gebhart/patrepeval huggingface dataset:
Suppression of cyclooxygenase‐2 gene transcription by humulon of beer hop extract studied with reference to glucocorticoid (2000)

In murine osteoblastic MC3T3-E1 cells which produced prostaglandin E2 as a bone resorption factor, the cyclooxygenase-2 induction by tumor necrosis factor alpha (TNFalpha) was suppressed by dexamethasone with an IC(50) of 1 nM. Humulon isolated from hop extract for beer brewing was reported previously as an inhibitor of bone resorption [Tobe, H. et al. (1997) Biosci. Biotech. Biochem. 61, 158-159]. We showed that the compound suppressed the TNFalpha-dependent cyclooxygenase-2 induction with an IC(50) of as low as about 30 nM as demonstrated experimentally by catalytic activity assay, Northern blot analysis and promoter analysis. Reporter gene experiments suggested that humulon blocked the cyclooxygenase-2 expression mediated by NFkappaB and NF-IL6, but the intracellular glucocorticoid receptor was not involved. The catalytic activity of cyclooxygenase-2 was inhibited by humulon with an IC(50) of as high as 1.6 microM. These results showed that humulon suppressed cyclooxygenase-2 induction at the step of transcription.
Deep Video Precoding (2019)

Several groups worldwide are currently investigating how deep learning may advance the state-of-the-art in image and video coding. An open question is how to make deep neural networks work in conjunction with existing (and upcoming) video codecs, such as MPEG H.264/AVC, H.265/HEVC, VVC, Google VP9 and AOMedia AV1, AV2, as well as existing container and transport formats, without imposing any changes at the client side. Such compatibility is a crucial aspect when it comes to practical deployment, especially when considering the fact that the video content industry and hardware manufacturers are expected to remain committed to supporting these standards for the foreseeable future. We propose to use deep neural networks as precoders for current and future video codecs and adaptive video streaming systems. In our current design, the core precoding component comprises a cascaded structure of downscaling neural networks that operates during video encoding, prior to transmission. This is coupled with a precoding mode selection algorithm for each independently-decodable stream segment, which adjusts the downscaling factor according to scene characteristics, the utilized encoder, and the desired bitrate and encoding configuration. Our framework is compatible with all current and future codec and transport standards, as our deep precoding network structure is trained in conjunction with linear upscaling filters (e.g., the bilinear filter), which are supported by all web video players. Extensive evaluation on FHD (1080p) and UHD (2160p) content and with widely-used H.264/AVC, H.265/HEVC and VP9 encoders, as well as a preliminary evaluation with the current test model of VVC (v.6.2rc1), shows that coupling such standards with the proposed deep video precoding allows for 8% to 52% rate reduction under encoding configurations and bitrates suitable for video-on-demand adaptive streaming systems. The use of precoding can also lead to encoding complexity reduction, which is essential for cost-effective cloud deployment of complex encoders like H.265/HEVC, VP9 and VVC, especially when considering the prominence of high-resolution adaptive video streaming.
A novel inhibitor of vacuolar ATPase, FR167356, which can discriminate between osteoclast vacuolar ATPase and lysosomal vacuolar ATPase (2004)

1 Vacuolar ATPase (V-ATPase) has been proposed as a drug target in lytic bone diseases. Studies of bafilomycin derivatives suggest that the key issue regarding the therapeutic usefulness of V-ATPase inhibitors is selective inhibition of osteoclast V-ATPase. Previous efforts to develop therapeutic inhibitors of osteoclast V-ATPase have been frustrated by a lack of synthetically tractable and biologically selective leads. Therefore, we tried to find novel potent and specific V-ATPase inhibitors, which have new structural features and inhibition selectivity, from random screening using osteoclast microsomes. Finally, a novel V-ATPase inhibitor, FR167356, was obtained through chemical modification of a parental hit compound. 2 FR167356 inhibited not only H+ transport activity of osteoclast V-ATPase but also H+ extrusion from cytoplasm of osteoclasts, which depends on the V-ATPase activity. As expected, FR167356 remarkably inhibited bone resorption in vitro. 3 FR167356 also showed inhibitory effects on other V-ATPases, renal brush border V-ATPase, macrophage microsome V-ATPase and lysosomal V-ATPase. However, FR167356 was approximately seven-fold less potent in inhibiting lysosomal V-ATPase compared to osteoclast V-ATPase. Moreover, LDL metabolism in cells, which depends on acidification of lysosome, was blocked merely at higher concentration than bone resorption, suggesting that FR167356 inhibits V-ATPase of osteoclast ruffled border membrane still more selectively than lysosome at the cellular level. 4 These results from the experiments seem to indicate that osteoclast V-ATPase may be different from lysosomal V-ATPase in respect of their structure. 5 FR167356 had a novel chemical structural feature as well as inhibitory characteristics distinctly different from any previously known V-ATPase inhibitor family. Therefore, FR167356 is thought to be a useful tool for estimating the essential characteristics of V-ATPase inhibitors for drug development.
Infusional chemoradiation for rectal and anal cancers. (1999)

