gebhart/patrepeval huggingface dataset:
Medicinal chemistry approaches for the treatment and prevention of Alzheimer's disease (2002)

Alzheimer's disease (AD) is the most common form of dementia, which is characterised by progressive deterioration of memory and higher cortical functions that ultimately result in total degradation of intellectual and mental activities. Modern strategies in the search of new therapeutic approaches are based on the morphological and biochemical characteristics of AD, and focused on following directions: agents that compensate the hypofunction of cholinergic system, agents that interfere with the metabolism of beta-amyloid peptide, agents that protect nerve cells from toxic metabolites formed in neurodegenerative processes, agents that activate other neurotransmitter systems that indirectly compensate for the deficit of cholinergic functions, agents that affect the process of the formation of neurofibrillary tangles, anti-inflammatory agents that prevent the negative response of nerve cells to the pathological process. The goal of the present review is the validation and an analysis from the point of view of medicinal chemistry of the principles of the directed search of drugs for the treatment and prevention of AD and related neurodegenerative disorders. It is based on systematization of the data on biochemical and structural similarities in the interaction between physiologically active compounds and their biological targets related to the development of such pathologies. The main emphasis is on cholinomimetic, anti-amyloid and anti-metabolic agents, using the data that were published during the last 3 to 4 years, as well as the results of clinical trials presented on corresponding websites.
Role of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in the development of an acute neutrophil inflammatory response in mice (1996)

The intraperitoneal injection into mice of casein preparations containing bacteria induced a rapid accumulation of neutrophils within 3 hours due to selective release of mature cells from the bone marrow. Significant increases in the concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) occurred in the peritoneal cavity during the process, but the intraperitoneal injection of neither CSF induced a significant accumulation of neutrophils and the coinjection of G-CSF and casein failed to enhance the neutrophil response. The lack of involvement of either CSF in the neutrophil migration was confirmed by the development of typical neutrophil exudates when casein was injected into mice with inactivation of the genes encoding GM-CSF, G-CSF, or the beta-common chain of the GM-CSF receptor. However, preinjection of G-CSF increased the number of marrow neutrophils available for migration and did result in increased numbers of neutrophils in the peritoneal cavity after casein injection. Typical eosinophil inflammatory responses to the injection of casein or thioglycollate occurred in GM-CSF -/ -mice but not in beta c -/- mice, suggesting that interleukin-5 was necessary for this response.
A Naturally Occurring Mutation in FcγRIIA: A Q to K127 Change Confers Unique IgG Binding Properties to the R131 Allelic Form of the Receptor (1998)

FcγRIIa is widely expressed on hematopoietic cells. There are two known allelic polymorphic forms of FcγRIIa, FcγRIIa-R131 and FcγRIIa-H131, which differ in the amino acid at position 131 in the second Ig-like domain. In contrast to FcγRIIa-R131, FcγRIIa-H131binds hIgG2 but not mIgG1, and this differential binding has clinical implications for host defense, autoimmune disease, immunohematologic disease, and response to therapeutic monoclonal antibodies. We identified a novel FcγRIIA genotype in a healthy individual homozygous for FcγRIIA R/R131 in whom a C to A substitution at codon 127 changes glutamine (Q) to lysine (K) in one of the two FcγRIIA genes. This individual's homozygosity for FcγRIIA-R/R131 leads to the prediction that the receptors on her cells would not bind hIgG2. Monocyte and neutrophil phagocytosis of hIgG2-opsonized erythrocytes was significantly higher (P &lt; .05) for cells from this K/Q127, R/R131 individual than for Q/Q127, R/R131 donors. Platelet aggregation stimulated by an mIgG1 anti-CD9 antibody in this individual was significantly different (P &lt; .05) from Q/Q127, H/R131 and Q/Q127, H/H131 donors and similar to Q/Q127, R/R131. Our data show that the K127/R131 receptors have a unique phenotype, binding both hIgG2 and mIgG1. Further functionally significant mutations in human Fcγ receptors and possible novel mechanisms for inherited differences in disease susceptibility should be sought with unbiased screening methods.
Interferon-gamma in the first-line therapy of ovarian cancer: a randomized phase III trial (2000)

