gebhart/patrepeval huggingface dataset:
Comprehensive Proteomic Analysis of Breast Cancer Cell Membranes Reveals Unique Proteins with Potential Roles in Clinical Cancer (2003)

Proteins associated with cancer cell plasma membranes are rich in known drug and antibody targets as well as other proteins known to play key roles in the abnormal signal transduction processes required for carcinogenesis. We describe here a proteomics process that comprehensively annotates the protein content of breast tumor cell membranes and defines the clinical relevance of such proteins. Tumor-derived cell lines were used to ensure an enrichment for cancer cell-specific plasma membrane proteins because it is difficult to purify cancer cells and then obtain good membrane preparations from clinical material. Multiple cell lines with different molecular pathologies were used to represent the clinical heterogeneity of breast cancer. Peptide tandem mass spectra were searched against a comprehensive data base containing known and conceptual proteins derived from many public data bases including the draft human genome sequences. This plasma membrane-enriched proteome analysis created a data base of more than 500 breast cancer cell line proteins, 27% of which were of unknown function. The value of our approach is demonstrated by further detailed analyses of three previously uncharacterized proteins whose clinical relevance has been defined by their unique cancer expression profiles and the identification of protein-binding partners that elucidate potential functionality in cancer.
Penetration and binding of antibodies in experimental human solid tumors grown in mice. (1989)

Monoclonal antibody localization to human carcinoma xenografts in nude mice was investigated by injecting biotinylated antibody. The antibody used in most experiments, MA103, reacts with a widely distributed human antigen present at a high density on the cell surface and has a relatively high effective affinity, 5.8 x 10(9) M-1. Various doses of antibody were injected, and tumors were collected at various times after injection. Frozen sections were stained by the immunoperoxidase method to detect bound antibody, and adjacent sections were stained with the same antibody in vitro to demonstrate total antigen distribution. In complementary experiments, unconjugated MA103 was injected in high doses to determine whether subsequent in vitro staining of frozen sections by biotinylated MA103 would be inhibited. The results demonstrate that: (a) approximately 0.5 mg antibody was sufficient to saturate antigenic sites on viable tumors cells; (b) saturation was achieved on viable tumor cells throughout the tumor 3 days after injection; (c) in necrotic areas, some antigen was accessible to antibody in vivo, but a considerable fraction of the antigen was inaccessible; (d) at 1 day after injection, stained cells were confined to areas near the blood vessels in the stroma; (e) for i.p. tumors, there was no difference between i.p. and i.v. injection of antibody and no indication of solid tumor penetration directly from the peritoneal cavity; and (f) nonspecific localization of a nonreactive biotinylated monoclonal antibody was weakly detectable and when present was seen as diffuse staining in the connective tissue only. A more limited range of experiments was performed with a second biotinylated antibody, MH99, which reacts with an epithelial cell surface antigen also recognized by many other antibodies, including 17-1A, AUA1, and KS1/4. Results were generally similar, except that a higher dose, 1.5 mg, was required to obtain homogeneous dark staining of tumor cells, and there appeared to be a considerable amount of antigen in viable areas of the tumor that was not accessible in vivo, possibly because it was intracellular. This approach appears to demonstrate tumor localization of antibody more impressively than other methods that have been used. This is partly because of the excellent resolution attained, since the reactive antibody produces a sharp membrane-staining pattern that is totally absent using a nonreactive control antibody. In addition, use of a target antigen that is predominantly on the cell surface, as opposed to cytoplasmic or secreted, is probably important. These data will be of value in attempting to use antibodies for immunotherapy.
Atmospheric New Particle Formation Enhanced by Organic Acids (2004)

Atmospheric aerosols often contain a substantial fraction of organic matter, but the role of organic compounds in new nanometer-sized particle formation is highly uncertain. Laboratory experiments show that nucleation of sulfuric acid is considerably enhanced in the presence of aromatic acids. Theoretical calculations identify the formation of an unusually stable aromatic acid-sulfuric acid complex, which likely leads to a reduced nucleation barrier. The results imply that the interaction between organic and sulfuric acids promotes efficient formation of organic and sulfate aerosols in the polluted atmosphere because of emissions from burning of fossil fuels, which strongly affect human health and global climate.
Amorphous thin films for terrestrial solar cells (1982)

