gebhart/patrepeval huggingface dataset:
Constrained and general dynamic rate shaping of compressed digital video (2002)

We introduce the concept of dynamic rate shaping, a technique to adapt the rate of compressed video bitstreams (MPEG-1, MPEG-2, H.261, as well as JPEG) to dynamically varying bit rate constraints. The approach provides an interface (or filter) between the encoder and the network, with which the encoder's output can be perfectly matched to the network's quality of service characteristics. Since the presented algorithms do not require interaction with the encoder, they are fully applicable to precoded, stored video (e.g., video-on-demand systems). By decoupling the encoder and the network, universal interoperability can be achieved. In essence, DRS bridges the gap between CBR and VBR video, allowing a continuum of possibilities between the two. A set of low-complexity algorithms for so-called unconstrained dynamic rate shaping are presented, and both optimal and extremely fast designs are discussed. Experimental results are provided using actual MPEG-2 bitstreams.
Efficient Translation of Rotavirus mRNA Requires Simultaneous Interaction of NSP3 with the Eukaryotic Translation Initiation Factor eIF4G and the mRNA 3′ End (2000)

In contrast to the vast majority of cellular proteins, rotavirus proteins are translated from capped but nonpolyadenylated mRNAs. The viral nonstructural protein NSP3 specifically binds the 3'-end consensus sequence of viral mRNAs and interacts with the eukaryotic translation initiation factor eIF4G. Here we show that expression of NSP3 in mammalian cells allows the efficient translation of virus-like mRNA. A synergistic effect between the cap structure and the 3' end of rotavirus mRNA was observed in NSP3-expressing cells. The enhancement of viral mRNA translation by NSP3 was also observed in a rabbit reticulocyte lysate translation system supplemented with recombinant NSP3. The use of NSP3 mutants indicates that its RNA- and eIF4G-binding domains are both required to enhance the translation of viral mRNA. The results reported here show that NSP3 forms a link between viral mRNA and the cellular translation machinery and hence is a functional analogue of cellular poly(A)-binding protein.
Protective vaccination with a recombinant fragment of Clostridium botulinum neurotoxin serotype A expressed from a synthetic gene in Escherichia coli (1995)

A completely synthetic gene encoding fragment C, a approximately 50-kDa fragment, of botulinum neurotoxin serotype A was constructed from oligonucleotides. The gene was expressed in Escherichia coli, and full-sized product was produced as judged by Western blot (immunoblot) analysis. Crude extracts of E. coli expressing the gene were used to vaccinate mice and evaluate their survival against challenge with active toxin. Mice given three subcutaneous vaccinations were protected against an intraperitoneal administration of 10(6) 50% lethal doses (ID50) of serotype A toxin. The same mice survived when challenged with 3 LD50 of botulinum toxin serotype E but died when challenged with 10 LD50 of serotype E or 3 LD50 of serotype B. Purified fragment C was compared with the botulinum toxoid vaccine in a vaccination and challenge study. Fragment C was as efficacious in protecting against challenge with active botulinum neurotoxin serotype A as the toxoid vaccine. This recombinant protein product has many properties that make it a good candidate for human use to protect against botulinum toxin.
Citrus Flavonoids Stimulate Secretion by Human Colonic T84 Cells , (1993)

Flavonoids, compounds containing a 2-phenylbenzo(gamma)pyrane nucleus, are universally distributed among vascular plants. Even though flavonoids are ingested in a normal diet in average quantities of 1 g daily, their effects on the digestive system have only been recently investigated. This study used an in vitro model of colonic secretion, monolayers of T84 colonic adenocarcinoma cells mounted in Ussing chambers, to demonstrate that 100 mumol/L of either tangeritin or nobiletin, polymethoxylated flavonoids contained in citrus fruits, stimulated sustained electrogenic chloride secretion with a maximal short-circuit current of 3.3 microA/cm2. In contrast, naringin and hesperidin, glycosylated citrus flavonoids, stimulated minimal secretion, suggesting that carbohydrate substitutions inhibited their secretory potential. The secretion stimulated by tangeritin and nobiletin was synergistic with carbachol but not with vasoactive intestinal peptide and was inhibited by barium chloride, bumetanide, H-89, and Cl- depletion. These properties suggest that tangeritin and nobiletin stimulated Cl- secretion via the cAMP pathway; however, these flavonoids did not stimulate cAMP production to the extent seen with vasoactive intestinal peptide. These flavonoids did not autooxidize, suggesting that reactive oxygen species did not mediate this secretion. These observations suggest that dietary citrus flavonoids may modulate colonic secretion, possibly through direct interaction with intracellular secretory pathways.
Standards for PET Image Acquisition and Quantitative Data Analysis (2009)

