gebhart/patrepeval huggingface dataset:
Enzymatic activity of prostate‐specific antigen and its reactions with extracellular serine proteinase inhibitors (1990)

Prostate-specific antigen (PSA) is one of the three most abundant prostatic-secreted proteins in human semen. It is a serine proteinase that, in its primary structure, manifests extensive similarities with that of the Arg-restricted glandular kallikrein-like proteinases. When isolated from semen by the addition of chromatography on aprotinin-Sepharose to a previously described procedure, PSA displayed chymotrypsin-like activity and cleaved semenogelin and the semenogelin-related proteins in a rapid and characteristic pattern, but had no trypsin-like activity. About one third of the purified protein was found to be enzymatically inactive, due to cleavage carboxy-terminal of Lys145. Active PSA formed SDS-stable complexes with alpha 1-antichymotrypsin, alpha 2-macroglobulin-analogue pregnancy zone protein. PSA formed inhibitory complexes with alpha 1-antichymotrypsin at a molar ratio of 1:1, a reaction in which PSA cleaved the inhibitor in a position identical to that reported from the reaction between chymotrypsin and alpha 1-antichymotrypsin. The formation of stable complexes between PSA and alpha 1-antichymotrypsin occurred at a much slower rate than that between chymotrypsin and alpha 1-antichymotrypsin, and at a similar or slightly slower rate than that between PSA and alpha 2-macroglobulin. When added to normal blood plasma in vitro, active PSA formed stable complexes both with alpha 2-macroglobulin and alpha 1-antichymotrypsin. This complex formation may be a crucial determinant of the turnover of active PSA in intercellular fluid or blood plasma in vivo.
Spread-spectrum watermarking of audio signals (2003)

Watermarking has become a technology of choice for a broad range of multimedia copyright protection applications. Watermarks have also been used to embed format-independent metadata in audio/video signals in a way that is robust to common editing. In this paper, we present several novel mechanisms for effective encoding and detection of direct-sequence spread-spectrum watermarks in audio signals. The developed techniques aim at (i) improving detection convergence and robustness, (ii) improving watermark imperceptiveness, (iii) preventing desynchronization attacks, (iv) alleviating estimation/removal attacks, and finally, (v) establishing covert communication over a public audio channel. We explore the security implications of the developed mechanisms and review watermark robustness on a benchmark suite that includes a combination of audio processing primitives including: time- and frequency-scaling with wow-and-flutter, additive and multiplicative noise, resampling, requantization, noise reduction, and filtering.
The Clinical use of Colony Stimulating Factors (1991)

Colony stimulating factors and interleukins regulate proliferation, differentiation, and functional activation of hematopoietic cells of multiple lineages. These hematopoietic growth factors are proving effective in vivo in stimulation of granulopoiesis in clinical situations associated with myelosuppression. G-CSF and GM-CSF promote accelerated granulocyte recovery following chemotherapy, or allogeneic or autologous bone marrow transplantation, in patients with cancer. In congenital defects of granulocyte production or in acquired disorders such as idiopathic neutropenia or aplastic anemia, CSF administration can lead to recovery of functioning granulocytes. This has resulted in a reduction in the morbidity and mortality associated with these diseases and now permits both a dose and a schedule intensification of chemotherapy. In myeloid leukemia and myelodysplastic syndromes, CSF treatment, particularly G-CSF, has proved effective for certain patients in improving neutrophil, platelet, and occasionally red cell production while reducing blast cells. The recombinant growth factors are generally well tolerated with few limiting toxicities at dose levels that effectively stimulate hematopoiesis.
A biological approach to mucositis. (2004)

