gebhart/patrepeval huggingface dataset:
Functional bioactive recombinant acylation stimulating protein is distinct from C3a anaphylatoxin (1997)

Acylation stimulating protein (ASP) acts upon adipose tissue to stimulate triglyceride synthesis and glucose transport. The aim of the present study was to produce recombinant ASP and to measure its bioactivity. The cDNA region of the parent complement C3 sequence coding for ASP (C3adesArg) was cloned and expressed in E. coli. Bioactivity of the purified recombinant material was tested by determining its effect on triglyceride synthesis, glucose transport, and competition binding assays. In standard assays, concentrations of 5.5 microM recombinant ASP (rASP) stimulated triglyceride synthesis comparably to plasma ASP (pASP): 228% versus 237%, respectively, in 3T3 preadipocytes and 568% versus 440% in human differentiated adipocytes. rASP also increased glucose transport in L6 myocytes (163% at 10 microm rASP) and in human differentiated adipocytes (334% rASP vs. 329% pASP at 5 microM). rASP competitively displaced radiolabeled plasma ASP from high affinity association with the cell surface in both human differentiated adipocytes and 3T3 preadipocyte fibroblasts. Furthermore, immunoprecipitation of rASP and pASP with a specific monoclonal antibody abolished stimulation of cellular triglyceride synthesis. Lastly, we contrasted the structure:function activities of the arginated (C3a) and desarginated (ASP) proteins. The lipogenic activity and the anaphylatoxic activity result from distinct structural domains of the polypeptides. Thus rASP retains full biologic ASP activity and may provide a tool to study structure-function relationships in this physiologic system.
Lubricant-infused micro/nano-structured surfaces with tunable dynamic omniphobicity at high temperatures (2013)

Omniphobic surfaces that can repel fluids at temperatures higher than 100 °C are rare. Most state-of-the-art liquid-repellent materials are based on the lotus effect, where a thin air layer is maintained throughout micro/nanotextures leading to high mobility of liquids. However, such behavior eventually fails at elevated temperatures when the surface tension of test liquids decreases significantly. Here, we demonstrate a class of lubricant-infused structured surfaces that can maintain a robust omniphobic state even for low-surface-tension liquids at temperatures up to at least 200 °C. We also demonstrate how liquid mobility on such surfaces can be tuned by a factor of 1000.
Mechanisms of apoptosis avoidance in cancer (1999)

Defects in the programmed cell death mechanisms can extend cell lifespan, contributing to neoplastic cell expansion independently of cell division. Deficiencies in apoptosis also contribute to carcinogenesis by creating a permissive environment for genetic instability and accumulation of gene mutations, permitting disobeyance of cell cycle checkpoints which would normally induce apoptosis, facilitating growth factor- and hormone-independent cell survival, supporting anchorage-independent survival during metastasis, reducing dependence on oxygen and nutrients, promoting resistance to immune-based destruction, and conferring resistance to cytotoxic anticancer drugs and radiation. Though much remains to be learned, identification of gene families that control the physiological cell death pathway has provided the basis for improved understanding of tumor biology. This review describes some of the recent progress made towards delineating the biochemistry and molecular biology of apoptosis control, and briefly summarizes the progress in identifying specific road blocks to apoptosis induction in cancers. These advances are beginning to reveal novel strategies for combating cancer by restoring apoptosis sensitivity.
Thrombospondin-1 Induces Endothelial Cell Apoptosis and Inhibits Angiogenesis by Activating the Caspase Death Pathway (2000)

Thrombospondin-1 (TSP1) is a potent natural inhibitor of angiogenesis. Although TSP1 has been reported to induce endothelial cell apoptosis in vitro and to downregulate neovascularization in vivo, the molecular mechanisms that link these two processes have yet to be established. Here we report that TSP1 mediates endothelial cell apoptosis and inhibits angiogenesis in association with increased expression of Bax, decreased expression of Bcl-2, and processing of caspase-3 into smaller proapoptotic forms. The ability of TSP1 to induce both endothelial cell apoptosis in vitro and to suppress angiogenesis in vivo was blocked by the caspase-3 inhibitor z-DEVD-FMK. TSP1 also attenuated VEGF-mediated Bcl-2 expression in endothelial cells in vitro and angiogenesis in vivo. Furthermore, TSP1 induced endothelial cell apoptosis and inhibited neovascularization in sponge implants in SCID mice. We conclude that TSP1 induces endothelial cell apoptosis and inhibits neovascularization by altering the profile of survival gene expression and activating caspase-3.
Long-term outcome in relation to renal sympathetic activity in patients with chronic heart failure (2005)

