gebhart/patrepeval huggingface dataset:
Transcriptional Activators Differ in Their Responses to Overexpression of TATA-Box-Binding Protein (1995)

We investigated how overexpression of human TATA-box-binding protein (TBP) affects the action of estrogen receptor (ER) and compared the response with that of other activators. When ER activates a simple promoter, consisting of a response element and either the collagenase or tk TATA box, TBP overexpression potentiates transcription. TBP potentiates only estrogen-induced and not basal transcription and does so independent of spacing between response element and TATA box. TBP overexpression also reduces autoinhibition by overexpressed ER, suggesting that one target of the autoinhibition may be TBP itself. Both AF-1 and AF-2 domains of ER are potentiated by TBP, and each domain binds TBP in vitro. Like ER, chimeric GAL4/VP16 and GAL4/Tat activators are also potentiated by TBP, as is the synergistic activation by ER and GAL4/VP16 on a complex promoter. Unlike ER, GAL4/Sp1 and GAL4/NF-I become less potent when TBP is overexpressed. Furthermore, synergy between ER and Sp1 or between ER and NF-I, whether these are supplied by transfected GAL4 fusions or by the endogenous genes, is inhibited by TBP overexpression. Thus, ER resembles VP16 in response to TBP overexpression and is different from Sp1 and NF-I, which predominate over ER in setting the response on complex promoters.
CD28-B7 blockade prevents the development of experimental autoimmune glomerulonephritis (2000)

Experimental autoimmune glomerulonephritis (EAG), an animal model of Goodpasture's disease, can be induced in Wistar Kyoto (WKY) rats by a single injection of rat glomerular basement membrane (GBM) in adjuvant. EAG is characterized by circulating and deposited anti-GBM antibodies, accompanied by focal necrotizing glomerulonephritis with crescent formation. The role of T cells in the pathogenesis of EAG remains unclear. T-cell costimulation is provided by ligation of CD28 with either B7.1 (CD80) or B7.2 (CD86) on antigen-presenting cells, and can be inhibited by a soluble form of CTLA4 (CTLA4-Ig) that binds to both B7.1 and B7.2. We examined the effect of CD28-B7 blockade on the development of EAG using native CTLA4-Ig or mutant CTLA4-Ig (Y100F-Ig), which selectively blocks B7.1. Native CTLA4-Ig treatment ameliorated EAG by several measures, including the levels of circulating anti-GBM antibodies, albuminuria, the deposition of IgG and fibrin in the glomeruli, the severity of glomerular abnormalities, and the numbers of infiltrating T cells and macrophages. Y100F-Ig resulted in a similar reduction in the severity of nephritis, but produced no overall reduction in circulating anti-GBM antibodies, although there was a reduction in IgG2a antibodies. We concluded that CD28-B7 blockade reduced autoantibody production and cellular infiltration of glomeruli, and prevented target organ injury. Our results suggest a key role for B7. 1 in costimulation of Th1-like autoimmune responses in the rat, and show that glomerular injury in EAG is largely dependent on cell-mediated mechanisms.
DEVELOPMENT OF LOW GLUCOSINOLATE MUSTARD (1990)

The objective of this study was to develop low glucosinolate mustard (Brassica juncea Coss.). This was accomplished through an interspecific cross between an Indian type 3-butenyl glucosinolate containing B. juncea selection and a "Bronowski-gene(s)" containing low glucosinolate B. campestris L. followed by backcrossing to the B. juncea parent. Seed of BC 1 F 2 plants, and selected plants of BC 1 F 3 and BC 1 F 4 generations were analyzed for glucosinolate content by gas chromatography. Total aliphatic glucosinolate contents of individual BC 1 F 2 plants ranged from 57 to 204 μmol g −1 meal. A single BC 1 F 3 plant grown from the BC 1 F 2 plant with the lowest glucosinolate content, identified as 1058, was found to contain less than 1 μmol g −1 meal of total aliphatic glucosinolates. The glucosinolate content in individual plants of the BC 1 F 4 generation of plant 1058 ranged from 0.8 to 2.9 μmol g −1 meal. Field grown progeny of 1058 at three locations in 1987 and at one location in 1988 in Saskatchewan contained less than 10 μmol g −1 meal of total aliphatic glucosinolates. Therefore, the low glucosinolate characteristic of selection 1058 can be considered genetically stable. Progeny of plant 1058 had plant morphology and seed coat reticulation of B. juncea, but poor fertility (&lt; 5 seeds per pod). The development of this low glucosinolate plant is an achievement that should allow the breeding of canola quality oilseed B. juncea mustard.Key words: Mustard, glucosinolate, Brassica juncea, interspecific cross
Heritable Custom Genomic Modifications in Caenorhabditis elegans via a CRISPR–Cas9 System (2013)

