gebhart/patrepeval huggingface dataset:
Production of infectious genotype 1a hepatitis C virus (Hutchinson strain) in cultured human hepatoma cells (2006)

Infections with hepatitis C virus (HCV) are marked by frequent viral persistence, chronic liver disease, and extraordinary viral genetic diversity. Although much has been learned about HCV since its discovery, progress has been slowed by a lack of permissive cell culture systems supporting its replication. Productive infections have been achieved recently with genotype 2a virus, but cirrhosis and liver cancer are typically associated with genotype 1 HCV, which is more prevalent and relatively resistant to IFN therapy. We describe production of infectious genotype 1a HCV in cells transfected with synthetic RNA derived from a prototype virus (H77-S). Viral proteins accumulated more slowly in H77-S transfected cells than in cells transfected with genotype 2a (JFH-1) RNA, but substantially more H77-S RNA was secreted into supernatant fluids. Most secreted RNA was noninfectious, banding in isopycnic gradients at a density of 1.04-1.07 gm/cm(3), but infectivity was associated with H77-S particles possessing a density of 1.13-1.14 gm/cm(3). The specific infectivity of H77-S particles (5.4 x 10(4) RNA copies per focus-forming unit) was significantly lower than JFH-1 virus (1.4 x 10(2) RNA copies per focus-forming unit). Infection with either virus was blocked by CD81 antibody. Sera from genotype 1a-infected individuals neutralized H77-S virus, but had little activity against genotype 2a virus, suggesting that these genotypes represent different serotypes. The ability of this genotype 1a virus to infect cultured cells will substantially benefit antiviral and vaccine discovery programs.
Optimizing virtual machines using hybrid virtualization (2011)

It is crucial to minimize virtualization overhead for virtual machine deployment. The conventional ×86 CPU is incapable of classical trap-and-emulate virtualization, leading that paravirtualization was the optimal virtualization strategy formerly. Since architectural extensions are introduced to support classical virtualization, hardware assisted virtualization becomes a competitive alternative method. Hardware assisted virtualization is superior in CPU and memory virtualization, yet paravirtualization is still valuable in some aspects as it is capable of shortening the disposal path of I/O virtualization. Thus we propose the hybrid virtualization which runs the paravirtualized guest in the hardware assisted virtual machine container to take advantage of both. Experiment results indicate that our hybrid solution outweighs origin paravirtualization by nearly 30% in memory intensive test and 50% in microbenchmarks. Meanwhile, compared with the origin hardware assisted virtual machine, hybrid guest owns over 16% improvement in I/O intensive workloads.
A germline deletion of p14ARF but not CDKN2A in a melanoma-neural system tumour syndrome family (2001)

The melanoma-astrocytoma syndrome is characterized by a dual predisposition to melanoma and neural system tumours, commonly astrocytoma. Germline deletions of the region on 9p21 containing the CDKN2A and CDKN2B genes and CDKN2A exon 1beta have been reported in kindreds, implicating contiguous tumour suppressor gene deletion as a cause of this syndrome. We describe a family characterized by multiple melanoma and neural cell tumours segregating with a germline deletion of the p14(ARF)-specific exon 1beta of the CDKN2A gene. This deletion does not affect the coding or minimal promoter sequences of either the CDKN2A or CDKN2B genes. Our results are consistent with either: (i) loss of p14(ARF) function being the critical abnormality associated with this syndrome, rather than contiguous loss of both the CDKN2A and CDKN2B genes as suggested previously; or (ii) disruption of expression of p16 by mechanisms as yet unknown.
Signal Transducer and Activator of Transcription 3 Is Required for the Oncogenic Effects of Non–Small-Cell Lung Cancer–Associated Mutations of the Epidermal Growth Factor Receptor (2006)

