gebhart/patrepeval huggingface dataset:
[Structure and function of melatonin receptors]. (1998)

Melatonin receptors belong to the super-family of G protein-coupled receptors. They modulate a large spectrum of physiological functions including regulation of circadian rhythms and seasonal reproduction. Pharmacological evidence suggests the expression of two types of receptors, called Mel1 and Mel2. So far, only Mel1 receptors have been cloned and classified into three subtypes (Mel1A, Mel1B, Mel1C). Mel1 receptors are expressed in the brain, the retina and several other peripheral tissues. All Mel1 subtypes show comparable pharmacological profiles including inhibition of adenylyl cyclase. Cloning and expression of two allelic isoforms of the Mel1 receptor from Xenopus laevis has revealed another signalling pathway, inhibition of cGMP levels via the soluble guanylyl cyclase pathway. The two isoforms are differentially coupled to the cAMP and cGMP pathways indicating the existence of functional differences between melatonin receptors. Future research topics will include cloning of the Mel2 receptor, receptor regulation and the elucidation of melatonin receptor's function in peripheral tissues.
Elusive HIV-Suppressor Factors Found (1995)

Rome—A team of U.S. and Italian researchers led by Robert Gallo and Paolo Lusso appear to have solved a longstanding mystery in AIDS research. They have identified three previously known immune system molecules that suppress the replication of the AIDS virus, HIV. Researchers had been trying to identify these so-called suppressor factors since they were first postulated by AIDS researcher Jay Levy 6 years ago. Science will be publishing a paper describing this finding in the 15 December issue. The news embargo on the research was lifted a week early to coincide with publication by Nature of a letter by Reinhard Kurth and colleagues, announcing the discovery of a different factor that may also play a role in HIV suppression
Ensemble Methods: Foundations and Algorithms (2012)

An up-to-date, self-contained introduction to a state-of-the-art machine learning approach, Ensemble Methods: Foundations and Algorithms shows how these accurate methods are used in real-world tasks. It gives you the necessary groundwork to carry out further research in this evolving field. After presenting background and terminology, the book covers the main algorithms and theories, including Boosting, Bagging, Random Forest, averaging and voting schemes, the Stacking method, mixture of experts, and diversity measures. It also discusses multiclass extension, noise tolerance, error-ambiguity a
The Attenuation Of Poliovirus Neurovirulence (1987)

Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and ...Read More
Morphologic edge detection (1987)

Edge operators based on gray-scale morphologic operations are introduced. These operators can be efficiently implemented in near real time machine vision systems which have special hardware support for gray-scale morphologic operations. The simplest morphologic edge detectors are the dilation residue and erosion residue operators. The underlying motivation for these and some of their combinations are discussed and justified. Finally, the blur-minimum morphologic edge operator is defined. Its inherent noise sensitivity is less than the dilation or the erosion residue operators. Some experimental results are provided to show the validity of these morphologic operators. When compared with the enhancement/thresholding edge detectors and the cubic facet second derivative zero-crossing edge operator, the results show that all the edge operators have similar performance when the noise is small. However, as the noise increases, the second derivative zero-crossing edge operator and the blur-minimum morphologic edge operator have much better performance than the rest of the operators. The advantage of the blur-minimum edge operator is that it is less computationally complex than the facet edge operator.
Trichomonas vaginalisLipophosphoglycan Triggers a Selective Upregulation of Cytokines by Human Female Reproductive Tract Epithelial Cells (2006)

