gebhart/patrepeval huggingface dataset:
Augmentation of lung antineutrophil elastase capacity with recombinant human alpha-1-antitrypsin (1987)

To evaluate the potential use of recombinant DNA-produced alpha-1-antitrypsin (alpha-1-AT) to augment the lung antineutrophil elastase defenses in alpha-1-AT deficiency, we compared the kinetics of intravenously administered recombinant produced alpha-1-AT (r alpha-1-AT) and purified normal human plasma alpha-1-AT (p alpha-1-AT) in the blood and lung of rhesus monkeys. The r alpha-1-AT was produced in yeast transformed with an expressing plasmid containing a full-length human alpha-1-AT complementary deoxyribonucleic acid and purified to greater than 99% homogeneity. The r alpha-1-AT has a molecular weight of 45,000, no carbohydrates, and is identical in sequence to normal plasma alpha-1-AT except for an additional N-terminal acetylmethionine. Despite its lack of carbohydrates, the r alpha-1-AT inhibited human neutrophil elastase with an association rate constant similar to that of p alpha-1-AT. Rhesus monkeys were infused intravenously with 120 mg/kg of r alpha-1-AT (n = 13) or p alpha-1-AT (n = 12) and the serum, urine, and lung epithelial lining fluid (ELF) concentrations of these molecules quantified at various intervals.(ABSTRACT TRUNCATED AT 250 WORDS)
CD40 cross-linking bypasses the absolute requirement for CD4 T cells during immunization with melanoma antigen gene-modified dendritic cells. (2001)

Genetic immunization of mice with dendritic cells (DCs) engineered to express a melanoma antigen generates antigen-specific, MHC-restricted, CD4-dependent protective immune responses. We wanted to determine the role of CD4 cells and CD40 ligation of MART-1 gene-modified DC in an animal model of immunotherapy for murine melanoma. CD4 knock-out (CD4KO) or antibody-depleted mice were immunized with DC adenovirally transduced with the MART-1 gene (AdVMART1/DC) with or without CD40 cross-linking. Tumor protection was absent in CD4-depleted mice, but protection was reestablished when the CD40 receptor was engaged using three different constructs. Transduction of DCs with vectors expressing the Th1 cytokines interleukin (IL)-2, IL-7, or IL-12 could not reproduce the CD40-mediated maturation signal in this model. CD8 T-cell depletion in CD4KO mice immunized with CD40-ligated DCs abrogated the protective response. Pooled analysis of CD40 cross-linking of AdVMART1/DC administered to wild-type C57BL/6 mice revealed an overall enhancement of antitumor immunity. However, this effect was inconsistent between replicate studies. In conclusion, maturation of AdVMART1-transduced DCs through the CD40 ligation pathway can promote a protective CD8 T-cell-mediated immunity that is independent of CD4 T-cell help.
Metal Porphyrins for Oxygen Reduction in PEMFC (2007)

A short literature review on alternative catalysts for the cathodic oxygen reduction in acid (H2SO4) and polymer electrolyte membrane fuel cell (PEMFC) with special emphasis on pyrolyzed macrocycles and precursor materials from metals, organic molecules and N-containing elements has been conducted. Furthermore, various catalytic materials comprising two different concentrations of iron and cobalt tetramethoxyphenyl porphyrins and perovskites were prepared by both the impregnation and precipitation reactions. Screening tests of the individual catalytic materials and their mixtures were carried out in half-cell measurements using the rotating disc electrode (RDE) in 0.5M H2SO4 and at room temperature. Cyclic voltammograms were recorded at a scan rate of 10 mV s-1 both with and without rotations. The peak potential at 0 rpm was used to study and compare the catalytic activities towards oxygen reduction reaction (ORR). Concentrations of 30wt% Fe and Co/TMPP have shown increased performance characteristics, while those with lower or increased contents, acid-treated and mixed with perovskite have displayed lower activities. Polarization data for the catalyst containing 30wt% FeTMPP was also obtained. Acid leaching of the pyrolysis products has resulted in substantial decrease o the metals from the pyrolysis products supported on carbon. TEM, BET-surface area and EDX analyses on the samples have shown high aggregation of the metals with crystalline structure, surface areas depending on the compositions of the catalysts and increased surface concentration of the metals with absence of nitrogen on the moiety.
Coded multicarrier DS-CDMA in the presence of partial band interference (2002)