Quantitative (18)F-FDG PET is increasingly being recognized as an important tool for diagnosis, determination of prognosis, and response monitoring in oncology. However, PET quantification with, for example, standardized uptake values (SUVs) is affected by many technical and physiologic factors. As a result, some of the variations in the literature on SUV-based patient outcomes are explained by differences in (18)F-FDG PET study methods. Various technical and clinical studies have been performed to understand the factors affecting PET quantification. On the basis of the results of those studies, several recommendations and guidelines have been proposed with the aims of improving the image quality and the quantitative accuracy of (18)F-FDG PET studies. In this contribution, an overview of recommendations and guidelines for quantitative (18)F-FDG PET studies in oncology is provided. Special attention is given to the rationale underlying certain recommendations and to some of the differences in various guidelines.
Severe Acute Respiratory Syndrome Coronavirus Infection Causes Neuronal Death in the Absence of Encephalitis in Mice Transgenic for Human ACE2 (2008)

Infection of humans with the severe acute respiratory syndrome coronavirus (SARS-CoV) results in substantial morbidity and mortality, with death resulting primarily from respiratory failure. While the lungs are the major site of infection, the brain is also infected in some patients. Brain infection may result in long-term neurological sequelae, but little is known about the pathogenesis of SARS-CoV in this organ. We previously showed that the brain was a major target organ for infection in mice that are transgenic for the SARS-CoV receptor (human angiotensin-converting enzyme 2). Herein, we use these mice to show that virus enters the brain primarily via the olfactory bulb, and infection results in rapid, transneuronal spread to connected areas of the brain. This extensive neuronal infection is the main cause of death because intracranial inoculation with low doses of virus results in a uniformly lethal disease even though little infection is detected in the lungs. Death of the animal likely results from dysfunction and/or death of infected neurons, especially those located in cardiorespiratory centers in the medulla. Remarkably, the virus induces minimal cellular infiltration in the brain. Our results show that neurons are a highly susceptible target for SARS-CoV and that only the absence of the host cell receptor prevents severe murine brain disease.
Sequence Similarities Between Human Immunodeficiency Virus gp41 and Paramyxovirus Fusion Proteins (1987)

Cell fusion is a characteristic cytopathic effect induced by the human immunodeficiency virus (HIV) that leads to the formation of syncytia between infected lymphocytes. Although this process has been shown to occur following the specific binding of the 110-120 kD externalized envelope molecule of the virus with the CD4 glycoprotein, the region of the HIV envelope that directly mediates cell fusion is unknown. In an attempt to identify this fusion domain, we compared the amino acid sequences from the envelope molecules of several HIV isolates to the fusion proteins of paramyxoviruses. We found that the amino terminal region of the HIV transmembrane protein gp41 had a striking degree of similarity with the fusion domain of the respiratory syncytial virus. Moreover, similar sequences were noted in the fusion proteins of other paramyxoviruses and the transmembrane envelope proteins of a variety of lentiviruses suggesting that a functional relationship exists between these glycoproteins. This finding indicates that the amino terminal region of the HIV gp41 molecule may mediate cell fusion for this virus, and could be an important target in the design of immunologic strategies for the prevention of HIV infection in vivo.
Targeted Delivery of IFNγ to Tumor Vessels Uncouples Antitumor from Counterregulatory Mechanisms (2005)

