gebhart/patrepeval huggingface dataset:
Human Parainfluenza Virus Type 3 (PIV3) Expressing the Hemagglutinin Protein of Measles Virus Provides a Potential Method for Immunization against Measles Virus and PIV3 in Early Infancy (2000)

Recombinant human parainfluenza virus type 3 (PIV3) was used as a vector to express the major protective antigen of measles virus, the hemagglutinin (HA) glycoprotein, in order to create a bivalent PIV3-measles virus that can be administered intranasally. The measles virus HA open reading frame (ORF) was inserted as an additional transcriptional unit into the N-P, P-M, or HA-neuraminidase (HN)-L gene junction of wild-type PIV3 or into the N-P or P-M gene junction of an attenuated derivative of PIV3, termed rcp45L. The recombinant PIV3 (rPIV3) viruses bearing the HA inserts replicated more slowly in vitro than their parental viruses but reached comparable peak titers of >/=10(7.5) 50% tissue culture infective doses per ml. Each of the wild-type or cold-passaged 45L (cp45L) PIV3(HA) chimeric viruses replicated 5- to 10-fold less well than its respective parent virus in the upper respiratory tract of hamsters. Thus, insertion of the approximately 2-kb ORF itself conferred attenuation, and this attenuation was additive to that conferred by the cp45L mutations. The attenuated cp45L PIV3(HA) recombinants induced a high level of resistance to replication of PIV3 challenge virus in hamsters and induced very high levels of measles virus neutralizing antibodies (>1:8,000) that are well in excess of those known to be protective in humans. rPIV3s expressing the HA gene in the N-P or P-M junction induced about 400-fold more measles virus-neutralizing antibody than did the rPIV3 with the HA gene in the HN-L junction, indicating that the N-P or P-M junction appears to be the preferred insertion site. Previous studies indicated that the PIV3 cp45 virus, a more attenuated version of rcp45L, replicates efficiently in the respiratory tract of monkeys and is immunogenic and protective even when administered in the presence of very high titers of passively transferred PIV3 antibodies (A. P. Durbin, C. J. Cho, W. R. Elkins, L. S. Wyatt, B. Moss, and B. R. Murphy, J. Infect. Dis. 179:1345-1351, 1999). This suggests that this intranasally administered PIV3(HA) chimeric virus can be used to immunize infants with maternally acquired measles virus antibodies in whom the current parenterally administered live measles virus vaccine is ineffective.
Terminal complement complexes concomitantly stimulate proliferation and rescue of Schwann cells from apoptosis (2000)

The consequences of sublytic terminal complement complex (TCC) assembly on Schwann cell proliferation and apoptosis were examined by using purified complement proteins (C5*-9) or antibody-sensitized Schwann cells in the presence of a serum that was depleted of the seventh component of complement (C7dHS) and reconstituted with purified C7. Stimulation of cultured Schwann cells with antibody plus 10% C7dHS and C7 or C5*-9 induced DNA synthesis over antibody plus 10% C7dHS alone or in Schwann cells in which C5*-9 insertion was inhibited by heat inactivation, respectively. Cell cycle analysis with propidium iodide showed that, at 24 h, viable Schwann cells in defined medium were synchronized in G1/G0 phase. C5*-9 shifted 64% of these cells into S or G2/M phases in a manner similar to beta-neuregulin (beta-NRG), a known Schwann cell mitogen. Furthermore, antibody with 10% C7dHS and C7 or purified C5*-9 induced proliferation of viable Schwann cells. These effects were mediated by signal-transduction pathways involving p44 ERK1 (extracellular-regulated kinase 1), Gi proteins, and protein kinase C. Culturing in defined medium for 24 h resulted in apoptosis of up to 50% of Schwann cells that was prevented by treatment with beta-NRG or TCC. Sublytic C5*-9 significantly inhibited apoptosis 41% by 24 h, as determined by a terminal deoxyuridine triphosphate-biotin nick end labeling assay, and also decreased annexin-V binding at 4 h. Collectively, these data suggest that sublytic TCC, like beta-NRG, is a potent Schwann cell trophic factor that is capable of stimulating mitogenesis and apoptotic rescue. TCC assembly on Schwann cells during inflammatory demyelination of peripheral nerves may promote survival of mature cells to enhance repair and remyelination processes.
Moving Toward Simpler, Highly Functional Multilateral Completions (2002)