Combined-modality therapy, including irradiation and concurrently administered chemotherapy, has become the mainstay of therapy for anal and rectal cancers. Several important lessons have been learned from clinical trials over the last several decades. Simultaneous delivery of large (bolus) doses of 5-fluorouracil with irradiation is associated with improved survival compared to irradiation alone, but at a price of increased normal tissue toxicity. These side effects can be ameliorated by using protracted venous infusion for chemotherapy, which is analogous to the observations in radiation oncology that fractionation spares late tissue toxicity. The protracted venous infusion approach is efficacious, has a wide therapeutic index, and permits concurrent systemic treatment of micrometastatic disease and radiation sensitization. Protracted venous infusion chemoradiation is also used in the preoperative management of rectal cancer and in the nonoperative management of anal cancers. Newer radiosensitizing agents, three-dimensional radiotherapy planning, and conformal radiotherapy treatment offer additional hope for the future that even more patients with rectal and anal cancers may benefit from combined-modality therapy with acceptable toxicity.
The p38 mitogen-activated protein kinase pathway plays a critical role in thrombin-induced endothelial chemokine production and leukocyte recruitment (2001)

Thrombin, the terminal serine protease in the coagulation cascade, is a proinflammatory molecule in vivo and induces endothelial activation in vitro. The cellular signaling mechanisms involved in this function are unknown. The role of the p38 mitogen-activated protein kinase (MAPK) signaling pathway in thrombin-induced chemokine production was studied. Phosphorylation of both p38 MAPK and its substrate, ATF-2, was observed in human umbilical vein endothelial cells (HUVECs) stimulated with thrombin, with a maximum after 5 minutes of stimulation. Using the selective p38 MAPK inhibitor SB203580, there was a significant decrease in thrombin-induced interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) protein production and messenger RNA steady-state levels. In addition, SB203580 decreased IL-8 and MCP-1 production induced by the thrombin receptor-1 agonist peptide (TRAP), suggesting functional links between the thrombin G protein-coupled receptor and the p38 MAPK pathway. Furthermore, endothelial activation in the presence of SB203580 decreased the chemotactic activity of thrombin-stimulated HUVEC supernatant on neutrophils and monocytic cells. In contrast, the p42/p44 MAPK pathway did not appear to be involved in thrombin- or TRAP-induced endothelial chemokine production, because there was no reduction in the presence of the p42/p44-specific inhibitor PD98059. These results demonstrate that the p38 rather than p42/44 MAPK signaling pathway plays an important role in thrombin-induced endothelial proinflammatory activation and suggest that inhibition of p38 MAPK may be an interesting target for anti-inflammatory strategies in vascular diseases combining thrombosis and inflammation. (Blood. 2001;98:667-673)
Death Pronouncement by Registered Nurses (1992)

Executive director of the Visiting Nurse Association of Eastern Montgomery County, a department of Abington Memorial Hospital, Abington, Pennsylvania
Satellite cell senescence underlies myopathy in a mouse model of limb-girdle muscular dystrophy 2H (2012)

