gebhart/patrepeval huggingface dataset:
UNified Instruction/Translation/Data (UNITD) coherence: One protocol to rule them all (2010)

We propose UNITD, a unified hardware coherence framework that integrates translation coherence into the existing cache coherence protocol. In UNITD coherence protocols, the TLBs participate in the cache coherence protocol just like the instruction and data caches, without requiring any changes to the existing coherence protocol. UNITD eliminates the need for the software TLB shootdown routine, a procedure known to be performance costly and non-scalable. We evaluate snooping and directory UNITD coherence protocols on multicore processors with 2-16 cores, and we demonstrate that UNITD reduces the performance penalty associated with TLB coherence to almost zero.
Study of the Interference Affecting the Performance of the Theremin (2012)

The theremin is one of the earliest electronic musical instruments. It is named after the Russian physics Professor Lev S. Termen who invented it in 1919. This musical instrument belongs to a very short list of devices which are played without physical contact between the musician and the instrument. theremin players complain about the interference that any object in a radius of approximately 3 meters produces when playing the theremin, modifying the intonation of the instrument. This is a problem when playing in small scenarios, with other musicians which move around it. With the aim of reducing the degree of interference from nearby obstacles, some metallic isolating bars conforming an antenna array can be placed around the theremin pitch antenna. The paper shows different simulations calculated with the commercial software Ansoft HFSS, a tool which allows three-dimensional full wave electromagnetic field simulation, with radio frequencies, millimeter and micro waves, and experimental measures, both showing a reduction in the effect of the interference.
Generation of a 3D indexed Petunia insertion database for reverse genetics (2008)

BLAST searchable databases containing insertion flanking sequences have revolutionized reverse genetics in plant research. The development of such databases has so far been limited to a small number of model species and normally requires extensive labour input. Here we describe a highly efficient and widely applicable method that we adapted to identify unique transposon-flanking genomic sequences in Petunia. The procedure is based on a multi-dimensional pooling strategy for the collection of DNA samples; up to thousands of different templates are amplified from each of the DNA pools separately, and knowledge of their source is safeguarded by the use of pool-specific (sample) identification tags in one of the amplification primers. All products are combined into a single sample that is subsequently used as a template for unidirectional pyrosequencing. Computational analysis of the clustered sequence output allows automatic assignment of sequences to individual DNA sources. We have amplified and analysed transposon-flanking sequences from a Petunia transposon insertion library of 1000 individuals. Using 30 DNA isolations, 70 PCR reactions and two GS20 sequencing runs, we were able to allocate around 10 000 transposon flanking sequences to specific plants in the library. These sequences have been organized in a database that can be BLAST-searched for insertions into genes of interest. As a proof of concept, we have performed an in silico screen for insertions into members of the NAM/NAC transcription factor family. All in silico-predicted transposon insertions into members of this family could be confirmed in planta.
SIMULATION OF PROKARYOTIC GENETIC CIRCUITS (1998)

Biochemical and genetic approaches have identified the molecular mechanisms of many genetic reactions, particularly in bacteria. Now a comparably detailed understanding is needed of how groupings of genes and related protein reactions interact to orchestrate cellular functions over the cell cycle, to implement preprogrammed cellular development, or to dynamically change a cell's processes and structures in response to environmental signals. Simulations using realistic, molecular-level models of genetic mechanisms and of signal transduction networks are needed to analyze dynamic behavior of multigene systems, to predict behavior of mutant circuits, and to identify the design principles applicable to design of genetic regulatory circuits. When the underlying design rules for regulatory circuits are understood, it will be far easier to recognize common circuit motifs, to identify functions of individual proteins in regulation, and to redesign circuits for altered functions.
Evolution of the wide area network (2002)

This paper describes the dramatic changes taking place in the architecture and capabilities of the wide area network as it evolves from a collection of several service-specific networks, each typically supporting only one transport protocol, to a single multiprotocol network supporting a variety of services. The paper also discusses the technological forces driving this evolution and considers its practical implications.
Synthesis of Long‐Circulating, Backbone Degradable HPMA Copolymer–Doxorubicin Conjugates and Evaluation of Molecular‐Weight‐Dependent Antitumor Efficacy (2013)