Oral mucositis is a common toxicity associated with both antineoplastic head and neck radiation and chemotherapy. In addition to exacting a terrible symptomatic toll, mucositis is associated with a number of adverse health and economic outcomes. Furthermore, its presence may compromise the use of optimum agents, doses, or dosing schedules. The current lack of an approved, effective mucositis treatment has sparked interest in the development of interventions that are based on the biological mechanisms that lead to mucosal injury. While our understanding of the molecular and cellular pathways leading to mucositis is still evolving, it is now clear that the condition represents the culmination of a dynamic sequence of events that involve all cells and tissues in the mucosa. Five phases characterize the pathophysiologic progression that results in mucositis: initiation, upregulation and message generation, signaling and amplification, ulceration, and healing. Each phase offers a potential target for therapeutic intervention.
RETRIEVING AND INTEGRATING DATA FROM MULTIPLE INFORMATION SOURCES (1993)

With the current explosion of data, retrieving and integrating information from various sources is a critical problem. Work in multidatabase systems has begun to address this problem, but it has primarily focused on methods for communicating between databases and requires significant effort for each new database added to the system. This paper describes a more general approach that exploits a semantic model of a problem domain to integrate the information from various information sources. The information sources handled include both databases and knowledge bases, and other information sources (e.g. programs) could potentially be incorporated into the system. This paper describes how both the domain and the information sources are modeled, shows how a query at the domain level is mapped into a set of queries to individual information sources, and presents algorithms for automatically improving the efficiency of queries using knowledge about both the domain and the information sources. This work is implemented in a system called SIMS and has been tested in a transportation planning domain using nine Oracle databases and a Loom knowledge base.
Simultaneous multithreading (1995)

This paper examines simultaneous multithreading, a technique permitting several independent threads to issue instructions to a superscalar's multiple functional units in a single cycle. We present several models of simultaneous multithreading and compare them with alternative organizations: a wide superscalar, a fine-grain multithreaded processor, and single-chip, multiple-issue multiprocessing architectures. Our results show that both (single-threaded) superscalar and fine-grain multithreaded architectures are limited their ability to utilize the resources of a wide-issue processor. Simultaneous multithreading has the potential to achieve 4 times the throughput of a superscalar, and double that of fine-grain multithreading. We evaluate several cache configurations made possible by this type of organization and evaluate tradeoffs between them. We also show that simultaneous multithreading is an attractive alternative to single-chip multiprocessors; simultaneous multithreaded processors with a variety of organizations outperform corresponding conventional multiprocessors with similar execution resources.While simultaneous multithreading has excellent potential to increase processor utilization, it can add substantial complexity to the design. We examine many of these complexities and evaluate alternative organizations in the design space.
Inhibition of tumor necrosis factor activity minimizes target organ damage in experimental autoimmune uveoretinitis despite quantitatively normal activated T cell traffic to the retina (1996)

Recent studies demonstrated that administration of a p55-tumor necrosis factor (TNF) receptor IgG-fusion protein (TNFR-IgG) prevented the clinical onset of experimental autoimmune encephalomyelitis but did not alter the number or tissue distribution of autoantigen-specific CD4+ effector T cells which trafficked into the central nervous system. To determine whether specific target tissues of autoimmune damage remain intact after TNFR-IgG treatment despite the presence of inflammatory cells within the tissues, we examined rats with experimental autoimmune uveoretinitis (EAU), as in this model, the main target of autoreactive CD4+ T cells, the retinal rod outer segments (ROS), can be examined readily by light microscopy. As judged by direct ophthalmoscopy, the onset of inflammation in the anterior chamber of the eye in EAU following administration of TNFR-IgG was delayed by 6 days compared to untreated controls, but the magnitude of the response was only slightly less than controls. Histological examination of the retinae and direct assessment of retinal inflammation revealed a disproportionate sparing of ROS in the TNFR-IgG-treated animals despite a level of retinal inflammation not substantially less than controls in which ROS damage was marked. Analysis of retinal leukocytes by immunofluorescence microscopy and flow cytometry indicated that approximately equal numbers of CD4+ alpha beta TCR+ lymphocytes were present in treated and control retinae, more than 30% of CD4+ cells in both experimental groups expressed the CD25 or MRC OX40 activation markers and most cells, which would include the CD4+ T lymphocytes, were activated as evidenced by MHC class II expression. Fewer activated macrophages and granulocytes were present in the treated retinae, possibly reflecting the lower level of tissue damage and subsequent accumulation of these inflammatory cells. The results demonstrate directly that a tissue specifically targeted for autoimmune destruction can be protected despite the influx of fully activated CD4+ T cells.
Radiation reduction during percutaneous coronary intervention (2017)