Mutations in the E3 ubiquitin ligase tripartite motif-containing 32 (TRIM32) are responsible for the disease limb-girdle muscular dystrophy 2H (LGMD2H). Previously, we generated Trim32 knockout mice (Trim32-/- mice) and showed that they display a myopathic phenotype accompanied by neurogenic features. Here, we used these mice to investigate the muscle-specific defects arising from the absence of TRIM32, which underlie the myopathic phenotype. Using 2 models of induced atrophy, we showed that TRIM32 is dispensable for muscle atrophy. Conversely, TRIM32 was necessary for muscle regrowth after atrophy. Furthermore, TRIM32-deficient primary myoblasts underwent premature senescence and impaired myogenesis due to accumulation of PIAS4, an E3 SUMO ligase and TRIM32 substrate that was previously shown to be associated with senescence. Premature senescence of myoblasts was also observed in vivo in an atrophy/regrowth model. Trim32-/- muscles had substantially fewer activated satellite cells, increased PIAS4 levels, and growth failure compared with wild-type muscles. Moreover, Trim32-/- muscles exhibited features of premature sarcopenia, such as selective type II fast fiber atrophy. These results imply that premature senescence of muscle satellite cells is an underlying pathogenic feature of LGMD2H and reveal what we believe to be a new mechanism of muscular dystrophy associated with reductions in available satellite cells and premature sarcopenia.
A general method for the quaternization of N,N-dimethyl benzylamines with long chain n-alkylbromides (2004)

Benzalkonium bromides (BAK) are an important class of cationic surfactants with both industrial and commercial uses. They are used as preservatives for ophthalmic, nasal and parenteral products and they are also used as a topical antiseptic and medical equipment disinfectant. In this work a universal method for the preparation of these compounds is described. Using quaternization of N,N-dimethylbenzylamines with long-chain n-alkylbromides we have prepared C8, C10, C12, C14, C16, C18 and C20 homologues of the benzalkonium bromides (BAK).
The pro‐sequence facilitates folding of human nerve growth factor fromEscherichia coliinclusion bodies (2001)

Nerve growth factor (beta-NGF), a neurotrophin required for the development and survival of specific neuronal populations, is translated as a prepro-protein in vivo. While the presequence mediates translocation into the endoplasmic reticulum, the function of the pro-peptide is so far unknown. As the pro-sequences of several proteins are known to promote folding of the mature part, the renaturation behaviour of recombinant human beta-NGF pro-protein was compared to that of the mature form. Expression of rh-pro-NGF in Escherichia coli led to the formation of inclusion bodies (IBs). The presence of the covalently attached pro-sequence significantly increased the yield and rate of refolding with concomitant disulfide bond formation when compared to the in vitro refolding of mature NGF (rh-NGF). Physicochemical characterization revealed that rh-pro-NGF is a dimer. The pro-peptide could be removed by limited proteolysis with trypsin yielding biologically active, mature rh-NGF. Furthermore, rh-pro-NGF exhibited biological activity in the same concentration range as rh-NGF.
Evidence for cross-genotype neutralization of hepatitis C virus pseudo-particles and enhancement of infectivity by apolipoprotein C1 (2005)

The lack of a cell culture system to support hepatitis C virus (HCV) replication has hampered studies of this frequent cause of chronic liver disease. However, pseudotyped retroviral particles (pp) bearing the HCV envelope glycoproteins have provided a different approach to HCV studies. We used genotype 1a pp to detect neutralizing antibodies (NtAb) in eight chimpanzees and four humans infected with 1a strains, and developed pp of genotypes 2a, 3a, 4a, 5a, and 6a to study crossreactivity. NtAb was detected in one of four chimpanzees and none of three humans with acute resolving infection, suggesting that NtAb is not required for HCV clearance. NtAb were detected at high titer in two of four chimpanzees and, in Patient H, all with persistent infection; responses paralleled humoral responses to envelope 1 and 2 proteins and, in some cases, correlate also with antibodies to the hypervariable region 1, previously thought to be the primary site of neutralization. NtAb raised during 1a infections could neutralize HCVpp of genotypes 4a, 5a, and 6a but had only limited reactivity against 2a and 3a. The detection of high-titer NtAb with cross-genotype reactivity has important implications for the development of active and passive immune-prophylaxis strategies against HCV. Finally, we found that HCVpp infectivity was enhanced by human or chimpanzee sera; apolipoprotein C1 alone or as a component of high-density lipoproteins caused this enhancement. Future studies of the in vivo role of apolipoprotein C1 might provide additional insights into the infection process of HCV.
A pilot dose‐escalation study of the effects of nordihydroguareacetic acid on hormone and prostate specific antigen levels in patients with relapsed prostate cancer (2008)