This paper discusses the development, application, and operational advantages of a TAML Level 3 multilateral completion system. It combines the simplicity of lower-level systems with the extended functionality of full re-entry into both the mainbore and lateral completions of wells that do not require pressure integrity at the junction.To obtain re-entry and flow control in both wellbores of a multilateral application, the previous mindset was to add more completion equipment to handle the need for more functionality. The early well completions categorized as Level 3 multilaterals were constructed using a flow-through guidestock and slotted liner or screen in the lateral, which was anchored back to the mainbore by a liner hanger packer. Flow was allowed through the flow-through guidestock from the mainbore completion, where it became commingled with the lateral production via perforations or slots in the lateral liner overlap in the mainbore. The challenge was to provide a means for allowing mainbore reentry. With this increased functionality, Level 3 could be a viable, simple replacement for Level 4 ML's as well as the Level 1 and 2 completions.With a focus on simplicity, design iterations led to the development of a system that would be mechanically basic (no moving parts) and easy to install. To date, more than 80 Level 3 Hook Hanger junctions have been completed, with most in the Orinoco Heavy Oil Belt in Venezuela. The authors will summarize several case studies, explain decision-making parameters for selecting this type of multilateral completion system, and discuss its application in Canadian oil and gas operations.Introduction. To obtain reentry and flow control in both wellbores of a multilateral application, the mindset has been to add more completion equipment for more functionality. In an effort to make multilateral risks more acceptable, Baker Oil Tools began to develop multilateral completion systems that were simpler and less risky to install. Even though there are six multilateral categories, most multilateral applications fall into two simple groups:wells that require pressure integrity at the junction, andwells that do not require pressure integrity at the junction.For maximum functionality in both groups, the focus is on developing Level 3 (pressure integrity not required) and Level 6 (pressure integrity required) multilateral systems that address a wide variety of multilateral well applications.TAML Classifications. In an effort to provide parity when comparing multilateral systems industry wide, a classification system was developed by TAML (Technology Advancement for Multilaterals), a consortium group comprised of operators and service companies. The classification system divides wells into
Stacked high-ε gate dielectric for gigascale integration of metal–oxide–semiconductor technologies (1998)

Advances in lithography and thinner SiO2 gate oxides have enabled the scaling of metal–oxide–semiconductor technologies to sub-0.25 μm feature size. A major hurdle in the gate dielectric scaling using conventional thermally grown SiO2 has been excessive tunneling that occurs in ultrathin (&amp;lt;25 Å) SiO2. High dielectric constant materials such as Ta2O5 have been suggested as a substitute for SiO2. However, these materials have high concentrations of bulk fixed charge, unacceptable levels of Si–Ta2O5 interface trap states, and low silicon interface carrier mobilities. This letter summerizes an elegant solution to these issues through synthesis of a thermally grown SiO2(15 Å)–Ta2O5(30 Å)–SiO2(5–10 Å) dielectric with improvements in leakage, tunneling, charge trapping behavior, and interface substructure. Transistors fabricated using this stacked gate dielectric exhibit excellent subthreshold, saturation, and drive currents.
Fast wavelet transforms and numerical algorithms I (1991)

Abstract A class of algorithms is introduced for the rapid numerical application of a class of linear operators to arbitrary vectors. Previously published schemes of this type utilize detailed analytical information about the operators being applied and are specific to extremely narrow classes of matrices. In contrast, the methods presented here are based on the recently developed theory of wavelets and are applicable to all Calderon‐Zygmund and pseudo‐differential operators. The algorithms of this paper require order O ( N ) or O ( N log N ) operations to apply an N × N matrix to a vector (depending on the particular operator and the version of the algorithm being used), and our numerical experiments indicate that many previously intractable problems become manageable with the techniques presented here.
Ileal bile acid transporter inhibition, CYP7A1 induction, and antilipemic action of 264W94 (2002)