Somatic mutations in the epidermal growth factor receptor (EGFR) occur frequently in lung cancer and confer sensitivity to EGFR kinase inhibitors gefitinib and erlotinib. These mutations, which occur in the kinase domain of the protein, also render EGFR constitutively active and transforming. Signal transducers and activators of transcription 3 (STAT3) transduces signals from a number of oncogenic tyrosine kinases and contributes to a wide spectrum of human malignancies. Here, we show that STAT3 is activated by mutant EGFRs and is necessary for its downstream phenotypic effects. Inhibiting STAT3 function in fibroblasts abrogates transformation by mutant EGFR. In non-small-cell lung cancer cells, STAT3 activity is regulated by EGFR through modulation of STAT3 serine phosphorylation. Inhibiting STAT3 function increases apoptosis of these cells, suggesting that STAT3 is necessary for their survival. Finally, a group of genes constituting a STAT3 signature is enriched in lung tumors with EGFR mutations. Thus, STAT3 is a critical mediator of the oncogenic effects of somatic EGFR mutations and targeting STAT3 may be an effective strategy for treating tumors characterized by these mutations.
Insulin Production by Human Embryonic Stem Cells (2001)

Type 1 diabetes generally results from autoimmune destruction of pancreatic islet beta-cells, with consequent absolute insulin deficiency and complete dependence on exogenous insulin treatment. The relative paucity of donations for pancreas or islet allograft transplantation has prompted the search for alternative sources for beta-cell replacement therapy. In the current study, we used pluripotent undifferentiated human embryonic stem (hES) cells as a model system for lineage-specific differentiation. Using hES cells in both adherent and suspension culture conditions, we observed spontaneous in vitro differentiation that included the generation of cells with characteristics of insulin-producing beta-cells. Immunohistochemical staining for insulin was observed in a surprisingly high percentage of cells. Secretion of insulin into the medium was observed in a differentiation-dependent manner and was associated with the appearance of other beta-cell markers. These findings validate the hES cell model system as a potential basis for enrichment of human beta-cells or their precursors, as a possible future source for cell replacement therapy in diabetes.
Cytokine production in synovial tissue of mice with collagen-induced arthritis (CIA) (1997)

The kinetics of cytokine production in arthritic limbs of mice with CIA was determined by using modified immunohistochemical techniques. Tissue cryostat sections of undecalcified whole paws were analysed for the presence of tumour necrosis factor-alpha (TNF-alpha), IL-6, IL-2, IL-4, IL-5 interferon-gamma (IFN-gamma), transforming growth factor-beta 2 (TGF-beta2) and TGF-beta3. Locally produced TNF-alpha, IL-6 and TGF-beta2 were observed within the lining layer, sublining and pannus at all stages of disease. The staining of TNF-alpha was particularly intense at the cartilage-pannus junction. In contrast to the monokines, IFN-gamma and TGF-beta3 were only expressed in scattered cells within the deeper layers of the synovia. Interestingly, IFN-gamma was not present in the late phase of CIA, despite the continued presence of TNF-alpha and IL-6 in the pannus. Production of IL-2, IL-4 or IL-5 was not detected in any joint. The observed pattern of a relative paucity of T cell-derived cytokines and an abundance of monokines during the late phase of T cell-dependent CIA indicates that the synovial cytokine pattern previously described in rheumatoid arthritis (RA) is fully compatible with a pathogenic role of T cells. The temporal as well as spatial dissociation between expression of T cell-derived cytokines and monokines indicates that T cell-independent mechanisms may also be of importance in the triggering of monokine production during arthritis.
LARD: A new lymphoid-specific death domain containing receptor regulated by alternative pre-mRNA splicing (1997)

Fas and TNF-R1 are cysteine-rich cell surface receptors related to the low-affinity nerve growth factor receptor family. Engagement of these receptors by their respective ligands, FasL and tumor necrosis factor, leads to apoptosis that is signaled through a conserved intracellular portion of the receptor termed the "death domain." We have cloned a new member of this family, lymphocyte-associated receptor of death (LARD), which leads to spontaneous apoptosis when expressed in 293T cells. The expression of LARD is more tightly regulated than that of either Fas or TNF-R1 as it is found predominantly on lymphocytes (T and B cells) but not on macrophages or a number of transformed lymphocyte cell lines. Alternative pre-mRNA splicing generates at least 11 distinct isoforms of LARD. The full-length isoform, LARD-1, extends to include the transmembrane and death domains, whereas the other isoforms encode potentially secreted molecules. Naive B and T cells express very little LARD-1 but express combinations of the other isoforms. Upon T cell activation, a programmed change in alternative splicing occurs so that the full-length, membrane-bound LARD-1 predominates. This may have implications for the control of lymphocyte proliferation following activation.
A New Triantennary Galactose-Targeted PEGylated Gene Carrier, Characterization of Its Complex with DNA, and Transfection of Hepatoma Cells (2004)