We adapted the CRISPR-Cas9 system for template-mediated repair of targeted double-strand breaks via homologous recombination in Caenorhabditis elegans, enabling customized and efficient genome editing. This system can be used to create specific insertions, deletions, and base pair changes in the germline of C. elegans.
Learning a Distance Metric from Relative Comparisons (2003)

This paper presents a method for learning a distance metric from rel-ative comparison such as “A is closer to B than A is to C”. Taking a Support Vector Machine (SVM) approach, we develop an algorithm that provides a flexible way of describing qualitative training data as a set of constraints. We show that such constraints lead to a convex quadratic programming problem that can be solved by adapting standard meth-ods for SVM training. We empirically evaluate the performance and the modelling flexibility of the algorithm on a collection of text documents. 1
Corneometiy measurements to evaluate skin dryness in the modified soap chamber test* (1995)

Comeometer is an useful instrument to quantify observed dryness only when transepidermal water loss has recovered a value close to its baseline value. For both visual and instrumental assessments of skin dryness, waiting 3 to 5 days after patch removal in the Modified Soap Chamber Test will provide the most valuable results.
Tumor-derived hyaluronan induces formation of immunosuppressive macrophages through transient early activation of monocytes (2007)

Macrophages (Mvarphi) in most solid tumors exhibit a distinct immunosuppressive phenotype, but the mechanisms that allow tumor microenvironments to "educate" Mvarphi are incompletely understood. Here, we report that culture supernatants (TSNs) from several types of tumor cell lines can drive monocytes to become immunosuppressive Mvarphi. Kinetic experiments revealed that soon after exposure to these TSNs, monocytes began to provoke transient proinflammatory responses and then became refractory to subsequent stimulation. Other TSNs that failed to cause such temporary preactivation did not alter Mvarphi polarization. Consistent with these results, we observed that the monocytes/Mvarphi in different areas of human tumor samples exhibited distinct activation patterns. Moreover, we found that hyaluronan fragments constitute a common factor produced by various tumors to induce the formation of immunosuppressive Mvarphi, and also that upregulation of hyaluronan synthase-2 in tumor cells is correlated with the ability of the cells to cause Mvarphi dysfunction. These results indicate that soluble factors derived from tumor cells, including hyaluronan fragments, co-opt the normal development of Mvarphi to dynamically educate the recruited blood monocytes in different niches of a tumor. The malignant cells can thereby avoid initiation of potentially dangerous Mvarphi functions and create favorable conditions for tumor progression.
Molecular cloning and expression of cDNA encoding the enzyme that controls conversion of high-mannose to hybrid and complex N-glycans: UDP-N-acetylglucosamine: alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I. (1991)

UDP-GlcNAc:alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I (GnT I; EC 2.4.1.101) catalyzes an essential first step in the conversion of high-mannose N-glycans to hybrid and complex N-glycans. Cloning of the gene encoding this enzyme was carried out by mixed oligonucleotide-primed polymerase chain reaction amplification of rabbit liver single-stranded cDNA using sense and antisense 20- to 24-base-pair (bp) primers. A rabbit liver library in phage lambda gt10 yielded a 2.5-kilobase (kb) cDNA with a 447-amino acid coding sequence. None of the nine asparagine residues were in an Asn-Xaa-(Ser or Thr) sequence, indicating that the protein is not N-glycosylated. There is no sequence homology to other previously cloned glycosyltransferases, but GnT I appears to have a domain structure typical of these enzymes--i.e., a short amino-terminal domain, a transmembrane domain, a "neck" region, and a large carboxyl-terminal catalytic domain. RNA was transcribed off the 2.5-kb cDNA, and in vitro translation with rabbit reticulocyte lysate yielded a 52-kDa protein with GnT I activity.
New Set of Orthogonal Protecting Groups for the Modular Synthesis of Heparan Sulfate Fragments (2003)