264W94 was designed to inhibit the ileal bile acid transporter (IBAT). Evaluated in vitro, 264W94 dose-dependently inhibited sodium-dependent uptake of 10 micro M [(3)H]taurocholic acid (TC) by rat and monkey brush border membrane vesicles with IC(50)s of 0.24 micro M and 0.41 micro M, and had a competitive profile with K(i) of 0.2 micro M against TC in Chinese hamster ovary cells expressing human IBAT. In distal ileum in situ, 1-10 micro M of 264W94 rapidly decreased uptake of 3mM TC by 24-39%, with corresponding decreases in biliary recovery. In rats and mice in vivo, oral 264W94 decreased absorption of TC analog, 23,25-(75)Se-homocholic acid taurine ((75)SeHCAT; quantitated in feces), with ED(30) of 0.02 mg/kg bid. (75)SeHCAT traced through the GI-tract revealed that peak (97%) inhibition of (75)SeHCAT absorption by the distal quarter of small intestine occurred at 4 h after single dose of 264W94 (0.1 mg/kg). Inhibition of IBAT by 264W94 in rats was associated with compensatory, same-day, 4-fold induction of hepatic cholesterol 7alpha-hydroxylase (CYP7A1) activity, exhibiting normal diurnal fluctuation for 3 days of dosing. In diet induced hypercholesterolemic rats, 264W94 (0.03-1.0 mg/kg bid) dose-dependently reduced serum LDL+VLDL cholesterol up to 61%. In conclusion, 264W94 is a potent new cholesterol lowering agent that acts through inhibition of IBAT and exhibits activity in a human model.
The Kinetics of Ligand Binding by an Adenine-Sensing Riboswitch (2005)

A riboswitch within the 5' untranslated region (UTR) of the Bacillus subtilis pbuE mRNA binds adenine and related analogues in the absence of protein factors; excess adenine added to bacterial growth media triggers activation of a reporter gene that carries this riboswitch. To assess whether the riboswitch reaches thermodynamic equilibrium, or is operated by the kinetics of ligand binding and RNA transcription, we examined the detailed equilibrium and kinetic parameters for the complex formation between the aptamer domain of this riboswitch and the ligands adenine, 2-aminopurine (2AP), and 2,6-diaminopurine (DAP). Using a fluorescence-based assay, we have confirmed that adenine and 2AP have nearly equal binding affinity, with KD values for 2AP ranging from 250 nM to 3 microM at temperatures ranging from 15 to 35 degrees C, while DAP binds with much higher affinity. The association rate constant, however, favors adenine over DAP and 2AP by 3- and 10-fold, respectively, at 25 degrees C. Furthermore, the rate constants for adenine association and dissociation with the aptamer suggest that the pbuE riboswitch could be either kinetically or thermodynamically controlled depending upon the time scale of transcription and external variables such as temperature. We cite data that suggest kinetic control under certain conditions and illustrate with a model calculation how the system can switch between kinetic and equilibrium control. These findings further support the hypothesis that many riboswitches rely on the kinetics of ligand binding and the speed of RNA transcription, rather than simple ligand affinity, to establish the concentration of metabolite needed to trigger riboswitch function.
Acoustics: An Introduction to Its Physical Principles and Applications. 1989 Edition (1990)

First Page
Low-density lipoprotein receptor-deficient mice are protected against lethal endotoxemia and severe gram-negative infections. (1996)

Lipoproteins can bind lipopolysaccharide (LPS) and decrease the LPS-stimulated production of pro-inflammatory cytokines. We investigated the effect of increased plasma concentrations of low-density-lipoproteins (LDL) on survival and cytokine production after a lethal challenge with either LPS or live Gram-negative bacteria in LDL receptor deficient mice (LDLR-/-). The LDLR-/- mice challenged with LPS had an eightfold increased LD50 when compared with the wild type controls (C57Bl/6J), while tumor necrosis factor alpha (TNFalpha) and interleukin-1 alpha (IL-1 alpha) plasma concentrations were decreased twofold. LDLR-/- mice had significantly lower and delayed mortality than control mice after infection with Klebsiella pneumoniae. No differences in the outgrowth of bacteria in the organs were present between the two groups, while circulating cytokine concentrations were decreased twofold in LDLR-/- mice. In contrast, the LPS-stimulated in vitro production of cytokines by peritoneal macrophages of LDLR-/- mice was significantly increased compared with controls. This increase was associated with enhanced specific binding of LPS to the macrophages of LDLR-/- mice. In conclusion, endogenous LDL can protect against the lethal effects of endotoxin and Gram-negative infection. At least part of this protection is achieved through decreased in vivo production of pro-inflammatory cytokines, in spite of increased cytokine production capacity.
Enzymatic degradation of uric acid by uricase-loaded human erythrocytes. (1975)

