gebhart/patrepeval huggingface dataset:
Pharmacologic characterization of Botulinum toxin for basic science and medicine (1997)

The use of Botulinum neurotoxin (BoNT) is increasing in both clinical and basic science. Clinically, intramuscular injection of nanogram quantities of BoNT is fast becoming the treatment of choice for a spectrum of disorders including movement disorders such as torticollis, blepharospasm, Meige Disease, and hemifacial spasm (Borodic et al., 1991, 1994a; Jankovic and Brin, 1991; Clarke, 1992). Neuroscientists are using BoNTs as tools to develop a better understanding of the mechanisms underlying the neurotransmitter release process. Consequently, our ability to accurately and reliably quantify the biologic activity of botulinum toxin has become more important than ever. The accurate measurement of the pharmacologic activity of BoNTs has become somewhat problematic with the most significant problems occurring with the clinical use of the toxins. The biologic activity of BoNTs has been measured using a variety of techniques including assessment of whole animal responses to in vitro effects on neurotransmitter release. The purpose of this review is to examine the approaches employed to characterize, quantify and investigate the actions of the BoNTs and to provide a guide to aid investigators in determining which of these methods is most appropriate for their particular application or use.
Comparative evaluation of the antitumor activity of antiangiogenic proteins delivered by gene transfer (2001)

Although the systemic administration of a number of different gene products has been shown to result in the inhibition of angiogenesis and tumor growth in different animal tumor models, the relative potency of those gene products has not been studied rigorously. To address this issue, recombinant adenoviruses encoding angiostatin, endostatin, and the ligand-binding ectodomains of the vascular endothelial growth factor receptors Flk1, Flt1, and neuropilin were generated and used to systemically deliver the different gene products in several different preexisting murine tumor models. Single i.v. injections of viruses encoding soluble forms of Flk1 or Flt1 resulted in approximately 80% inhibition of preexisting tumor growth in murine models involving both murine (Lewis lung carcinoma, T241 fibrosarcoma) and human (BxPC3 pancreatic carcinoma) tumors. In contrast, adenoviruses encoding angiostatin, endostatin, or neuropilin were significantly less effective. A strong correlation was observed between the effects of the different viruses on tumor growth and the activity of the viruses in the inhibition of corneal micropocket angiogenesis. These data underscore the need for comparative analyses of different therapeutic approaches that target tumor angiogenesis and provide a rationale for the selection of specific antiangiogenic gene products as lead candidates for use in gene therapy approaches aimed at the treatment of malignant and ocular disorders.
Chronic regulation of arterial blood pressure by ANP: role of endogenous vasoactive endothelial factors (1998)

Atrial natriuretic peptide (ANP) exerts a chronic hypotensive effect due to a decrease in total peripheral resistance (TPR). This study examines if chronic ANP-dependent vasodilation is attributable to differences in the cardiovascular regulatory activity of vascular endothelium (VE), based on evidence that ANP affects synthesis/release and target cardiovascular effects of endothelin-1 (ET-1), C-type natriuretic peptide (CNP), and nitric oxide (NO). To determine if the synthetic activity of resistance vasculature VE is chronically altered by plasma ANP activity, we measured ET-1, CNP, and endothelial constitutive NO synthase (ecNOS) concentration and total NOS enzyme activity in homogenates of kidney, heart, lung, hindquarter skeletal muscle, and brain from hypotensive transgenic mice with elevated plasma ANP, hypertensive knockout mice (-/-) characterized by the absence of ANP, and the corresponding normotensive wild-type (NT, +/+) mice. Tissue distribution and abundance patterns of ET-1, CNP, ecNOS, and NOS enzyme activity were comparable between the different genotypes and did not differ significantly between mutant and control mice. Antagonism of ETA/B receptors in -/- and +/+ mice in vivo with SB-209670 reduced arterial blood pressure (ABP) significantly and comparably in both genotypes (-27 +/- 4 and -25 +/- 2% change for -/- and +/+ mice, respectively) independent of any significant changes in heart rate (HR) (-6 +/- 8 and -4 +/- 4% change for -/- and +/+ mice, respectively). Immunoneutralization of CNP-specific guanylate cyclase-linked receptors (GC-B) with monoclonal antibodies (3G12) increased ABP slightly, but not significantly, by similar relative amounts in both -/- (10 +/- 6% change) and +/+ mice (8 +/- 3% change), without changing HR significantly (4 +/- 1% change for both +/+ and -/- mice). Inhibition of NOS activity (by NG-nitro-L-arginine methyl ester) significantly increased ABP, but the changes were comparable between -/- (53 +/- 5% change) and +/+ mice (50 +/- 6% change) and occurred in the absence of significant changes in HR (-1 +/- 5 and 7 +/- 5% change for -/- and +/+ mice, respectively). We conclude that the differences in ABP associated with chronic variations in endogenous ANP activity are not due to alterations in synthesis or responsiveness of the cardiovascular system to the effects of ET-1, CNP, or NO.
A Novel T Cell Cytokine Stimulates Interleukin-6 in Human Osteoblastic Cells (1999)