Six strategically chosen monosaccharide building blocks, which are protected by a novel set of four orthogonal protecting groups (Lev, Fmoc, TBDPS, and All), can be employed for the efficient synthesis of the 20 disaccharide moieties found in heparan sulfate. The properly protected disaccharide building blocks can be converted into glycosyl donors and acceptors, which can be used for the modular synthesis of a wide range of well-defined oligosaccharides that differ in sulfation pattern. [structure: see text]
Inhibition of HIV-1 Replication by a Nonnucleoside Reverse Transcriptase Inhibitor (1990)

A series of dipyridodiazepinones have been shown to be potent inhibitors of human immunodeficiency virus-1 (HIV-1) reverse transcriptase (RT). One compound, BI-RG-587, had a Ki of 200 nanomolar for inhibition of HIV-1 RT that was noncompetitive with respect to deoxyguanosine triphosphate. BI-RG-587 was specific for HIV-1 RT, having no effect on feline and simian RT or any mammalian DNA polymerases. BI-RG-587 inhibited HIV-1 replication in vitro as demonstrated by in situ hybridization, inhibition of protein p24 production, and the lack of syncytia formation in cultured human T cell lines and freshly isolated human peripheral blood lymphocytes. Cytotoxicity studies of BI-RG-587 on human cells showed a high therapeutic index (greater than 8000) in culture.
Separation of Large and Small Granules from Horseshoe Crab (Tachypleus tridentatus) Hemocytes and Characterization of Their Components1 (1993)

We designed a method for separating two types of granules, a smaller (S) but dense and a larger (L) but less dense granule from hemocytes of the horseshoe crab (Tachypleus tridentatus), using continuous sucrose density gradient centrifugation. The isolated L-granules contained at least three clotting factors plus a clottable protein, coagulogen, as the major component. The known anti-lipopolysaccharide factor and 7 additional unknown protein components were also present in the L-granules. Two known natural substrates, Pro-rich protein and 8.6 kDa protein, for limulus transglutaminase [Tokunaga, F., Yamada, M., Miyata, T., Ding, Y.-L., Hiranaga-Kawabata, M., Muta, T., Iwanaga, S., Ichinose, A., & Davie, E.W. (1993) J. Biol. Chem. 268, 252-261] were present in the L-granules. On the other hand, the isolated S-granules contained antimicrobial tachyplesins I and II (17 amino acids in length) as the major component, in addition to 6 unidentified proteins with molecular masses of less than 30 kDa. The structural analyses of tachyplesin analogs indicated that all these peptides of mature form are stored in the S-granules, together with a processing intermediate containing the COOH-terminal Gly-Lys sequence. We also found an Arg-rich protein of 22 kDa and a Leu-rich protein of 30 kDa in S-granules. Based on these observations, we speculate that protein components in L-granules, which probably contain all the factors essential for the limulus clotting system, participate in immobilization of invading microbes and that factors in the S-granules containing tachyplesins contribute to a self-defense system against invaders.
Cerebrospinal fluid neurogranin and YKL ‐40 as biomarkers of Alzheimer's disease (2015)

CSF neurogranin and YKL-40 do not improve the diagnostic accuracy of either prodromal AD or AD dementia when compared to the core CSF AD biomarkers. Nevertheless, the CSF level of neurogranin is selectively increased in AD dementia, whereas YKL-40 is increased in both AD and FTD suggesting that synaptic degeneration and glial activation may be important in these neurodegenerative conditions.
Asymptotically optimal block quantization (1979)