Continuous daily dosing with NDGA is reasonably well tolerated but is associated with transaminitis in some patients, that occurs after several months on therapy. There were apparent effects on the rate of increase in PSA. Further study is required to determine the optimum pharmacokinetics and antitumour effects of this therapy.
Age-dependent resistance to Porcine reproductive and respiratory syndrome virus replication in swine (2009)

These findings show that animal age, perhaps due to increased innate immune resistance, strongly influences the outcome of acute PRRSV infection, whereas an antibody response is triggered at a low threshold of infection that is independent of age. Prolonged infection was not due to IL-10-mediated immunosuppression, and PRRSV did not elicit a specific IFN gamma response, especially in non-adult animals. Equivalent antibody responses were elicited in response to virulent and attenuated viruses, indicating that the antigenic mass necessary for an immune response is produced at a low level of infection, and is not predicted by viremic status. Thus, viral replication was occurring in lung or lymphoid tissues even though viremia was not always observed.
Triggering the Interferon Response: The Role of IRF-3 Transcription Factor (1999)

The interferon (IFN) regulatory factors (IRF) consist of a growing family of related transcription proteins first identified as regulators of the IFN-alpha/beta gene promoters, as well as the IFN-stimulated response element (ISRE) of some IFN-stimulated genes. IRF-3 was originally identified as a member of the IRF family based on homology with other IRF family members and on binding to the ISRE of the IFN-stimulated gene 15 (ISG15) promoter. Several recent studies have focused attention on the unique molecular properties of IRF-3 and its role in the regulation of IFN gene expression. IRF-3 is expressed constitutively in a variety of tissues, and the relative levels of IRF-3 mRNA do not change in virus-infected or IFN-treated cells. Following virus infection, IRF-3 is posttranslationally modified by protein phosphorylation at multiple serine and threonine residues, located in the carboxy-terminus of IRF-3. Phosphorylation causes the cytoplasmic to nuclear translocation of IRF-3, stimulation of DNA binding, and increased transcriptional activation, mediated through the association of IRF-3 with the CBP/p300 coactivator. The purpose of this review is to summarize recent investigations demonstrating the important role of IRF-3 in cytokine gene transcription. These studies provide the framework for a model in which virus-dependent phosphorylation of IRF-3 alters protein conformation to permit nuclear translocation, association with transcriptional partners, and primary activation of IFN and IFN-responsive genes.
Protein redistribution in model membranes: clearing of M13 coat protein from calcium-induced gel-phase regions in phosphatidylserine/phosphatidylcholine multilamellar vesicles (1987)

A model system of M13 bacteriophage coat protein reconstituted into multilamellar vesicles composed of phosphatidylserine (PS) and phosphatidylcholine (PC) is used to examine protein redistribution in membranes in the presence of Ca2+. The reconstitution procedure is analyzed by using protease digestion and gel permeation chromatography of radioactively labeled coat protein and is found to incorporate coat protein into lipid vesicles predominantly in the in vivo orientation and without aggregation. Quenching of protein tryptophanyl fluorescence by spin-labeled PC is used to determine the local lipid environment of the coat protein in binary lipid mixtures. The distribution of coat protein between fluid liquid-crystal (LC) and Ca2+-induced gel (G) phases in PS/PC multilayers, expressed as a concentration ratio RLC/G, is found to be 25 +/- 5 in favor of the fluid phase, indicating significant clearing of membrane protein from Ca2+-induced gel-phase regions.
Cell injury releases endogenous adjuvants that stimulate cytotoxic T cell responses (2000)

General immunostimulants (adjuvants) are essential for generating immunity to many antigens. In bacterial infections, adjuvants are provided by components of the microorganism, e.g., lipopolysaccharide. However, it is unclear what provides the adjuvant effect for immune responses that are generated to tumors and many viruses. Here we show that cell injury and death of tumor or even normal cells provide a potent adjuvant effect for the stimulation of cytotoxic T lymphocyte responses. This adjuvant activity is constitutively present in the cytoplasm of cells and is increased in the cytoplasm of cells dying by apoptosis. The release of these components stimulates immune responses both locally and at a distance, and provides a simple mechanism to alert the immune system to potential danger in almost all pathological situations.
Evidence of Infection with H4 and H11 Avian Influenza Viruses among Lebanese Chicken Growers (2011)