This paper presents a multicarrier asynchronous direct sequence (DS) code division multiple access (CDMA) system, wherein the output of a convolutional encoder modulates multiple bandlimited DS-CDMA waveforms which are transmitted in parallel at different carrier frequencies. The receiver detects and combines signals for the desired user and feeds a soft decision Viterbi decoder. The performance of this system is compared to that of a conventional single carrier DS-CDMA system with a RAKE receiver, assuming a slowly varying, frequency selective, Rayleigh fading channel and assuming the presence of AWGN, multiple access interference, and partial-band interference. Results will demonstrate similar performance at roughly equal receiver complexity in the absence of partial-band interference, and superior performance of the multicarrier system in the presence of partial-band interference.
Eszopiclone: its use in the treatment of insomnia. (2007)

Eszopiclone is the S-isomer of racemic zopiclone, a cyclopyrrolone with sedative-hypnotic activity that has been available in Europe, Canada, and Latin America since 1987. Eszopiclone acts by binding to the GABA(A) receptor. In contrast to the benzodiazepine (BZD) hypnotics, eszopiclone has more selectivity for certain subunits of the GABA(A) receptor. Oral eszopiclone is rapidly absorbed and extensively distributed to body tissues including the brain. Peak plasma concentrations are attained 1.0-1.6 hours after a 3 mg dose, while the mean elimination half-life is 6 hours. The half-life increases with age to about 9.0 hours in patients 65 years or older. Eszopiclone's pharmacokinetic (PK) profile is not substantially modified in patients suffering from renal failure or mild-to-moderate hepatic impairment, although patients with severe hepatic insufficiency should have a reduced dose. The subjective perception of improved sleep following eszopiclone 2 or 3 mg treatment has been demonstrated in randomized, double-blind, placebo-controlled studies of up to 6 months' duration. In these studies the drug significantly reduced sleep onset latency (SOL), the number of awakenings, and wake time after sleep onset (WASO) whereas total sleep time (TST) and quality of sleep were increased in non-elderly and elderly subjects. Sleep laboratory studies of the effects of eszopiclone have confirmed the drug's clinical efficacy in subjects with chronic primary insomnia. Eszopiclone, unlike BZD hypnotics, does not significantly alter values corresponding to slow wave sleep (SWS or stages 3 and 4) and rapid eye movement (REM) sleep. Rebound insomnia following withdrawal of eszopiclone has been examined in only one study. Discontinuation of the active treatment with 2 mg was followed by rebound insomnia in non-elderly subjects. Three-mg doses of eszopiclone administered for a period of up to 12 months was associated with a sustained beneficial effect on sleep induction and maintenance, with no occurrence of tolerance. The most common side-effects were unpleasant or bitter taste, headache, dyspepsia, pain, diarrhea, dry mouth, upper respiratory infection, urinary tract infection, dizziness, and accidental injury. New adverse events (withdrawal symptoms) including anxiety, abnormal dreams, hyperesthesia, nausea, and upset stomach were recorded in one study on the days following eszopiclone 2 or 3 mg discontinuation. Although dependence and abuse potential have not been formally assessed, unpublished data show that eszopiclone at doses of 6 and 12 mg produces euphoria effects similar to those of diazepam 20 mg in BZD drug addicts. In conclusion, available evidence tends to indicate that eszopiclone is effective and safe for the treatment of chronic primary insomnia in non-elderly and elderly subjects. Tolerance did not occur during active drug administration for a 12-month period. Thus eszopiclone can be efficacious not only during short- and intermediate-term administration but also in patients requiring prolonged regular drug usage.
Predicted Roles for Hypothetical Proteins in the Low-Temperature Expressed Proteome of the Antarctic ArchaeonMethanococcoidesburtonii (2005)