&lt;B&gt;Aims&lt;/B&gt; Although cardiac sympathetic activation is associated with adverse outcome in patients with chronic heart failure (CHF), the influence of renal sympathetic activity on outcome is unknown. We assessed the hypothesis that renal noradrenaline (NA) spillover is a predictor of the combined endpoint of all-cause mortality and heart transplantation in CHF. &lt;B&gt;Methods and results&lt;/B&gt; Sixty-one patients with CHF, New York Heart Association (NYHA) I-IV (66% NYHA III-IV), and left ventricular ejection fraction (LVEF) 26±9% (mean ± SD) were studied with cardiac and renal catheterizations at baseline and followed for 5.5 ± 3.7 years (median 5.5 years, range 12 days to 11.6 years). Nineteen deaths and 13 cases of heart transplantation were registered. Only renal NA spillover above median, 1.19 (interquartile range 0.77-1.43) nmol/min, was independently associated with an increased relative risk (RR) of the combined endpoint (RR 3.1, 95% CI 1.2-7.6, &lt;I&gt;P&lt;/I&gt; = 0.01) in a model also including total body NA spillover, LVEF, glomerular filtration rate (GFR), renal blood flow, cardiac index, aetiology, and age. &lt;B&gt;Conclusion&lt;/B&gt; Renal noradrenergic activation has a strong negative predictive value on outcome independent of overall sympathetic activity, GFR, and LVEF. These findings suggest that treatment regimens that further reduce renal noradrenergic stimulation could be advantageous by improving survival in patients with CHF.
Amyotrophic lateral sclerosis: Part 1. Clinical features, pathology, and ethical issues in management (1985)

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease of the motor system in adults that occurs in sporadic, familial, and Western Pacific forms. Involvement of non-motor pathways has been increasingly recognized, both clinically and pathologically. Although the usual course is relentlessly progressive with death in half the cases within three years from onset, it can sometimes be protracted. Degeneration and loss of large motor neurons in the cerebral cortex, brainstem, and cervical and lumbar spinal cord are characteristic. Marked reduction in the number of large myelinated fibers is notable in the cervical and lumbar ventral roots. Peripheral nerves show reduced numbers of large myelinated fibers, acute axonal degeneration at all levels, and distal axonal atrophy. Motor end-plates reveal small or absent nerve terminals. Subclinical non-motor system involvement includes neuronal loss in Clarke's nucleus and dorsal root ganglia, degeneration of non-motor tracts in the spinal cord, loss of receptors in the dorsal horns of the spinal cord, and myelinated fiber loss with segmental demyelination in sensory and mixed nerves. The serious implications of the diagnosis of ALS make it mandatory to exclude similar potentially treatable disorders. Management should be multidisciplinary, and discussions with the patient and family members should be frank and frequent. Discussions about ventilatory support should take place early in the disease so that death from respiratory failure can be prevented, when that is desired, and conversely to obviate the discontent and anger that accompany involuntary life on a ventilator.
Randomised controlled trial of CRP rapid test as a guide to treatment of respiratory infections in general practice (2000)

Based on the present study, the use of the CRP rapid test in support of a possible antibiotic treatment for respiratory infections in general practice cannot be recommended.
Salvage of myocardial function by coronary artery reperfusion 1, 2, and 3 hours after occlusion in conscious dogs. (1983)