In 1948 W. R. Bennett used a companding model for nonuniform quantization and proposed the formula <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">D \: = \: \frac{1}{12N^{2}} \: \int \: p(x) [ É(x) ]^{-2} \dx</tex> for the mean-square quantizing error where <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">N</tex> is the number of levels, <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p</tex> (x) is the probability density of the input, and <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">E \prime</tex> (x) is the slope of the compressor curve. The formula, an approximation based on the assumption that the number of levels is large and overload distortion is negligible, is a useful tool for analytical studies of quantization. This paper gives a heuristic argument generalizing Bennett's formula to block quantization where a vector of random variables is quantized. The approach is again based on the asymptotic situation where <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">N</tex> , the number of quantized output vectors, is very large. Using the resulting heuristic formula, an optimization is performed leading to an expression for the minimum quantizing noise attainable for any block quantizer of a given block size <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">k</tex> . The results are consistent with Zador's results and specialize to known results for the one- and two-dimensional cases and for the case of infinite block length <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">(k \rightarrow \infty)</tex> . The same heuristic approach also gives an alternate derivation of a bound of Elias for multidimensional quantization. Our approach leads to a rigorous method for obtaining upper bounds on the minimum distortion for block quantizers. In particular, for <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">k = 3</tex> we give a tight upper bound that may in fact be exact. The idea of representing a block quantizer by a block "compressor" mapping followed with an optimal quantizer for uniformly distributed random vectors is also explored. It is not always possible to represent an optimal quantizer with this block companding model.
Human papillomavirus and cervical neoplasia: A case‐control study in Taiwan (1995)

As part of a large-scale, community-based cervical neoplasia screening project in rural Taiwan, a case-control study was undertaken to evaluate the etiologic role of human papillomavirus (HPV) infection in this mainly monogamous (2% reported having multiple sexual partners) female population. A total of 88 biopsy-confirmed cases and 261 cytologically normal controls were selected for the study. The case group included 40 cases of cervical intraepithelial neoplasia (CIN) 1, 9 of CIN 2, 36 of CIN 3 and 3 cases of invasive cancer. Cervical swabs collected at screening from study subjects were tested for HPV DNA by an LI consensus primer polymerase chain reaction (PCR)-based technique. HPV DNA was found in 92% of high-grade cases (CIN 2-3 and invasive cancer); 54% of low-grade cases (CIN 1); and 9% of controls. HPV was significantly associated with both high-grade and low-grade cervical neoplasia. As reported in Western countries, HPV 16 was the predominant type among HPV-positive high-grade cases. However, HPVs 52 and/or 58 combined were the most common types among HPV-positive low-grade cases and controls. Among women without any high-risk HPV infection (types 16, 18, 31 or 45), those with multiple-type HPV infection had a higher risk for high-grade cervical neoplasia than those with single-type infection. Overall, 91% of high-grade cases and 50% of low-grade cases could be attributed to HPV infection. Our results show that, even in this monogamous population, HPV is the major risk factor for high-grade cervical neoplasia.
DNA‐Templated Homo‐ and Heterodimerization of Peptide Nucleic Acid Encoded Oligosaccharides that Mimick the Carbohydrate Epitope of HIV (2009)

All under control: The programmability of hybridization has been utilized to generate a combinatorial library of structures that emulate the topologies of complex carbohydrates interacting with an antibody that shows broad-spectrum activity against HIV. This simple method involves attaching oligosaccharides tagged with peptide nucleic acids onto DNA templates in a controlled manner (see schematic picture). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Real world outcomes of metastatic pancreatic cancer (mPC) patients (pts) treated with liposomal irinotecan (nal-IRI) in the US. (2018)