Rheumatoid arthritis (RA) is an autoimmune disease characterized by a heavy lymphocytic infiltration into the synovial cavity, resulting in the secretion of a variety of cytokines which ultimately leads to destruction of joint tissue. Among the infiltrating cells are activated T cells which produce specific cytokines capable of osteoclast progenitor cell expansion, fusion, and activation. Cultures of activated human T cells and human osteoblasts (hOBs) were used to study the possibility that lymphokines may act on osteoblasts to produce the osteoclastogenic factor interleukin-6 (IL-6). Purified T cells were activated with a combination of anti-CD3 and anti-CD28 antibodies, cocultured with hOBs in direct physical contact or separated by a transwell system, and conditioned media (CM) were assayed for IL-6 production. After a 72 h incubation period, activated T cell-hOB interaction resulted in a 100-fold increase of IL-6 production over basal levels. The immunosuppressant cyclosporine A (CsA) inhibited T cell tumor necrosis factor alpha and IL-6 production but did not inhibit the T cell induction of IL-6 from hOB. Assay of activated T-cell CM on hOB revealed that a soluble factor, not cell-cell contact, was the major inducer of IL-6. The induction of IL-6 mRNA by both activated T cell CM and CsA-treated activated T cell CM was confirmed by Northern blot analysis. Neutralizing antibodies to IL-13 and IL-17 did not affect IL-6 production. These findings suggest that activated T cells produce a novel, potent, IL-6 inducing factor that may be responsible for the bone loss observed in RA patients.
An object-oriented implementation of an adaptive classification of job openings (2002)

Automating job classification is challenging because it involves a large number of dynamic classes and features, concept drift uncertainty, and noisy data. We present a software solution to this problem that consists of an incremental learning subsystem and a job classifier. We also describe our design and implementation using object-oriented systems modeling, a complete object-oriented approach that supports analysis, specification and design, and has a smooth mapping to most oriented-object programming languages. Some experimental results and comparisons to other learning/classification algorithms are given. A production version of the software written in C/sup ++/ is performing with superior accuracy.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Influence of time after the removal of nocodazole from nuclear donors on the development of reconstituted embryos in bovine nuclear transplantation. (1995)

The present study examined the influence of post-cleavage time of nuclear donors on the development of reconstituted embryos in bovine nuclear transfer. Blastomeres of 16-cell stage embryos derived from in vitro-maturation, fertilization and culture were used as nuclear donor source. They were treated with 10 microM nocodazole for 12 hr. Blastomeres that cleaved within 3 hr after the removal of nocodazole were used for the study. Metaphase II (M-II) oocytes were used as recipient cytoplasm. In experiment 1, donor blastomeres at 6, 11 and 15 hr after the removal of nocodazole and donor blastomeres not treated with nocodazole were transferred into ethanol-exposed and enucleated oocytes. The reconstituted embryos produced by donor blastomeres at 6 hr after the removal of nocodazole had a significantly higher developmental rate to the blastocyst stage than those at 15 hr and the untreated groups (P < 0.01). In experiment 2, blastomeres at 6 hr after the removal of nocodazole used as nuclear donors were transferred into ethanol-exposed and enucleated M-II oocytes. The reconstituted embryos with ethanol-exposed and enucleated oocytes as recipient cytoplasm had a significantly higher rate of initial-cleavage (P < 0.05) and development to the blastocyst stage (P < 0.01) than non ethanol-exposed and enucleated M-II oocytes. These results demonstrate that the development of reconstituted embryos was improved when cleaved donor blastomeres after the removal of nocodazole were immediately transferred (at 3-6 hr post-cleavage) into activated enucleated oocytes by exposure to ethanol.
Characterization of the cancer chemopreventive NRF2-dependent gene battery in human keratinocytes: demonstration that the KEAP1–NRF2 pathway, and not the BACH1–NRF2 pathway, controls cytoprotection against electrophiles as well as redox-cycling compounds (2009)

