gebhart/patrepeval huggingface dataset:
Medicinal chemistry and therapeutic potential of muscarinic M3 antagonists (2009)

Muscarinic acetylcholine receptors belong to the G-protein-coupled receptors family. Currently five different receptor subtypes have been identified and cloned. M3 receptor subtypes are coupled to G(q) family proteins and increase phosphatidyl inositol hydrolysis and calcium release from internal stores. They are widely distributed both in the central nervous system and in the periphery. At the central level, M3 receptor subtypes are involved in modulation of neurotransmitter release, temperature homeostasis, and food intake, while in the periphery they induce smooth muscle contraction, gland secretion, indirect relaxation of vascular smooth muscle, and miosis. The main therapeutic applications of M3 antagonists include overactive bladder (OAB), chronic obstructive pulmonary disease (COPD), and pain-predominant irritable bowel syndrome (IBS). The introduction of selective M3 antagonists has not improved clinical efficacy compared with the old non-selective antimuscarinics but has reduced the rate of adverse events mediated by the blockade of cardiac M2 receptors (tachycardia) and central M1 receptors (cognitive impairment). Improved tolerability has been obtained also with controlled release or with inhaled formulations. However, there is still a need for safer M3 antagonists for the treatment of COPD and better-tolerated and more effective compounds for the therapy of OAB. New selective muscarinic M3 antagonists currently in early discovery and under development have been designed to address these issues. However, as M3 receptors are widely located in various tissues including salivary glands, gut smooth muscles, iris, and ciliary muscles, further clinical improvements may derive from the discovery and the development of new compounds with tissue rather than muscarinic receptor subtype selectivity.
CEACAM1 Expression in Cutaneous Malignant Melanoma Predicts the Development of Metastatic Disease (2002)

Expression of the cell adhesion molecule CEACAM1 in the primary tumors in melanoma patients is associated with the subsequent development of metastatic disease. This raises the possibility of a functional role for this cell adhesion molecule in the metastatic spread it indicates.
Clinical management of hypophosphatasia (2015)

HPP is a rare disease that manifests in different ways across the life course. Accurate diagnosis depends upon the use of appropriate age-related normative data. A new therapy is undergoing clinical trials; the preliminary published data is encouraging, but the scope of clinical application remains to be determined.
Levodopa for idiopathic restless legs syndrome: Evidence‐based review (2007)

Restless legs syndrome (RLS) is a sensory motor disorder characterized by a distressing urge to move the legs and sometimes also other parts of the body usually accompanied by a marked sense of discomfort or pain in the leg or other affected body part. The prevalence of RLS is estimated at 2.7 to 5% of adults and it is more common in women. The treatment of RLS with levodopa has been reported thus a systematic synthesis of evidence is necessary to evaluate the effectiveness and safety of levodopa for RLS. Systematic review of randomized or quasi-randomized, double blind trials on levodopa. Relief of restless legs symptoms marked on a validated scale, subjective sleep quality, sleep quality measured by night polysomnography and actigraphy, quality of life measured by subjective measures, adverse events associated with the treatments. Nine eligible clinical trials were included. The subjective analyses of these studies showed contradictory results, although the objective analyses showed that treatment group had a statistically significant improvement of periodic leg movement (PLM) index, favoring the treatment group. The most commonly adverse event seen was gastrointestinal symptoms. The short-term treatment with levodopa was demonstrated effective and safety for PLM, but there was only few trials assessing long-term treatment and the augmentation phenomenon in RLS. Further long-term randomized controlled trials using standard follow-up measurements as the International RLS Study Group Rating Scale are necessary.
Structure, mechanism and engineering of plant natural product glycosyltransferases (2009)