Trichomonas vaginalis is one of the most common nonviral sexually transmitted human infections and, worldwide, has been linked to increased incidence of human immunodeficiency virus type 1 transmission, preterm delivery, low birth weight, cervical cancer, and vaginitis. The molecular pathways that are important in initiating host inflammatory and immune responses to T. vaginalis are poorly understood. Here we report interactions of human cervicovaginal epithelial cells with the most abundant cell surface glycoconjugate of the parasite, the T. vaginalis lipophosphoglycan (LPG). Purified LPG mediated the adhesion of parasites to human vaginal epithelial cells in a dose-dependent manner. Furthermore, T. vaginalis LPG (but not LPG from Tritrichomonas foetus, the causative agent of bovine trichomoniasis) induced a selective upregulation of chemotactic cytokines by human endocervical, ectocervical, and vaginal epithelial cells, which do not express Toll-like receptor 4/MD2. The T. vaginalis LPG triggered interleukin 8 (IL-8), which promotes the adhesion and transmigration of neutrophils across the endothelium, and macrophage inflammatory protein 3alpha, which is a chemoattractant for immune cells and is essential for dendritic cell maturation. These effects were dose dependent and sustained in the absence of cytotoxicity and IL-1beta release and utilized, at least in part, a signaling pathway independent from the Toll-like/IL-1 receptor adaptor protein MyD88.
Activation of pyruvate dehydrogenase in perfused rat heart by dichloroacetate (Short Communication) (1973)

The activity of pyruvate dehydrogenase was assayed in extracts of rat hearts perfused in vitro with media containing glucose and insulin+/-acetate+/-dichloroacetate. Dichloroacetate (100mum, 1mm or 10mm) increased the activity of pyruvate dehydrogenase in perfusions with glucose or glucose+acetate. Evidence is given that dichloroacetate may facilitate the conversion of pyruvate dehydrogenase from an inactive (phosphorylated) form into an active (dephosphorylated) form.
Identification of daptomycin-binding proteins in the membrane of Enterococcus hirae (1995)

Daptomycin, a lipopeptide antibiotic active against gram-positive bacteria, was preliminarily shown to inhibit lipoteichoic acid (LTA) synthesis as a consequence of membrane binding in the presence of Ca2+ (P. Canepari, M. Boaretti, M. M. Lleó, and G. Satta, Antimicrob. Agents Chemother. 34:1220-1226, 1990). In the present study, it is shown that, along with binding bacterial-membrane components, daptomycin binds the protein fraction with a noncovalent bond, as suggested by the instability of the bond in the presence of ionic detergents such as sodium dodecyl sulfate. Analysis of membrane proteins by isoelectric focusing electrophoresis reveals that five bands with isoelectric points ranging from 5.9 to 6.2 bind radioactive daptomycin. These proteins are therefore called daptomycin-binding proteins. In an attempt to correlate these proteins to the main inhibition observed during LTA synthesis, two-dimensional thin-layer chromatography of lipids synthesized during daptomycin treatment was performed. A threefold increase in diglucosyl diacylglycerol is demonstrated, while the compounds phosphatidyl-alpha-kojibiosyldiacylglycerol, glycerophospho-phosphatidyl-alpha-kojibiosyldiacylglycerol, and glycerophospho-kojibiosyldiacylglycerol, which follow diglucosyl diacylglycerol in LTA synthesis, decrease progressively with time during the course of daptomycin treatment.
Characterization of Dietary Energy in Swine Feed and Feed Ingredients: A Review of Recent Research Results (2014)

Feed is single most expensive input in commercial pork production representing more than 50% of the total cost of production. The greatest proportion of this cost is associated with the energy component, thus making energy the most important dietary in terms of cost. For efficient pork production, it is imperative that diets are formulated to accurately match dietary energy supply to requirements for maintenance and productive functions. To achieve this goal, it is critical that the energy value of feeds is precisely determined and that the energy system that best meets the energy needs of a pig is used. Therefore, the present review focuses on dietary supply and needs for pigs and the available energy systems for formulating swine diets with particular emphasis on the net energy system. In addition to providing a more accurate estimate of the energy available to the animal in an ingredient and the subsequent diet, diets formulated using the this system are typically lower in crude protein, which leads to additional benefits in terms of reduced nitrogen excretion and consequent environmental pollution. Furthermore, using the net energy system may reduce diet cost as it allows for increased use of feedstuffs containing fibre in place of feedstuffs containing starch. A brief review of the use of distiller dried grains with solubles in swine diets as an energy source is included.
Western immunoblot and flagellum enzyme-linked immunosorbent assay for serodiagnosis of Lyme borreliosis (1990)