Progress in amorphous semiconductor solar cell technology at RCA Laboratories and other research organizations is reviewed. The performance of cells is discussed for homojunction p‐i‐n structures and structures utilizing hydrogenated amorphous alloys of Si–C, Si–F, Si–Ge, and B–Si. Recently, several organizations have reported conversion efficiencies in the range of 6.0 %–7.5 % for homojunction p‐i‐n cells and structures using alloys of Si–C–H and Si–F–H. The effects of various impurities on solar‐cell performance are discussed. We also present data on the diffusion of various contact materials and dopants in amorphous Si at elevated temperatures.
PCR hot start using primers with the structure of molecular beacons (hairpin-like structure) (2000)

A new technique of PCR hot start using oligonucleotide primers with a stem-loop structure is developed here. The molecular beacon oligonucleotide structure without any chromophore addition to the ends was used. The 3'-end sequence of the primers was complementary to the target and five or six nucleotides complementary to the 3'-end were added to the 5'-end. During preparation of the reaction mixture and initial heating, the oligonucleotide has a stem-loop structure and cannot serve as an effective primer for DNA polymerase. After heating to the annealing temperature it acquires a linear structure and primer extension can begin.
Direct solid phase sequencing of genomic and plasmid DNA using magnetic beads as solid support (1989)

Approaches to direct solid phase sequencing of genomic and plasmid DNA have been developed using magnetic beads, coated with streptavidin, as solid support. The DNA is immobilized through selective incorporation of biotin into one of the strands. A single stranded template, suitable for sequencing, is obtained through strand-specific elution. Using this concept, in vitro amplified plasmid DNA and chromosomal DNA were sequenced directly from single colonies. The solid phase approach ensures that the amplification and the sequencing reactions can be performed under optimal conditions. The system was found to be suitable for sequencing using both isotope- and fluorescent-labelled primers.
Active coherent beam combining of diode lasers (2011)

We have demonstrated active coherent beam combination (CBC) of up to 218 semiconductor amplifiers with 38.5 W cw output using up to eleven one-dimensional 21-element individually addressable diode amplifier arrays operating at 960 nm. The amplifier array elements are slab-coupled-optical-waveguide semiconductor amplifiers (SCOWAs) set up in a master-oscillator-power-amplifier configuration. Diffractive optical elements divide the master-oscillator beam to seed multiple arrays of SCOWAs. A SCOWA was phase actuated by adjusting the drive current to each element and controlled using a stochastic-parallel-gradient-descent (SPGD) algorithm for the active CBC. The SPGD is a hill-climbing algorithm that maximizes on-axis intensity in the far field, providing phase locking without needing a reference beam.
Preparation and optical properties of hybrid sol–gel systems containg doubly anchored oligoarylenevinylenes (1996)

R. J. P. Corriu, P. Hesemann and G. F. Lanneau, Chem. Commun., 1996, 1845 DOI: 10.1039/CC9960001845
Effects of fecal microorganisms and their chloroform-resistant variants derived from mice, rats, and humans on immunological and physiological characteristics of the intestines of ex-germfree mice (1994)

In order to elucidate the nature of intestinal flora affecting the immunological and physiological parameters of the intestine, we produced several kinds of ex-germfree mice associated with fecal organisms and their chloroform-resistant variants derived from mice, rats, and humans. The phenotypes of intraepithelial lymphocytes were changed to those in conventional mice, particularly the increased positive percentage of alpha beta T-cell-receptor and Thy-1-bearing T cells, on association of the microorganisms (MF) and their chloroform resistant variants (MChl) derived from mice, but not rats and humans, with germfree mice. The cytolytic activity of intraepithelial lymphocytes was expressed only in the MF and MChl groups. The induction of the synthesis of fucosyl asialo GM1 glycolipid, the expression of major histocompatibility complex class II molecule, an increase in the mitotic indices of colonic epithelial cells, and a decrease in lactase activity of the small intestinal epithelial cells also occurred only in the two groups. On the other hand, the cecal size (cecal weight/body weight ratio) was reduced in the mice of all groups examined here, there being approximately the same amount and composition of organic acids, such as acetic acid, butyric acid, and propionic acid, in the cecal contents. Taken together, the results suggest that mouse-specific and chloroform-resistant microorganisms, which are difficult to cultivate at present, may contribute to alteration of the immunological and epithelial characteristics of the mouse intestine. Another factor derived from the intestinal flora, for example, bacterial metabolites such as organic acids, may also affect the cecal size.
Synthesis of Two Mirror Image 4-Helix Junctions Derived from Glycerol Nucleic Acid (2008)

