gebhart/patrepeval huggingface dataset:
Minireview: G Protein-Coupled Estrogen Receptor-1, GPER-1: Its Mechanism of Action and Role in Female Reproductive Cancer, Renal and Vascular Physiology (2012)

Using cDNA cloning strategies commonly employed for G protein-coupled receptors (GPCR), GPCR-30 (GPR30), was isolated from mammalian cells before knowledge of its cognate ligand. GPR30 is evolutionarily conserved throughout the vertebrates. A broad literature suggests that GPR30 is a Gs-coupled heptahelical transmembrane receptor that promotes specific binding of naturally occurring and man-made estrogens but not cortisol, progesterone, or testosterone. Its "pregenomic" signaling actions are manifested by plasma membrane-associated actions familiar to GPCR, namely, stimulation of adenylyl cyclase and Gβγ-subunit protein-dependent release of membrane-tethered heparan bound epidermal growth factor. These facts regarding its mechanism of action have led to the formal renaming of this receptor to its current functional designate, G protein-coupled estrogen receptor (ER) (GPER)-1. Further insight regarding its biochemical action and physiological functions in vertebrates is derived from receptor knockdown studies and the use of selective agonists/antagonists that discriminate GPER-1 from the nuclear steroid hormone receptors, ERα and ERβ. GPER-1-selective agents have linked GPER-1 to physiological and pathological events regulated by estrogen action, including, but not limited to, the central nervous, immune, renal, reproductive, and cardiovascular systems. Moreover, immunohistochemical studies have shown a positive association between GPER-1 expression and progression of female reproductive cancer, a relationship that is diametrically opposed from ER. Unlike ER knockout mice, GPER-1 knockout mice are fertile and show no overt reproductive anomalies. However, they do exhibit thymic atrophy, impaired glucose tolerance, and altered bone growth. Here, we discuss the role of GPER-1 in female reproductive cancers as well as renal and vascular physiology.
Inhibitors of urokinase reduce size of prostate cancer xenografts in severe combined immunodeficient mice. (1997)

Proteolytic enzymes are required to mediate tumor cell invasion and metastasis. The urokinase plasminogen activator (uPA) is commonly overexpressed by many human cancers. Therefore, uPA is a logical target to inhibit cancer invasion and metastasis. However, uPA inhibitors also reduce tumor growth. We used a mutated form of plasminogen activator inhibitor type 1 to conform a correlation between the inactivation of uPA and tumor size; we have compared these results with the action of p-aminobenzamidine and amiloride, known inhibitors of uPA. Our results show that blocking uPA by uPA inhibitors reduces tumor size in experimental animals. Our molecular simulation of docking inhibitors to the urokinase reveals that all tested small molecule inhibitors bind in proximity of uPA's specificity pocket, a critical site for future search of novel anticancer uPA inhibitors.
CMOS compatible horizontal nanoplasmonic slot waveguides TE-pass polarizer on silicon-on-insulator platform (2013)

An ultra-compact broadband TE-pass polarizer was proposed and demonstrated on the silicon-on-insulator (SOI) platform, using the horizontal nanoplasmonic slot waveguide (HNSW). Detailed design principle was presented, taking advantage of the distinct confinement region of the TE and TM modes in the HNSW. TM mode cut-off could be achieved when waveguide width was below 210 nm. Proof-of-concept devices were subsequently fabricated in a CMOS-compatible process. The optimized device had an active region length of 1 μm, three orders of magnitude smaller than similar device previously demonstrated on the SOI platform. More than 16 dB polarization extinction ratio was achieved across 80 nm wavelength range, with a relatively low insertion loss of 2.2dB. The compact device size and excellent broadband performance could provide a simple yet satisfactory solution to the polarization dependent performance drawback of the silicon photonics devices on the SOI platform.
Interleukin‐12 is required for interferon‐γ production and lethality in lipopolysaccharide‐induced shock in mice (1995)