Human infections with H5, H7, and H9 avian influenza viruses are well documented. Exposure to poultry is the most important risk factor for humans becoming infected with these viruses. Data on human infection with other low pathogenicity avian influenza viruses is sparse but suggests that such infections may occur. Lebanon is a Mediterranean country lying under two major migratory birds flyways and is home to many wild and domestic bird species. Previous reports from this country demonstrated that low pathogenicity avian influenza viruses are in circulation but highly pathogenic H5N1 viruses were not reported. In order to study the extent of human infection with avian influenza viruses in Lebanon, we carried out a seroprevalence cross-sectional study into which 200 poultry-exposed individuals and 50 non-exposed controls were enrolled. We obtained their sera and tested it for the presence of antibodies against avian influenza viruses types H4 through H16 and used a questionnaire to collect exposure data. Our microneutralization assay results suggested that backyard poultry growers may have been previously infected with H4 and H11 avian influenza viruses. We confirmed these results by using a horse red blood cells hemagglutination inhibition assay. Our data also showed that farmers with antibodies against each virus type clustered in a small geographic area suggesting that unrecognized outbreaks among birds may have led to these human infections. In conclusion, this study suggests that occupational exposure to chicken is a risk factor for infection with avian influenza especially among backyard growers and that H4 and H11 influenza viruses may possess the ability to cross the species barrier to infect humans.
Red cell 2,3‐diphosphoglycerate and oxygen affinity (1977)

The ease with which haemoglobin releases oxygen to the tissues is controlled by erythrocytic 2,3-diphosphoglycerate (2,3-DPG) such that an increase in the concentration of 2,3-DPG decreases oxygen affinity and vice versa. This review article describes the synthesis and breakdown of 2,3-DPG in the Embden-Meyerof pathway in red cells and briefly explains the molecular basis for its effect on oxygen affinity. Interaction of the effects of pH, Pco2, temperature and 2,3-DPG on the oxyhaemoglobin dissociation curve are discussed. The role of 2,3-DPG in the intraerythrocytic adaptation to various types of hypoxaemia is described. The increased oxygen affinity of blood stored in acid-citrate-dextrose (ACD) solution has been shown to be due to the decrease in the concentration of 2,3-DPG which occurs during storage. Methods of maintaining the concentration of 2,3-DPG in stored blood are described. The clinical implication of transfusion of elderly people, anaemic or pregnant patients with ACD stored blood to anaesthetically and surgically acceptable haemoglobin concentrations are discussed. Hypophosphataemia in association with parenteral feeding reduces 2,3-DPG concentration and so increases oxygen affinity. Since post-operative use of intravenous fluids such as dextrose or dextrose/saline also lead to hypophosphataemia, the addition of inorganic phosphorus to routine post-operative intravenous fluid may be advisable. Disorders of acid-base balance effect oxygen affinity not only by the direct effect of pH on the oxyhaemoglobin dissociation curve but by its control of 2,3-DPG metabolism. Management of acid-base disorders and pre-operative aklalinization of patients with sickle cell disease whould take account of this. It is known that anaesthesia alters the position of the oxyhaemoglobin dissociation curve, but it is thought that this is independent of any effects which anaesthetic agents may have on 2,3-DPG concentration. In vitro manipulation of 2,3-DPG concentration with steroids has already been carried out. Elucidation of the role of 2,3-DPG in the control of oxygen affinity may ultimately lead to iatrogenic manipulation of oxygen affinity in vivo.
A FMCW Radar Distance Measure System based on LabVIEW (2011)

This paper presents a acquisition and process system for frequency modulation continuous wave (FMCW) radar. The procedure is designed by LabVIEW7.0. The system adopts FMCW radar sensor and high-quality data acquisition card.The intermediate frequency(IF) signal of the FMCW radar can be collected in time. The intermediate frequency, distance and velocity forward vehicle can be calculated by an improved algorithm.It can give the alarm when the collide danger is predicted, and it can assist the driver to brake control, thus some collision accidents will be avoided.The design method of the system and test data are given simultaneously. The effectiveness of the designed system is verified by some real tests.