Intraperitoneal treatment with interferon-gamma (IFN-gamma) has been shown to achieve surgically documented responses in the second-line therapy of ovarian cancer. To assess its efficacy in the first-line therapy, we conducted a randomized controlled trial with 148 patients who had undergone primary surgery for FIGO stage Ic-Illc ovarian cancer. In the control arm women received 100 mg/m(-2) cisplatin and 600 mg/m(-2) cyclophosphamide, the experimental arm included the above regimen with IFN-gamma 0.1 mg subcutaneously on days 1, 3, 5, 15, 17 and 19 of each 28-day cycle. Progression-free survival at 3 years was improved from 38% in controls to 51% in the treatment group corresponding to median times to progression of 17 and 48 months (P= 0.031, relative risk of progression 0.48, confidence interval 0.28-0.82). Three-year overall survival was 58% and 74% accordingly (n.s., median not yet reached). Complete clinical responses were observed in 68% with IFN-gamma versus 56% in controls (n.s.). Toxicity was comparable in both groups except for a mild flu-like syndrome, experienced by most patients after administration of IFN-gamma. Thus, with acceptable toxicity, the inclusion of IFN-gamm in the first-line chemotherapy of ovarian cancer yielded a benefit in prolonging progression-free survival.
CHIRAL DRUG MARKET SHOWS SIGNS OF MATURITY (1997)

RETURN TO ISSUEPREVNewsNEXTCHIRAL DRUG MARKET SHOWS SIGNS OF MATURITYAs first generation of patents is expiring, pessimism grows on future ofracemic switchesSTEPHEN C. STINSONView Author Information C&EN Northeast News BureauCite this: Chem. Eng. News 1997, 75, 42, 38–70Publication Date (Print):October 20, 1997Publication History Published online12 November 2010Published inissue 20 October 1997https://pubs.acs.org/doi/10.1021/cen-v075n042.p038https://doi.org/10.1021/cen-v075n042.p038newsACS PublicationsCopyright © 1997 AMERICAN CHEMICAL SOCIETYArticle Views17Altmetric-Citations16LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options SUBJECTS:Pharmaceuticals Get e-Alerts
Sex, Hormones, and Hysterectomies (2000)

In this issue of the Journal, Shifren and coworkers1 postulate that the reduction in androgens resulting from bilateral oophorectomy is associated with sexual dysfunction in some women and that testosterone replacement can reverse this decline in sexual function and also improve psychological well-being. The potential importance of these postulates is substantial.Recent survey data suggest that the prevalence of sexual dysfunction among women in the United States is approximately 40 percent.2 Many of these women have had hysterectomies, about 600,000 of which are performed here annually.3 Bilateral oophorectomy is performed in conjunction with hysterectomy in about half of women 40 . . .
A Mixed-Reality Part-Task Trainer for Subclavian Venous Access (2013)

An SCVA mixed simulator offers a realistic representation of subclavian central venous access and offers new debriefing capabilities.
Bacterial proteases: production, isolation and utilization in animal nutrition. (1998)

Under conditions of submerged fermentation of Bacillus licheniformis strain L-3 in 15-L MBR-Schulzer bioreactor, the maximum production of proteolytic enzymes was achieved in the nutrient medium which contained 1% milk powder, 0.3% yeast autolysate, 0.5% corn starch and malt (20 ml per 100 ml of the medium). The preparation obtained of extracellular alkaline bacterial Ser-protease of the subtilisin type is characterized by optimum pH 9.8-10.2 good up to a temperature stability (65 degrees C) and has molecular weight cca of 26 kDa. The use of chemical mutagens (HNO2, 5-bromouracil) has enabled to select new strains (L-3N and L-3U) whose protease activity is 1.8-2.2 times higher as compared to the original Bacillus licheniformis strain L-3. The addition of these enzymes to the fodder has a positive effect on the retention of nitrogen substances.
Enterprise Application-Specific Data Management (2010)