Nonviral gene vectors remain inefficient in vivo largely because of their rapid clearance from the circulation and also their nonspecific association with the extracellular matrix. To overcome such drawbacks, cationic lipoplexes are now frequently coated with hydrophilic polymers such as PEGs to reduce nonspecific interactions, and ligands are also linked to their surface to obtain cell-specific gene transfer. In view of the development of vectors for systemic gene delivery, we have designed and studied lipoplexes that carry a triantennary galactosyl ligand attached to the distal end of a (PEG)45-conjugated lipid. We incorporated this targeted PEGylated lipid into lipoplexes using two strategies of formulation, i.e., using either preformed micelles or liposomes. We demonstrated that the incorporation of PEG chains stabilized lipoplexes and masked, but only partially, the positive charges exposed on the surface of the particles. We have also shown that incorporation into lipoplexes of a lipidated PEG chain, bearing a ligand at its distal end, yielded particles that exhibited an accessible ligand throughout the whole range of cationic lipid to DNA ratios. We obtained a targeted transfection in HepG2 cells with one of the formulations. Our results strengthen the validity of using a ligand carried by a long PEG spacer arm for targeted gene transfer.
Restriction of interferon gamma responsiveness and basal expression of the myeloid human Fc gamma R1b gene is mediated by a functional PU.1 site and a transcription initiator consensus. (1994)

The restricted expression of the human Fc gamma R1b gene to myeloid cells is likely to be regulated by a combination of transcription factors that may not be solely expressed in myeloid cells, but act together to restrict the expression of the gene to myeloid cells. Low basal expression of the human Fc gamma R1b gene is specifically upregulated by interferon gamma (IFN-gamma). A 181-bp region of 5' flanking sequence contains several key regulatory motifs that include the extended gamma response region (XGRR) and the PIE region. The XGRR contains the 39-bp gamma response region originally defined in the highly homologous Fc gamma R1a gene. The XGRR is in close proximity to the 21-bp PIE motif that is conserved in the promoters of some other myeloid genes. The PIE motif contains a consensus site for the macrophage and B cell transcription factor, PU.1, and is adjacent to the cluster of transcription start sites. An active transcription initiator, Inr, consensus spans the start sites and appears to direct transcription initiation of this TATA-less gene. In this study, we demonstrate that the PIE region contains a functional PU.1 site that binds a human PU.1-like protein and that associated factors present in myeloid extracts also bind in this PIE region. Mutational analysis reveals an absolute requirement for an intact PU.1 box for both basal and IFN-gamma inducible expression of this gene. In addition, mutations in the Inr greatly reduce basal and inducible transcription. Insertion of a strong TATA box downstream from the Inr or at -30 bp from the transcription start sites restores basal and inducible activity in the presence of a mutated PU.1 site. We also demonstrate that indeed, when the XGRR is positioned in the context of a heterologous TATA containing promoter, it is able to respond equivalently to either IFN-alpha or IFN-gamma. However, IFN-alpha responsiveness does not occur in the context of the physiological Fc gamma R1b TATA-less basal promoter. Our results suggest that a human PU.1-like factor acts as a "bridging factor" between the upstream IFN-gamma enhancer and the Inr dependent preinitiation complex. These findings indicate that the structure of the basal promoter in combination with restricted activators like PU.1 are important in regulating the expression of this gene.
Fibroblast Growth Factor 19 and 7α-Hydroxy-4-Cholesten-3-one in the Diagnosis of Patients With Possible Bile Acid Diarrhea (2012)

Serum FGF19 could be developed as a simple blood test to increase the diagnostic rates of BAD.
Purified lymphocyte function-associated antigen-3 (LFA-3) activates human thymocytes via the CD2 pathway. (1988)