Glycosylation is a key mechanism in determining chemical complexity and diversity of plant natural products, and influencing their chemical properties and bioactivities. Uridine diphosphate glycosyltransferases (UGTs) are the central players in these glycosylation processes for decorating natural products with sugars. Crystal structures of plant UGTs have revealed their exquisite architectures and provided the structural basis for understanding their catalytic mechanism and substrate specificity. Structure-based UGT engineering can alter substrate specificity; compromise or enhance catalytic efficiency; and confer reversibility to the glycosylation reaction. This review highlights the structural insights on plant UGTs and successes in glycosylation engineering.
Differences in the distribution, phenotype and gene expression of subretinal microglia/macrophages in C57BL/6N (Crb1rd8/rd8) versus C57BL6/J (Crb1wt/wt) mice (2015)

When compared to C57BL/6J mice, C57BL/6N mice demonstrate increased accumulation of subretinal MG/MΦ, displaying phenotypical, morphological, and gene-expression characteristics consistent with a pro-inflammatory shift. These changes become more prominent with aging and are likely due to the combination of the rd8 mutation and yet unidentified permissive/modulatory genes in the C57BL/6N mice. In contrast, aging leads to a scavenging phenotype in the C57BL/6J subretinal microglia/macrophages.
The IBM System/360 Model 91: Some Remarks on System Development (1967)

The primary goal of the System/360 Model 91 development program was to produce the highest performance capability that advanced design philosophy and extensions of System/360 circuit technology could achieve, within a balanced development schedule. “Performance,” as used here, means general computer availability and high-speed execution of general problem programs.
The clearance concept with special reference to determination of glomerular filtration rate in patients with fluid retention (2014)

In subjects without fluid retention, the total plasma clearance of a renal filtration indicator (inulin, (99m) Tc-DTPA, (51) Cr-EDTA) is close to the urinary plasma clearance. Conversely, in patients with fluid retention (oedema, pleural effusions, ascites), there is a substantial discrepancy between the total plasma clearance and the urinary plasma clearance. This is owing to delayed indicator distribution to smaller or larger parts of the interstitial space, which in patients with ascites may simulate a peritoneal dialysator. In patients with fluid retention, urinary plasma clearance should be assessed to obtain a correct measurement of the glomerular filtration rate (GFR). In theory, total plasma clearance with late samples (24-h, 48-h) may be applied in patients with fluid retention, but validation hereof has not been performed. Until such studies are completed, it is recommended that patients with fluid retention have their GFR measured by a urinary plasma clearance technique with controlled quantitative urinary sampling within a few hours after indicator injection.
Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family (1985)

We have isolated and sequenced a full-length cDNA clone encoding rat glyceraldehyde-3-phosphate-dehydrogenase (GAPDH, E.C.1.2.1.12). The entire mRNA is 1269 nucleotides long exclusive of poly(A) and contains respectively 71 and 196 bases of 5' and 3' non-coding regions. Primer extension as well as S1 nuclease protection experiments clearly established that a single (or at least a highly prominent) GAPDH mRNA species is expressed in all rat tissues examined. This sequence allowed the determination of the hitherto unknown primary structure of rat GAPDH which is 333 aminoacids long. Comparison between GAPDH sequences from rat, man and chicken revealed a high degree of sequence conservation at both nucleotide and protein levels.
Role of Promotion in Life Insurance Marketing: An Empirical Study (2011)

In an emerging economy like India where the rate of literacy is very low and the rural economy is pre-dominant, the role of promotion becomes very important in any marketing strategy. The life insurance services depend on effective promotional measures. This study tries to analyse the differences in the perception of the executives (of the promotional variables) with respect to their age, gender, education, experience and organization. The various elements involved in the life insurance policy promotion strategy are outlined as: Advertising and publicizing; Personal selling; Incentives; Unity and honesty; A rational and tangible reason; Creative strategy; Targeting an ideal mix of high worthy customers.This study relies on assumption that age, gender, education, experience and organization have no effect on the perception (of the promotional elements) of the executives. The study was conducted in south Orissa spreading over two districts with more than 200 life insurance executives put through the data collection process. Various elementary statistical tools such as mean and variance were applied to find any variation among the different classes of respondents with regard to the various promotional variables. Further, to find out significant variation among these different classes, one-way ANOVA and t-Test were applied. In the long run, this study will help the life insurance companies in understanding its frontline sales force with respect to creating an effective promotion strategy to reach more and more prospective customers.
Quenched disorder in a liquid-crystal biosensor: Adsorbed nanoparticles at confining walls (2005)

