gebhart/patrepeval huggingface dataset:
Dexmedetomidine: A Novel Sedative-Analgesic Agent (2001)

Since the first report of clonidine, an alpha2-adrenoceptor agonist, the indications for this class of drugs have continued to expand. In December 1999, dexmedetomidine was approved as the most recent agent in this group and was introduced into clinical practice as a short-term sedative (<24 hours). Alpha2-adrenoceptor agonists have several beneficial actions during the perioperative period. They decrease sympathetic tone, with attenuation of the neuroendocrine and hemodynamic responses to anesthesia and surgery; reduce anesthetic and opioid requirements; and cause sedation and analgesia. They allow psychomotoric function to be preserved while letting the patient rest comfortably. With this combination of effects, alpha2-adrenoceptor agonists may offer benefits in the prophylaxis and adjuvant treatment of perioperative myocardial ischemia. Furthermore, their role in pain management and regional anesthesia is expanding. Side effects consist of mild to moderate cardiovascular depression, with slight decreases in blood pressure and heart rate. The development of new, more selective alpha2-adrenoceptor agonists with improved side effect profiles may provide a new concept for the administration of perioperative anesthesia and analgesia. This review aims to give background information to improve understanding of the properties and applications of the novel alpha2-adrenoceptor agonist, dexmedetomidine.
Role of FGF19 induced FGFR4 activation in the regulation of glucose homeostasis (2009)

FGF19, FGF21, and FGF23 form a unique subfamily of fibroblast growth factors. Because they contain intra-molecular disulfide bonds and show reduced affinity toward heparan sulfate located in the extracellular space, it is thought that, in contrast to other FGFs, they function as endocrine hormones. FGF23 and its co-receptor alphaKlotho are involved in the control of aging, but it is not known if the same holds true for FGF19, which can also signal through alphaKlotho. However, considerable evidence supports a role for FGF19 in controlling various aspects of metabolism. We have recently fully characterized FGF19/FGFR/co-factor interactions and signaling, and in the current manuscript discuss the contribution of the FGF19/FGFR4 axis to bile acid and glucose regulation.
Ubiquitination and degradation of Syk and ZAP-70 protein tyrosine kinases in human NK cells upon CD16 engagement (2001)

Syk and ZAP-70 nonreceptor protein tyrosine kinases (PTKs) are essential elements in several cascades coupling immune receptors to intracellular responses. The critical role of these kinases in promoting the propagation of intracellular signaling requires a tight regulation of their activity, thus the existence of a negative feedback loop regulating their expression can be hypothesized. Herein, we have investigated whether ubiquitin-dependent proteolysis could be a mechanism responsible for controlling the fate of Syk and ZAP-70 after their immunoreceptor-induced activation. We found that both Syk and ZAP-70 become ubiquitinated in response to aggregation of the low affinity Fc receptor for IgG (CD16) on human natural killer cells. We confirmed the identity of the major in vivo ubiquitinated kinase species by performing an in vitro ubiquitination assay. In addition, we found that after CD16 stimulation, ubiquitinated forms of Syk and ZAP-70 associate with the receptor complex. After CD16 engagement, we also observed a decrease in the stability of Syk and ZAP-70 PTKs that is counteracted by pretreatment with either proteasome or lysosomal inhibitors. Moreover, in the presence of the proteasome inhibitor, epoxomicin, we observed an accumulation of ubiquitinated forms of both kinases. Our findings provide evidence of ligand-induced ubiquitination of nonreceptor PTKs belonging to the Syk family and propose the ubiquitin-dependent proteasome-mediated degradation pathway as a mechanism for attenuating the propagation of intracellular signaling initiated by immune receptor engagement.
Wallace Fenn and the Journal of Applied Physiology (1998)

I first became aware that a third was being considered when Wallace Fenn casually mentioned it to some of us
Liquefaction of coagulated human semen (1984)