Western immunoblot with a whole-cell lysate was compared with an enzyme-linked immunosorbent assay with a purified flagellum antigen of Borrelia burgdorferi for serodiagnosis of Lyme borreliosis. The assays showed similar sensitivities and specificities in detecting immunoglobulin M and/or immunoglobulin G antibodies in sera from 68 patients with neuroborreliosis and 44 controls with meningitis and encephalitis or with multiple sclerosis. Flagellum enzyme-linked immunosorbent assay is more easily standardized and seems to be a more suitable diagnostic test in a routine laboratory.
Novel Lipid Mediators Promote Resolution of Acute Inflammation (2010)

The resolution of acute inflammation is a process that allows for inflamed tissues to return to homeostasis. Resolution was held to be a passive process, a concept now overturned with new evidence demonstrating that resolution is actively orchestrated by distinct cellular events and endogenous chemical mediators. Among these, lipid mediators, such as the lipoxins, resolvins, protectins, and newly identified maresins, have emerged as a novel genus of potent and stereoselective players that counter-regulate excessive acute inflammation and stimulate molecular and cellular events that define resolution. Given that uncontrolled, chronic inflammation is associated with many cardiovascular pathologies, an appreciation of the endogenous pathways and mediators that control timely resolution can open new terrain for therapeutic approaches targeted at stimulating resolution of local inflammation, as well as correcting the impact of chronic inflammation in cardiovascular disorders. Here, we overview and update the biosynthesis and actions of proresolving lipid mediators, highlighting their diverse protective roles relevant to vascular systems and their relation to aspirin and statin therapies.
The Effect of Antihistamines on the Immediate Allergic Response: A Comparative Review (1993)

Antihistamines are believed to reduce the sneezing and rhinorrhea associated with allergic rhinitis, primarily by competitive antagonism of histamine for H1 cellular receptors, but additional mechanisms of action may contribute to their clinical efficacy. To improve our understanding of H1 antihistamine action, we studied the effects of pretreatment with terfenadine, cetirizine, ketotifen, azatadine, diphenhydramine, and azelastine on increases in vascular permeability, mast cell activation, and sneezing induced by nasal challenge with antigen. All studied antihistamines reduced sneezing, indicating that they all effectively antagonize histamine after its release. In addition, terfenadine and topically administered azatadine blocked the release of histamine. Studies with cetirizine and azelastine revealed that these antihistamines significantly reduced sulfidopeptide leukotriene levels. Terfenadine and azelastine also reduced kinin production. These results confirm that antihistamines are effective in reducing sneezing and, in some cases, vascular permeability. The findings of these studies also illustrate that the various antihistamines have multiple and different mechanisms of action that may have implications for their clinical uses.
Genetic Mutations Associated with Cigarette Smoking in Pancreatic Cancer (2009)

Cigarette smoking doubles the risk of pancreatic cancer, and smoking accounts for 20% to 25% of pancreatic cancers. The recent sequencing of the pancreatic cancer genome provides an unprecedented opportunity to identify mutational patterns associated with smoking. We previously sequenced >750 million bp DNA from 23,219 transcripts in 24 adenocarcinomas of the pancreas (discovery screen). In this previous study, the 39 genes that were mutated more than once in the discovery screen were sequenced in an additional 90 adenocarcinomas of the pancreas (validation screen). Here, we compared the somatic mutations in the cancers obtained from individuals who ever smoked cigarettes (n = 64) to the somatic mutations in the cancers obtained from individuals who never smoked cigarettes (n = 50). When adjusted for age and gender, analyses of the discovery screen revealed significantly more nonsynonymous mutations in the carcinomas obtained from ever smokers (mean, 53.1 mutations per tumor; SD, 27.9) than in the carcinomas obtained from never smokers (mean, 38.5; SD, 11.1; P = 0.04). The difference between smokers and nonsmokers was not driven by mutations in known driver genes in pancreatic cancer (KRAS, TP53, CDKN2A/p16, and SMAD4), but instead was predominantly observed in genes mutated at lower frequency. No differences were observed in mutations in carcinomas from the head versus tail of the gland. Pancreatic carcinomas from cigarette smokers harbor more mutations than do carcinomas from never smokers. The types and patterns of these mutations provide insight into the mechanisms by which cigarette smoking causes pancreatic cancer.
Synthesis, biophysical properties, and nuclease resistance properties of mixed backbone oligodeoxynucleotides containing cationic internucleoside guanidinium linkages: Deoxynucleic guanidine/DNA chimeras (1998)