Erythrocytes containing pig liver uricase have been prepared by hypotonic hemolysis in the presence of the enzyme. Uricase is shown to be active within the erythrocytes and to degrade uric acid as rapidly as it enters the cells when high intracellular enzyme concentrations are employed. The kinetics and characteristics of uric acid entry are shown to be the same for hemolysed and normal erythrocytes. At physiological concentrations of uric acid, loaded erythrocytes can degrade a maximum of about 21 mumol uric acid/liter erythrocytes per min. The possible application of enzyme-loaded erythrocytes to medicine is discussed.
Increased dependence of Schottky barrier height on metal work functions due to a thin-oxide layer (1988)

Ultraviolet illumination has been used to form a few monolayers of GaAs oxide in dry oxygen on both p-type and n-type GaAs(100) surfaces. Some of the oxides have been annealed to form Ga-rich oxide surfaces. Six metals with a wide range of work functions and different reactivity with the oxide layer have been used to form Schottky contacts on clean GaAs and on the thin-oxide layers. Large variations from the Schottky barrier height on clean GaAs have been observed for both doping types due to the photo-oxidation of the GaAs surfaces. The trend in Schottky barrier change is toward the ideal Schottky limit where the metal work function determines the barrier height. The GaAs Fermi level is shown to move in a much wider region of the band gap for the oxidized surfaces than for clean surfaces, however, it is still confined to a midgap region.
Total Laparoscopic Hysterectomy Using Multifunction Grasping, Coagulating, and Cutting Forceps (2004)

We describe the use of multifunction grasping, coagulating, and cutting forceps in total laparoscopic hysterectomy (LH) and compare surgery time, estimated blood loss, and costs for a series of 123 LH performed by the principal author at one of two community hospitals in Seattle between January 2001 and July 2002. The first 73 were performed using bipolar Kleppinger forceps (Richard Wolf Instruments, Vernon Hills, Illinois), endoscopic scissors (Karl Storz Endovision, Charlton, Massachusetts), and a monopolar spatula electrode (Jarit Surgical Instruments, Hawthorne, New York); the last 50 cases were performed using the PlasmaKinetic™ (PK) (Gyrus Medical, Maple Grove, Minnesota) multifunction cutting forceps and the monopolar spatula electrode. We were able to compare patient data in two surgery categories: LH alone (43 patients, 26 using the Kleppinger forceps and endoscopic scissors, 17 using the PK system), and laparoscopic hysterectomy with bilateral salpingo-oopherectomy (30 patients, 20 using Kleppinger forceps and endoscopic scissors, 10 using the PK system). In the remaining 50 cases, the addition of other secondary procedures precluded effective statistical comparisons. We found significantly lower estimated blood loss in both surgery categories when using the PK cutting forceps, but no differences in mean surgery time. Costs for disposable instrumentation parts and handling were approximately $70 greater per procedure with the PK system. Using the PK cutting forceps eliminated some instrument exchanges and the requirement for a third instrument cannula. We also noted significantly less plume, quicker coagulation, and less tissue char when coagulating with the PK forceps compared to the Kleppinger forceps.
A Click And Bricks Strategy For eGovernment (2004)

Two of the central challenges of e-government are the need for "joined-up" government through agency collaboration, and the need to provide "citizen-centred" government, where services and information are integrated at the point of delivery. Electronic service delivery provides the hoped for panacea to enable not only administrative efficiencies in the functions of government, but also services that are centred on the needs of the citizen. The implementation of e-government however, presents challenges regarding the achievement of inter-agency collaboration and highlights the importance of developing multiple access channels. This paper reports from an in-depth case study detailing first, the strategy the Irish government adopted for electronic service delivery and second, provides detailed analysis from the pioneering efforts of an individual county council into agency collaboration and a unique method of service provision. Two survey questionnaires conducted with staff of the county council and citizens of the county, reveal critical success factors in developing inter-agency collaboration and raise important concerns expressed by citizens into data privacy, social inclusion and the digital divide.
Transcriptional activity of the dominant gut mucosal microbiota in chronic inflammatory bowel disease patients (2010)