Structural DNA nanotechnology relies on Watson-Crick base pairing rules to assemble DNA motifs into diverse arrangements of geometric shapes and patterns. While substantial effort has been devoted to expanding the programmability of natural DNA, considerably less attention has been given to the development of nucleic acid structures based on non-natural DNA polymers. Here we describe the use of glycerol nucleic acid (GNA), a simple polymer based on an acyclic repeating unit, as an alternative genetic material for assembling nucleic acid nanostructures independent of RNA or DNA recognition. We synthesized two 4-helix junctions based entirely on GNA self-pairing and showed that GNA provides easy access to highly stable nanostructures with left- and right-handed helical configurations.
Fungal Membrane Responses Induced by Plant Defensins and Thionins (1996)

Treatment of hyphae of Neurospora crassa with antifungal plant defensins, i.e. Rs-AFP2 and Dm-AMP1 isolated from radish and dahlia seed, respectively, induced a rapid K+ efflux, Ca2+ uptake, and alkalinization of the incubation medium. The Rs-AFP2-induced alkalinization of the incubation medium could be inhibited with G-protein inhibitors. alpha-Hordothionin, an antifungal thionin from barley seed, caused a sustained increased Ca2+ uptake at subinhibitory concentrations but only a transient increased uptake at inhibitory concentrations. alpha-Hordothionin also caused increased K+ efflux and alkalinization of the medium, but these fluxes occurred more rapidly compared to those caused by plant defensins. Furthermore, alpha-hordothionin caused permeabilization of fungal hyphae to the non-metabolite alpha-aminoisobutyric acid and, in addition, altered the electrical properties of artificial lipid bilayers, consistently leading to rupture of the lipid bilayers. The plant defensins did not form ion-permeable pores in artificial membranes and did not exhibit substantial hyphal membrane permeabilization activity. Our results are consistent with the notion that thionins inhibit fungal growth as a result of direct protein-membrane interactions, whereas plant defensins might act via a different, possibly receptor-mediated, mechanism.
Intratumor OX40 stimulation inhibits IRF1 expression and IL‐10 production by Treg cells while enhancing CD40L expression by effector memory T cells (2011)

Treg cells maintain the tumor microenvironment in an immunosuppressive state preventing an effective anti-tumor immune response. A possible strategy to overcome Treg-cell suppression focuses on OX40, a costimulatory molecule expressed constitutively by Treg cells while being induced in activated effector T cells. OX40 stimulation, by the agonist mAb OX86, inhibits Treg-cell suppression and boosts effector T-cell activation. Here we uncover the mechanisms underlying the therapeutic activity of OX86 treatment dissecting its distinct effects on Treg and on effector memory T (Tem) cells, the most abundant CD4+ populations strongly expressing OX40 at the tumor site. In response to OX86, tumor-infiltrating Treg cells produced significantly less interleukin 10 (IL-10), possibly in relation to a decrease in the transcription factor interferon regulatory factor 1 (IRF1). Tem cells responded to OX86 by upregulating surface CD40L expression, providing a licensing signal to DCs. The CD40L/CD40 axis was required for Tem-cell-mediated in vitro DC maturation and in vivo DC migration. Accordingly, OX86 treatment was no longer therapeutic in CD40 KO mice. In conclusion, following OX40 stimulation, blockade of Treg-cell suppression and enhancement of the Tem-cell adjuvant effect both concurred to free DCs from immunosuppression and activate the immune response against the tumor.
A 16×16 CMOS Proton Camera Array for Direct Extracellular Imaging of Hydrogen-Ion Activity (2008)