Backbone degradable, linear, multiblock N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-doxorubicin (DOX) conjugates are synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization followed by chain extension via thiol-ene click reaction. The examination of molecular-weight-dependent antitumor activity toward human ovarian A2780/AD carcinoma in nude mice reveals enhanced activity of multiblock, second-generation, higher molecular weight conjugates when compared with traditional HPMA copolymer-DOX conjugates. The examination of body weight changes during treatment indicates the absence of non-specific adverse effects.
Disposition and metabolic fate of prasugrel in mice, rats, and dogs (2007)

The disposition and metabolism of prasugrel, a thienopyridine prodrug and a potent inhibitor of platelet aggregation in vivo, were investigated in mice, rats, and dogs. Prasugrel was rapidly absorbed and extensively metabolized. In the mouse and dog, maximum plasma concentration of radioactivity was observed in less than 1 h after an oral [14C]prasugrel dose. Most of the administered prasugrel dose was recovered in the faeces of rats and dogs (72% and 52-73%, respectively), and in mice urine (54%). Prasugrel is hydrolysed by esterases to a thiolactone, which is subsequently metabolized to thiol-containing metabolites. The main circulating thiol-containing metabolite in the three animal species is the pharmacologically active metabolite, R-138727. The thiol-containing metabolites are further metabolized by S-methylation and conjugation with cysteine.
Genetic and neurobiological aspects of attention deficit hyperactive disorder: a review. (1994)

This paper reviews key studies that have addressed genetic and neurobiological aspects in attention deficit hyperactive disorder. Genetic studies can be divided into three distinct types: twin, adoption, and family studies. Evidence for a particular mode of inheritance and the possible specific genetic abnormalities are also explored. There is strong evidence of genetic involvement in this condition, although a clear-cut mode of inheritance and specific genetic abnormalities are yet to be determined. Neurobiological aspects such as the neuroanatomical and neurochemical evidence of various neurotransmitter system involvement is explored. Frontal lobe and dopamine and norepinephrine neurotransmitter systems appear to be involved in attention deficit hyperactive disorder.
CD33‐related siglecs as potential modulators of inflammatory responses (2012)

The immune system must be tightly regulated to prevent unwanted tissue damage caused by exaggerated immune and inflammatory reactions. Inhibitory and activating immune receptors play a crucial role in this function via phosphotyrosine-dependent signaling pathways. A significant body of evidence has accumulated suggesting that the siglec family of sialic acid binding Ig-like lectins makes an important contribution to this immunoregulation. The CD33-related siglecs are a distinct subset of inhibitory and activating receptors, expressed primarily on leukocytes in a cell type-specific manner. Here, we critically assess the in vitro and in vivo evidence on the functional role for CD33-related siglecs in modulation of inflammatory and immune responses.
Polarized incandescent light emission from carbon nanotubes (2003)

Polarized light emission from multiwalled carbon nanotube (MWNT) bundles due to current heating is observed. The spectra of the emitted light fit well with the blackbody radiation distribution. And the emitted light is partially polarized with a degree of 0.33 along the axis of MWNT bundle, which is qualitatively explained in terms of one-dimensional structure of carbon nanotubes (CNTs). Negative temperature-dependent resistance is also observed, which is different from normal metal filaments. The MWNT bundles are very stable at high temperature in vacuum during light emitting, indicating that CNTs can be a good candidate as polarized incandescent light sources.
Pituitary adenylate cyclase‐activating polypeptide regulates forebrain neural stem cells and neurogenesis in vitro and in vivo (2006)

