gebhart/patrepeval huggingface dataset:
N-arginine dibasic convertase (nardilysin) isoforms are soluble dibasic-specific metalloendopeptidases that localize in the cytoplasm and at the cell surface (2000)

N-arginine (R) dibasic (NRD) convertase (nardilysin; EC 3.4.24.61), a metalloendopeptidase of the M16 family, specifically cleaves peptide substrates at the N-terminus of arginines in dibasic motifs in vitro. In rat testis, the enzyme localizes within the cytoplasm of spermatids and associates with microtubules of the manchette and axoneme. NRD1 and NRD2 convertases, two NRD convertase isoforms, differ by the absence (isoform 1) or presence (isoform 2) of a 68-amino acid insertion close to the active site. In this study, we overexpressed both isoforms, either by vaccinia virus infection of BSC40 cells or transfection of COS-7 cells. The partially purified enzymes exhibit very similar biochemical and enzymic properties. Microsequencing revealed that NRD convertase is N-terminally processed. Results of immunocytofluorescence, immunoelectron microscopy and subcellular fractionation studies argue in favour of a primary cytosolic localization of both peptidases. Although the putative signal peptide did not direct NRD convertase into microsomes in an in vitro translation assay, biotinylation experiments clearly showed the presence of both isoforms at the cell surface. In conclusion, although most known processing events at pairs of basic residues are achieved by proprotein convertases within the secretory pathway, NRD convertase may fulfil a similar function in the cytoplasm and/or at the cell surface.
Carbon Monoxide: a Putative Neural Messenger (1993)

Carbon monoxide, an activator of guanylyl cyclase, is formed by the action of the enzyme heme oxygenase. By in situ hybridization in brain slices, discrete neuronal localization of messenger RNA for the constitutive form of heme oxygenase throughout the brain has been demonstrated. This localization is essentially the same as that for soluble guanylyl cyclase messenger RNA. In primary cultures of olfactory neurons, zinc protoporphyrin-9, a potent selective inhibitor of heme oxygenase, depletes endogenous guanosine 3',5'-monophosphate (cGMP). Thus, carbon monoxide, like nitric oxide, may be a physiologic regulator of cGMP. These findings, together with the neuronal localizations of heme oxygenase, suggest that carbon monoxide may function as a neurotransmitter.
Characterization of the 2'-5'-oligoadenylate synthetase ubiquitin-like family (2003)

The interferon-induced 2'-5'-oligoadenylate synthetases (OAS) are important for the antiviral activity of interferons. The human and murine OAS gene families each contain four genes: OAS1, OAS2, OAS3 and OASL, all having one or more conserved OAS units composed of five translated exons. The OASL gene has both an OAS unit and a C-terminus of two ubiquitin-like repeats. In this study, we demonstrate that murine Oasl1 protein is inactive while murine Oasl2 is active as an OAS. Further more, murine Oasl2 requires double-stranded RNA as co-factor. The affinity of murine Oasl2 for the double-stranded RNA activator is higher than that of human OAS1 (p42 isoform). We propose a model for the evolutionary origin of the murine Oasl1 and Oasl2 genes. The identification of a human orthologue (hOASL2) to the murine Oasl2 gene establishes that the OASL gene was duplicated prior to the radiation of the rodent and primate groups. We suggest that murine Oasl2, which has both enzymatic activity and a ubiquitin-like domain, is a functional intermediate between the active OAS species and the inactive human OASL1/murine Oasl1 proteins. In addition, we propose that murine Oasl1 appears to have gained a hitherto uncharacterized function independent of 2'-5'-linked oligoadenylate synthesis.
Medical Imaging for the Tracking of Micromotors (2018)

Micro/nanomotors are useful tools for several biomedical applications, including targeted drug delivery and minimally invasive microsurgeries. However, major challenges such as in vivo imaging need to be addressed before they can be safely applied on a living body. Here, we show that positron emission tomography (PET), a molecular imaging technique widely used in medical imaging, can also be used to track a large population of tubular Au/PEDOT/Pt micromotors. Chemisorption of an iodine isotope onto the micromotor's Au surface rendered them detectable by PET, and we could track their movements in a tubular phantom over time frames of up to 15 min. In a second set of experiments, micromotors and the bubbles released during self-propulsion were optically tracked by video imaging and bright-field microscopy. The results from direct optical tracking agreed with those from PET tracking, demonstrating that PET is a suitable technique for the imaging of large populations of active micromotors in opaque environments, thus opening opportunities for the use of this mature imaging technology for the in vivo localization of artificial swimmers.
Structure-Based Design of Novel Class II c-Met Inhibitors: 1. Identification of Pyrazolone-Based Derivatives (2012)