Over the past twenty-five years, silicon CMOS technology has firmly established itself as the dominant platform in the microelectronics industry. This has resulted in many recent initiatives to fabricate CMOS-based microelectrodes for the stimulation and recording of electrical activity of neurons. CMOS technology offers the potential for monolithic integration of sensors and electronics and it serves as an appropriate platform to facilitate the integration of large arrays of sensors into a small geometry. The extracellular pH of a cell culture is a particularly important indicator of global cellular metabolism, but up until now, this property has typically been measured with invasive and expensive techniques such as miniaturized glass microelectrodes, fluorescent ratio imaging microscopy and magnetic resonance spectroscopy. CMOS provides a scalable, low cost, mass manufacturing platform, and offers the potential to develop sensor arrays that can perform non-invasive and long term imaging on cultured cells. In this paper, we present the first 16x16 proton camera array for direct imaging of the hydrogen-ion activity of cell cultures grown in vitro. The proton camera is based on a single-chip ion-sensitive field-effect transistor (ISFET) sensor array technology that can be implemented using a standard commercial CMOS process.
Selective Immobilization of DNA and Antibody Probes on Electrode Arrays:  Simultaneous Electrochemical Detection of DNA and Protein on a Single Platform (2007)

A proof of concept procedure for the electroaddressable covalent immobilization of DNA and protein on arrayed electrodes along with simultaneous detection of multiple bioagents in the same sample solution is described. Carboxyphenyldiazonium was selectively deposited onto five of nine individually addressable electrodes in an array via bias assisted assembly. Amine functionalized DNA probes were covalently coupled to the carboxyl surface via carbodiimide chemistry. This was followed by the covalent immobilization of diazonium-antibody conjugates into the remaining four electrodes via cyclic voltammetry. Simultaneous electrochemical detection of a DNA sequence related to the breast cancer BRCA1 gene and the human cytokine protein interleukin-12, which is a substantial component in the immune system response and attack of tumor cells, is reported. These results demonstrate the possibility of selective patterning of diverse biomolecules on a single device and may have significant implications for future development of microarrays and biosensors.
LIF and BMP signaling generate separate and discrete types of GFAP-expressing cells (2005)

Bone morphogenetic protein (BMP) and leukemia inhibitory factor (LIF) signaling both promote the differentiation of neural stem/progenitor cells into glial fibrillary acidic protein (GFAP) immunoreactive cells. This study compares the cellular and molecular characteristics, and the potentiality, of GFAP(+) cells generated by these different signaling pathways. Treatment of cultured embryonic subventricular zone (SVZ) progenitor cells with LIF generates GFAP(+) cells that have a bipolar/tripolar morphology, remain in cell cycle, contain progenitor cell markers and demonstrate self-renewal with enhanced neurogenesis - characteristics that are typical of adult SVZ and subgranular zone (SGZ) stem cells/astrocytes. By contrast, BMP-induced GFAP(+) cells are stellate, exit the cell cycle, and lack progenitor traits and self-renewal--characteristics that are typical of astrocytes in the non-neurogenic adult cortex. In vivo, transgenic overexpression of BMP4 increases the number of GFAP(+) astrocytes but depletes the GFAP(+) progenitor cell pool, whereas transgenic inhibition of BMP signaling increases the size of the GFAP(+) progenitor cell pool but reduces the overall numbers of astrocytes. We conclude that LIF and BMP signaling generate different astrocytic cell types, and propose that these cells are, respectively, adult progenitor cells and mature astrocytes.
N-Terminomics identifies HtrA1 cleavage of thrombospondin-1 with generation of a proangiogenic fragment in the polarized retinal pigment epithelial cell model of age-related macular degeneration (2018)

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly population. Variants in the HTRA1-ARMS2 locus have been linked to increased AMD risk. In the present study we investigated the impact of elevated HtrA1 levels on the retina pigment epithelial (RPE) secretome using a polarized culture system. Upregulation of HtrA1 alters the abundance of key proteins involved in angiogenesis and extracellular matrix remodeling. Thrombospondin-1, an angiogenesis modulator, was identified as a substrate for HtrA1 using terminal amine isotope labeling of substrates in conjunction with HtrA1 specificity profiling. HtrA1 cleavage of thrombospondin-1 was further corroborated by in vitro cleavage assays and targeted proteomics together with small molecule inhibition of HtrA1. While thrombospondin-1 is anti-angiogenic, the proteolytically released N-terminal fragment promotes the formation of tube-like structure by endothelial cells. Taken together, our findings suggest a mechanism by which increased levels of HtrA1 may contribute to AMD pathogenesis. The proteomic data has been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier. For quantitative secretome analysis, project accession: PXD007691, username: reviewer45093@ebi.ac.uk, password: 1FUpS6Yq. For TAILS analysis, project accession: PXD007139, username: reviewer76731@ebi.ac.uk, password: sNbMp7xK.
Identification of residues in the estrogen receptor that confer differential sensitivity to estrogen and hydroxytamoxifen. (1993)