Liquefaction of coagulated human semen was inhibited by o-phenanthroline; subsequent addition of Zn2+ reversed this inhibition, but not if the coagulum was repeatedly washed before Zn2+ was added. No liquefaction of the coagulum occurred when Fe2+ was added (in a 1:3 molar ratio to o-phenanthroline), and the gel repeatedly washed. This o-phenanthroline-depleted coagulum was liquefied by resuspended pellet from ultracentrifuged pooled seminal plasma. In denatured and reduced semen coagulate, we identified the 52 kDa, 71 kDa, and 76 kDa protein bands of the predominant seminal vesicle protein. The protein was not present in the supernatant after centrifugation of coagulated semen, and it was degraded to several minor basic proteins when semen liquefied. These findings imply that the predominant seminal vesicle protein functions as the structural protein of coagulated semen. In much the same way as in ejaculated semen, the 52 kDa, 71 kDa, and 76 kDa protein bands in seminal vesicle secretion collected postmortem were digested to minor basic proteins after incubating the secretion with resuspended pellet from ultracentrifuged seminal plasma. This pellet contained the membrane-bound succinyl(alanine)3-p-nitroanilide hydrolysing peptidase of prostatic origin which, like the liquefaction process, was active in the presence of EGTA, inhibited by non-chelated Zn2+, and inactivated by o-phenanthroline--an inactivation that was reversed by Zn2+.
Elucidation of Functional Groups on Gram-Positive and Gram-Negative Bacterial Surfaces Using Infrared Spectroscopy (2004)

Surface functional group chemistry of intact Gram-positive and Gram-negative bacterial cells and their isolated cell walls was examined as a function of pH, growth phase, and growth media (for intact cells only) using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. Infrared spectra of aqueous model organic molecules, representatives of the common functional groups found in bacterial cell walls (i.e., hydroxyl, carboxyl, phosphoryl, and amide groups), were also examined in order to assist the interpretation of the infrared spectra of bacterial samples. The surface sensitivity of the ATR-FTIR spectroscopic technique was evaluated using diatom cells, which possess a several-nanometers-thick layer of glycoprotein on their silica shells. The ATR-FTIR spectra of bacterial surfaces exhibit carboxyl, amide, phosphate, and carbohydrate related features, and these are identical for both Gram-positive and Gram-negative cells. These results provide direct evidence to the previously held conviction that the negative charge of bacterial surfaces is derived from the deprotonation of both carboxylates and phosphates. Variation in solution pH has only a minor effect on the secondary structure of the cell wall proteins. The cell surface functional group chemistry is altered neither by the growth phase nor by the growth medium of bacteria. This study reveals the universality of the functional group chemistry of bacterial cell surfaces.
Geometrical compaction in one dimension for channel routing (1987)

A channel router which is to be effective for general-purpose automatic routing must be able to use different sets of routing criteria priorities, in a controllable manner. We present an approach to channel routing with compaction in which channel compaction is adaptable to several routing criteria priorities. We show how overall channel routing performance can be improved by taking advantage of this versatility in channel compaction. We indicate some routing capabilities which cannot be effectively achieved by simply post-processing the output of a traditional gridded channel router. Our solution to this problem is outlined and some results obtained from our router are compared with those of other published channel routers.
Focused image recovery from two defocused images recorded with different camera settings (1995)

Two new methods are presented for recovering the focused image of an object from only two blurred images recorded with different camera parameter settings. The camera parameters include lens position, focal length, and aperture diameter. First a blur parameter sigma is estimated using one of our proposed depth-from-defocus methods. Then one of the two blurred images is deconvolved to recover the focused image. The first method is based on a spatial domain convolution/deconvolution transform. This method requires only the knowledge of sigma of the camera's point spread function (PSF). It does not require information about the actual form of the camera's PSF. The second method, in contrast to the first, requires full knowledge of the form of the PSF. As part of the second method, we present a calibration procedure for estimating the camera's PSF for different values of the blur parameter sigma. In the second method, the focused image is obtained through deconvolution in the Fourier domain using a Wiener filter. For both methods, the results of experiments on actual defocused images recorded by a CCD camera are given. The first method requires much less computation than the second method. The first method gives satisfactory results for up to medium levels of blur and the second method gives good results for up to relatively high levels of blur.
Insulating and semiconductive jackets for medium and high voltage underground power cable applications (1995)