Several cytokines, in particular tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), have been shown to be responsible for pathological reactions which may lead to shock and death observed in infection with Gram-negative bacteria and in response to endotoxins (lipopolysaccharides, LPS). Priming of mice with the avirulent Bacille Calmette Guérin (BCG) vaccine strain of Mycobacterium bovis increases the sensitivity of mice to the lethal effect of LPS and results in an efficient priming for cytokine production. In response to low doses (1 microgram/mouse) of LPS, BCG-primed mice produce interleukin-12 (IL-12) which controls IFN-gamma production, as demonstrated by the ability of neutralizing anti-IL-12 antibodies to suppress IFN-gamma production. However, the concentration of the biologically active IL-12 p70 heterodimer is similar in the serum of both BCG-primed or unprimed mice, reaching levels of 1-3 ng/ml at 3-6 h after LPS injection, whereas IFN-gamma production was observed only in BCG-primed mice. The priming effect of BCG on IFN-gamma production appears to be mostly due to its ability to increase TNF-alpha production, which acts as cofactor with LPS-induced IL-12 in inducing IFN-gamma production, as shown by the ability of injection of TNF-alpha and LPS (1 microgram/mouse), but not LPS alone, to induce IFN-gamma production. However, in addition to TNF-alpha, other LPS-induced cofactor(s) are required in cooperation with IL-12 to induce optimal IFN-gamma production, because co-injection of TNF-alpha and IL-12, sufficient to induce serum concentrations of both cytokines higher and more persistent than those obtained by injection of LPS, was not sufficient to induce IFN-gamma production in vivo. Neutralizing anti-IL-12 antibodies, in addition to inhibiting the in vivo LPS-induced IFN-gamma production, also completely protect BCG-primed mice injected with up to 10 micrograms of LPS from shock-induced death. Thus, IL-12 is required for IFN-gamma production and lethality in an endotoxic shock model in mice.
The 2001 Bethesda System<SUBTITLE>Terminology for Reporting Results of Cervical Cytology</SUBTITLE> (2002)

Bethesda 2001 was developed with broad participation in the consensus process. The 2001 Bethesda System terminology reflects important advances in biological understanding of cervical neoplasia and cervical screening technology.
Leukocyte antigen CD34 is expressed by a subset of cultured endothelial cells and on endothelial abluminal microprocesses in the tumor stroma. (1990)

It has been reported that the human haemopoietic progenitor cell antigen CD34 is also expressed by vascular structures. To investigate its precise vascular localization, we have studied the cellular and subcellular distribution of CD34 in normal tissues and pathologic tissues with neovascularization. In normal resting tissues, anti-CD34 antibodies, ICH3 and QBEND-10 predominantly stain the luminal endothelial membrane, whereas the abluminal membrane is negative or weakly positive. In contrast, a striking staining of endothelial abluminal microprocesses (EAM) was found in the tumor stroma. These structures, measuring up to 20 microns in length, could be observed in thick vibratome sections both at the tips of vascular sprouts and, also frequently, on fully formed microvessels. The number of vascular sprouts and EAM varied widely between different tumors. CD34-stained EAM were sparsely present in fetal tissue of 10 weeks gestation, but they could not be demonstrated in granulation tissue of wound healing. By immunoelectron microscopy, the EAM were continuous with the cytoplasm of endothelial cells showing an immature phenotype as seen in regeneration. In cultured human umbilical vein endothelium, CD34 was preferentially found on a small subset of cells with the morphologic appearance of migrating cells. These findings suggest that CD34 is an endothelial marker for EAM present during angiogenesis.
New roles of low density lipoproteins and vitamin E in the pathogenesis of atherosclerosis. (1995)

Accumulation of oxidized low density lipoproteins in macrophages and smooth muscle cells causes foam cell formation, an initial step in atherosclerosis. Active oxygen species are considered important in the pathogenesis of the disease. Antioxidants, such as tocopherols and tocotrienols have been considered to prevent the deleterious effects of active oxygen species. We found native low density lipoproteins can stimulate directly smooth muscle cell proliferation, it is associated with an increase of protein kinase C activity. d-alpha-Tocopherol, biologically most active form of vitamin E, inhibits both cell proliferation and protein kinase C activity. The effect of d-alpha-tocopherol is not related to its radical scavenging properties. Transforming growth factor-beta secreted by smooth muscle cells as growth inhibitor. Low density lipoproteins decrease the release of transforming growth factor-beta from smooth muscle cells thus activating growth. d-alpha-Tocopherol activates the cellular release of transforming growth factor-beta. These new aspects explain the important role of low density lipoproteins and vitamin E in increasing and decreasing the risk of atherosclerosis, respectively.
Synthesis, antimicrobial and anti-cancer activities of some new N-ethyl, N-benzyl and N-benzoyl-3-indolyl heterocycles (2012)