Because of its immunomodulatory and anticancer activities, IFNgamma has been used as an anticancer drug in several clinical studies, unfortunately with modest results. Attempts to increase the response by increasing the dose or by repeated continuous injection often resulted in lower efficacy, likely due to counterregulatory effects. We show here that targeted delivery of low doses of IFNgamma to CD13, a marker of angiogenic vessels, can overcome major counterregulatory mechanisms and delay tumor growth in two murine models that respond poorly to IFNgamma. Tumor vascular targeting was achieved by coupling IFNgamma to GCNGRC, a CD13 ligand, by genetic engineering technology. The dose-response curve was bell-shaped. Maximal effects were induced with a dose of 0.005 microg/kg, about 500-fold lower than the dose used in patients. Nontargeted IFNgamma induced little or no effects over a range of 0.003 to 250 microg/kg. Studies on the mechanism of action showed that low doses of targeted IFNgamma could activate tumor necrosis factor (TNF)-dependent antitumor mechanisms, whereas high doses of either targeted or nontargeted IFNgamma induced soluble TNF-receptor shedding in circulation, a known counterregulatory mechanism of TNF activity. These findings suggest that antitumor activity and counterregulatory mechanisms could be uncoupled by tumor vascular targeting with extremely low doses of IFNgamma.
Infection with Mycobacterium kansasii and efficacy of vaccination against tuberculosis. (1983)

The purpose of the present study was to examine further the recent hypothesis that subcutaneous infection with Mycobacterium kansasii resulted in the generation of a cell-mediated hypersensitivity reaction ('Koch' reaction) which could, it was argued, subsequently interfere with the generation of acquired immunity following vaccination of the animal with BCG. The results of the present study were unable to confirm this hypothesis in that they show, firstly, that subcutaneous M. kansasii infection was associated with the development of substantial Arthus-like reactivity which masked the detection of any subsequent delayed response, and that furthermore, attempts to adoptively transfer this form of delayed reaction by means of passive transfer of cells were unsuccessful. Furthermore, the results show that, despite the presence of the M. kansasii infection, BCG-vaccinated animals were fully resistant to subsequent aerosol-delivered challenge with virulent M. tuberculosis.
The A+T-rich genome of Herpesvirus saimiri contains a highly conserved gene for thymidylate synthase. (1986)

Herpesvirus saimiri (HVS) is the prototype member of a distinctive subset of lymphotropic herpesviruses (the gamma 2 subgroup) with A+T-rich coding sequences. In this paper, we show that cells productively infected with HVS contain high concentrations of a virus-specified thymidylate synthase (5,10-methylenetetrahydrofolate:dUMP C-methyltransferase, EC 2.1.1.45); we identify the active polypeptide and present the sequence of the virus gene. The predicted amino acid sequence of the 294-residue subunit of the virus enzyme is 70% homologous with the sequence of the human enzyme and about 50% homologous with prokaryotic thymidylate synthases, illustrating the remarkable structural constraints imposed by the thymidylate synthase function. However, the presence of the enzyme is not a conserved property of herpesviruses. We find no evidence for a virus-encoded thymidylate synthase activity (or a homology to a thymidylate synthase sequence) in G+C-rich representatives of alpha 1 (e.g., herpes simplex viruses, 66-68% G+C), beta (i.e., human cytomegalovirus, 58-59% G+C), and gamma 1 (i.e., Epstein-Barr virus, 60% G+C) herpesvirus subgroups. The production of excess thymidylate by a virus thymidylate synthase in cells infected with an A+T-rich herpesvirus would provide one plausible source of biased mutations by the virus-encoded replicative enzymes, which we have previously suggested as the likely general cause of differences in the mean nucleotide compositions of herpesvirus genomes.
Broadly Neutralizing Monoclonal Antibodies 2F5 and 4E10 Directed against the Human Immunodeficiency Virus Type 1 gp41 Membrane-Proximal External Region Protect against Mucosal Challenge by Simian-Human Immunodeficiency Virus SHIV Ba-L (2009)