Defining the cellular and molecular mechanisms of interaction of developing thymocytes with nonlymphoid cells of the thymic microenvironment is critical for understanding normal thymus function. We have previously shown that the CD2/LFA-3 adhesion pathway is important in the interaction of thymocytes with a variety of LFA-3+ nonlymphoid thymic microenvironment cell types. Moreover, T cell activation via the CD2 (alternative, Ag independent) pathway is considered an important mechanism for intrathymic T cell proliferation. To study the relevance of CD2/LFA-3 interactions to human thymocyte activation, we have used purified LFA-3 Ag in several in vitro assays of thymocyte proliferation. Whereas LFA-3 Ag alone did not induce thymocyte proliferation, LFA-3 Ag in combination with the anti-CD2 antibody, CD2.1, and rIL-2 induced marked thymocyte proliferation. Additionally, the anti-CD28 antibody, Kolt2, could substitute for rIL-2, resulting in thymocyte activation induced by LFA-3 Ag in combination with antibodies CD2.1 and Kolt2. In both triggering systems, LFA-3 induced thymocyte activation was dependent upon the concentration of LFA-3 Ag. LFA-3 Ag-dependent thymocyte activation was directed primarily toward CD1-, mature thymocytes. Finally, intact SRBC that express the sheep homolog of LFA-3, T11TS, in combination with antibody CD2.1 and rIL-2 could also induce thymocyte activation. These data suggest that interaction of LFA-3 molecules with thymocyte CD2 molecules may provide a component of the stimulus for normal intrathymic thymocyte activation leading to thymocyte proliferation.
Assay for G Protein-Dependent Activation of Phospholipase C β Using Purified Protein Components (2003)

The activity of mammalian phosphoinositide-specific phospholipase C beta (PLC beta) is regulated by the alpha q family of G protein alpha subunits and by beta gamma subunits thought to be released from Gi. Interactions between G protein subunits and PLC beta can be assayed by measuring the stimulation of PLC beta enzymatic activity on reconstituting the purified G protein subunits with purified PLC beta on artificial phospholipid vesicles containing the substrate, phosphatidylinositol-4,5-bisphosphate (PIP2). These vesicles are doped with [3H]-inositol PIP2 and the rate of hydrolysis is determined by quantitating the amount of [3H]-inositol triphosphate (IP3) released from the vesicle into the aqueous phase. This assay provides a relatively simple method for assessing the activity PLC activity and its ability to be regulated by beta gamma and alpha(q) subunits. It can also be used to assess the functionality of the components after modification by mutagenesis, chemical modification, or in the presence of competing molecules.
Effect of the Composition of Polypyrrole Substrate on the Electrodeposition of Copper and Nickel (1996)

Electrodeposition of copper and nickel on a variety of substrates including conductive polymer films with two different compositions has been studied. The enhancement of the copper and nickel electrodeposition rate was observed for composite polypyrrole films with cation‐exchange properties in comparison to undoped polypyrrole films with anion‐exchange properties. Significant enhancement of the nickel electrodeposition rate on both types of conductive polymer vs. the bare gold electrode was also found. An explanation of these effects is presented. An electrochemical quartz crystal microbalance (EQCM) with 10 MHz AT‐cut piezoelectrodes was used in this study. Use of the EQCM technique allowed for simultaneous monitoring of voltamperometric and resonance frequency vs. potential or time characteristics. The thickness of electropolymerized polypyrrole films as well as the amounts of electrodeposited metals were controlled by monitoring the EQCM resonant frequency. The nucleation density has been determined from scanning electron microscope experiments.
Mithramycin- and 4'-6-diamidino-2-phenylindole (DAPI)-DNA staining for fluorescence microspectrophotometric measurement of DNA in nuclei, plastids, and virus particles. (1981)

The properties of two DNA-specific fluorochromes, 4'-6-diamidino-2-phenylindole (DAPI) and mithramycin, have been analyzed as reagents to quantitate cellular DNA by fluorescence microspectrophotometry. Optimal staining conditions and concentrations, and the effects of other cellular materials to which the dyes bind, have been evaluated in measurements of the DNA of rat, chick, and yeast nuclei, Gonyostomum chloroplasts, and T4 particles. Use of either fluorochrome permits a high degree of resolution of different DNA quantities in nuclei and in cell organelles, and the DAPI-DNA complex is sufficiently fluorescent to permit quantitation of the DNA content in genomes as small as those of individual T4 bacteriophage particles. Fluorescence of mithramycin- or DAPI-stained DNA is proportional to DNA quantity when DNA of the same has composition is compared. Quantitation does not appear to be affected discernably by the state of the DNA, whether in different stages of the cell cycle, in condensed chromosomes, or in noncycling, differentiated nuclei. The use of chicken red blood cells is recommended as an internal monitor for variations in staining conditions.
Hantavirus Transmission in the United States (1997)