The percutaneous coronary intervention (PCI) procedure is associated with potentially high levels of radiation exposure and therefore increased risk of adverse radiation-induced outcomes, ranging from cataract to malignancy. Frame rate reduction and selective fluoroscopy storage may help reduce radiation exposure. In this study, we evaluated the efficacy of a radiation reduction protocol that uses a lower frame rate and selective storage of fluoroscopic images in terms of its effect on reducing the radiation dose during PCI.The new protocol incorporated a lower frame rate as compared with the conventional protocol, and used selective storage of fluoroscopic images. We reviewed the medical records of patients who underwent PCI under the conventional protocol from January 2013 to December 2013, and compared them with those who underwent PCI with the new protocol from January 2015 to December 2015. The primary endpoint was radiation dose reduction expressed as cumulative air kerma and dose-area product (DAP). The image quality was assessed by 3 independent well-trained cardiologists.One hundred fifty-five patients were enrolled in the conventional protocol group, and 152 were enrolled in the radiation reduction protocol group (total, n = 307). There was no statistical significance in terms of the baseline characteristics, including body mass index. Overall, the radiation reduction protocol group showed a significant reduction in both cumulative air kerma (1634.39 ± 717.95 vs 2074.75 ± 1003.72 mGy, P < .001) and DAP (12344.86 ± 5371.75 vs 15312.19 ± 7136.58 μGy m, P < .001). Image quality was acceptable in both groups.The radiation reduction protocol, which uses a lower frame rate and selective storage of fluoroscopic images, may be an alternative approach to reducing PCI radiation dose.
Lipid Emulsion Reverses Levobupivacaine-induced Responses in Isolated Rat Aortic Vessels (2011)

These results indicate that reversal of levobupivacaine-induced vasodilation by LE is mediated mainly through the attenuation of levobupivacaine-mediated inhibition of L-type calcium channel-dependent contraction and, in part, by inhibition of levobupivacaine-induced nitric oxide release. LE-mediated reversal of responses induced by local anesthetics may be related to their lipid solubility.
Heart wall myofibers are arranged in minimal surfaces to optimize organ function (2012)

Heart wall myofibers wind as helices around the ventricles, strengthening them in a manner analogous to the reinforcement of concrete cylindrical columns by spiral steel cables [Richart FE, et al. (1929) Univ of Illinois, Eng Exp Stn Bull 190]. A multitude of such fibers, arranged smoothly and regularly, contract and relax as an integrated functional unit as the heart beats. To orchestrate this motion, fiber tangling must be avoided and pumping should be efficient. Current models of myofiber orientation across the heart wall suggest groupings into sheets or bands, but the precise geometry of bundles of myofibers is unknown. Here we show that this arrangement takes the form of a special minimal surface, the generalized helicoid [Blair DE, Vanstone JR (1978) Minimal Submanifolds and Geodesics 13-16], closing the gap between individual myofibers and their collective wall structure. The model holds across species, with a smooth variation in its three curvature parameters within the myocardial wall providing tight fits to diffusion magnetic resonance images from the rat, the dog, and the human. Mathematically it explains how myofibers are bundled in the heart wall while economizing fiber length and optimizing ventricular ejection volume as they contract. The generalized helicoid provides a unique foundation for analyzing the fibrous composite of the heart wall and should therefore find applications in heart tissue engineering and in the study of heart muscle diseases.
Synthesis of Cluster Galactosides with High Affinity for the Hepatic Asialoglycoprotein Receptor (1995)