Deregulation of c-Met receptor tyrosine kinase activity leads to tumorigenesis and metastasis in animal models. More importantly, the identification of activating mutations in c-Met, as well as MET gene amplification in human cancers, points to c-Met as an important target for cancer therapy. We have previously described two classes of c-Met kinase inhibitors (class I and class II) that differ in their binding modes and selectivity profiles. The class II inhibitors tend to have activities on multiple kinases. Knowledge of the binding mode of these molecules in the c-Met protein led to the design and evaluation of several new class II c-Met inhibitors that utilize various 5-membered cyclic carboxamides to conformationally restrain key pharmacophoric groups within the molecule. These investigations resulted in the identification of a potent and novel class of pyrazolone c-Met inhibitors with good in vivo activity.
Prolonged intermittent virus shedding during an outbreak of canine influenza A H3N2 virus infection in dogs in three Chicago area shelters: 16 cases (March to May 2015) (2016)

OBJECTIVE To estimate an appropriate isolation period for dogs infected with canine influenza A H3N2 virus on the basis of the duration of virus shedding. DESIGN Retrospective case series. ANIMALS 16 dogs, from 3 Chicago area shelters, naturally infected with canine influenza A H3N2 virus. PROCEDURES Medical records of 16 affected dogs were reviewed. Nasal swab specimens from each dog had been tested periodically for a minimum of 15 days following an initial positive real-time reverse transcriptase PCR (rRT-PCR) assay result for influenza A virus shedding. Amplicons were purified, quantified, and sequenced by the Sanger DNA sequencing technique. Virus isolation and sequence results of canine influenza A H3N2 virus from nasal swab specimens were obtained in conjunction with signalment, description of clinical signs, type of treatment, and outcome. RESULTS Viruses from each dog were identified as canine influenza A H3N2 virus on the basis of DNA sequencing. The interval between first and last positive rRT-PCR assay results ranged from 13 to 24 days, whereas the time interval from first reported clinical signs to last positive assay results ranged from 15 to 26 days. Isolation of canine influenza A H3N2 virus was successful in the late shedding period from nasal swab specimens of 4 dogs at 15 and 20 days after the first positive rRT-PCR assay result and 18 to 20 days after the first clinical signs. Clinical signs resolved for all dogs that remained in the shelters during the testing period. CONCLUSIONS AND CLINICAL RELEVANCE Dogs infected with H3N2 virus should be isolated for a period of ≥ 21 days following onset of illness. Even when resolution of clinical signs occurs sooner than 21 days, shedding of H3N2 virus may persist.
3D triangulation system based on out-of-axis aperture configuration for micro-scaled objects shape measurement (2011)

In three-dimensional (3-D) measurement systems based on triangulation, a stereoscopic angle between two distinct viewpoints encodes the depth information. This angle generally generates some distortion known as keystone distortion. In this paper an original 3-D optical configuration in addition with a digital light processing system (DLP) is presented which prevents keystone distortion, resulting in less calibration and post-processing work. The DLP is used to project incoherent white light fringes pattern at high frame rate (30 Hz) on a specimen and a CCD camera dynamically captures this projected pattern. Using a phase shifting algorithm, the reconstruction of the 3-D shape of the specimen is finally computed. This optical configuration is based on an « out of axis » aperture method combined with an afocal design for both projection and acquisition. With the combination of these two properties, the stereoscopic effect is obtained without any keystone distortion and a unique objective lens instead of two in a classical 3-D measurement system is used. As a result of this unique objective lens, the global volume of the measurement device can be easily minimized. This system was designed with the optical software Zemax to limit geometric and chromatic aberrations and to control the diffraction effect. Experiments showed that high surface profile accuracy can be obtained on a variety of surfaces, allowing reverse engineering on micro-scaled objects or precise 3-D measurements of macro-scaled objects. Also a depth resolution value under 2 &mu;m for a scanned area around 7.5x5.5mm is obtained under experimental conditions.
Identification and structural analysis of the tetrasaccharide NeuAc.alpha.(2.fwdarw.6)Gal.beta.(1.fwdarw.4)GlcNAc.beta.(1.fwdarw.3)Fuc.alpha.1.fwdarw.O-linked to serine 61 of human factor IX (1993)