We have generated mutant mouse estrogen receptors which differ in their sensitivity to estrogen and the antiestrogen 4-hydroxytamoxifen. Mutation of the glycine at position 525 and the methionine and/or serine at positions 521/522 virtually abolishes the ability of the receptor to bind estradiol and stimulate transcription. In contrast, the mutant receptors retain the partial agonist activity exhibited by the wild-type receptor in the presence of 4-hydroxytamoxifen. The mutations do not affect the expression and DNA-binding activity of the receptor, but do abolish the estrogen-induced increase in the mobility of the receptor-DNA complex observed with the wild-type receptor. Other mutant receptors that were able to bind and stimulate transcription in the presence of estradiol also failed to show the agonist-induced increase in the mobility of the receptor-DNA complex, suggesting that it is unlikely to reflect the formation of a hormone-dependent transcriptional activation function.
Two anthranilate synthase genes in Arabidopsis: defense-related regulation of the tryptophan pathway. (1992)

Arabidopsis thaliana has two genes, ASA1 and ASA2, encoding the alpha subunit of anthranilate synthase, the enzyme catalyzing the first reaction in the tryptophan biosynthetic pathway. As a branchpoint enzyme in aromatic amino acid biosynthesis, anthranilate synthase has an important regulatory role. The sequences of the plant genes are homologous to their microbial counterparts. Both predicted proteins have putative chloroplast transit peptides at their amino termini and conserved amino acids involved in feedback inhibition by tryptophan. ASA1 and ASA2 cDNAs complement anthranilate synthase alpha subunit mutations in the yeast Saccharomyces cerevisiae and in Escherichia coli, confirming that both genes encode functional anthranilate synthase proteins. The distributions of ASA1 and ASA2 mRNAs in various parts of Arabidopsis plants are overlapping but nonidentical, and ASA1 mRNA is approximately 10 times more abundant in whole plants. Whereas ASA2 is expressed at a constitutive basal level, ASA1 is induced by wounding and bacterial pathogen infiltration, suggesting a novel role for ASA1 in the production of tryptophan pathway metabolites as part of an Arabidopsis defense response. Regulation of key steps in aromatic amino acid biosynthesis in Arabidopsis appears to involve differential expression of duplicated genes.
Identification of eukaryotic mRNAs that are translated at reduced cap binding complex eIF4F concentrations using a cDNA microarray (1999)

Although most eukaryotic mRNAs need a functional cap binding complex eIF4F for efficient 5' end- dependent scanning to initiate translation, picornaviral, hepatitis C viral, and a few cellular RNAs have been shown to be translated by internal ribosome entry, a mechanism that can operate in the presence of low levels of functional eIF4F. To identify cellular mRNAs that can be translated when eIF4F is depleted or in low abundance and that, therefore, may contain internal ribosome entry sites, mRNAs that remained associated with polysomes were isolated from human cells after infection with poliovirus and were identified by using a cDNA microarray. Approximately 200 of the 7000 mRNAs analyzed remained associated with polysomes under these conditions. Among the gene products encoded by these polysome-associated mRNAs were immediate-early transcription factors, kinases, and phosphatases of the mitogen-activated protein kinase pathways and several protooncogenes, including c-myc and Pim-1. In addition, the mRNA encoding Cyr61, a secreted factor that can promote angiogenesis and tumor growth, was selectively mobilized into polysomes when eIF4F concentrations were reduced, although its overall abundance changed only slightly. Subsequent tests confirmed the presence of internal ribosome entry sites in the 5' noncoding regions of both Cyr61 and Pim-1 mRNAs. Overall, this study suggests that diverse mRNAs whose gene products have been implicated in a variety of stress responses, including inflammation, angiogenesis, and the response to serum, can use translational initiation mechanisms that require little or no intact cap binding protein complex eIF4F.