High-affinity ligands for the asialoglycoprotein receptor, which is uniquely localized on the parenchymal liver cell and recognizes oligoantennary galactosides, might be utilized as homing device to specifically target drugs or genes to parenchymal liver cells. In the present study, the synthesis of galactose-terminated triantennary glycosides, provided with various spacers between the beta-galactopyranosyl moieties and the branching point of the dendrite, is described. N-[Tris[[(methylthio)methoxy]methyl]methyl]-N alpha-[1-(6- methyladipy)]glycinamide (3b) was glycosylated with monogalactosyl derivatives, containing propanediol or ethylene glycol units as hydrophilic spacer moieties, to yield the corresponding cluster galactosides. To determine the affinity of the cluster galactosides for the asialoglycoprotein receptor, we have performed competition studies of [125I]ASOR binding, a specific ligand for the asialoglycoprotein receptor, to isolated parenchymal cells. The affinity for the asialoglycoprotein receptor significantly increased with increasing spacer length. N-[[[Tris-O-(beta-D-galactopyranosyl)-3,6,9-trioxaunde- canoxy]methoxy]methyl]-N-alpha-[1-(6-methyladipyl)]glycinami de (4e), a cluster galactoside provided with a 20 A spacer, possessed an at least 2000-fold higher affinity for the receptor than N-[[tris-O-(beta-D-galactopyranosyl)methyl]methyl]-N alpha-[1-(6- methyladipyl)]glycinamide (4a), a cluster galactoside lacking the spacer. It is concluded that vicinal galactosyl moieties within a cluster galactoside are more optimal recognized by the galactose binding sites of the asialoglycoprotein receptor upon proper spacing. The most potent galactoside, TG(20A), may constitute an attractive targeting device for the specific delivery of drugs and/or genes to the parenchymal liver cell.
Optimization of an enrichment process for circulating tumor cells from the blood of head and neck cancer patients through depletion of normal cells (2008)

The optimization of a purely negative depletion, enrichment process for circulating tumor cells (CTCs) in the peripheral blood of head and neck cancer patients is presented. The enrichment process uses a red cell lysis step followed by immunomagnetic labeling, and subsequent depletion, of CD45 positive cells. A number of relevant variables are quantified, or attempted to be quantified, which control the performance of the enrichment process. Six different immunomagnetic labeling combinations were evaluated as well as the significant difference in performance with respect to the blood source: buffy coats purchased from the Red Cross, fresh, peripheral blood from normal donors, and fresh peripheral blood from human cancer patients. After optimization, the process is able to reduce the number of normal blood cells in a cancer patient's blood from 4.05 x 10(9) to 8.04 x 10(3) cells/mL and still recover, on average, 2.32 CTC per mL of blood. For all of the cancer patient blood samples tested in which CTC were detected (20 out of 26 patients) the average recovery of CTCs was 21.7 per mL of blood, with a range of 282 to 0.53 CTC. Since the initial number of CTC in a patient's blood is unknown, and most probably varies from patient to patient, the recovery of the CTC is unknown. However, spiking studies of a cancer cell line into normal blood, and subsequent enrichment using the optimized protocol indicated an average recovery of approximately 83%. Unlike a majority of other published studies, this study focused on quantifying as many factors as possible to facilitate both the optimization of the process as well as provide information for current and future performance comparisons. The authors are not aware any other reported study which has achieved the performance reported here (a 5.66 log(10)) in a purely negative enrichment mode of operation. Such a mode of operation of an enrichment process provides significant flexibility in that it has no bias with respect to what attributes define a CTC; thereby allowing the researcher or clinician to use any maker they choose to define whether the final, enrich product contains CTCs or other cell type relevant to the specific question (i.e., does the CTC have predominantly epithelial or mesenchymal characteristics?).
The duration of the suicidal process: how much time is left for intervention between consideration and accomplishment of a suicide attempt? (2009)

The process from the emergence of suicidal thoughts to the accomplishment of a suicide attempt, and thus the time for intervention, generally is short. However, in a considerable number of suicide attempters, there is at least some readiness for interpersonal contact with partner, family, or friends. Professional helpers appear to have limited potential for intervention during this phase. Thus, spreading information on signs of suicidality and interventional measures among the general population should be incorporated into suicide prevention strategies.
Characterization of METH-1/ADAMTS1 Processing Reveals Two Distinct Active Forms (2000)

