins), are detected in both the outer membrane fraction and the culture supernatant. We present here the nucleotide sequence of genes yop20 and yop25 from Yersinia enterocolitica O:9. Protein Yop25 is very similar to YopE, the corresponding protein from Yersinia pestis, Y. pseudotuberculosis, and Y. enterocolitica O:8 (A. Forsberg and H. Wolf-Watz, J. Bacteriol. 172:1547-1555, 1990). This is the first report of a yop20 sequence of yersiniae. We present evidences that Yops are not membrane proteins. Their detection in the membrane fraction results either from copurification of large aggregates of extracellular Yops with the membrane fraction or from the adsorption of released proteins to the cell surface. In contrast with Yops, protein P1 has characteristics of a true membrane protein. The release of Yops by Y. enterocolitica occurs by a novel secretion mechanism that does not involve the cleavage of a typical signal sequence or the recognition of a carboxy-terminal domain.
College of American Pathologists Conference XXVI on clinical relevance of prognostic markers in solid tumors. Report of the Prostate Cancer Working Group. (1995)

Critical analysis of the evidence supporting the use of prognostic markers is needed for these to be used most appropriately in patient management. The College of American Pathologists recently sponsored a national conference to review the status of tumor markers for carcinomas of the breast, colon, and prostate gland. The conclusions of the Prostate Cancer Working Group are presented in this report. Currently, the TNM (Tumor, Lymph Node, Metastasis) staging system, histologic grading (Gleason system), and serum prostate-specific antigen are recommended for general use as prognostic markers in prostate cancer. Data support the use of DNA ploidy analysis in specific clinical settings, although general use is not currently recommended. The Working Group concluded that other markers do not have sufficient support in the literature to recommend routine use at the present time.
Optimal routing in mixed media networks with integrated voice and data traffic (2003)

A large mixed-media network which consists of a low-delay terrestrial subnetwork and a high-bandwidth satellite subnetwork is considered. Voice and data traffic are transmitted and routed through the same network. It is shown how to route both types of traffic via ground and/or satellite links by means of static, deterministic procedures. Two common voice/data integrated protocols, namely the fixed boundary and the movable boundary schemes, for the satellite channel are investigated, and the performance of both is evaluated. The optimal splitting ratios for voice and data at the SIMPs (Satellite Interface Message Processors) are found using a powerful numerical optimization package, (FSQP).< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Drosophila roadblock and Chlamydomonas Lc7 (1999)

Eukaryotic organisms utilize microtubule-dependent motors of the kinesin and dynein superfamilies to generate intracellular movement. To identify new genes involved in the regulation of axonal transport in Drosophila melanogaster, we undertook a screen based upon the sluggish larval phenotype of known motor mutants. One of the mutants identified in this screen, roadblock (robl), exhibits diverse defects in intracellular transport including axonal transport and mitosis. These defects include intra-axonal accumulations of cargoes, severe axonal degeneration, and aberrant chromosome segregation. The gene identified by robl encodes a 97-amino acid polypeptide that is 57% identical (70% similar) to the 105-amino acid Chlamydomonas outer arm dynein-associated protein LC7, also reported here. Both robl and LC7 have homology to several other genes from fruit fly, nematode, and mammals, but not Saccharomyces cerevisiae. Furthermore, we demonstrate that members of this family of proteins are associated with both flagellar outer arm dynein and Drosophila and rat brain cytoplasmic dynein. We propose that roadblock/LC7 family members may modulate specific dynein functions.
Partial video sequence caching scheme for VOD systems with heterogeneous clients (1998)

Video on demand (VOD) is one of the key applications in the information era. A hinge factor to its widespread use is the huge bandwidth required to transmit digitized video to a large group of clients with widely varying requirements. This paper addresses issues of heterogeneous clients by proposing a program caching scheme called the partial video sequence (PVS) caching scheme. The PVS caching scheme decomposes video sequences into a number of parts by using a scalable video compression algorithm. Video parts are selected to be cached in local video servers based on the amount of bandwidth that would be demanded from the distribution network and central video server if it was only kept in the central video server. We also show that the PVS caching scheme is suitable for handling vastly varying client requirements.
Learning a Joint Embedding Space of Monophonic and Mixed Music Signals for Singing Voice (2019)

Previous approaches in singer identification have used one of monophonic vocal tracks or mixed tracks containing multiple instruments, leaving a semantic gap between these two domains of audio. In this paper, we present a system to learn a joint embedding space of monophonic and mixed tracks for singing voice. We use a metric learning method, which ensures that tracks from both domains of the same singer are mapped closer to each other than those of different singers. We train the system on a large synthetic dataset generated by music mashup to reflect real-world music recordings. Our approach opens up new possibilities for cross-domain tasks, e.g., given a monophonic track of a singer as a query, retrieving mixed tracks sung by the same singer from the database. Also, it requires no additional vocal enhancement steps such as source separation. We show the effectiveness of our system for singer identification and query-by-singer in both the same-domain and cross-domain tasks.
Nicotinamide riboside is uniquely and orally bioavailable in mice and humans (2016)