A series of 1-(N-substituted-1H-indol-3-yl)-3-arylprop-2-ene-1-ones (2a, b-4a, b) were prepared and allowed to react with urea, thiourea or guanidine to give pyrimidine derivatives 5a, b-13a, b. Reaction of 2a, b-4a, b with ethyl acetoacetate in the presence of a base gave cyclohexanone derivatives 14a, b-16a, b. Reaction of the latter compounds with hydrazine hydrate afforded indazole derivatives 17a, b-19a, b. On the other hand, reaction of 2a, b-4a, b with some hydrazine derivatives, namely hydrazine hydrate, acetyl hydrazine, phenylhydrazine and benzylhydrazine hydrochloride, led to the formation of pyrazole derivatives 20a, b-31a, b. Moreover, reaction of 2a, b-4a, b with hydroxylamine hydrochloride gave isoxazole derivatives 32a, b-34a, b. The newly synthesized compounds were tested for their antimicrobial activity and showed that 4-(N-ethyl-1H-indol-3-yl)-6-(p-chlorophenyl)-pyrimidine-2-amine (11b) was the most active of all the test compounds towards Candida albicans compared to the reference drug cycloheximide. Eighteen new compounds, namely pyrimidin-2(1H)-ones 5a, b-7a, b, pyrimidin-2(1H)-thiones 8a, b-10a, b and pyrimidin-2-amines 11a, b-13a, b derivatives, were tested for their in vitro antiproliferative activity against HEPG2, MCF7 and HCT-116 cancer cell lines. 4-(N-ethyl-1H-indol-3-yl)-6-(p-methoxyphenyl)-pyrimidin-2-amine (11a) was found to be highly active with IC(50) of 0.7 μmol L⁻¹.
Pseudomonas aeruginosa variants isolated from patients with cystic fibrosis are killed by a bactericidal protein from human polymorphonuclear leukocytes (1991)

The susceptibility of paired mucoid and nonmucoid variants of Pseudomonas aeruginosa isolated from 13 patients with cystic fibrosis (CF) to killing by a 55,000-Da bactericidal protein (BP55) from human polymorphonuclear leukocytes was studied. Mucoid and nonmucoid variants were equally sensitive to killing by BP55 at both pH 5.6 and pH 7.2. Eleven of the isolates were resistant to the bactericidal activity of 10% normal human serum but were as sensitive as the serum-sensitive isolates to BP55. Similarly, the 15 isolates with lipopolysaccharides (LPS) containing O-polysaccharide side chains (smooth LPS) were as sensitive to BP55 as those isolates with rough LPS.P. aeruginosa isolates from patients in poor clinical condition were more likely to have LPS of the smooth type and to be resistant to killing by 10% human serum than the isolates from patients in good clinical condition. We have concluded that the susceptibility of the P. aeruginosa isolates from patients with CF to killing by BP55 does not correlate with mucoid or nonmucoid variations, with the presence or absence of smooth LPS, or with the sensitivity or resistance to killing by normal human serum.
Adiponectin, a key adipokine in obesity related liver diseases. (2011)

Non-alcoholic fatty liver disease (NAFLD) comprising hepatic steatosis, non-alcoholic steatohepatitis (NASH), and progressive liver fibrosis is considered the most common liver disease in western countries. Fatty liver is more prevalent in overweight than normal-weight people and liver fat positively correlates with hepatic insulin resistance. Hepatic steatosis is regarded as a benign stage of NAFLD but may progress to NASH in a subgroup of patients. Besides liver biopsy no diagnostic tools to identify patients with NASH are available, and no effective treatment has been established. Visceral obesity is a main risk factor for NAFLD and inappropriate storage of triglycerides in adipocytes and higher concentrations of free fatty acids may add to increased hepatic lipid storage, insulin resistance, and progressive liver damage. Most of the adipose tissue-derived proteins are elevated in obesity and may contribute to systemic inflammation and liver damage. Adiponectin is highly abundant in human serum but its levels are reduced in obesity and are even lower in patients with hepatic steatosis or NASH. Adiponectin antagonizes excess lipid storage in the liver and protects from inflammation and fibrosis. This review aims to give a short survey on NAFLD and the hepatoprotective effects of adiponectin.
Realization of low defect density, ultrathick, strained InGaAs/GaAs multiple quantum well structures via growth on patterned GaAs (100) substrates (1990)