Enterprise applications are presently built on a 20-year old data management infrastructure that was designed to meet a specific set of requirements for OLTP systems. In the meantime, enterprise applications have become more sophisticated, data set sizes have increased, requirements on the freshness of input data have been strengthened, and the time allotted for completing business processes has been reduced. To meet these challenges, enterprise applications have become increasingly complicated to make up for short-comings in the data management infrastructure. To address this issue we investigate recent trends in data management such as main memory databases, column stores and compression techniques with regards to the workload requirements and data characteristics derived from actual customer systems. We show that a main memory column store is better suited for to days enterprise systems, which we validate by using SAP's Net Weaver Business Warehouse Accelerator and a realistic set of data from an inventory management application.
Strategy for Cross-Protection amongShigella flexneriSerotypes (1999)

Based upon the lipopolysaccharide (LPS) structure and antigenicity of Shigella group B, a strategy for broad cross-protection against 14 Shigella flexneri serotypes was designed. This strategy involves the use of two S. flexneri serotypes (2a and 3a), which together bear the all of the major antigenic group factors of this group. The novel attenuated strains used in these studies were S. flexneri 2a strain CVD 1207 (DeltaguaB-A DeltavirG Deltaset1 Deltasen) and S. flexneri 3a strain CVD 1211 (DeltaguaB-A DeltavirG Deltasen). Guinea pigs were immunized with an equal mixture of these strains and later challenged (Sereny test) with a wild-type S. flexneri serotype 1a, 1b, 2b, 4b, 5b, Y, or 6 strain of demonstrated virulence in the same model. Guinea pigs that were immunized with these two vaccine strains produced serum and mucosal antibodies that cross-reacted with all the S. flexneri serotypes tested (except of S. flexneri serotype 6) as assessed by enzyme-linked immunosorbent assay, immunoblotting, and slide agglutination. Furthermore, the combination vaccine conferred significant protection against challenge with S. flexneri serotypes 1b, 2b, 5b, and Y but not with serotypes 1a, 4b, or (as predicted) 6.
Supramolecular Halogen Bond Passivation of Organic–Inorganic Halide Perovskite Solar Cells (2014)

Organic-inorganic halide perovskites, such as CH3NH3PbX3 (X = I(-), Br(-), Cl(-)), are attracting growing interest to prepare low-cost solar cells that are capable of converting sunlight to electricity at the highest efficiencies. Despite negligible effort on enhancing materials' purity or passivation of surfaces, high efficiencies have already been achieved. Here, we show that trap states at the perovskite surface generate charge accumulation and consequent recombination losses in working solar cells. We identify that undercoordinated iodine ions within the perovskite structure are responsible and make use of supramolecular halogen bond complexation to successfully passivate these sites. Following this strategy, we demonstrate solar cells with maximum power conversion efficiency of 15.7% and stable power output over 15% under constant 0.81 V forward bias in simulated full sunlight. The surface passivation introduces an important direction for future progress in perovskite solar cells.
Spatial-light-modulator-based electro-optical imaging system (1992)

We describe a novel electro-optical system that can image objects over a long range of distance without involving any mechanical movement.
The evolving role of submucosal injectables for treating internal sphincteric deficiency. (1998)

Each of the previously mentioned materials can be used in procedures performed on an outpatient basis using sedation and local anesthesia. Teflon usually requires general anesthesia. None of these materials, however, should be used in acute conditions involving cystitis, urolithiasis, or infection. Table 4 summarizes the postoperative care after a bulking agent injection. There are obvious advantages to using injectable materials for ISD, one of which is that the outpatient procedure is usually done under local anesthesia. It does not have the risks inherent in open surgical procedures like slings or artificial sphincters, and it causes minimal increase of urethral resistance to detrusor-generated micturition force. Such procedures are obviously easier and faster to perform with less cost and rapid recovery followed by a return to regular activity within 48 hours. In conclusion, injection therapy for urinary incontinence is appropriate, but the most effective substance has probably not yet been determined.
Experimental identification of chemical carcinogens, risk evaluation, and animal-to-human correlations (1978)