Recent studies suggest that adult neurogenesis can contribute significantly to recovery from brain damage. As a result, there is strong interest in the field in identifying potentially therapeutic factors capable of promoting increased expansion of endogenous neural stem cell (NSC) populations and increased neurogenesis. In the present study, we have investigated the effects of PACAP on the NSC populations of the embryonic and adult forebrain. Our results demonstrate that the PACAP receptor, PAC1-R, is expressed by both embryonic and adult NSCs. The activation of PACAP signaling in vitro enhanced NSC proliferation/survival through a protein kinase A (PKA)-independent mechanism. In contrast, PACAP promoted NSC self-renewal and neurogenesis through a mechanism dependent on PKA activation. Finally, we determined that the intracerebroventricular infusion of PACAP into the adult forebrain was sufficient to increase neurogenesis significantly in both the hippocampus and the subventricular zone. These results demonstrate PACAP is unique in that it is capable of promoting NSC proliferation/survival, self-renewal, and neurogenesis and, therefore, may be ideal for promoting the endogenous regeneration of damaged brain tissue.
DPC4 , A Candidate Tumor Suppressor Gene at Human Chromosome 18q21.1 (1996)

About 90 percent of human pancreatic carcinomas show allelic loss at chromosome 18q. To identify candidate tumor suppressor genes on 18q, a panel of pancreatic carcinomas were analyzed for convergent sites of homozygous deletion. Twenty-five of 84 tumors had homozygous deletions at 18q21.1, a site that excludes DCC (a candidate suppressor gene for colorectal cancer) and includes DPC4, a gene similar in sequence to a Drosophila melanogaster gene (Mad) implicated in a transforming growth factor-beta (TGF-beta)-like signaling pathway. Potentially inactivating mutations in DPC4 were identified in six of 27 pancreatic carcinomas that did not have homozygous deletions at 18q21.1. These results identify DPC4 as a candidate tumor suppressor gene whose inactivation may play a role in pancreatic and possibly other human cancers.
Molecular characterization of two bacteriophages isolated from Desulfovibrio vulgaris NCIMB 8303 (Hildenborough) (1992)

A preliminary endonuclease restriction map of a bacteriophage isolated from Desulfovibrio vulgaris has been established. BamHI cleaved whole phage DNA into four fragments while HindIII cut the same DNA into seven fragments. Mapping studies succeeded in linking the four BamHI fragments into two DNA segments; however, no linkage between the two segments was detected. These data imply that two phages were induced from cultures of D. vulgaris and that the two segments represented the DNA from these phages. Support for this hypothesis came from size approximation of restriction enzyme fragments, electron micrographs, and density gradients.
Integrin &#945;v&#946;3 as a Therapeutic Target for Blocking Tumor-Induced Angiogenesis (2003)

The integrin receptor alphavbeta3 has been shown to play a critical role in several distinct processes, such as angiogenesis, osteoclast-mediated bone resorption and tumor metastasis. Its expression is upregulated in newly synthesized blood vessels produced in response to a variety of tumors and purified angiogenic factors. Studies show that alphavbeta3 is a critical target downstream from perhaps all angiogcnic factors. Proof-of-principle that alphavbeta3 antagonists such as monoclonal antibodies and small molecules block angiogenesis and tumor growth has been obtained in several animal models. Many endogenous inhibitors of angiogenesis such as angiostatin, endostatin and tumstatin seem to work through the alphavbeta3 receptor further emphasizing the critical role of this receptor in angiogenesis. In addition, the alphavbeta3 receptor has been clearly implicated in several pathological processes such as rheumatoid arthritis, osteoporosis, and metastasis of prostate cancer to bone. Thus alphavbeta3 may prove to be an important target for pharmacological intervention in more than one clinical setting.
Differential Expression of CXCR4 Is Associated with the Metastatic Potential of Human Non–Small Cell Lung Cancer Cells (2005)

Differential expression of CXCR4 is associated with the metastatic potential of human NSCLC, raising the possibility that blockade of CXCR4/stromal cell-derived factor-1 interaction may lead the way to design novel therapeutic tools for the treatment of metastatic NSCLC patients.
Error monitoring issues for common channel signaling (1994)