The synthesis of mixed backbone oligodeoxynucleotides (18-mers) consisting of positively charged guanidinium linkages along with negatively charged phosphodiester linkages is carried out. The use of a base labile-protecting group for guanidinium linkage offers a synthetic strategy similar to standard oligonucleotide synthesis. The nuclease resistance of the oligodeoxyribonucleotides capped with guanidinium linkages at 5' and 3' ends are reported. The hybridization properties and sequence specificity of binding of these deoxynucleic guanidine/DNA chimeras with complementary DNA or RNA are described.
Recent progress in migraine pathophysiology: role of cortical spreading depression and magnetic resonance imaging (2013)

Migraine is characterised by debilitating pain, which affects the quality of life in affected patients in both the western and the eastern worlds. The purpose of this article is to give a detailed outline of the pathophysiology of migraine pain, which is one of the most confounding pathologies among pain disorders in clinical conditions. We critically evaluate the scientific basis of various theories concerning migraine pathophysiology, and draw insights from brain imaging approaches that have unraveled the prevalence of cortical spreading depression (CSD) in migraine. The findings supporting the role of CSD as a physiological substrate in clinical pain are discussed. We also give an exhaustive overview of brain imaging approaches that have been employed to solve the genesis of migraine pain, and its possible links to the brainstem, the neocortex, genetic endophenotypes, and pathogenetic factors (such as dopaminergic hypersensitivity). Furthermore, a roadmap is proposed to provide a better understanding of pain pathophysiology in migraine, to enable the development of strategies using leads from brain imaging studies for the identification of early biomarkers, efficient prognosis, and treatment planning, which eventually may help in alleviating some of the devastating impact of pain morbidity in patients afflicted with migraine.
Liposomal Irinotecan Achieves Significant Survival and Tumor Burden Control in a Triple Negative Breast Cancer Model of Spontaneous Metastasis (2018)

Triple negative breast cancer (TNBC) represents a significant therapeutic challenge due to its highly aggressive nature and lack of effective treatment options. Liposomal irinotecan (nal-IRI, ONIVYDE) was approved in 2015 (by the Food and Drug Administration, European Medicines Agency, and Therapeutic Goods Administration) and is a topoisomerase inhibitor indicated, in combination with fluorouracil and leucovorin, for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy. This study investigates the potential therapeutic benefit of nal-IRI for the treatment of advanced TNBC in a clinically relevant mouse model of spontaneous metastasis (LM2-4). Female SCID mice were orthotopically inoculated with TNBC LM2-4-luc cells in the lower mammary fat pad. Following primary tumor resection, bioluminescence imaging (BLI) was used to monitor both metastasis formation and spread as well as response to treatment with nal-IRI. Weekly treatment with 10 mg/kg of nal-IRI provided a 4.9-times longer median survival compared to both 50 mg/kg irinotecan treated and untreated animals. The survival benefit was supported by a significant delay in the regrowth of the primary tumor, effective control, and eventual regression of metastases assessed using longitudinal BLI, which was confirmed at the study end point with magnetic resonance (MR) imaging and post-mortem observation. This preclinical investigation demonstrates that, at a five-times lower dose compared to the free drug, liposomal irinotecan provides significant survival benefit and effective management of metastatic disease burden in a clinically relevant model of spontaneous TNBC metastases. These findings support the evaluation of nal-IRI in patients with advanced and metastatic TNBC.
Rapid Development of a Potent Photo‐triggered Inhibitor of the Serine Hydrolase RBBP9 (2012)