The membrane-proximal external region (MPER) of HIV-1, located at the C terminus of the gp41 ectodomain, is conserved and crucial for viral fusion. Three broadly neutralizing monoclonal antibodies (bnMAbs), 2F5, 4E10, and Z13e1, are directed against linear epitopes mapped to the MPER, making this conserved region an important potential vaccine target. However, no MPER antibodies have been definitively shown to provide protection against HIV challenge. Here, we show that both MAbs 2F5 and 4E10 can provide complete protection against mucosal simian-human immunodeficiency virus (SHIV) challenge in macaques. MAb 2F5 or 4E10 was administered intravenously at 50 mg/kg to groups of six male Indian rhesus macaques 1 day prior to and again 1 day following intrarectal challenge with SHIV(Ba-L). In both groups, five out of six animals showed complete protection and sterilizing immunity, while for one animal in each group a low level of viral replication following challenge could not be ruled out. The study confirms the protective potential of 2F5 and 4E10 and supports emphasis on HIV immunogen design based on the MPER region of gp41.
E7050: A dual c‐Met and VEGFR‐2 tyrosine kinase inhibitor promotes tumor regression and prolongs survival in mouse xenograft models (2009)

c-Met is the cellular receptor for hepatocyte growth factor (HGF) and is known to be dysregulated in various types of human cancers. Activation of the HGF/c-Met pathway causes tumor progression, invasion, and metastasis. Vascular endothelial growth factor (VEGF) is also known as a key molecule in tumor progression through the induction of tumor angiogenesis. Because of their key roles in tumor progression, these pathways provide attractive targets for therapeutic intervention. We have generated a novel, orally active, small molecule compound, E7050, which inhibits both c-Met and vascular endothelial growth factor receptor (VEGFR)-2. In vitro studies indicate that E7050 potently inhibits phosphorylation of both c-Met and VEGFR-2. E7050 also potently represses the growth of both c-met amplified tumor cells and endothelial cells stimulated with either HGF or VEGF. In vivo studies using E7050 showed inhibition of the phosphorylation of c-Met and VEGFR-2 in tumors, and strong inhibition of tumor growth and tumor angiogenesis in xenograft models. Treatment of some tumor lines containing c-met amplifications with high doses of E7050 (50-200 mg/kg) induced tumor regression and disappearance. In a peritoneal dissemination model, E7050 showed an antitumor effect against peritoneal tumors as well as a significant prolongation of lifespan in treated mice. Our results indicate that E7050 is a potent inhibitor of c-Met and VEGFR-2 and has therapeutic potential for the treatment of cancer.
Endothelial progenitor cells: diagnostic and therapeutic considerations (2006)

Endothelial progenitor cells (EPCs) may be defined as adherent cells derived from peripheral blood- or bone marrow-derived mononuclear cells demonstrating acLDL uptake and isolectin-binding capacity. The number of circulating EPCs inversely correlates with the number of cardiovascular risk factors and is reduced in cardiovascular disease. This measurement may therefore serves as a surrogate marker for cardiovascular disease risk. EPC numbers can be modified by various means. However, the effectiveness of risk-factor modification on EPC number and function is currently unknown. Furthermore, EPCs may be used as a potential therapy for a variety of vascular disease states including ischaemia, restenosis and pulmonary hypertension. This review provides an update on multiple factors that affect EPC number as well as highlighting the potential use of EPCs as a novel marker of vascular dysfunction. Furthermore, potential gene- and/or EPC-based approaches to a number of vascular disease states are explored.
Autoimmune Disease in Lyn-Deficient Mice Is Dependent on an Inflammatory Environment Established by IL-6 (2009)