Experimental methods for the identification of chemical carcinogens have been extensively developed, including animal bioassay methods, animal models for cancer induction at major organ sites, models for the study of the effects of carcinogens in cells and tissues in culture and methods for the study of molecular events (metabolic activation, binding and detoxification of carcinogens; DNA damage and repair; mutagenicity). Current sources of documentation on carcinogenicity data are reviewed. The number of “known carcinogens” will vary considerably, depending on the criteria adopted for accepting evidence of carcinogenicity. Criteria for the evaluation of risks, benefits, and technological alternatives for public policy on environmental carcinogens are reviewed and the following steps discussed: registration of environmental chemical carcinogens and their uses; risk evaluation (considering sources, adequacy, quality and limits of the evidence; quantitative dose–response extrapolation within the same biological system; and species and model conversion factors); benefits evaluation; analysis of technological alternatives; comparative judgment and decision; open public documentation. The problem of animal-to-human correlations is considered, particularly for respiratory carcinogenesis. A laboratory approach is reviewed which includes: development and study of whole animal models for carcinogenesis, analysis of animal tissue responses to carcinogens in vivo and through in vitro culture methods for morphological and biochemical studies, and development of in vitro culture methods for human target tissues. This approach is aimed at providing an experimentally controlled and quantifiable method for the correlation of animal and human observations in carcinogenesis.
Wnt signaling regulates transendothelial migration of monocytes (2006)

The Wnt-signaling pathway plays a critical role in directing cell fate during embryogenesis. Several lines of evidence also suggest a role in inflammatory processes. Here, we analyzed whether Wnt signaling plays a role in leukocyte inflammatory responses. Monocytes from healthy donors expressed different Frizzled receptors, which are ligands for the Wnt molecules. Activation of the Wnt/beta-catenin pathway by LiCl or Wnt3a increased beta-catenin protein levels in monocytes but not in granulocytes. It is interesting that the activation of Wnt/beta-catenin signaling via Wnt3a in monocytes resulted in a decrease in migration through an endothelial layer (human dermal microvascular endothelial cell-1). Further experiments revealed that the decrease in transendothelial migration was associated with specific monocyte adherence to endothelial cells after Wnt exposure. The specificity was verified by a lack of Wnt3a-induced adhesion to fibronectin, laminin, or collagen compared with endothelial interaction. Analysis of the distribution of beta-catenin revealed a Wnt3a-induced increase of beta-catenin in the cytoplasm. Wnt3a exposure did not result in any activation of the classical Wnt-target gene c-myc or a Wnt-target gene involved in cell adhesion (Connexin43). Our study implicates for the first time a role of canonical Wnt signaling in inflammatory processes in monocytes.
Left ventricular diastolic parameters in 288 normal subjects from 20 to 80 years old (1995)

Left ventricular diastolic indexes are influenced by several variables. In order to evaluate the relationship of these indexes to age, heart rate, sex and to standard echo parameters, 288 normal subjects aged from 20 to 80 years, divided into six age groups, underwent a two-dimensional colour Doppler examination. Doppler examination was performed from the apical four chamber view to evaluate transmitral flow; isovolumic relaxation time (IVRT) was measured from an apical five chamber view. In order to obtain a sufficient number of subjects for an adequate statistical analysis, seven hospitals were involved in the study. Univariate analysis showed that age influences the peak velocity of the E (r = -0.46) and A waves (r = 0.46), the E/A ratio (peak velocities) (r = -0.69), the A wave integral (r = 0.48) and the E/A integral ratio (r = -0.57), the early and late filling fractions (r = -0.48 and r = 0.51 respectively), and the E wave deceleration (r = -0.43) and deceleration time (r = 0.36). In subjects older than 70 years an inversion of the E/A wave ratio was observed. Multivariate analysis confirmed that age has an important influence on left ventricular diastolic indexes but also demonstrated that heart rate has a significant influence. Sex, ejection fraction (EF), and the dimensions of the mitral annulus and the left ventricular posterior wall had less influence on left ventricular diastolic indexes. The mean values of E and A wave acceleration, deceleration and peak velocity were used to depict left ventricular filling morphology in various age groups for three different heart rate values. The conclusions of the study, are: (1) normal left ventricular diastolic parameters were obtained as mean values at seven different hospitals (2) when evaluating left ventricular diastolic function parameters it is important to take into account age and heart rate; E/A inversion in older subjects should be considered the normal mitral flow pattern.
Two prohormones for gastrin-releasing peptide are encoded by two mRNAs differing by 19 nucleotides. (1986)