In 1996, investigation of a hantavirus pulmonary syndrome (HPS) outbreak in southern Argentina found evidence of person-to-person transmission of a hantavirus. The infection control ramifications of this finding led to this review of hantavirus epidemiology in the United States; the review suggests that Sin Nombre virus infection is rarely, if ever, transmitted from person to person and that existing guidelines for prevention of HPS remain appropriate for North America.
Seed-Mediated Synthesis of Palladium Nanorods and Branched Nanocrystals and Their Use as Recyclable Suzuki Coupling Reaction Catalysts (2009)

In this study, we have used a simple seed-mediated synthesis process to prepare uniform Pd nanorods with average lengths of approximately 200 and 300 nm through the addition of 50-100 microL of 0.004 M copper acetate solution into the growth solution for the first time. Because of their long lengths, they nicely settled to the bottom of the reaction vial and can easily be separated from the suspended faceted particles. The nanorods have an average diameter of approximately 20 nm, so they have high aspect ratios of 10-15 or more. They can readily self-assemble into high-density packing structures on substrates. By increasing the volume of the copper acetate solution added to 250 microL, extensively branched Pd nanocrystals were obtained. The crystal structures of both particle morphologies have been examined. The nanorods possess a penta-twinned structure. Different growth directions have been found for the branched nanocrystals. The growth mechanism of these nanostructures was studied in great detail. A mixture of short Pd rods and faceted particles was formed first and elongated into long rods or branched nanocrystals with the assistance of copper atom deposition. A reduction potential of copper lower than that of palladium leads to periodic deposition and reoxidation of copper atoms on the growing rods and faceted particles. Use of other metal ions did not form long nanorods and branched nanocrystals. UV-vis spectra of the 200 nm Pd nanorods showed a significant absorption band in the near-infrared region with band maximum at approximately 1800 nm, while the 300 nm rods have band maxima of 2000-2100 nm. Both the nanorods and branched nanocrystals were found to serve as highly efficient and recyclable catalysts for catalyzing a Suzuki coupling reaction between phenylboronic acid and iodobenzene. They are also thermally stable under the reflux condition and can be easily removed from the product solution. These novel Pd nanostructures should find use in other palladium-catalyzed reactions.
Saliva or Nasopharyngeal Swab Specimens for Detection of SARS-CoV-2 (2020)

In this letter, the investigators report that saliva specimens and nasopharyngeal swab specimens had similar sensitivity in the detection of SARS-CoV-2 RNA in both symptomatic and asymptomatic persons.
Antiviral activity of ganciclovir, 9-(1,3-dihydroxy-2-propoxymethyl) guanine against woodchuck hepatitis virus: quantitative measurement of woodchuck hepatitis virus DNA using storage phosphor technology. (1998)

Our results show that ganciclovir inhibits viral replication in woodchucks chronically infected with woodchuck hepatitis virus. No signs of toxicity were observed. After dot-blot hybridization, storage phosphor imaging was proven superior to X-ray autoradiography for measuring viral DNA. Storage phosphor technology is highly sensitive, quantitative and easy to handle. By comparing mean values and confidence intervals before and during therapy, treatment effects can be distinguished from natural fluctuations.
Synthesis of the Selectively Protected Garamine Derivatives as Aminoglycoside Intermediates (2003)

in ototoxicity and nephrotoxicity have lessened their use inrecent years, these drawback have been met with improveddosing regimens and have stimulated the development ofsemi-synthetic derivatives such as isepamicin and arbekacin.Isepamicin is a novel broad-spectrum aminoglycoside whichpossesses high level of stability to aminoglycoside inactivat-ing enzymes and low level