e16229 Background: The NAPOLI-1 study, a randomized phase 3 study in patients with mPDAC previously treated with gemcitabine-based therapy, demonstrated an improvement in overall survival (OS), progression-free survival (PFS), and objective response rate with nal-IRI + folinic acid/ leucovorin (5-FU/LV) vs. 5-FU/LV. In this analysis, we describe real world characteristics and outcomes of mPDAC pts treated with nal-IRI in the US. Methods: This retrospective observational study utilized data from Flatiron Health’s longitudinal database derived from electronic health records data from over 265 diverse cancer clinics. Patient characteristics, OS, time-to-treatment failure (TTF), and adverse events (AEs) abstracted from structured lab data were assessed in adult pts diagnosed with mPDAC who received nal-IRI treatment between November 18, 2015 and August 31, 2017. Results: Of the 257 mPDAC pts treated with nal-IRI, 51% were male, 28% had a pancreatectomy, and median age was 67 (IQR: 61-74). Among pts with an ECOG score recorded at nal-IRI initiation (n=189), 20% had an ECOG of 2 or greater. Following diagnosis of metastatic or recurrent disease, 57% of pts received nal-IRI in the first or second line, and 43% in third line or later. Median OS was 5.59 months [95% CI 4.83,7.33] for pts receiving nal-IRI as the first or second treatment (n=145) and 4.11 months [95% CI 3.38, 4.9] for those receiving it in third or later lines (n=112), respectively. TTF was 2.33 [1.64, 3.02] for those treated in first or second line, and 1.64 [1.38, 1.87] for those in third line or later. Among pts for whom reasons for discontinuation were available(n=186), disease progression (57%), disease-related symptoms (17%), and treatment toxicity (14%) were reported most often. Structured AEs were generally consistent with those reported in NAPOLI-1. Conclusions: In this real world US population with older median age and poorer performance status, median OS, TTF, and structured AEs were similar to those reported in NAPOLI-1. As would be expected, pts receiving nal-IRI treatment in earlier lines had a higher median OS.
The Microbe as a Source of Food (1972)

INTRODUCTION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . WHY SINGLE CELL PROTEIN? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . MICROBIAL CELL PRODUCTION .... Microorganisms used . Substrates used. . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . Culture conditions . Harvesting and drying . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CoMPOSITION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chemical composition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Protein content . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Amino acid composition . Vitamin content . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . NUTRITIVE VALUE • . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Evaluation of protein quality . Feeding studies with animals and man . Human tolerance tests . Eff ect of processing . Questions related to SCP utilization. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . NUCLEIC ACIDS . Nucleic acid content in foods . Risks due to high N A intake . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . Studies on the eff ect of NA consumption . Tolerable intake of NA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . Reduction of NA content in sCPo . EVALUATION OF PRODUcr SAFETY . Test procedure . New products and natural toxicity ' . . . . . . . . . . . Practical experience of SCP toxicity testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ECONOMIC CoNSIDERATIONS . sCP for feed use .. . .. . SCPasfood . LARGE-SCALE PROJECTS ......... . GENERAL CoMMENTS .
Disseminated Histoplasmosis (1980)

GOODWIN, ROBERT A. JR. M.D.; SHAPIRO, JOHN L. M.D.; THURMAN, GRAFTON H. M.D.; THURMAN, STEPHEN S. M.D.; DES PREZ, ROGER M. M.D. Author Information
Philip Levine Award Lecture: Blood Group Antigens as Markers for Normal Differentiation and Malignant Change in Human Tissues (1987)

Journal Article Philip Levine Award Lecture: Blood Group Antigens as Markers for Normal Differentiation and Malignant Change in Human Tissues Get access Kenneth O. Lloyd, Ph.D. Kenneth O. Lloyd, Ph.D. Memorial Sloan-Kettering Cancer Center, New York, New York Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 87, Issue 1, 1 January 1987, Pages 129–139, https://doi.org/10.1093/ajcp/87.1.129 Published: 01 January 1987 Article history Received: 15 July 1986 Accepted: 15 July 1986 Published: 01 January 1987
The EUV program at ASML: an update (2003)

With the realization of the &alpha;-tool, ASML is progressing with the pre-commercialization phase of its EUVL development. We report on the progress in the development of several key modules of the &alpha;-tool, including the source, wafer stage and reticle stage, wafer handling, baseframe, and optics modules. We demonstrate that the focus sensor meets its vacuum requirements, and that both stages after limited servo optimization approach the required scanning performance. A particle detection system has been built for the qualification of the reticle handling module, and preliminary results show that 50nm particles can be detected. The optics lifetime program showed substantial progress by utilizing caplayers to MoSi samples in order to suppress oxidation caused by H<sub>2</sub>O molecules under EUV illumination: a suppression &ge; 100x is achieved, compared to uncapped MoSi.