Growth of low defect density highly strained InxGa1−xAs/GaAs multiple quantum well (MQW) structures of thicknesses suited for application in spatial light modulator (SLM) devices operating in infrared has been thwarted by the occurrence of strain-induced defects. Exploiting the notion of strain relief at mesa edges, we report here the first realization of very low defect density MQW structures of thickness as high as 2.38 μm at x=0.20. This has opened up the possibility of realizing a variety of reflective and transmissive SLM structures which also fruitfully exploit the transparent nature of the substrate.
Nanodisc-Incorporated Hemagglutinin Provides Protective Immunity against Influenza Virus Infection (2009)

Every year, influenza virus infection causes significant mortality and morbidity in human populations. Although egg-based inactivated viral vaccines are available, their effectiveness depends on the correct prediction of the circulating viral strains and is limited by the time constraint of the manufacturing process. Recombinant subunit vaccines are easier to manufacture with a relatively short lead time but are limited in their efficacy partly because the purified recombinant membrane proteins in the soluble form most likely do not retain their native membrane-bound structure. Nanodisc (ND) particles are soluble, stable, and reproducibly prepared discoid shaped nanoscale structures that contain a discrete lipid bilayer bound by two amphipathic scaffold proteins. Because ND particles permit the functional reconstitution of membrane/envelope proteins, we incorporated recombinant hemagglutinin (HA) from influenza virus strain A/New Caledonia/20/99 (H1N1) into NDs and investigated their potential to elicit an immune response to HA and confer immunity to influenza virus challenge relative to the commercial vaccines Fluzone and FluMist. HA-ND vaccination induced a robust anti-HA antibody response consisting of predominantly the immunoglobulin G1 (IgG1) subclass and a high hemagglutination inhibition titer. Intranasal immunization with HA-ND induced an anti-HA IgA response in nasal passages. HA-ND vaccination conferred protection that was comparable to that of Fluzone and FluMist against challenge with influenza virus strain A/Puerto Rico/8/1934 (H1N1).
Characterization of two members of the rho gene family from the yeast Saccharomyces cerevisiae. (1987)

The rho genes comprise an evolutionarily conserved family with significant homology to the ras oncogene family. Two members of the rho family were isolated from the yeast Saccharomyces cerevisiae and characterized by DNA sequence analysis. The yeast genes RHO1 and RHO2 are 70% and 57% identical, respectively, to the rho gene of the marine snail Aplysia, and they are 53% identical to each other. Inactivation of these genes showed that RHO1 is required for cell viability, while RHO2 is not an essential gene. A mutant allele of RHO1 (RHO1-His68) was constructed with a mutation analogous to one that activates the transforming potential of the human HRAS gene. Diploid strains containing RHO1-His68 in either low or high copy number are unable to sporulate, and the mutant allele is dominant over wild-type RHO1. The requirement for RHO1 cannot be circumvented by introduction of high copy number plasmids containing either the gene encoding the catalytic subunit of cAMP-dependent protein kinase or the mutant allele RAS2-Val19. Despite the conservation between the rho and ras gene families, the finding that RHO1 functions independently of the adenylate cyclase cAMP-dependent protein kinase cascade suggests that rho and ras are involved in distinct biochemical pathways.
Dark-field Optical Coherence Microscopy (2010)

Dark-field illumination is known to enhance contrast in microscopy. Here we introduce this principle to optical coherence microscopy and show tomograms of live cell samples with improved scattering signal and suppressed specular reflection.
STATES OF HEART (1999)

This article examines early colonial Kaqchikel Maya notions of the self, souls, and the heart. By integrating ethnohistorical data and contemporary ethnographic observations, we show that Kaqchikeles viewed the self as contingent on a dynamic balance of cosmic forces acting on the individual. The ways in which these forces are seen to effect one's state of being are documented through an extensive discussion of Kaqchikel metaphors of the heart and soul. We conclude by noting the importance of understanding processes of continuity (as well as change) in cultural constructions and argue for the continued utility of such approaches in ethnohistorical research.
Reliability analysis for wind turbines (2006)