Lyn-deficient mice develop Ab-mediated autoimmune disease resembling systemic lupus erythematosus where hyperactive B cells are major contributors to pathology. In this study, we show that an inflammatory environment is established in Lyn(-/-) mice that perturbs several immune cell compartments and drives autoimmune disease. Lyn(-/-) leukocytes, notably B cells, are able to produce IL-6, which facilitates hyperactivation of B and T cells, enhanced myelopoiesis, splenomegaly, and, ultimately, generation of pathogenic autoreactive Abs. Lyn(-/-) dendritic cells show increased maturation, but this phenotype is independent of autoimmunity as it is reiterated in B cell-deficient Lyn(-/-) mice. Genetic deletion of IL-6 on a Lyn-deficient background does not alter B cell development, plasma cell accumulation, or dendritic cell hypermaturation, suggesting that these characteristics are intrinsic to the loss of Lyn. However, hyperactivation of B and T cell compartments, extramedullary hematopoiesis, expansion of the myeloid lineage and autoimmune disease are all ameliorated in Lyn(-/-)IL-6(-/-) mice. Importantly, our studies show that although Lyn(-/-) B cells may be autoreactive, it is the IL-6-dependent inflammatory environment they engender that dictates their disease-causing potential. These findings improve our understanding of the mode of action of anti-IL-6 and B cell-directed therapies in autoimmune and inflammatory disease treatment.
Comparison of genetic changes in schistosome-related transitional and squamous bladder cancers using comparative genomic hybridization (2000)

The development of bladder tumors has been associated with a number of causative agents, including schistosomiasis. Schistosome-related cancers show different clinical and pathological features compared with non-schistosome-related bladder cancers, occurring in younger patients, and being predominantly of squamous cell type. This study addresses the difference between squamous and transitional tumor types in the presence of schistosome infection as a measure of the relationship between tumor genotype and phenotype. We have used comparative genomic hybridization to analyze primary muscleinvasive schistosome-related bladder tumors in 54 patients. Twenty-six of these tumors were squamous cell carcinomas; the remaining 28 were of transitional cell type. On average, transitional cell tumors showed 1.8 times the number of chromosomal aberrations as squamous cell tumors (14.4 versus 8.2, P: < 0.001). For both groups combined, the most prevalent genetic alterations were losses of 8p and 18q, and gains of 8q. Transitional cell cancers also showed frequent losses involving 5q, 9p, 10q, 11p and 11q, and gains at 1q and 17q. Loss of 11p was significantly more frequent in TCC than in SCC tumors (50 versus 4%, P: = 0.01). Squamous cell cancers showed more frequent losses of 17p and 18p than transitional tumors, which was clearly significant given the overall reduced frequency of changes in squamous cancers (P: = 0.001 and P: = 0.03, respectively). These data show that different histologic subgroups of bladder tumors are characterized by distinct patterns of chromosomal alterations. The genetic changes found in the transitional cell group are similar to those reported in non-schistosome-related transitional cell tumors, but differ from tumors exhibiting squamous differentiation.
Intelligent video smoother for multimedia communications (1997)

Multimedia communications often require intramedia synchronization for video data to prevent potential playout discontinuity resulting from network delay variation (jitter) while still achieving satisfactory playout throughput. In this paper, we propose a neural network (NN) based intravideo synchronization mechanism, called the intelligent video smoother (IVS), operating at the application layer of the receiving end system. The IVS is composed of an NN traffic predictor, an NN window determinator, and a window-based playout smoothing algorithm. The NN traffic predictor employs an on-line-trained back-propagation neural network (BPNN) to periodically predict the characteristics of traffic modeled by a generic interrupted Bernoulli process (IBP) over a future fixed time period. With the predicted traffic characteristics, the NN window determinator determines the corresponding optimal window by means of an off-line-trained BPNN in an effort to achieve a maximum of the playout quality (Q) value. The window-based playout smoothing algorithm then dynamically adopts various playout rates according to the window and the number of packets in the buffer. Finally, we show that via simulation results and live video scenes, compared to two other playout approaches, IVS achieves high-throughput and low-discontinuity playout under a mixture of IBP arrivals.
Design and implementation of a low temperature near-field scanning optical microscope (1994)

The design and implementation of a low temperature (T≥1.5 K), near-field scanning optical microscope are described herein. This microscope, which is based on the recently developed tapered fiber probe, is optimized for luminescence imaging and spectroscopy of mesoscopic semiconductor systems.
Prospective Study of Serologic Tests for Lyme Disease (2008)

Except in patients with erythema migrans, both test systems were sensitive for support of the diagnosis of Lyme disease. However, with current methods, 2-tier testing was associated with slightly better specificity.