Using liquid chromatography-mass spectrometry, 528 proteins were identified that are expressed during growth at 4 degrees C in the cold adapted archaeon, Methanococcoides burtonii. Of those, 135 were annotated previously as unique or conserved hypothetical proteins. We have performed a comprehensive, integrated analysis of the latter proteins using threading, InterProScan, predicted subcellular localization and visualization of conserved gene context across multiple prokaryotic genomes. Functional information was obtained for 55 proteins, providing new insight into the physiology of M. burtonii. Many of the proteins were predicted to be involved in DNA/RNA binding or modification and cell signaling, suggesting a complex, uncharacterized regulatory network controlling cellular processes during growth at low-temperature. Novel enzymatic functions were predicted for several proteins, including a putative candidate gene for the posttranslational modification of the key methanogenesis enzyme coenzyme M methyl reductase. A bacterial-like CRISPR locus was identified as a strong candidate for archaeal-bacterial lateral gene transfer. Gene context analysis proved a valuable augmentation to the other predictive methods in several cases, by revealing conserved gene associations and annotations in other microbial genomes. Our results underscore the importance of addressing the "hypothetical protein problem" for a complete understanding of cell physiology.
Prefabricated Engineered Bone Flaps: An Experimental Model of Tissue Reconstruction in Plastic Surgery (1998)

In light of the recently described experimental technique of in vivo bone reconstitution with biotechnologic methods (from bone marrow stromal cells) and the prefabrication flap procedures, the possibility to obtain autologous bone growth in a myocutaneous flap, thus creating a composite osteomyocutaneous preformed flap, is postulated. Human bone marrow stromal cells were delivered into the latissimus dorsi of athymic mice by a porous hydroxyapatite ceramic model. Eight weeks after the implantation, histologic examination revealed the presence of spongious bone tissue. A simple myocutaneous flap was thus transformed into a composite osteomyocutaneous flap. This flap is called the biotechnologic prefabricated flap, because it was the result of ex vivo expanded osteogenic precursor cells and in vivo bone tissue neoformation. The shape of the bone flap was exactly the same as the shape of the ceramic model used. A possible clinical application may be the correction of skeletal defects. The advantages of this procedure are simple surgical execution, the possibility of preshaping the graft to the exact characteristics of the defect, and the availability of autogenous donor tissue without donor site morbidity.
Technical and Clinical Aspects of Cascade Filtration Plasma Exchange (CFPE) (1983)

Cascade filtration plasma exchanges (CFPE) were realized using an hemofiltration system (HFS) coupled to 2 filters with different pore sizes. The first one (F1 = plasma-separator; Asahi plasmaflo HI-05) separates plasma from whole blood, the second one (F2 = plasma filter; Asahi XK-60, Kuraray EVAL 2A or 4A) filtrates high molecular weight (MW) components from the separated plasma. F2 filtrate returns to patient mixed with blood cells and 4% Albumin solution or Plasmion R replacing plasma discarded (about 0.5-0.8 I for 1-1.5 plasma mass (PM) treated). The HFS is able i) to modulate the different pressures (venous pressure, F1 and F2 transmembrane pressures (TMp] using pumps speed variators, ii) to recirculate and concentrate extracted plasma and iii) to know F2 treated PM. Blood pressure, pulse rate and electrocardiogram were monitored during each CFPE session. Nineteen CFPE were performed for 8 patients selected among our PE indications, this selection taking into account presence or not of risk factors linked to disease e and/or to patient. Anti-histamine drugs were always infused before CFPE session. On a biological point of view, the problem lies into F2 selectivity which is relatively good for low (as Albumin) and high (as IgM) MW molecules which are returned to patient or discarded, but should be improved for the intermediate ones (as IgG). On a technical point of view, the plasma substitute quantity is reduced about six times. But the control of F2 TMp is not perfectly and the PM to be treated has to be investigated.(ABSTRACT TRUNCATED AT 250 WORDS)
Spot size reducer for standard single-mode fibers utilizing a graded-index fiber tip (1997)

We propose and demonstrate a spot-size reducing fiber tip for the first time. The reducer promises low-loss coupling between standard single-mode fibers and various waveguides, such as dispersion compensated fibers, erbium-doped fibers, and planar waveguides having small spot diameters.
Increased Stability of Bcl-2 mRNA in B-Cell Chronic Lymphocytic Leukemia (CLL). (2004)