Insulating jackets extend cable life by retarding the ingress of water and soluble ions from the ground, minimizing cable installation damage and mitigating neutral corrosion. The physical properties of jacketing materials are discussed, along with the evolution of polyethylene jacketing compounds and the requirements of compatible red cable identification compounds.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Variable parameter Gaussian mixture hidden Markov modeling for speech recognition (2003)

To improve recognition, speech signals corrupted by a variety of noises can be used in speech model training. Published hidden Markov modeling of speech uses multiple Gaussian distributions to cover the spread of the speech distribution caused by the noises, which distracts the modeling of speech event itself and and possibly sacrifices the performance on clean speech. We extend GMHMM by allowing state emission parameters to change as function of an environment-dependent continuous variable. At the recognition time, a set of HMMs specific to the given the environment is instantiated and used for recognition. Variable parameter (VP) HMM with parameters modeled as a polynomial function of the environment variable is developed. Parameter estimation based on EM-algorithm is given. With the same number of mixtures, VPHMM reduces WER by 40% compared to conventional multi-condition training.
A Divalent Recombinant Immunotoxin Formed by a Disulfide Bond between the Extension Peptide Chains (2001)

Recombinant immunotoxin for the treatment of cancer was made by connecting toxins to 'carcinoma-specific' antibodies that selectively bind to cancer cells, then kills them without harming the normal cells. The divalent recombinant immunotoxin, [B3(Fab)-ext-PE38]2, is a derivative of B3(Fab)-PE38. B3(Fab)-PE38 was made by fusing the Fab domain of the monoclonal antibody (MAb) B3 to PE38, a truncated mutant form of Pseudomonas exotoxin (PE). In this study, B3(Fab)-ext-PE38 was constructed, which has the hinge region of the B3(Fab)-PE38 extended with the peptide extension, G4C(G4S)2, and connected to the C3 connector. The Cys residue of the extension peptide chain makes the disulfide bond between the two Fab domains. The extension sequence (ext) makes the dimerization of B3(Fab)-ext-PE38 easier to form the divalent immunotoxin, because it decreases the steric hindrance between the two PE38s. The constructed genes were expressed in E. coli as inclusion bodies. Polypeptides that were obtained from the inclusion body were refolded, and the active forms were purified. The ID50 values of the divalent molecule, [B3(Fab)-ext-PE38]2, were about 4 ng/ml on A431 cell lines, about 1 ng/ml on CRL1739 cell lines, and 5 ng/ml on MCF-7 cell lines. The [B3(Fab)-ext-PE38]2 showed about a 12-fold higher cytotoxicity on CRL1739 cell lines than B3(scFv)-PE40 did.
Immunoassay as a Screening Tool for Industrial Toxicants (1986)

Immunoassay techniques may represent useful screening tools to assist analysts interested in the presence and amounts of organic toxicants in biological fluids. The widespread application of immunoassay methods in medicinal and forensic (drugs of abuse) chemistry has resulted in such screening methodologies. Four methodologies of potential benefit are considered: the free radical assay technique, the enzyme-mediated immunoassay technique, radioimmunoassay, and hemagglutination. Each of these immunoassays is based on the competitive displacement of the labeled drug (or toxicant) from the antibody complex by the unlabeled drug-toxicant in the sample.
Redesign of Substrate Specificity and Identification of the Aminoglycoside Binding Residues of Eis from Mycobacterium tuberculosis (2013)