We analyze the response of a nematic liquid-crystal film, confined between parallel walls, to the presence of nanoscopic particles adsorbed at the walls. This is done for a variety of patterns of adsorption (random and periodic) and operational conditions of the system that can be controlled in experimental liquid-crystal-based devices. We compute simulated optical textures and the total optical output of the sensor between crossed polars, as well as the correlation function for the liquid-crystal tensor order parameter; we use these observables to discuss the gradual destruction of the original uniform orientation. For large concentrations of particles adsorbed in random patterns, the liquid crystal at the center of the sensor adopts a multidomain state, characterized by a small correlation length of the tensor order parameter, and also by a loss of optical anisotropy under observation through crossed polars. In contrast, for particles adsorbed in periodic patterns, the nematic at the center of the cell can remain in a monodomain orientation state, provided the patterns in opposite walls are synchronized.
Expression and clinical significance of PD-L1 and BRAF expression in nasopharyngeal carcinoma (2019)

Tumor PD-L1 expression and BRAF mutation are associated with poor outcomes in patients with NPC. This study was retrospectively registered in ClinicalTrials.gov (NCT03989297) on 2019-6-18.
Neural probabilistic motor primitives for humanoid control (2018)

We focus on the problem of learning a single motor module that can flexibly express a range of behaviors for the control of high-dimensional physically simulated humanoids. To do this, we propose a motor architecture that has the general structure of an inverse model with a latent-variable bottleneck. We show that it is possible to train this model entirely offline to compress thousands of expert policies and learn a motor primitive embedding space. The trained neural probabilistic motor primitive system can perform one-shot imitation of whole-body humanoid behaviors, robustly mimicking unseen trajectories. Additionally, we demonstrate that it is also straightforward to train controllers to reuse the learned motor primitive space to solve tasks, and the resulting movements are relatively naturalistic. To support the training of our model, we compare two approaches for offline policy cloning, including an experience efficient method which we call linear feedback policy cloning. We encourage readers to view a supplementary video ( https://youtu.be/CaDEf-QcKwA ) summarizing our results.
Identification of a region of beta 2-glycoprotein I critical for lipid binding and anti-cardiolipin antibody cofactor activity. (1993)

beta 2-Glycoprotein I (beta 2-GPI), a phospholipid-binding plasma protein, is an absolute requirement (cofactor) for the binding of autoimmune-type anti-cardiolipin (aCL) antibodies to cardiolipin (CL). The nature of this cofactor activity and the specific regions of the molecule involved have not yet been determined. We have identified a preparation of beta 2-GPI that lacks aCL antibody cofactor activity. Analysis of the structural differences between the active and inactive forms enabled identification of the region of beta 2-GPI critically important for aCL cofactor activity. The active form of beta 2-GPI bound CL and displayed cofactor activity down to 1 microgram/ml. The inactive form failed to bind CL and possessed no cofactor activity even at concentrations up to 94 micrograms/ml, indicating that the ability of beta 2-GPI to bind lipids is an absolute requirement for aCL cofactor activity. Both forms possessed identical N-terminal sequences and were recognized as essentially immunoreactively identical by polyclonal antisera to beta 2-GPI. However, the inactive form has undergone proteolytic cleavage and exists primarily as a "clipped" molecule, the polypeptide chain being cleaved between Lys-317 and Thr-318 (a potential thrombin cleavage site), with the two cleaved segments linked as a disulfide-bonded complex. This indicates that the C-terminal region is critically important for beta 2-GPI to bind lipid and for aCL cofactor activity. The clipped form of beta 2-GPI would not be suitable for use as aCL cofactor and its use may have led some investigators to conclude incorrectly that beta 2-GPI does not interact with aCL antibodies.
Treatment of systemic fungal infections with liposomal amphotericin B (1989)