The effects of coronary artery occlusion and reperfusion at 1 hour (1-hr group), 2 hours (2-hr group), and 3 hours (3-hr group) were compared with a permanently occluded group (P group) on measurements of overall left ventricular and regional endocardial function over a 4-week period. The studies were conducted in conscious dogs 1-2 weeks after recovery from instrumentation with solid state left ventricular pressure gauges, aortic, and left atrial catheters, hydraulic occluders, and Doppler flow transducers on the left anterior descending or left circumflex coronary arteries, and multiple pairs of ultrasonic transducers implanted in the endocardial third of the left ventricular free wall to measure endocardial segment shortening. During coronary artery occlusion, similar effects were observed in the four groups. At 1 hour after coronary artery occlusion, three classes of ischemia-induced dysfunction were observed; dyskinetic (systolic shortening completely lost and replaced by paradoxical bulging), severely hypokinetic (systolic shortening depressed by 65-95%), and moderately hypokinetic (systolic shortening depressed by 40-65%). Compared with the P group, significant (P less than 0.05) return of systolic shortening and velocity of shortening gradually occurred over the 4-week period following reperfusion in all classes of segments in the 1-hour group. In the 2-hour group, systolic shortening returned in the moderately and severely hypokinetic segments, but was slight and not significant in the dyskinetic segments. In the 3-hour group, significant systolic shortening returned only in the moderately hypokinetic segments. The effects of isoproterenol, 0.04 micrograms/kg per min, and exercise were compared on "salvaged" dyskinetic segments prior to and at 1, 2, 3, and 4 weeks after coronary artery occlusion and reperfusion. The responses to isoproterenol were significantly depressed at 1 week after reperfusion and gradually recovered over the 4-week period. At 3-4 weeks after reperfusion, severe exercise also increased shortening and velocity of shortening in "salvaged" segments. Thus, in the conscious dog, coronary artery reperfusion at 1 hour after coronary artery occlusion results in substantial return of endocardial function even in the most severely ischemic myocardium. The "salvaged" myocardium responds adequately to myocardial stress with increases in the extent and velocity of systolic shortening, as long as 3-4 weeks after reperfusion are allowed for recovery. However, after 3 hours of coronary artery occlusion, little salvage of regional myocardial function can be induced by acute reperfusion in this model.
Seroepidemiology for MERS coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in Egypt, June 2013 (2013)

We describe a novel spike pseudoparticle neutralisation assay (ppNT) for seroepidemiological studies on Middle East respiratory syndrome coronavirus (MERSCoV) and apply this assay together with conventional microneutralisation (MN) tests to investigate 1,343 human and 625 animal sera. The sera were collected in Egypt as a region adjacent to areas where MERS has been described, and in Hong Kong, China as a control region. Sera from dromedary camels had a high prevalence of antibody reactive to MERS-CoV by MERS NT (93.6%) and MERS ppNT (98.2%) assay. The antibody titres ranged up to 1,280 and higher in MN assays and 10,240 and higher in ppNT assays. No other investigated species had any antibody reactivity to MERS-CoV. While seropositivity does not exclude the possibility of infection with a closely related virus, our data highlight the need to attempt detection of MERSCoV or related coronaviruses in dromedary camels. The data show excellent correlation between the conventional MN assay and the novel ppNT assay. The newly developed ppNT assay does not require Biosafety Level 3 containment and is thus a relatively high-throughput assay, well suited for large-scale seroepidemiology studies which are needed to better understand the ecology and epidemiology of MERS-CoV.
Characterization of IL-6 receptor expression by monoclonal and polyclonal antibodies. (1989)

mAb and polyclonal antibodies against human IL-6R were prepared by using a murine transfectant cell line expressing the human IL-6R and a synthetic oligopeptide made on the basis of the deduced amino acid sequence as immunogens. Immunoprecipitation of radiolabeled IL-6R with these antibodies showed that the Mr of a mature IL-6R was 80 kDa and its value was reduced to 50K after treatment with O- and N-glycanase and neuraminidase, indicating that IL-6R is a glycoprotein. Two mAb recognizing different epitopes were prepared. One, PM1 inhibited the binding of 125I-IL-6 to the receptor and blocked the IL-6-dependent growth of a T lymphoma line, KT3. PM1 could not bind to IL-6R when it was saturated with IL-6, indicating that this antibody recognizes the IL-6 binding or the adjacent site on IL-6R. The other, MT18 was not inhibited by IL-6 for its recognition of IL-6R, therefore, this could be used for cytofluorometric staining of normal cells. Nonstimulated B cells expressed undetectable amount of IL-6R regardless of the expression of surface IgD. However, after the stimulation with PWM, IL-6R was observed on IgD- B cells with a relatively large size, but subtly on IgD- small B cells and not on IgD+ B cells, fitting the function of IL-6 which acts on activated B cells to induce Ig production. In contrast, IL-6R was detected on non-stimulated CD4+/CD8- and CD4-/CD8+ T cells. The level of IL-6R on both T cell subpopulations was not significantly changed after stimulation with phytohemagglutinin.
STUDIES ON THE TRANSMISSION OF HUMAN VIRAL HEPATITIS TO MARMOSET MONKEYS (1967)