The upsurge in drug-resistant tuberculosis (TB) is an emerging global problem. The increased expression of the enhanced intracellular survival (Eis) protein is responsible for the clinical resistance to aminoglycoside (AG) antibiotics of Mycobacterium tuberculosis . Eis from M. tuberculosis (Eis_Mtb) and M. smegmatis (Eis_Msm) function as acetyltransferases capable of acetylating multiple amines of many AGs; however, these Eis homologues differ in AG substrate preference and in the number of acetylated amine groups per AG. The AG binding cavity of Eis_Mtb is divided into two narrow channels, whereas Eis_Msm contains one large cavity. Five bulky residues lining one of the AG binding channels of Eis_Mtb, His119, Ile268, Trp289, Gln291, and Glu401, have significantly smaller counterparts in Eis_Msm, Thr119, Gly266, Ala287, Ala289, and Gly401, respectively. To identify the residue(s) responsible for AG binding in Eis_Mtb and for the functional differences from Eis_Msm, we have generated single, double, triple, quadruple, and quintuple mutants of these residues in Eis_Mtb by mutating them into their Eis_Msm counterparts, and we tested their acetylation activity with three structurally diverse AGs: kanamycin A (KAN), paromomyin (PAR), and apramycin (APR). We show that penultimate C-terminal residue Glu401 plays a critical role in the overall activity of Eis_Mtb. We also demonstrate that the identities of residues Ile268, Trp289, and Gln291 (in Eis_Mtb nomenclature) dictate the differences between the acetylation efficiencies of Eis_Mtb and Eis_Msm for KAN and PAR. Finally, we show that the mutation of Trp289 in Eis_Mtb into Ala plays a role in APR acetylation.
Clinical and biologic effects of combination therapy with gamma-interferon and tumor necrosis factor (1992)

Tumor necrosis factor (TNF) and gamma-interferon (gamma-IFN) are cytokines with synergistic biologic and antiproliferative effects in vitro and in mouse models. The biologic effects of the combination of TNF and gamma-IFN, however, have not been studied well in humans. A Phase I trial was conducted of TNF and gamma-IFN therapy in 24 patients with advanced malignancies to determine the tolerability of the combination and the biologic effects of TNF and gamma-IFN in vivo. Both TNF and gamma-IFN were administered as 30-minute intravenous infusions three times per week. Doses of TNF ranged from 25 to 100 micrograms/m2; all patients received 100 micrograms/m2 of gamma-IFN. Dose-limiting toxicity consisted primarily of orthostatic hypotension and constitutional symptoms. The maximum tolerated dose level (MTDL) of 50 micrograms/m2 of TNF and 100 micrograms/m2 of IFN-gamma was less than the maximum tolerated dose (MTD) observed in previous Phase I trials of gamma-IFN and TNF alone. Biologic responses were studied in seven patients treated at the MTDL. Serum interleukin-2 receptor levels and neopterin secretion were enhanced significantly 24 hours after therapy (P = 0.002); enhancement of monocyte Fc receptor levels had borderline statistical significance (P = 0.07). With the exception of the mean fluorescent intensity on monocytes positive for histocompatibility antigen HLA-DR (P = 0.03), HLA Class I and II cell surface protein expression was not increased. The combination significantly enhanced indoleamine dioxygenase activity and serum beta 2-microglobulin expression (P less than 0.04) but not 2',5'-oligoadenylate synthetase activity, bactericidal function, or chemiluminescence. These results were compared retrospectively with those observed in previous Phase I trials of gamma-IFN and TNF alone. The combination of TNF and gamma-IFN significantly increased urinary kynurenine levels more than either TNF alone or gamma-IFN alone. Given the limitations inherent in any retrospective analysis, however, the enhancement in the other biologic parameters measured at the MTDL during this trial did not differ significantly from the changes observed at the MTD of either TNF or gamma-IFN alone. It was concluded that the combination of TNF and gamma-IFN, when administered at the MTDL of the combination, does not offer any enhancement in biologic responses over either agent alone.
Effect of Four Different Vegetable Oils (Red Palm Olein, Palm Olein, Corn Oil, Coconut Oil) on Antioxidant Enzymes Activity of Rat Liver (2011)