O-Linked fucose has been found attached to Thr/Ser residues within the sequence Cys-X-X-Gly-Gly-Thr/Ser-Cys in the N-terminal EGF domains of several coagulation/fibrinolytic proteins. Carbohydrate composition and mass spectrometric analyses of tryptic and thermolytic peptides containing the corresponding site (Ser-61) in the first EGF domain of human factor IX indicated the presence of a tetrasaccharide containing one residue each of sialic acid, galactose, N-acetylglucosamine, and fucose. The Ser-61 tetrasaccharide was not susceptible to alpha-fucosidase digestion. Fragments generated during mass spectrometric analysis indicated that fucose was the attachment sugar residue. The involvement of fucose in the carbohydrate-peptide linkage was confirmed by two-dimensional 1H NMR spectroscopic analysis of the glycopeptide containing factor IX residues 57-65. The complete structure of the tetrasaccharide was obtained by methylation analysis and two-dimensional 1H TOCSY and ROESY experiments as NeuAc alpha(2-->6)Gal beta(1-->4)GlcNAc beta(1-->3)Fuc alpha 1-->O-Ser61.
Role of 5 alpha-reductase inhibitors in the treatment of advanced prostatic carcinoma. (1991)

Everything we know about the biology of the prostate supports the concept that DHT is the obligate androgen responsible for normal and hyperplastic growth. Whether this selectivity is maintained during malignant transformation is unknown. The consistent emergence of androgen-insensitive disease highlights the spectrum of biologic evolution this cancer is capable of. If the tumor is dependent only on DHT for neoplastic growth, the unique characteristics of a 5 alpha-reductase inhibitor offer several potential actions that warrant a systematic evaluation.
Effects of Nandrolone Decanoate and Antiresorptive Therapy on Vertebral Density in Osteoporotic Postmenopausal Women (1989)

Conventional antiresorptive therapy for osteoporosis can delay bone loss, but secondary inhibition of bone formation appears to prevent an increase in bone density. Recently, anabolic steroid therapy has been shown to increase total body calcium and forearm density in osteoporotic patients, perhaps by causing an increase in bone formation. It is not known if these agents affect vertebral density. We have measured vertebral mineral density in 71 postmenopausal osteoporotic women before and after treatment with either the anabolic steroid nandrolone decanoate or antiresorptive therapy. After a mean treatment period of 14 months, there was a mean increase of 20% in vertebral mineral density in the former group, and no significant change in the latter group. The difference in the time-weighted mean rates of change between the two groups was significant. The results suggest that nandrolone decanoate therapy increases bone formation.
ELIMINATION OF LEUKEMIA CELLS FROM HUMAN BONE MARROW USING FLOATING BEADS (1988)

A new in vitro immunophysical method of removing leukemia or lymphoma cells from autologous bone marrow is described. This new technique makes use of low-density polypropylene beads (density: 0.91) coated with a monoclonal antibody anti-CALLA (antibody ALB2). To ascertain its ability to selectively remove human B/pre-B hematopoietic cells, this technique was applied to normal human bone marrow cell suspensions contaminated with 1-5% of tumor cells. Samples were incubated with the floating beads at 4 degrees C on a rotating wheel for 60 min, followed by a 10-min decantation period, after which the beads bearing the tumor cells floated on the surface, whereas unbound normal marrow cells remained in suspension and were easily recovered free of beads. To demonstrate the feasibility of our method, 2 types of assays were carried out, one using target cell radiolabeled with 111indium, and the other a clonogenic assay. The first assays were to calibrate the different parameters (cellular density, quantity of beads, incubation time) with tumor cell lines: Namalwa (CALLA+) and Molt 4 (CALLA-). These 2 cells lines being able to clone, it is hard to envisage clonogenic assays. In this case, it is very hazardous to evaluate correctly the remaining clonogenic units of Namalwa cells. It is why radiolabelling assays were used for these first experiments. The second assays were to study a model close to the clinical setting and to control the safety of the beads on normal bone marrow cells. In this case, the mixture experiments in which only Namalwa cells were able to clone were evaluated with clonogenic assays, which are more sensitive than radiolabeling assays. A 3- to 4-log reduction of tumor load was achieved with 1-step treatment, and an average of 5-log depletion was obtained by repeating the process twice, as ascertained by the clonogenic assay. Viability, average recovery of nucleated cells, and stem cells potential following the purge were excellent.
Characterization of Double-Strand Break-Induced Recombination: Homology Requirements and Single-Stranded DNA Formation (1992)