Inoculation of human serums or plasmas obtained during the early acute phase of viral hepatitis induced chemical and morphological hepatic disease in marmosets in two out of five experimental series. The disease was transmissible in series from marmoset to marmoset with an apparent increased virulence of the causative agent in later marmoset passages. The chemical evidence for the disease was elevation of the activity of SGOT and SICD and of serum bilirubin. In serial liver biopsy specimens interpreted under code, a hepatitis, exhibiting some of the characteristics of human viral hepatitis, was readily distinguishable from nonspecific changes. The morphological changes preceded the biochemical alterations and persisted after them. The data reported in these studies indicate that marmosets may be susceptible to human hepatitis. If these observations are confirmed, these animals may provide good experimental models for this disease. Final proof that the hepatitis observed in marmosets is caused by agents of human viral hepatitis is still lacking.
Retrovirus Vectors: Promise and Reality (1989)

Article de synthese sur les avantages et desavantages des retrovirus comme vecteurs de transfert de DNA
Preparation of 4-Retinamidophenyl- and 4-Retinamidobenzyl-C-glycosyl and C-Glucuronosyl Analogues of the Glucuronide of 4-Hydroxyphenyl-Retinamide as Potential Stable Cancer Chemopreventive Agents (1994)

Abstract Glucuronide metabolites of retinoic acid and its analogues have been suggested to be active cancer chemopreventive analogues of the parent molecules. However, these metabolites are susceptible to β-glucuronidase and acid-catalyzed cleavage and it is not clear whether these carbohydrate conjugates must be hydrolyzed back to the parent molecule to show activity. Thus, the multistep syntheses of stable C-glycosyl and C-glucuronosyl analogues of the known glucuronide metabolite of the breast cancer chemopreventive agent 4-hydroxyphenylretinamide (4-HPR) are outlined. The chemical and enzymatic stability of these compounds has been evaluated relative to the glucuronide of 4-HPR.
Detection of in vivo-induced IL-1 mRNA in murine cells by flow cytometry (FC) and fluorescent in situ hybridization (FISH). (1992)

Flow cytometry (FC) and fluorescent in situ hybridization (FISH) were used to detect in vivo induced IL-1 alpha (a) messenger RNA. Spleen cells and thioglycollate-induced peritoneal exudate cells (PEC) were harvested from Balb/C mice three hours after intraperitoneal injection of 20 micrograms LPS. Cells from each population were phenotyped for MAC or IAd, fixed in 4% paraformaldehyde and then permeabilized with 70% ETOH. RNA-RNA FISH was performed by incubating suspended cells at 37 degrees C for 17 hours with biotinylated sense IL-1a, antisense IL-1a or antisense IL-2 probes in 50% formamide. Hybridized cells were washed in 2X SSC, treated with RNAse, stained with avidin conjugated to fluorescein (FITC) or allophycocyanin (APC) and analyzed immediately by FC. Initially, avidin-FITC was used to detect hybridized probe. Dual fluorescent FC analysis of IL-1a mRNA expression in LPS stimulated IAd+ cells showed an increase in mean fluorescent intensity (MFI) of 51 log channels (0.25 logs) when compared to unstimulated cells. Additionally, induction of specific IL-1a mRNA expression in cells from LPS treated animals was illustrated by increases in percent positive cells (24%) and in equivalent soluble fluorescein molecules (ESFM) bound (47%) when compared to cells from vehicle treated mice. Unhybridized cells and cells hybridized with control antisense IL-2 probe did not exhibit increases in MFI or ESFM. In subsequent experiments on MAC+ PEC, the use of avidin-APC to detect bound probe resulted in a greater separation between the FISH signals of antisense IL-1a and control sense probe (121 log channels, 0.6 logs) than that seen with FITC.(ABSTRACT TRUNCATED AT 250 WORDS)
Identification and localization of the gene for EXTL, a third member of the multiple exostoses gene family. (1997)

Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by multiple bony outgrowths from the juxtaepiphyseal region of long bones. In a small proportion of cases, these exostoses progress to malignant chondrosarcomas. Genetic linkage of this disorder has been described to three independent loci on chromosomes 8q24.1 (EXT1), 11p11-13 (EXT2), and 19p (EXT-3). The EXT1 and EXT2 genes were isolated recently and show extensive sequence homology to each other. These genes are deleted in exostoses-derived tumors, supporting the hypothesis that they encode tumor suppressors. We have identified a third gene that shows striking sequence similarity to both EXT1 and EXT2 at the nucleotide and amino acid sequence levels, and have derived its entire coding sequence. Although the mRNA transcribed from this gene is similar in size to that from EXT1 and EXT2, its pattern of expression is quite different. We have localized this gene by fluorescence in situ hybridization to metaphase chromosomes and by whole genome radiation hybrid mapping to chromosome 1p36.1 between DIS458 and DIS511, region that frequently shows loss of heterozygosity in a variety of tumor types. This gene, EXTL (for EXT-like), is therefore a new member of the EXT gene family and is a potential candidate for several disease phenotypes.
Effectiveness of Transmucosal Sedation for Special Needs Populations in the Ambulatory Care Setting (2014)

Transmucosal is an alternative route for administering medications (ie, dexmedetomidine, midazolam, naloxone) that can be effective for procedural or moderate sedation in patients with special needs when other routes are not practical or are contraindicated. Special needs populations include children, older adults, pregnant and breast-feeding women, and people with disabilities or conditions that limit their ability to function and cope. Understanding the perioperative nurse's role in the care of patients receiving medications via the transmucosal route can lead to better clinical outcomes. Successful use of the transmucosal route requires knowledge of when to administer a medication, how often and how much of a medication should be administered, the onset and duration of action, the adverse effects or contraindications, and the key benefits. In addition, a case study approach suggests that transmucosal sedation can decrease patient stress and anxiety related to undergoing medical procedures or surgery in the ambulatory care setting.
Promising Role of Engineered Gene Circuits in Gene Therapy (2011)

Synthetic biology is concerned with applying the engineering paradigm of systems design to biological systems in order to produce predictable and robust systems with novel functionalities that do not exist in nature. The circuit-like connectivity of biological parts and their ability to collectively process logical operations was first appreciated nearly 50 years ago. This inspired attempts to describe biological regulation schemes with mathematical models and to apply circuit analogies from established frameworks in electrical engineering(McAdams & Arkin A,2000). Meanwhile, breakthroughs in genomic research and genetic engineering (e.g., recombinant DNA technology) were supplying the inventory and methods necessary to physically construct and assemble biomolecular parts. As a result, synthetic biology was born with the broad goal of engineering or “wiring” biological circuitry—be it genetic, protein, viral, pathway, or genomic—for manifesting logical forms of cellular control. Synthetic biology, equipped with the engineering-driven approaches of modularization, rationalization, and modeling, has progressed rapidly and generated an ever-increasing suite of genetic devices and biological modules. synthetic biology is seeking to use and expand the mechanisms that control biological organisms using engineering approaches. These approaches will be applied on all scales of biological complexity: from the basic units to novel interactions between these units to novel multi-component modules that generate complex logical behaviour, and even to completely or partially engineered cells(McAdams & Shapiro,1995). Bringing the engineering paradigm to biology will allow us to apply existing biological knowledge to biotechnological problems in a much more rational and systematic way than has previously been possible, and at the same time to expand the scope of what can be achieved this way. The introduction of design principles such as modularity of parts, standardization of parts and devices according to internationally recognized criteria, and the adaptation of available abstract design procedures to biological systems, coupled to novel technological breakthroughs that allow the decoupling of design and fabrication, will fundamentally change our current concepts of how to manipulate biological systems. In this sense, synthetic biology is not primarily a “discovery science”, but is ultimately about a new way of making things. By adapting natural biological mechanisms to the requirements of an engineering approach, the possibilities for re-assembling biological systems in a designed way will increase tremendously. While several of the fundamental scientific issues and current applied objectives of synthetic biology overlap with those in other, more mature fields, especially