To better understand the role of transcription factor NF-E2-related factor (NRF) 2 in the human and its contribution to cancer chemoprevention, we have knocked down its negative regulators, Kelch-like ECH-associated protein 1 (KEAP1) and broad-complex, tramtrack and bric à brac and cap'n'collar homology 1 (BACH1), in HaCaT keratinocytes. Whole-genome microarray revealed that knockdown of KEAP1 resulted in 23 messenger RNAs (mRNAs) being up-regulated > or = 2.0-fold. mRNA for aldo-keto reductase (AKR) 1B10, AKR1C1, AKR1C2 and AKR1C3 were induced to the greatest extent, showing increases of between 12- and 16-fold, whereas mRNA for glutamate-cysteine ligase catalytic and modifier subunits, NAD(P)H:quinone oxidoreductase-1 and haem oxygenase-1 (HMOX1) were induced between 2.0- and 4.8-fold. Knockdown of BACH1 increased HMOX1 135-fold but induced the other genes examined to a maximum of only 2.7-fold. Activation of NRF2, by KEAP1 knockdown, caused a 75% increase in the amount of glutathione in HaCaT cells and a 1.4- to 1.6-fold increase in their resistance to the electrophiles acrolein, chlorambucil and cumene hydroperoxide (CuOOH), as well as the redox-cycling agent menadione. Inhibition of glutathione synthesis during KEAP1 knockdown, by treatment with buthionine sulfoximine, abrogated resistance to acrolein, chlorambucil and CuOOH, but not to menadione. In contrast, knockdown of BACH1 did not increase glutathione levels or resistance to xenobiotics. Knockdown of NRF2 in HaCaT cells decreased glutathione to approximately 80% of normal homeostatic levels and similarly reduced their tolerance of electrophiles. Thus, the KEAP1-NRF2 pathway determines resistance to electrophiles and redox-cycling compounds in human keratinocytes through glutathione-dependent and glutathione-independent mechanisms. This study also shows that AKR1B10, AKR1C1 and AKR1C2 proteins have potential utility as biomarkers for NRF2 activation in the human.
Endometrial and vaginal effects of low-dose estradiol delivered by vaginal ring or vaginal tablet (2005)

Equivalent endometrial safety and efficacy in the relief of the symptoms and signs of urogenital estrogen deficiency were demonstrated for the 12 months' use of a low-dose estradiol-releasing vaginal ring and a vaginal estradiol tablet.
Recombinant influenza viruses as delivery vectors for hepatis B virus epitopes (2012)

These results suggest that chimeric influenza virus which contained foreign antigens can be used as dual vaccine against both HBV and influenza viruses.
Least-squares phase estimation from the phase difference (1988)

The purpose of this paper is to clarify the relationship between the isolated zero points in modulus distribution and the least-squares phase estimation from the phase difference. The concepts of phase and phase difference are reaffirmed. In addition, a necessary condition that makes the least-squares phase estimation feasible is derived by applying the concept of complete observability in estimation theory to the measurement of the phase difference. The occurrence of isolated zero points causes the conventional least-squares phase estimation to fail because the phase difference defined by this concept does not satisfy the necessary condition when isolated zero points occur. This condition also generates a new type of least-squares phase estimation that is feasible for phase retrieval even if zero points exist. One algorithm for realizing this new type of least-squares phase estimation is proposed, and its effectiveness is verified by using computer simulations. Two types of phase unwrapping are also presented: one is the exponential function type; the other results from the proposed least-squares phase-estimation algorithm.
Non‐destructive determination of fat, moisture and protein in salmon fillets by use of near‐infrared diffuse spectroscopy (1995)