Dysbiosis of the gut mucosa-associated microbiota (MAM) plays a pivotal role in the pathogenesis of chronic inflammatory bowel diseases (IBD). To date, dysbiosis only describes the altered composition of the different bacterial populations, but little is known about transcriptional activity, metabolism and the 'live' status of the MAM. In this study we investigated the transcriptional activity of the dominant intestinal bacterial populations in patients with IBD. Colonic mucosal biopsies from patients with active Crohn's disease (CD; n=10), active ulcerative colitis (UC; n=10) and healthy individuals (HI; n=10) were compared by 16S rRNA gene and rRNA profiles using clone libraries with more than 1700 sequenced clones. Bacterial richness was significantly lower in clone libraries based on rRNA compared to those based on the rRNA genes in the CD group (3.01 vs 3.91) and the UC group (3.61 vs 4.15), but showed no difference in HI (3.81 vs 3.85). The qualitative composition of rRNA and rRNA gene clone libraries was significantly different, with the phylum Bacteroidetes being the most active (P<0.01) compared to other populations in all clinical groups. In contrast, Actinobacteria and Firmicutes were inactive in the CD group, while Escherichia sp. were both abundant and active in the CD and UC groups. Most of the phylotypes showing the highest activity index ratios represented less than 1 % of the microbiota. Our findings indicate that specific bacterial populations are activated in IBD patients, while other groups are in an inactive or 'dormant' state. The transcriptional activity points to a more functional role of the intestinal mucosal microbiota and may lead to the identification of therapeutic targets in the active modulation of microbial factors.
Immunohistologic analysis of the distribution of cell adhesion molecules within the inflammatory synovial microenvironment (1989)

Antigen-independent binding of T lymphocytes to a variety of cell types has been shown to be mediated by receptor-ligand pairs of adhesion molecules. In forms of inflammatory synovitis (including rheumatoid arthritis), T cells home to synovium, become activated, and participate in the generation of chronic synovitis. Using indirect immunofluorescence assays on synovial frozen tissue sections and on synovial fibroblast cell lines, we studied the distribution of cell adhesion molecules on components of the synovial microenvironment in inflammatory synovitis. We reasoned that analysis of the cell types within synovium that express adhesion molecules might provide clues to lymphocyte-stromal interactions that occur in inflammatory synovitis. We found that antibodies against the lymphocyte function-associated antigen 3 (LFA-3) molecule and the intercellular adhesion molecule 1 (ICAM-1) both reacted with macrophage-like type A synovial cells and synovial fibroblasts, as well as with tissue macrophages and vessel endothelium. Using flow cytometry, we found that anti-LFA-3 and anti-ICAM-1 (but not antibodies against their ligands CD2 and LFA-1) reacted with synovial fibroblast cells cultured in vitro. Thus, these data demonstrate that the ligands for lymphocyte LFA-1 molecules (ICAM-1) and for T cell CD2 molecules (LFA-3) are widely distributed among cell types of the synovial microenvironment and provide numerous cell types with which lymphocytes can interact via these 2 adhesion pathways during the course of inflammatory synovitis.
Hepatic expression of glutamine synthetase in rats is controlled by STAT5 and TCF transcription factors† (2006)

In mammalian liver, high glutamine synthetase (GS) expression is restricted to hepatocytes surrounding the terminal venules. The most important enhancer of the GS gene is located approximately 2520 base pairs (bp) upstream from the transcriptional start point. The nature of the transcription factors that bind to the enhancers has remained enigmatic. In this study, we purified nuclear proteins binding to the element. Supershift assays and footprint experiments with purified protein identified activated STAT5 as a transcription factor binding to a site within the enhancer. In addition, a second binding site close to the STAT5 site was observed that also binds a protein present in nuclear extracts. Sequence analysis indicated that the second site may bind a member of the LEF/TCF transcription factor family. Reporter gene assays demonstrate that the STAT5 binding site mediates enhancement of expression whereas the LEF/TCF site functions as a silencer of growth hormone-mediated enhancement in normal hepatocytes. LEF/TCF-sites are known to function as silencers in the absence and as enhancers in the presence of activated beta-catenin. In conclusion, the GS 5' enhancer contains elements important for GS expression in cells carrying an activated form of beta-catenin as previously shown in experimentally induced hepatocellular carcinomas.