Nicotinamide riboside (NR) is in wide use as an NAD<sup>+</sup> precursor vitamin. Here we determine the time and dose-dependent effects of NR on blood NAD<sup>+</sup> metabolism in humans. We report that human blood NAD<sup>+</sup> can rise as much as 2.7-fold with a single oral dose of NR in a pilot study of one individual, and that oral NR elevates mouse hepatic NAD<sup>+</sup> with distinct and superior pharmacokinetics to those of nicotinic acid and nicotinamide. We further show that single doses of 100, 300 and 1,000 mg of NR produce dose-dependent increases in the blood NAD<sup>+</sup> metabolome in the first clinical trial of NR pharmacokinetics in humans. We also report that nicotinic acid adenine dinucleotide (NAAD), which was not thought to be en route for the conversion of NR to NAD<sup>+</sup>, is formed from NR and discover that the rise in NAAD is a highly sensitive biomarker of effective NAD<sup>+</sup> repletion.
ChemInform Abstract: Diastereoselective Oxidation of Substituted 1,2‐Dithiolan‐3‐ones. (1994)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Virtualization for high-performance computing (2006)

The specific demands of high-performance computing (HPC) often mismatch the assumptions and algorithms provided by legacy operating systems (OS) for common workload mixes. While feature- and application-rich OSes allow for flexible and low-cost hardware configurations, rapid development, and flexible testing and debugging, the mismatch comes at the cost of --- oftentimes significant --- performance degradation for HPC applications.The ubiquitous availability of virtualization support in all relevant hardware architectures enables new programming and execution models for HPC applications without loosing the comfort and support of existing OS and application environments. In this paper we discuss the trends, motivations, and issues in hardware virtualization with emphasis on their value in HPC environments.
Power-aware control speculation through selective throttling (2003)

With the constant advances in technology that lead to the increasing of the transistor count and processor frequency, power dissipation is becoming one of the major issues in high-performance processors. These processors increase their clock frequency by lengthening the pipeline, which puts more pressure on the branch prediction engine since branches take longer to be resolved. Branch mispredictions are responsible for around 28% of the power dissipated by a typical processor due to the useless activities performed by instructions that are squashed. This work focuses on reducing the power dissipated by mis-speculated instructions. We propose selective throttling as an effective way of triggering different power-aware techniques (fetch throttling, decode throttling or disabling the selection logic). The particular set of techniques applied to each branch is dynamically chosen depending on the branch prediction confidence level. For branches with a low confidence on the prediction, the most aggressive throttling mechanism is used whereas high confidence branch predictions trigger the least aggressive techniques. Results show that combining fetch bandwidth reduction along with select logic disabling provides the best performance both in terms of energy reduction and energy-delay improvement (14% and 9% respectively for 14 stages, and 17% and 12% respectively for 28 stages).
The CD40 Antigen and its Ligand (1994)

CD40 is an integral membrane protein found on the surface of B lymphocytes, dendritic cells, follicular dendritic cells, hematopoietic progenitor cells, epithelial cells, and carcinomas. It is a 45-50 kDa glycoprotein of 277 aa, which is a member of the tumor necrosis factor receptor superfamily. The CD40 gene maps to human chromosome 20q11-2-q13-2. CD40 binds to a ligand (CD40-L) which is an approximately 35 kDa glycoprotein of 261 aa, a member of the tumor necrosis factor superfamily. The CD40-L gene maps to human chromosome Xq24. This CD40-L is expressed on activated T cells, mostly CD4+ but also some CD8+ as well as basophils/mast cells. The CD40-L is defective in the X-linked hyper-IgM syndrome. Cross-linking of CD40 with immobilized anti-CD40 or cells expressing CD40-L induces B cells to proliferate strongly, and addition of IL-4 or IL-13 allows the generation of factor-dependent long-term normal human B cell lines and the secretion of IgE following isotype switching. Addition of IL-10 results in very high immunoglobulin production with limited cell proliferation. IL-10 induces naive B cells to produce IgG3, IgG1, and IgA1, and further addition of TGF beta permits the secretion of IgA2. Several evidences suggest that CD40-dependent activation of B cells is important for the generation of memory B cells within the germinal centers: (i) CD40 activated germinal center B cells cultured in the presence of IL-4 acquire a memory B cell phenotype, (ii) CD40 activated B cells can undergo isotype switching, (iii) the deficit of CD40-L results in the hyper-IgM syndrome characterized by lack of germinal centers in secondary lymphoid organ follicles and lack of IgG, IgA, and IgE, and (iv) CD40-L positive T cells are present in secondary follicles. Thymic epithelial cells, activated monocytes, and dendritic cells express CD40 antigen which may be involved in an enhanced cytokine production by these cells, allowing an amplification of T cell proliferation. Finally, as other members of the tumor necrosis factor receptor family have been shown to bind several ligands, it is possible that CD40 may bind other ligands that may trigger CD40 on different cell types such as hematopoietic cells or epithelial cells.
Intracellular delivery of bioactive AZT nucleotides by aryl phosphate derivatives of AZT (1993)