In the yeast Saccharomyces cerevisiae, a double-strand chromosome break created by the HO endonuclease is frequently repaired in mitotically growing cells by recombination between flanking homologous regions, producing a deletion. We showed that single-stranded regions were formed on both sides of the double-strand break prior to the formation of the product. The kinetics of the single-stranded DNA were monitored in strains with the recombination-deficient mutations rad52 and rad50 as well as in the wild-type strain. In rad50 mutants, single-stranded DNA was generated at a slower rate than in the wild type, whereas rad52 mutants generated single-stranded DNA at a faster rate. Product formation was largely blocked in the rad52 mutant. In the rad50 rad52 double mutant, the effects were superimposed in that the exonucleolytic activity was slowed but product formation was blocked. rad50 appears to act before or at the same stage as rad52. We constructed strains containing two ura3 segments on one side of the HO cut site and one ura3 region on the other side to characterize how flanking repeats find each other. Deletions formed preterentially between the homologous regions closest to the double-strand break. By varying the size of the middle ura3 segment, we determined that recombination initiated by a double-strand break requires a minimum homologous length between 63 and 89 bp. In these competition experiments, the frequency of recombination was dependent on the length of homology in an approximately linear manner.
The common variant of cystic fibrosis transmembrane conductance regulator is recognized by hsp70 and degraded in a pre-Golgi nonlysosomal compartment. (1993)

The most common cause of cystic fibrosis is deletion of Phe-508 (delta F508) from the cystic fibrosis transmembrane conductance regulator (CFTR). Previous studies have suggested that delta F508 CFTR is an unstable protein that retains a pattern of glycosylation specific to the endoplasmic reticulum. This report examines the mechanism responsible for the mislocalization of delta F508 CFTR in a human cystic fibrosis epithelial cell line overexpressing recombinant CFTR by virtue of adenovirus-mediated gene transfer. Immunoelectron microscopy confirmed that wild-type CFTR is delivered to the plasma membrane of these cells and that delta F508 CFTR is retained in the endoplasmic reticulum. Pulse-chase studies showed that newly synthesized CFTR complexes with the chaperone hsp70. The wild-type protein dissociates from hsp70 before its transport to the Golgi, and the protein is subsequently degraded in lysosomes. By contrast, the complex formed between delta F508 CFTR and hsp70 is retained in the endoplasmic reticulum and delta F508 CFTR is rapidly degraded in a pre-Golgi nonlysosomal compartment. Thus, hsp70 discriminates between the normal form of CFTR and the form of the protein that most commonly causes cystic fibrosis (delta F508). These findings clarify the mechanism by which mutation causing delta F508 affects the intracellular trafficking of CFTR and suggest another function for hsp70 in ensuring quality control during the biosynthesis of plasma-membrane proteins.
Gaze-contingent video compression with targeted gaze containment performance (2009)

A delay compensation algorithm is presented for a gaze-contingent video compression system (GCS) with a robust targeted gaze containment (TGC) performance. The TGC parameter allows varying compression levels of a gaze-contingent video stream by controlling its perceptual quality. The delay compensation model is based on the Kalman filter framework that models the human visual system with eye position and velocity data. The model predicts future eye position and constructs a high-quality coded region of interest (ROI) designed to contain a targeted number of gaze samples while reducing perceptual quality in the periphery of that region. Several model parameterization schemes were tested with 21 subjects using a delay range of 0.02 to 2 s and a TGC of 60 to 90%. The results indicate that the model was able to achieve TGC levels with compression of 1.4 to 2.3 times for TGC=90% and compression of 1.8 to 2.5 for TGC=60%. The lowest compression values were recorded for high delays, while the highest compression values were reported during small delays.
Inflammation in acute coronary syndromes (2002)