The serine hydrolases constitute a large class of enzymes that play important roles in physiology. There is great interest in the development of potent and selective pharmacological inhibitors of these proteins. Traditional active-site inhibitors often have limited selectivity within this superfamily and are tedious and expensive to discover. Using the serine hydrolase RBBP9 as a model target, we designed a rapid and relatively inexpensive route to highly selective peptoid-based inhibitors that can be activated by visible light. This technology provides rapid access to photo-activated tool compounds capable of selectively blocking the function of particular serine hydrolases.
Pediatric Cystic Fibrosis Sputum Can Be Chemically Dynamic, Anoxic, and Extremely Reduced Due to Hydrogen Sulfide Formation (2015)

Microbial infections are the major cause of morbidity and mortality in people living with CF, and yet microbial growth and survival in CF airways are not well understood. Insufficient information about the chemistry of the in vivo environment contributes to this knowledge gap. Our documentation of variable redox states corresponding to the presence or absence of sulfide begins to fill this void and motivates understanding of how different opportunistic pathogens adapt in these dynamic environments. Given the changing chemical state of CF sputum over time, it is important to consider a spectrum of aerobic and anaerobic lifestyles when studying CF pathogens in the laboratory. This work not only provides relevant constraints that can shape the design of laboratory experiments, it also suggests that sulfide might be a useful proxy for assessing the redox state of sputum in the clinic.
Rapid-Cycling Populations of Brassica (1986)

Rapid-cycling populations of six economically important species in the genus Brassica have unusual potential for resolving many problems in plant biology and for use in education. Rapid-cycling brassicas can produce up to ten generations of seed per year and serve as models for research in genetics, host-parasite relations, molecular biology, cell biology, plant biochemistry, population biology, and plant breeding. Brassicas are a highly diverse group of crop plants that have great economic value as vegetables and as sources of condiment mustard, edible and industrial oil, animal fodder, and green manure. These plants can also be used in the classroom as convenient, rapidly responding, living plant materials for "hands on" learning at all levels of our educational system.
Cannabidiol prevents infarction via the non-CB1 cannabinoid receptor mechanism (2004)

Cannabidiol, a non-psychoactive constituent of cannabis, has been reported as a neuroprotectant. Cannabidiol and Delta(9)-tetrahydrocannabinol, the primary psychoactive constituent of cannabis, significantly decreased the infarct volume at 4 h in the mouse middle cerebral artery occlusion model. The neuroprotective effects of Delta(9)-tetrahydrocannabinol but not cannabidiol were inhibited by SR141716, a cannabinoid CB1 receptor antagonist, and were abolished by warming of the animals to the levels observed in the controls. Delta(9)-Tetrahydrocannabinol significantly decreased the rectal temperature, and the hypothermic effect was inhibited by SR141716. These results surely show that the neuroprotective effect of Delta(9)-tetrahydrocannabinol are via a CB1 receptor and temperature-dependent mechanisms whereas the neuroprotective effects of cannabidiol are independent of CB1 blockade and of hypothermia.
Identification and determination of phenylacetylglutamine, a major nitrogenous metabolite in plasma of uremic patients. (1989)

Phenylacetylglutamine, a constituent of normal urine, was identified and quantitated in plasma ultrafiltrates from uremic patients. Its concentration ranged from 18 to 366 mumol/l, which shows a greater individual variation than those for the concentrations of urea and creatinine. The plasma level was reduced by hemodialysis. In ultrafiltrates from healthy subjects phenylacetylglutamine could not be detected with the methods used. Thus, it is a major nitrogenous metabolite that accumulates in uremia. A reverse phase HPLC method for the quantitative determination of phenylacetylglutamine in plasma ultrafiltrates is described.