Novel aryl phosphate derivatives of the anti-HIV nucleoside analogue AZT have been prepared by phosphorochloridate chemistry. These materials were designed to act as membrane-soluble prodrugs of the bioactive free nucleotides. In vitro evaluation revealed the compounds to have a pronounced, selective anti-HIV activity in CEM cells; the magnitude of the biological effect varied considerably depending on the nature of the phosphate blocking group. Moreover, several of the compounds retain marked antiviral activity in TK- (thymidine kinase-deficient) mutant CEM cells in which AZT was virtually inactive. These data strongly support the hypothesis that the AZT phosphate derivatives exert their biological effects via intracellular release of AZT nucleotide forms and suggest that the potential of nucleoside drugs in antiviral chemotherapy may be enhanced by suitable nucleotide delivery strategies.
Derivation, Characterization, and Differentiation of Human Embryonic Stem Cells (2004)

The derivation of human embryonic stem (hES) cells establishes a new avenue to approach many issues in human biology and medicine for the first time. To meet the increased demand for characterized hES cell lines, we present the derivation and characterization of six hES cell lines. In addition to the previously described immunosurgery procedure, we were able to propagate the inner cell mass and establish hES cell lines from pronase-treated and hatched blastocysts. The cell lines were extensively characterized by expression analysis of markers characteristic for undifferentiated and differentiated hES cells, karyotyping, telomerase activity measurement, and pluripotency assays in vitro and in vivo. Whereas three of the cell lines expressed all the characteristics of undifferentiated pluripotent hES cells, one cell line carried a chromosome 13 trisomy while maintaining an undifferentiated pluripotent state, and two cell lines, one of which carried a triploid karyotype, exhibited limited pluripotency in vivo. Furthermore, we clonally derived one cell line, which could be propagated in an undifferentiated pluripotent state.
Systemic Effects of Chronic Obstructive Pulmonary Disease: What We Know and What We Don't Know (but Should) (2007)

Chronic obstructive pulmonary disease (COPD) is associated with pulmonary and systemic inflammation. The latter is likely to contribute significantly to the pathobiology of numerous extrapulmonary effects of the disease--the so-called systemic effects of COPD. The clinical relevance of these systemic effects has been recently recognized; however, many important questions about its pathophysiology remain unanswered. This article reviews what is known about it and, more importantly, highlights what is not (but should be) known in order to stimulate research in this area, in the hope that a better understanding of this field may lead to better treatment options for patients with COPD.
Role of ischemia and deformation in the onset of compression-induced deep tissue injury: MRI-based studies in a rat model (2007)

A rat model was used to distinguish between the different factors that contribute to muscle tissue damage related to deep pressure ulcers that develop after compressive loading. The separate and combined effects of ischemia and deformation were studied. Loading was applied to the hindlimb of rats for 2 h. Muscle tissue was examined using MR imaging (MRI) and histology. An MR-compatible loading device allowed simultaneous loading and measurement of tissue status. Two separate loading protocols incorporated uniaxial loading, resulting in tissue compression and ischemic loading. Uniaxial loading was applied to the tibialis anterior by means of an indenter, and ischemic loading was accomplished with an inflatable tourniquet. Deformation of the muscle tissue during uniaxial loading was measured using MR tagging. Compression of the tissues for 2 h led to increased T2 values, which were correlated to necrotic regions in the tibialis anterior. Perfusion measurements, by means of contrast-enhanced MRI, indicated a large ischemic region during indentation. Pure ischemic loading for 2 h led to reversible tissue changes. From the MR-tagging experiments, local strain fields were calculated. A 4.5-mm deformation, corresponding to a surface pressure of 150 kPa, resulted in maximum shear strain up to 1.0. There was a good correlation between the location of damage and the location of high shear strain. It was concluded that the large deformations, in conjunction with ischemia, provided the main trigger for irreversible muscle damage.
Increased expression of bone morphogenetic protein‐7 in bone metastatic prostate cancer (2003)