Motivated by field data which showed a large number of link changeovers and incidences of link oscillations between in-service and out-of-service states in common channel signalling (CCS) networks, a number of analyses of the link error monitoring procedures in the SS7 protocol were performed by the authors. This paper summarizes the results obtained thus far and include the following: (a) results of an exact analysis of the performance of the error monitoring procedures under both random and bursty errors; (b) a demonstration that there exists a range of error rates within which the error monitoring procedures of SS7 may induce frequent changeovers and changebacks; (c) an analysis of the performance of the SS7 level-2 transmission protocol to determine the tolerable error rates within which the delay requirements can be met; (d) a demonstration that the tolerable error rate depends strongly on various link and traffic characteristics, thereby implying that a single set of error monitor parameters will not work well in all situations; and (e) some recommendations on a customizable/adaptable scheme of error monitoring with a discussion on their implementability. These issues may be particularly relevant in the presence of anticipated increases in SS7 traffic due to widespread deployment of advanced intelligent network (AIN) and personal communications service (PCS) as well as for developing procedures for high-speed SS7 links currently under consideration by standards bodies.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Intravenous rFVIIa Administered for Hemorrhage Control in Hypothermic Coagulopathic Swine with Grade V Liver Injuries (2001)

rFVIIa reduced blood loss and restored abnormal coagulation function when used in conjunction with liver packing in hypothermic and coagulopathic swine. No adverse effects were identified.
Molecular organization, structural features, and ligand binding characteristics of CD44, a highly variable cell surface glycoprotein with multiple functions (2000)

CD44 is a type I transmembrane protein and member of the cartilage link protein family. It is involved in cell-cell and cell-matrix interactions and signal transduction. Several CD44 ligands have been identified. CD44 is a major cell surface receptor for hyaluronan, a component of the extracellular matrix. It is implicated in diseases such as cancer and inflammation and therefore intensely studied. A characteristic feature of CD44 is the occurrence of many isoforms that are expressed in a cell-specific manner and differentially glycosylated. Although a number of CD44 isoforms have been characterized, the structural diversity of CD44 makes it often challenging to study (isoform-specific) CD44-ligand interactions at the molecular level of detail. The structural organization and ligand binding characteristics of CD44 are focal points of this review. On the basis of recent structural and mutagenesis studies, details of the CD44-hyaluronan interaction are beginning to be understood. Proteins 2000;39:103-111.
Neuraminidase activity in bacterial meningitis (1971)

The relation of neuraminidase to morbidity and mortality was examined in patients with Haemophilus influenzae, meningococcal, and pneumococcal meningitis. Ten strains of H. influenzae and eight strains of meningococci from infected cerebrospinal fluid (CSF) did not elaborate neuraminidase. Each of 27 strains of pneumococci from infected CSF elaborated both neuraminidase and N-acetylneuraminic acid (NANA) aldolase. There was no correlation between amount of neuraminidase secreted in vitro and survival of patients. Values for free and total NANA concentrations were derived from admission CSF samples of 63 patients with meningitis; 18 patients infected with Neisseria meningitidis, 10 with H. influenzae and 35 with Diplococcus pneumoniae. Mean values for total NANA were elevated in each type of bacterial meningitis; however, abnormal concentrations of free CSF NANA were detected only in 17 patients with pneumococcal meningitis. 11 of 18 patients with pneumococcal meningitis showing normal free CSF NANA concentrations were cured, whereas only 4 patients with abnormal free NANA levels survived without residua. Both coma and bacteremia occurred significantly more often among patients with elevated concentrations of free CSF NANA. The association of elevated concentrations of free CSF NANA with coma and with an adverse prognosis suggested that neuraminidase may be a factor in the pathogenesis of penumococcal meningitis.
An immunodominant La/SSB autoantibody proteome derives from public clonotypes (2013)