Extensive evidence supports a pathogenic role for both local and systemic inflammation in acute coronary syndromes. However, several important questions remain unanswered. Is the observed inflammatory process a precursor or a consequence of coronary plaque rupture? Is the inflammatory component of unstable coronary disease a potential therapeutic target? Finally, do infectious agents have a pathogenic role in coronary atherosclerosis and acute coronary syndromes?
Asparagine synthetase as a causal, predictive biomarker for l-asparaginase activity in ovarian cancer cells (2006)

L-Asparaginase (l-ASP), a bacterial enzyme used since the 1970s to treat acute lymphoblastic leukemia, selectively starves cells that cannot synthesize sufficient asparagine for their own needs. Molecular profiling of the NCI-60 cancer cell lines using five different microarray platforms showed strong negative correlations of asparagine synthetase (ASNS) expression and DNA copy number with sensitivity to l-ASP in the leukemia and ovarian cancer cell subsets. To assess whether the ovarian relationship is causal, we used RNA interference to silence ASNS in three ovarian lines and observed 4- to 5-fold potentiation of sensitivity to l-ASP with two of the lines. For OVCAR-8, the line that expresses the least ASNS, the potentiation was >500-fold. Significantly, that potentiation was >700-fold in the multidrug-resistant derivative OVCAR-8/ADR, showing that the causal relationship between ASNS expression and l-ASP activity survives development of classical multidrug resistance. Tissue microarrays confirmed low ASNS expression in a subset of clinical ovarian cancers as well as other tumor types. Overall, this pharmacogenomic/pharmacoproteomic study suggests the use of l-ASP for treatment of a subset of ovarian cancers (and perhaps other tumor types), with ASNS as a biomarker for patient selection.
Laparoscopic Colorectal Resection in the Obese Patient (2011)

Laparoscopic colorectal surgery is an accepted alternative to conventional open resection in the surgical approach of both benign and malignant diseases of the colon and rectum. Well-described benefits of laparoscopic surgery include accelerated recovery of bowel function, decreased post-operative pain and shorter hospital stay; these advantages could be particularly beneficial to high-risk patient groups, such as obese patients. At present, data regarding the application of the laparoscopic approach to colorectal resection in the obese is equivocal. We evaluate the available evidence to support laparoscopic colorectal resection in the obese patient population.
Evaluation of an ultrasonic method applied to the measurement of blood coagulation time (1997)

Clinical assessment of the blood clotting mechanism is usually made by measuring the time necessary for a sample of plasma to clot. In this work a semi-automatic method for measuring coagulation time is evaluated. It employs ultrasound, at 2.7 MHz, for monitoring variations of the viscosity in a plasma sample undergoing coagulation. The evaluation is performed by comparing measurements obtained by two well-known methods, the manual tilt tube and the fibrometer, with those obtained using the ultrasonic method. A total of 330 plasma samples from individuals with normal and altered homeostatic process were analysed. The experimental protocol follows two standard tests: the prothrombin time (141 samples) and the activated partial thromboplastin time (189 samples). The agreement between the three different methods is estimated statistically and it is shown that all the three can be used interchangeably for clinical purposes.
Recombinant methioninase infusion reduces the biochemical endpoint of serum methionine with minimal toxicity in high-stage cancer patients. (1998)

The tumor-specific increased minimal requirement for methionine has been shown to be a highly promising therapeutic target. To attack this target we have previously cloned the methioninase gene from Pseudomonas putida and produced recombinant methioninase (rMETase). A pilot Phase I clinical trial has been carried out to determine rMETase toxicity, rMETase pharmacokinetics, and serum MET-depletion in cancer patients. Patients with advanced breast cancer, lung cancer, renal cancer and lymphoma were given a single rMETase treatment at doses ranging from 5,000 to 20,000 units by i.v. infusion over 6-24 hours. No clinical toxicity was observed in any patient after rMETase treatment. rMETase levels reached 0.1 to 0.4 units per ml of serum in the patients which correspond to therapeutic levels in vitro. The lowest serum methionine levels in rMETase-treated patients were 0.1% of the pre-treatment levels corresponding to approximately 0.1 microM, which also correlates to therapeutic levels in vitro. The results of the rMETase pilot Phase I clinical trial therefore indicate that i.v. infusion of rMETase is safe and effectively depletes its biochemical target of serum methionine suggesting potential efficacy in future clinical trials.