• Forty-six patients with systemic fungal infections were treated with liposomal amphotericin B. Twenty-one patients had disseminated candidiasis, 19 had aspergillosis, and the rest had a variety of other fungal infections. Forty patients failed to respond to conventional amphotericin B therapy, and 6 patients were given liposomal amphotericin B because conventional amphotericin B caused severe side effects. Twenty-four patients had a complete response, and 22 patients failed to respond. No short- or long-term toxic reactions were observed. The acute side effects such as fever, chills, and potassium loss were infrequent and milder than those commonly observed with conventional amphotericin B. No chronic renal, hematologic, or central nervous system side effects were observed. Liposomal amphotericin B therapy was effective and less toxic than conventional amphotericin B therapy. (<i>Arch Intern Med</i>. 1989;149:2533-2536)
Dual-frequency planar antenna for handsets (1998)

Cellular telephone handsets are now being designed to have dual-mode capabilities. In particular, GSM and DCS1800 modes are used in Europe, and PCS and AMPS modes are used in the USA. A novel planar dualband internal antenna for handsets which operates in the ~0.9 and 1.8 GHz bands is proposed. The dual-band antenna has almost the same size as a conventional internal antenna operating in the 0.9 GHz band. Good dual-band operation was obtained for frequency ratios in the range 1.3 – 2.7.
The auto‐oxidation of tetrahydrobiopterin (1988)

The product of the aerobic oxidation of tetrahydrobiopterin, quinonoid dihydrobiopterin, is unstable and rapidly rearranges to form a 7,8-dihydropteridine. Kaufman [Kaufman, S. (1967) J. Biol. Chem. 242, 3934-3943] identified the stable product produced in 0.1 M phosphate pH 6.8, as 7,8-dihydrobiopterin. However, Armarego et al. [Armarego, W. L. F., Randles, D. and Taguchi, H. (1983) Eur. J. Biochem. 135 393-403] questioned this assignment because they found that the dihydroxypropyl group on C-6 was eliminated and 7,8-dihydropterin was the predominant product when the aerobic oxidation was performed in 0.1 M Tris pH 7.6. In the present study we demonstrate that the rearrangement of the unstable quinonoid dihydrobiopterin results in a mixture of these two 7,8-dihydropteridines at neutral pH, 25 degrees C. Furthermore, we find that the loss or retention of the alkyl side-chain is not solely dependent on the pH of the reaction mixture, as was previously assumed by Armarego et al., but rather is strongly influenced by the temperature and the type of buffer. In addition, we describe a new method for quantifying the relative amounts of these two 7,8-dihydropteridines in mixtures of unknown concentrations. This method relies on multicomponent analysis of second derivative spectra and results in values which agree with the concentrations determined directly by HPLC.
Cytokines and Other Mediators in Alopecia Areata (2010)

Alopecia areata, a disease of the hair follicles with multifactorial etiology and a strong component of autoimmune origin, has been extensively studied as far as the role of several cytokines is concerned. So far, IFN-gamma, interleukins, TNF-alpha, are cytokines that are well known to play a major role in the pathogenesis of the disease, while several studies have shown that many more pathways exist. Among them, MIG, IP-10, BAFF, HLA antigens, MIG, as well as stress hormones are implicated in disease onset and activity. Within the scope of this paper, the authors attempt to shed light upon the complexity of alopecia areata underlying mechanisms and indicate pathways that may suggest future treatments.
[Cd16In64S134]44−: 31‐Å Tetrahedron with a Large Cavity (2003)