The La/SSB autoantigen is a major target of long-term humoral autoimmunity in primary Sjögren's Syndrome (SS) and systemic lupus erythematosus. A majority of patients with linked anti-Ro60/Ro52/La responses target an NH2-terminal epitope designated LaA that is expressed on Ro/La ribonucleoprotein complexes and the surface membrane of apoptotic cells. In this study, we used high-resolution Orbitrap mass spectrometry to determine the clonality, isotype and V-region sequences of LaA-specific autoantibodies in seven patients with primary SS. Anti-LaA immunoglobulin (Ig)Gs purified from polyclonal sera by epitope-specific affinity chromatography were analysed by combined database and de-novo mass spectrometric sequencing. Autoantibody responses comprised two heavily mutated IgG1 kappa-restricted monoclonal species that were shared (public) across unrelated patients; one clonotype was specified by an IGHV3-30 heavy chain paired with IGKV3-15 light chain and the second by an IGHV3-43/IGKV3-20 pairing. Shared amino acid replacement mutations were also seen within heavy and light chain complementarity-determining regions, consistent with a common breach of B cell tolerance followed by antigen-driven clonal selection. The discovery of public clonotypic autoantibodies directed against an immunodominant epitope on La, taken together with recent findings for the linked Ro52 and Ro60 autoantigens, supports a model of systemic autoimmunity in which humoral responses against protein-RNA complexes are mediated by public sets of autoreactive B cell clonotypes.
Safety and in vivo Expression of a GNE-Transgene: A Novel Treatment Approach for Hereditary Inclusion Body Myopathy-2 (2009)

Hereditary inclusion body myopathy-2 (HIBM2) is an adult-onset, muscular disease caused by mutations in the GNE gene. HIBM2-associated GNE mutations causing hyposialyation have been proposed to contribute to reduced muscle function in patients with HIBM2, though the exact cause of this disease is unknown. In the current studies we examined pre-clinical in vivo toxicity, and expression of the plasmid-based, CMV driven wild-type GNE plasmid vector. The plasmid vector was injected intramuscularly (IM) or systemically (IV) into BALB/c mice, following encapsulation in a cationic liposome (DOTAP:Cholesterol). Single IM injections of the GNE-lipoplex at 40 microg did not produce overt toxicity or deaths, indicating that the no observable adverse effect level (NOAEL) dose for IM injection was >or=40 microg. Single intravenous (IV) infusion of GNE-lipoplex was lethal in 33% of animals at 100 microg dose, with a small proportion of animals in the 40 microg cohort demonstrating transient toxicity. Thus the NOAEL dose by the IV route was greater than 10 microg and less than or equal to 40 microg. Real-time RT-qPCR analysis demonstrated recombinant human GNE mRNA expression in 100% of muscle tissues that received IM injection of 40 microg GNE-lipoplex, at 2 weeks. These results indicate that GNE-lipoplex gene transfer is safe and can produce durable transgene expression in treated muscles. Our findings support future exploration of the clinical efficacy of GNE-lipoplex for experimental gene therapy of HIBM2.
Pre-existing immunity against Ad vectors (2014)

Pre-existing immunity against human adenovirus (HAd) serotype 5 derived vector in the human population is widespread, thus hampering its clinical use. Various components of the immune system, including neutralizing antibodies (nAbs), Ad specific T cells and type I IFN activated NK cells, contribute to dampening the efficacy of Ad vectors in individuals with pre-existing Ad immunity. In order to circumvent pre-existing immunity to adenovirus, numerous strategies, such as developing alternative Ad serotypes, varying immunization routes and utilizing prime-boost regimens, are under pre-clinical or clinical phases of development. However, these strategies mainly focus on one arm of pre-existing immunity. Selection of alternative serotypes has been largely driven by the absence in the human population of nAbs against them with little attention paid to cross-reactive Ad specific T cells. Conversely, varying the route of immunization appears to mainly rely on avoiding Ad specific tissue-resident T cells. Finally, prime-boost regimens do not actually circumvent pre-existing immunity but instead generate immune responses of sufficient magnitude to confer protection despite pre-existing immunity. Combining the above strategies and thus taking into account all components regulating pre-existing Ad immunity will help further improve the development of Ad vectors for animal and human use.
Matrix‐assisted infrared‐laser (2.94 μm) desorption/ionization mass spectrometry of large biomolecules (1990)

Abstract The matrix‐assisted desorption/ionization of large biomolecules with a wavelength of 2.94 μm in the infrared is reported. A mechanically Q‐switched Erbium‐YAG laser with a pulse width of ca. 200 ns was used for the experiments. A large variety of matrices have been used successfully, among them all matrices found useful for ultraviolet desorption and, in addition, carboxylic acids, glycerol and urea. Desorption of molecules at this wavelength and caffeic acid as a matrix results in ions with up to 13 charges per ion.