Abstract Modern wind turbines are complex aerodynamic, mechanical and electrical machines incorporating sophisticated control systems. Wind turbines have been erected in increasing numbers in Europe, the USA and elsewhere. In Europe, Germany and Denmark have played a particularly prominent part in developing the technology, and both countries have installed large numbers of turbines. This article is concerned with understanding the historic reliability of modern wind turbines. The prime objective of the work is to extract information from existing data so that the reliability of large wind turbines can be predicted, particularly when installed offshore in the future. The article uses data collected from the Windstats survey to analyse the reliability of wind turbine components from historic German and Danish data. Windstats data have characteristics common to practical reliability surveys; for example, the number of failures is collected for each interval but the number of turbines varies in each interval. In this article, the authors use reliability analysis methods which are not only applicable to wind turbines but relate to any repairable system. Particular care is taken to compare results from the two populations to consider the validity of the data. The main purpose of the article is to discuss the practical methods of predicting large‐wind‐turbine reliability using grouped survey data from Windstats and to show how turbine design, turbine configuration, time, weather and possibly maintenance can affect the extracted results. Copyright © 2006 John Wiley &amp;Sons, Ltd.
SIR97: a new tool for crystal structure determination and refinement (1999)

SIR 97 is the integration of two programs, SIR 92 and CAOS , the first devoted to the solution of crystal structures by direct methods, the second to refinement via least-squares–Fourier procedures. Several new features have been introduced in SIR 97 with respect to the previous version, SIR 92: greater automatization, increased efficiency of the direct methods section, and a powerful graphics interface. The program also provides publication tables and CIF files.
Hereditary breast cancer (1997)

Problems in accurate testing for breast cancer-associated genes remain. No reliable simple test exists because of the large number of mutations present in these genes. The implications of different mutations remain poorly understood. Guidelines for the management of carriers of the breast cancer-associated genes remain controversial.
Native Chemical Ligation of Thioamide-Containing Peptides: Development and Application to the Synthesis of Labeled α-Synuclein for Misfolding Studies (2012)

Thioamide modifications of the peptide backbone are used to perturb secondary structure, to inhibit proteolysis, as photoswitches, and as spectroscopic labels. Thus far, their incorporation has been confined to single peptides synthesized on solid phase. We have generated thioamides in C-terminal thioesters or N-terminal Cys fragments and examined their compatibility with native chemical ligation conditions. Most sequence variants can be coupled in good yields with either TCEP or DTT as the reductant, though some byproducts are observed with prolonged TCEP incubations. Furthermore, we find that thioamides are compatible with thiazolidine protection of an N-terminal Cys, so that multiple ligations can be used to construct larger proteins. Since the acid-lability of the thioamide prohibits on-resin thioester synthesis using Boc chemistry, we devised a method for the synthesis of thioamide peptides with a masked C-terminal thioester that is revealed in situ. Finally, we have shown that thioamidous peptides can be coupled to expressed protein fragments to generate large proteins with backbone thioamide labels by synthesizing labeled versions of the amyloid protein α-synuclein for protein folding studies. In a proof-of-principle experiment, we demonstrated that quenching of fluorescence by thioamides can be used to track conformational changes during aggregation of labeled α-synuclein.
Familial site-specific ovarian cancer is linked to BRCA1 on 17q12-21. (1994)

In a study of nine families with "site-specific" ovarian cancer (criterion: three or more cases of epithelial ovarian cancer and no cases of breast cancer diagnosed at age < 50 years) we have obtained evidence of linkage to the breast-ovarian cancer susceptibility gene, BRCA1 on 17q12-21. If the risk of cancer in these families is assumed to be restricted to the ovary, the best estimate of the proportion of families linked to BRCA1 is .78 (95% confidence interval .32-1.0). If predisposition to both breast and ovarian cancer is assumed, the proportion linked is 1.0 (95% confidence interval .46-1.0). The linkage of familial site-specific ovarian cancer to BRCA1 indicates the possibility of predictive testing in such families; however, this is only appropriate in families where the evidence for linkage to BRCA1 is conclusive.
Fast neural networks without multipliers (1993)

Multilayer perceptrons (MLPs) with weight values restricted to powers of two or sums of powers of two are introduced. In a digital implementation, these neural networks do not need multipliers but only shift registers when computing in forward mode, thus saving chip area and computation time. A learning procedure, based on backpropagation, is presented for such neural networks. This learning procedure requires full real arithmetic and therefore must be performed offline. Some test cases are presented, concerning MLPs with hidden layers of different sizes, on pattern recognition problems. Such tests demonstrate the validity and the generalization capability of the method and give some insight into the behavior of the learning algorithm.