Abstract B-cell CLL is characterized by the accumulation of mononuclear B cells that are resistant to apoptosis as a result of bcl-2 oncogene overexpression. Nucleolin has recently been identified as a bcl-2 mRNA stabilizing protein that binds specifically to a 139 base AU-rich instability element (ARE) (Sengupta et al., J. Biol. Chem.279:10855–10863, 2004). Thus, studies were done to address the question whether the increased levels of bcl-2 mRNA in CLL are related to stabilization of bcl-2 mRNA by nucleolin. B cells were isolated from the blood of 9 patients with CLL and 5 normal volunteers by density gradient centrifugation followed by positive selection with CD19 immuno-magnetic microbeads. Flow cytometric analysis indicated that greater than 90% of the CLL and normal B cells were CD19 positive and CD3 negative. Western blotting revealed that cytoplasmic nucleolin and total cellular bcl-2 protein levels were elevated 18-fold (p&amp;lt;0.001) and 5-fold (p&amp;lt;0.001) respectively, in CLL compared to normal B cells. To directly examine the ability of nucleolin to stabilize bcl-2 mRNA, in vitro RNA decay assays were carried out using capped and polyadenylated bcl-2 mRNA transcripts. The average half-life of the bcl-2 mRNA transcript containing the ARE instability element was 12.5 min in S100 extracts of normal B cells, but was increased to 39.7 min in CLL cell extracts. Purified recombinant nucleolin (280 nM) stabilized bcl-2 mRNA when added to S100 extracts of normal B cells, but had no significant effect on bcl-2 mRNA stability in CLL cell extracts. The results are consistent with the hypothesis that resistance of CLL cells to apoptosis is related to overexpression of cytoplasmic nucleolin and increased stability of bcl-2 mRNA. These findings warrant further investigation of nucleolin as a potential therapeutic target in CLL.
The Channel Kinases TRPM6 and TRPM7 Are Functionally Nonredundant (2005)

TRPM7 and its closest homologue, TRPM6, are the only known fusions of an ion channel pore with a kinase domain. Deletion of TRPM7 in DT40 B-lymphocytes causes growth arrest, Mg(2+) deficiency, and cell death within 24-48 h. Amazingly, in analogy to TRPM6-deficient patients who can live a normal life if provided with a Mg(2+)-rich diet, TRPM7-deficient DT40 B-lymphocytes show wild type cell growth if supplied with 5-10 mm Mg(2+) concentrations in their extracellular medium. Here we have investigated the functional relationship between TRPM6 and TRPM7. We show that TRPM7 deficiency in DT40 cells cannot be complemented by heterologously expressed TRPM6. Nevertheless, both channels can influence each other's biological activity. Our data demonstrate that TRPM6 requires TRPM7 for surface expression in HEK-293 cells and also that TRPM6 is capable of cross-phosphorylating TRPM7 as assessed using a phosphothreonine-specific antibody but not vice versa. TRPM6 and TRPM7 coexpression studies in DT40 B-cells indicate that TRPM6 can modulate TRPM7 function. In conclusion, although TRPM6 and TRPM7 are closely related and deficiency in either one of these molecules severely affects Mg(2+) homeostasis regulation, TRPM6 and TRPM7 do not appear to be functionally redundant but rather two unique and essential components of vertebrate ion homeostasis regulation.
Acousto-optic femtosecond pulse shaping in the ultraviolet (2005)

A simple method for ultraviolet acousto-optic pulse shaping of spectral phase and amplitude is described. The technique eliminates complications associated with the parametric transfer of the spectral phase of near-infrared pulses through nonlinear processes.
Metropolitan State University (1993)

Abstract Metropolitan State University, founded in the inner city to serve largely mature community college transfer students, gives students responsibility for planning their own curricula, with a competence‐based focus.
Changes in arterial blood pressure and heart rate induced by glucagon-like peptide-1-(7-36) amide in rats (1994)

This study was designed to determine the effects of glucagon-like peptides (GLP) on arterial blood pressure and heart rate. Although glucagon caused a minimal effect and GLP-1-(1-37) produced a moderate increase of both systolic and diastolic blood pressure, GLP-1-(7-36) amide induced the greatest increases in both parameters. Systolic and diastolic blood pressure and heart rate values increased when doses of the peptides were increased. By contrast, GLP-2 did not modify either arterial blood pressure or heart rate values. To determine whether the effects of GLP-1-(7-36) amide were mediated through catecholamines, the rats were pretreated with reserpine, propranolol, or phentolamine before administration of the peptide. In these three experimental groups, GLP-1-(7-36) amide increases mean arterial blood pressure and heart rate to the same level or even greater than that observed in nonpretreated rats. These findings indicate that GLP-1-(7-36) amide significantly increases arterial blood pressure and heart rate and that these effects are not mediated through catecholamines.
Suprachiasmatic Nucleus Clock Time in the Mammalian Circadian System (2007)