In our studies on the molecular biology of human gastrin-releasing peptide (GRP), we have discovered an example of a change in translational reading frame apparently produced through alternative RNA splicing. Complementary DNAs prepared from a pulmonary carcinoid tumor rich in GRP immunoreactivity had one of two different-sized internal DNA fragments after digestion with the restriction enzyme Pvu II. Nucleotide sequences of the two DNA fragments were identical except for 19 additional nucleotides present in the larger fragment. The region of the mRNA containing the 19 nucleotides corresponded to the carboxyl-terminal region of the human GRP precursor. The resulting shift in reading frame causes a difference of 10 amino acids in size and an overall sequence difference of 27 amino acids between the two GRP prohormones so formed. The change in reading frame described here is unusual in eukaryotes and is yet another mechanism to produce diversity in the generation of biological peptides.
Cytochrome-P-450-Dependent Metabolism of Retinoic Acid in Rat Skin Microsomes: Inhibition by Ketoconazole (1988)

Epidermal microsomes, prepared from neonatal Wistar or Sprague-Dawley rats, show low levels of retinoic acid (RA) metabolism. The specific activities (as fmol/min/mg protein) of epidermal microsomes, using [15–&lt;sup&gt;14&lt;/sup&gt;C]-RA as substrate, are 232 (Wistar rats) and 222 (Sprague-Dawley rats). Topical application of RA (1 mg) on 4-day-old rats induces a 3.3-and 3.9-fold increase in epidermis microsomal RA metabolism. A 4.6- to 8.1-fold increase is observed 24 h after topical application of 3-methylcholanthrene (0.5 mg). By contrast, phenobarbital (1 mg topically) has a much smaller inducing effect. So far the chemical structure of the metabolites has not been identified. The Rf values of two major compounds correspond with those of 4-hydroxy- and 4-ketoretinoic acid, formed after incubation of hamster liver microsomes in the presence of [15–&lt;sup&gt;14&lt;/sup&gt;C]-RA. The RA metabolism in rat epidermal micromes shows the typical characteristics of a cytochrome-P-450 (P450)-dependent enzyme system, i.e. a requirement for NADPH and oxygen and inhibition by CO and SKF-525A. Ketoconazole and miconazole, imidazole antifungal agents and inhibitors of some fungal and mammalian P450-dependent enzymes, inhibit in vitro RA metabolism by rat epidermal microsomes. 50% inhibition is achieved at 6.5 × 10&lt;sup&gt;-7&lt;/sup&gt; and ≧ 10&lt;sup&gt;-5&lt;/sup&gt; mol/l, respectively. The triazole antifungal agent, itraconazole, has no effect at concentrations up to 10&lt;sup&gt;-5&lt;/sup&gt; mol/l. Topical treatment of 4-day-old Wistar rats with ketoconazole, at doses of 1, 5 and 10 mg/kg, 1 h before the application of RA (1 mg/rat) results in a dose-dependent inhibition of RA metabolism by epidermal microsomes, prepared 24 h later. Our data show a P450-dependent RA metabolism in rat epidermal microsomes and suggest that ketoconazole may prove to be effective in maintaining biologically active levels of RA in epidermal cells.
Live pigs produced from genome edited zygotes (2013)

Transcription activator-like effector nuclease (TALEN) and zinc finger nuclease (ZFN) genome editing technology enables site directed engineering of the genome. Here we demonstrate for the first time that both TALEN and ZFN injected directly into pig zygotes can produce live genome edited pigs. Monoallelic as well as heterozygous and homozygous biallelic events were identified, significantly broadening the use of genome editor technology in livestock by enabling gene knockout in zygotes from any chosen mating.