These results suggest that high expression of BMP-7 in metastatic bone lesions of prostate cancer is related to osteoblastic metastasis. BMP-7 in the bone metastasis tissue indicates that the cells expressing BMP-7 probably originated from the prostate, because we have detected high expression of BMP-7 in the prostate. Prostate 54: 268-274, 2003.
Replication of hepatitis C virus (1996)

The mode of replication of the hepatitis C virus (HCV) remains poorly understood. Attempts to produce a tissue culture model containing replicating HCV have been largely unsuccessful. Recent studies on sera from patients chronically infected with HCV have shown that viral particles may be found in high- or low-density fractions. High-density fractions contain non-infectious virions whilst infectious particles can be derived from low-density material. Using appropriate infectious fractions we have successfully infected a number of human cell lines allowing studies of HCV replication to be initiated.
Characteristics of megavoltage cone‐beam digital tomosynthesis (2008)

This article reports on the image characteristics of megavoltage cone-beam digital tomosynthesis (MVCB DT). MVCB DT is an in-room imaging technique, which enables the reconstruction of several two-dimensional slices from a set of projection images acquired over an arc of 20 degrees-40 degrees. The limited angular range reduces the acquisition time and the dose delivered to the patient, but affects the image quality of the reconstructed tomograms. Image characteristics (slice thickness, shape distortion, and contrast-to-noise ratio) are studied as a function of the angular range. Potential clinical applications include patient setup and the development of breath holding techniques for gated imaging.
Controlling Mammalian Cell Spreading and Cytoskeletal Arrangement with Conveniently Fabricated Continuous Wavy Features on Poly(dimethylsiloxane) (2002)

This paper reports a simple and versatile technique for generating structures on the surfaces of poly(dimethylsiloxane) (PDMS), approximately sinusoidal waves with periods between 0.1 and 10 μm, and the use of these structures to study cell contact guidance.1 The features are generated by stretching PDMS slabs mechanically, oxidizing them in an oxygen plasma, and allowing them to relax. These surface features are similar to photolithographically fabricated grooves that have traditionally been used to investigate cell contact guidance, although their edges are rounded rather than angular. Bovine capillary endothelial cells align and elongate on these features. The morphology and cytoskeletal structure of the aligned cells are similar to those of cells described in previous studies of contact guidance on surfaces with other types of topography. These observations and comparisons indicate that sharp edges in the features defining the grooves are not essential in eliciting contact guidance. This technique provides a method for fabricating microfeatures for the studies of the interactions between cells and their environment that does not require a cleanroom or access to photolithographic tools.
Improving effector functions of antibodies for cancer treatment: Enhancing ADCC and CDC. (2009)

As platforms for therapeutic agents, monoclonal antibodies (MAbs) have already been approved, and several MAbs have demonstrated clinical effectiveness in a variety of malignancies. However, several issues have also been emerging in antibody therapy, such as high cost and insufficient drug action. Recently, to improve MAb activity in humans, effector functions have been subjects of focus, especially antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Extensive efforts have been made to enhance these effector functions of MAbs, and successful approaches have been reported by us and others, wherein the binding activity of MAbs to FcgammaRIIIa or C1q is increased by introducing amino acid mutations into heavy chain constant regions or through glyco-modification of Fc-linked oligosaccharides. In addition, one of the next approaches to optimizing therapeutic antibodies would be to combine multiple enhancing modifications into a single antibody platform to overcome the diverse mechanisms of clinical resistance of tumor cells. For this aim, we have recently developed a successful combination composed of ADCC-enhancing modification by the fucose depletion from Fc-linked oligosaccharides and CDC-enhancing modification by IgG1 and IgG3 isotype shuffling in heavy chains, which could be of great value for the development of third-generation antibody therapeutics.
Multiplex Real-Time PCR Assay for Simultaneous Detection of Acanthamoeba spp., Balamuthia mandrillaris , and Naegleria fowleri (2006)

Infections caused by Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris occur throughout the world and pose many diagnostic challenges. To date, at least 440 cases of severe central nervous system infections caused by these amebas have been documented worldwide. Rapid and specific identification of these free-living amebas in clinical samples is of crucial importance for efficient case management. We have developed a triplex real-time TaqMan PCR assay that can simultaneously identify Acanthamoeba spp., B. mandrillaris, and N. fowleri in the same PCR vessel. The assay was validated with 22 well-characterized amebic strains harvested from cultures and nine clinical specimens that were previously characterized by in vitro culture and/or immunofluorescence assay. The triplex assay demonstrated high specificity and a rapid test completion time of less than 5 h from the reception of the specimen in the laboratory. This assay was able to detect one single ameba per sample analyzed, as determined with cerebrospinal fluid spiked with diluted cultured amebas. This assay could become useful for fast laboratory diagnostic assessment of amebic infections (caused by free-living amebas) in laboratories with adequate infrastructure to perform real-time PCR testing.