Abstract Near infrared (NIR) diffuse spectroscopy was used to determine the fat, moisture and protein contents in whole and ground farmed atlantic salmon fillets. A remote fibre‐optic probe was used for NIR measurements on 50 whole salmon fillets. The constituent ranges were: 91‐205 g kg −1 fat, 599‐709g kg −1 moisture and 186‐209 g kg −1 protein. Principal component regression resulted in the following prediction errors for ground salmon fillets, expressed as root mean square error of cross validation: 6.6 g kg‐1 fat, 3.8 g kg −1 moisture and 2.0 g kg −1 protein. The corresponding prediction errors for non‐destructive measurements on whole salmon fillets were 10.8 g kg −1 fat, 8.5 g kg −1 moisture and 3.7 g kg −1 protein. Regression models using the 760‐1100 m range gave lower prediction errors than models using the 1100‐2500 mm or 760‐2500 nm ranges. The results show that fibre‐optic probe NIR instruments are suited to determine fat and moisture in whole salmon fillets non‐destructively.
A One Pot, One Step, Precision Cloning Method with High Throughput Capability (2008)

Current cloning technologies based on site-specific recombination are efficient, simple to use, and flexible, but have the drawback of leaving recombination site sequences in the final construct, adding an extra 8 to 13 amino acids to the expressed protein. We have devised a simple and rapid subcloning strategy to transfer any DNA fragment of interest from an entry clone into an expression vector, without this shortcoming. The strategy is based on the use of type IIs restriction enzymes, which cut outside of their recognition sequence. With proper design of the cleavage sites, two fragments cut by type IIs restriction enzymes can be ligated into a product lacking the original restriction site. Based on this property, a cloning strategy called 'Golden Gate' cloning was devised that allows to obtain in one tube and one step close to one hundred percent correct recombinant plasmids after just a 5 minute restriction-ligation. This method is therefore as efficient as currently used recombination-based cloning technologies but yields recombinant plasmids that do not contain unwanted sequences in the final construct, thus providing precision for this fundamental process of genetic manipulation.
Quantum-Limited Electrometer Based on Single Cooper Pair Tunneling (1996)

We propose a system comprising the small-capacitance double Josephson junction shunted as a whole by a small resistance $({R}_{S}\ensuremath{\ll}{R}_{Q}\ensuremath{\equiv}{h/4e}^{2})$. We have calculated the dynamic and noise characteristics of the system as functions of a polarization charge on the central electrode. It has been shown straightforwardly that the energy resolution of such an electrometer implying the ``backaction noise'' approaches the fundamental quantum limit $\ensuremath{\Elzxh}/2$ when $T\ensuremath{\rightarrow}0$.
Thermo-Sensitive Hydrogels Based on Interpenetrating Polymer Networks Made of Poly(N-isopropylacrylamide) and Polyurethane (2010)

A series of interpenetrating polymer networks (IPNs) of vinyl-terminated polyurethane (VTPU) and poly(N-isopropylacrylamide) (PNIPAAm) was prepared by free radical polymerization. The effects of IPN composition and cross-linking density on the thermo-responsive and mechanical properties have been studied in terms of particle size, dynamic mechanical thermal properties, transmittance, swelling and de-swelling behavior and water transport mechanism. Results showed that the swelling ability of hydrogels increased over four orders of magnitude in terms of diffusivity, and phase transition became faster with increasing N-isopropylacrylamide (NIPAAm) content. Regarding the mechanical reinforcement of swollen gel, a significant increase in compression properties has been obtained by forming IPNs with polyurethane, which was tailor-made depending on the IPN composition and structure of polyurethane. Furthermore, a cross-linking density increase in the NIPAAm domain augmented rubbery modulus, decreased water swelling and increased water deswelling of the IPNs.
A Time-Dependent Peak of Oxytocin Exists in Cerebrospinal Fluid but Not in Plasma of Humans (1983)