The integration of time from gene to system levels is an exciting feature of circadian biology. In mammals, clock cells in the suprachiasmatic nucleus (SCN) generate time by an autoregulatory transcription-(post)translational feedback loop. Clock activity in the SCN neurons is expressed as activity-dependent electric signals, which are coupled to those of other SCN neurons. The SCN spreads the time signals in a form of synchronized nerve impulses to central parasympathetic nuclei (e.g., dorsal motor nucleus of the vagus) and central sympathetic nuclei (e.g., intermediolateral cell column of the spinal cord). The vagal nerve innervates gastrointestinal and respiratory organs. Sympathetic signals to the adrenal gland are converted to hormonal (glucocorticoid) signals. Glucocorticoids released into the bloodstream bind to glucocorticoid receptors of peripheral organs, activate the mammalian Per1 gene in systemic cells, and reset the time of body clocks. Thus, the SCN-evoked time generated by specific genes localized to the SCN is converted to neuronal and hormonal signals and synchronizes the clocks in the whole body.
Central Action of Adrenomedullin to Inhibit Gastric Emptying in Rats (1997)

The central action of human adrenomedullin (AM) to influence gastric emptying and the peripheral mechanisms involved were studied in conscious rats. The 20-min rate of gastric emptying of a methylcellulose solution was assessed after intracisternal (ic) injection of AM or rat α-calcitonin gene-related peptide (αCGRP). AM and αCGRP dose-dependently inhibited gastric emptying with ic ED50 values of 120 and 100 pmol, respectively. Human proadrenomedullin N-terminal 20 peptide (150–600 pmol, ic) and AM (150 pmol, iv) had no effect. The inhibitory actions of AM and αCGRP (150 pmol, ic) were completely blocked by the CGRP antagonist, human CGRP-(8–37) injected ic at 30 μg, but not at 15 μg. The CRF antagonist,[ d-Phe12,Nle21,38,CαMeLeu37]CRF-(12–41) (10 μg/rat) injected ic prevented ic rat/human CRF (150 pmol)-induced 53% inhibition of gastric emptying while not modifying the effect of AM. The action of AM (150 pmol, ic) was abolished by bilateral adrenalectomy or the β-adrenergic blocker, propranolol (1 mg/kg, ip), but was not altered by indomethacin (5 mg/kg, ip) or subdiaphragmatic vagotomy. These results indicate that ic AM and αCGRP equipotently inhibit gastric emptying through mechanisms similarly antagonized by a high dose of CGRP-(8–37). The central AM action is mediated through adrenal-dependent, β-adrenergic pathways independently from activation of central CRF receptors.
The alternative complement pathway revisited (2008)

Alternative pathway amplification plays a major role for the final effect of initial specific activation of the classical and lectin complement pathways, but the quantitative role of the amplification is insufficiently investigated. In experimental models of human diseases in which a direct activation of alternative pathway has been assumed, this interpretation needs revision placing a greater role on alternative amplification. We recently documented that the alternative amplification contributed to 80-90% of C5 activation when the initial activation was highly specific for the classical pathway. The recent identification of properdin as a recognition factor directly initiating alternative pathway activation, like C1q in the classical and mannose-binding lectin in the lectin pathway initiates a renewed interest in the reaction mechanisms of complement. Complement and Toll-like receptors, including the CD14 molecule, are two main upstream recognition systems of innate immunity, contributing to the inflammatory reaction in a number of conditions including ischemia-reperfusion injury and sepsis. These systems act as "double-edged swords", being protective against microbial invasion, but harmful to the host when activated improperly or uncontrolled. Combined inhibition of complement and Toll-like receptors/CD14 should be explored as a treatment regimen to reduce the overwhelming damaging inflammatory response during sepsis. The alternative pathway should be particularly considered in this regard, due to its uncontrolled amplification in sepsis. The alternative pathway should be regarded as a dual system, namely a recognition pathway principally similar to the classical and lectin pathways, and an amplification mechanism, well known, but quantitatively probably more important than generally recognized.