The objective of the study was to evaluate the effect of four different vegetable oils [red palm olein (RPO), palm olein (PO), corn oil (CO), coconut oil (COC)] on antioxidant enzymes activity of rat liver. Sixty six Sprague Dawley male rats which were randomly divided into eleven groups of 6 rats per group and were treated with 15% of RPO, PO, CO and COC for 4 and 8 weeks. Rats in the control group were given normal rat pellet only while in treated groups, 15% of additional different vegetable oils were given. After 4 weeks of treatment the catalase (CAT) activity results showed that there was no significance difference (p > or = 0.05) between the control group and treated groups while after 8 weeks of treatment showed that there was no significant different (p > or = 0.05) between control group and RPO group but the treated rat liver with PO, CO and COC groups were the lowest and it were significantly lower (> or = 0.05) than control group. For superoxide dismutase (SOD) there was no significance difference (p > or = 0.05) between the control group and treated groups of vegetable oils after 4 and 8 weeks of treatment. Thus the study indicated that there was no significant (p > or = 0.05) effect on antioxidant enzyme (superoxide dismutase) but there was significant effect (p > or = 0.05) on catalase in rat liver.
Herpes Simplex Virus Type 1 Immediate-Early Protein ICP0 and Its Isolated RING Finger Domain Act as Ubiquitin E3 Ligases In Vitro (2002)

ABSTRACT Proteasome-dependent degradation of ubiquitinated proteins plays a key role in many important cellular processes. Ubiquitination requires the E1 ubiquitin activating enzyme, an E2 ubiquitin conjugating enzyme, and frequently a substrate-specific ubiquitin protein ligase (E3). One class of E3 ubiquitin ligases has been shown to contain a common zinc-binding RING finger motif. We have previously shown that herpes simplex virus type 1 ICP0, itself a RING finger protein, induces the proteasome-dependent degradation of several cellular proteins and induces the accumulation of colocalizing conjugated ubiquitin in vivo. We now report that both full-length ICP0 and its isolated RING finger domain induce the accumulation of polyubiquitin chains in vitro in the presence of E1 and the E2 enzymes UbcH5a and UbcH6. Mutations within the RING finger region that abolish the in vitro ubiquitination activity also cause severe reductions in ICP0 activity in other assays. We conclude that ICP0 has the potential to act as an E3 ubiquitin ligase during viral infection and to target specific cellular proteins for destruction by the 26S proteasome.
Secure SOurce-BAsed Loose Synchronization (SOBAS) for Wireless Sensor Networks (2012)

We present the Secure SOurce-BAsed Loose Synchronization (SOBAS) protocol to securely synchronize the events in the network, without the transmission of explicit synchronization control messages. In SOBAS, nodes use their local time values as a one-time dynamic key to encrypt each message. In this way, SOBAS provides an effective dynamic en-route filtering mechanism, where the malicious data is filtered from the network. With SOBAS, we are able to achieve our main goal of synchronizing events at the sink as quickly, as accurately, and as surreptitiously as possible. With loose synchronization, SOBAS reduces the number of control messages needed for a WSN to operate providing the key benefits of reduced energy consumption as well as reducing the opportunity for malicious nodes to eavesdrop, intercept, or be made aware of the presence of the network. Albeit a loose synchronization per se, SOBAS is also able to provide $(7.24 \mu)$s clock precision given today's sensor technology, which is much better than other comparable schemes (schemes that do not employ GPS devices). Also, we show that by recognizing the need for and employing loose time synchronization, necessary synchronization can be provided to the WSN application using half of the energy needed for traditional schemes. Both analytical and simulation results are presented to verify the feasibility of SOBAS as well as the energy consumption of the scheme under normal operation and attack from malicious nodes.
High-performance 50-nm-gate-length schottky-source/drain MOSFETs with dopant-segregation junctions (2005)

High-performance operation was achieved in a novel Schottky-source/drain MOSFET (SBT: Schottky barrier transistor), which has dopant-segregation (DS) Schottky source/drain. Sub-100 nm complementary DS-SBTs were fabricated using the CoSi/sub 2/ process, which was fully compatible with the current CMOS technology. Excellent CMOS performance was obtained without any channel-mobility degradation, and CMOS ring oscillator was successfully demonstrated. In addition, >20 % improvement in drive current over the conventional n-MOSFETs was confirmed in the n-type DS-SBTs around the gate length of 50 nm.