Oxytocin (OT) and the oxytocin-neurophysin (OT-Np) were measured by RIA in samples of cerebrospinal fluid (CSF) obtained sequentially at 0600, 1200, 1800, and 2400 h from six patients in whom intrathecal catheters were temporarily placed for CSF rhinorrhea. The highest levels of OT in CSF were found at 1200 h. An analysis of variance of sequential measures of the concentration of OT in samples of CSF obtained every 6 h over a 30-h period showed the mean levels (±sem) of OT at 1200 h, 6.41 ± 1.13 μU/ml and 5.06 ± 0.58 μU/ml, to be significantly higher (p < 0.05) than mean levels of OT at 0600 h, 2.50 ± 0.65 μU/ml; 1800 h, 2.63 ± 0.61 μU/ml and 2.64 ± 1.21 μU/ml; and 2400 h, 2.86 ± 1.13 μU/ml. The levels of OT-Np in CSF did not show a similar peak. In three of the patients simultaneous samples of blood were obtained for measurement of the same peptides, but no corresponding peak of OT or its Np was found in plasma of these three patients. The level of OT in CSF at all times was also significantly higher (p < 0.05) than the level of OT in plasma of these three patients. Levels of OT and OT-Np were measured by RIA of samples of plasma obtained hourly for a 24-h period from six healthy men and six healthy women. No diurnal variation of OT or its Np in the plasma of men or women was found. This pattern of OT in the CSF of humans is similar to the pattern of OT in the CSF of the Rhesus monkey, but in contrast to the lack of a clearly defined peak of OT in the CSF of the cat or the rat. These observations in humans reinforce the differences among species of the secretion of OT in the CSF.
Inhibition of Factor Xa by a Peptidyl-α-ketothiazole Involves Two Steps. Evidence for a Stabilizing Conformational Change (1999)

Recently, peptidylketothiazoles have been shown to be potent inhibitors of proteases, but the details of the interaction have not yet been studied. In the work presented here, the interaction of factor Xa, a coagulation protease, with the transition state inhibitor BnSO(2)-D-Arg-Gly-Arg-ketothiazole (C921-78) is characterized. C921-78 is a tight and selective inhibitor of the coagulation protease factor Xa (K(d) = 14 pM). The hydrolytic activity of factor Xa was inhibited by C921-78 in a time-dependent manner. The rate-limiting step of the bimolecular combination of inhibitor and enzyme was competitive with the substrate. Conversely, the inhibitor could be displaced from the active site of the enzyme after exposure of the preformed complex to an excess of substrate or to the active site inhibitor dansyl-Glu-Gly-Arg-chloromethyl ketone (DEGR-CMK) in a slow reaction. The formation of the C921-78-factor Xa complex resulted in a 60% increase in the magnitude of the fluorescence emission spectrum. Rapid mixing of the enzyme and inhibitor produces a monophasic fluorescence increase, compatible with spectral transition in a single step. The rate constant for this reaction increased hyperbolically with the concentration of C921-78, but the amplitude remained constant. These results are consistent with the initial formation of an enzyme-inhibitor complex (EI), followed by a unimolecular conversion of EI to EI linked to a spectral transition. The rate constants of the isomerization provide an estimate of 300000-fold stabilization. Thus, the inhibition of factor Xa by C921-78 follows a mechanism similar to that described classically for slow tight binding inhibitors. However, the two steps of the reaction cannot be kinetically separated by the rapid equilibrium assumption, and therefore, the formation of EI is partially rate-limiting, too. The driving energy for the unusually fast isomerization step may result from the highly favorable interactions of the inhibitor in the primary binding site.
Ancylostoma Factor Xa Inhibitor: Partial Purification and Its Identification as a Major Hookworm-Derived Anticoagulant In Vitro (1993)

Soluble protein extracts from adult Ancylostoma hookworms were found to contain an anticoagulant activity that markedly prolonged both the prothrombin time (PT) and partial thromboplastin time (PTT). By chromogenic peptide substrate and clotting time assays, the anticoagulant activity was attributed to a specific inhibitor of clotting factor Xa. The hookworm anticoagulant was partially purified by ion-exchange column chromatography. Those column fractions containing anti-Xa activity by chromogenic assay also prolonged the PT and PTT as well as the factor X (Stypven) clotting time. These data suggest that this potent factor Xa inhibitor is a major anticoagulant from the adult Ancylostoma hookworm.
Rapid enzymatic determination of urinary oxalate. (1989)

This new reagent kit for the quantitative measurement of oxalate in urine is a modification of an earlier Sigma oxalate assay procedure (procedure no. 590), a coupled enzyme assay involving oxalate oxidase and horseradish peroxidase. The new analytical procedure includes methods for processing urine specimens to eliminate interference with oxalate color development at 590 nm by ascorbic acid, divalent cations, and other urinary constituents. The reaction is complete in less than 5 min, and results are linearly related to oxalate concentration up to at least 1 mmol/L. Assay sensitivity and within-run and between-run precision were within the limits acceptable for other urinary oxalate procedures. Analytical recovery of added oxalate was close to 100%. This specific, simple, rapid procedure is suitable for routine clinical use.