METH-1/ADAMTS1 is a member of a newly described family of genes that contain metalloprotease, disintegrin, and thrombospondin-like motifs. We have recently shown that METH-1 protein is a potent inhibitor of angiogenesis. Here, we demonstrate that secreted human pro-METH-1 is processed in two consecutive steps to release both p87 and p65 active forms. The p87 form lacks the N-terminal prodomain and p65 results from an additional processing event in the C-terminal end. Generation of p87 was blocked with specific inhibitors of furin, and incubation of pro-METH-1 with purified furin released the p87 fragment but not p65. Generation of p65 required preformation of p87 and was suppressed by inhibitors of matrix metalloproteases. We demonstrate that matrix metalloproteases 2, 8, and 15 were able to release p65 when p87 was used as substrate. This second processing step removes two thrombospondin repeats from the carboxyl-terminal end of p87-METH-1 and alters the affinity of the protein to heparin and endothelial cultures. Furthermore, this deletion was associated with a reduced activity upon suppression of endothelial cell proliferation. We hypothesize that METH-1 processing is relevant for the modulation of the anti-angiogenic properties displayed by the protein.
Imeglimin: A Potential New Multi-Target Drug for Type 2 Diabetes (2015)

Imeglimin is a novel agent currently in development to treat type 2 diabetes. Laboratory studies have demonstrated that it has the potential to impact the three main pathophysiologic components of type 2 diabetes: impaired glucose uptake by muscle tissue, excess hepatic gluconeogenesis, and increased beta-cell apoptosis. Preliminary human studies that have been published within the last 2 years demonstrate that imeglimin improves hemoglobin A1c and fasting plasma glucose similarly when compared with metformin and with sitagliptin. There has also been a low incidence of adverse effects, especially hypoglycemia, reported in these early human studies. Currently, imeglimin is lacking long-term evidence to demonstrate any effects on its cardiovascular safety, and data on morbidity and mortality, though some studies are currently in progress. There is great potential for imeglimin, if FDA approved, to play a significant role in the type 2 diabetes management algorithm.
Natural Behavior Polymorphism Due to a cGMP-Dependent Protein Kinase of Drosophila (1997)

Naturally occuring polymorphisms in behavior are difficult to map genetically and thus are refractory to molecular characterization. An exception is the foraging gene (for), a gene that has two naturally occurring variants in Drosophila melanogaster food-search behavior: rover and sitter. Molecular mapping placed for mutations in the dg2 gene, which encodes a cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG). Rovers had higher PKG activity than sitters, and transgenic sitters expressing a dg2 complementary DNA from rover showed transformation of behavior to rover. Thus, PKG levels affected food-search behavior, and natural variation in PKG activity accounted for a behavioral polymorphism.
Unloading of juvenile muscle results in a reduced muscle size 9 wk after reloading (2000)

The role of satellite cells and DNA unit size in determining muscle size was examined by inhibiting postnatal skeletal muscle development by using hindlimb suspension. Satellite cell mitotic activity and DNA unit size were determined in the soleus muscles from hindlimb-suspended and age-matched weight-bearing rats before the initiation of hindlimb suspension, at the conclusion of a 28-day hindlimb-suspension period, 2 wk after reloading, and 9 wk after reloading. The body weights of hindlimb-suspended rats were significantly (P < 0.05) less than those of weight-bearing rats at the conclusion of hindlimb suspension, but they were the same (P > 0. 05) as those of weight-bearing rats 9 wk after reloading. The soleus muscle weight, soleus muscle weight-to-body weight ratio, myofiber diameter, nuclei per millimeter, and DNA unit size for the hindlimb-suspended rats were significantly (P < 0.05) smaller than for the weight-bearing rats at all recovery times. Satellite cell mitotic activity was significantly (P < 0.05) higher in the soleus muscles from hindlimb-suspended rats 2 wk after reloading, but it was the same (P > 0.05) as in weight-bearing rats 9 wk after reloading. Juvenile soleus muscles failed to achieve normal muscle size 9 wk after reloading because there was incomplete compensation for the hindlimb-suspension-induced interruptions in myonuclear accretion and DNA unit size expansion.