The hole story? A super-supertetrahedral anionic cluster of 214 atoms and 80 tetrahedral units is prepared. The crystal structure has finite tetrahedral units of [Cd16In64S134]44− ions composed of four T4 supertetrahedra (see picture). Each cluster is nearly a regular tetrahedron with edge lengths of 31.06 and 31.07 Å, and has large octahedral cavity (yellow sphere).
Ooplasmic donation in humans: The potential for epigenic modifications (2002)

Ooplasm donation, wherein ooplasm is transferred from a donor oocyte to a recipient oocyte in an effort to increase embryo viability, has been applied in the human, with resulting pregnancies and births. Neither the safety nor efficacy of this method has been adequately investigated. Mitochondrial heteroplasmy in the blood of children conceived using ooplasm donation has recently been described. A follow-up study of children born following the use of this technique primarily focused on the presence of mitochondria from the donor oocyte highlighting possible problems due to mitochondrial heteroplasmy. Other effects related to epigenetic events may also arise, but have not been addressed. Studies using inbred mouse strains reveal that genetically diverse ooplasms can impose diverse epigenetic modifications on parental genomes. Incompatibilities produced by combining maternal genome and ooplasm from different genotypes leads to defects in gene expression and development. Such defects can be heritable and observed in the next generation. Given the potential for epigenetic modifications to arise following ooplasm donation, the safety and efficacy of this method need to be evaluated in a suitable animal model.
Antigenic Competition Between and Endotoxic Adjuvant and a Protein Antigen (1971)

Antigenic competition between bovine gamma globulin (BGG) and endotoxin from a smooth strain (S-ET) and a rough (R-ET) heptoseless mutant strain of Salmonella minnesota was studied in mice. Both endotoxins acted as adjuvants for enhancing the antibody response to BGG. However, other work showed that the R-ET had minimal antigenicity, and it was used as a control for the competition studies. Antigenic competition between BGG and endotoxin as expressed by a suppression of the antibody response to BGG could not be demonstrated when varying adjuvant doses of S-ET or R-ET were injected simultaneously with a small constant dose of BGG into normal mice. However, mice presensitized with S-ET several weeks before immunization with the S-ET and BGG combination produced anti-BGG levels which were four to eightfold lower than in normal mice. Nearly complete suppression of the anti-BGG response could be obtained in presensitized mice by reducing the BGG dose 10-fold or by increasing the adjuvant dose of endotoxin. Mice pretreated with R-ET and challenged with BGG plus S-ET or R-ET showed no depression of the anti-BGG response. These and other experiments confirmed the immunological basis of the competitive effect.
Cardiac Fibroblast (2009)

The permanent cellular constituents of the heart include cardiac fibroblasts, myocytes, endothelial cells, and vascular smooth muscle cells. Previous studies have demonstrated that there are undulating changes in cardiac cell populations during embryonic development, through neonatal development and into the adult. Transient cell populations include lymphocytes, mast cells, and macrophages, which can interact with these permanent cell types to affect cardiac function. It has also been observed that there are marked differences in the makeup of the cardiac cell populations depending on the species, which may be important when examining myocardial remodeling. Current dogma states that the fibroblast makes up the largest cell population of the heart; however, this appears to vary for different species, especially mice. Cardiac fibroblasts play a critical role in maintaining normal cardiac function, as well as in cardiac remodeling during pathological conditions such as myocardial infarct and hypertension. These cells have numerous functions, including synthesis and deposition of extracellular matrix, cell-cell communication with myocytes, cell-cell signaling with other fibroblasts, as well as with endothelial cells. These contacts affect the electrophysiological properties, secretion of growth factors and cytokines, as well as potentiating blood vessel formation. Although a plethora of information is known about several of these processes, relatively little is understood about fibroblasts and their role in angiogenesis during development or cardiac remodeling. In this review, we provide insight into the various properties of cardiac fibroblasts that helps illustrate their importance in maintaining proper cardiac function, as well as their critical role in the remodeling heart.