gebhart/patrepeval huggingface dataset:
The maf Proto-oncogene Stimulates Transcription from Multiple Sites in a Promoter That Directs Purkinje Neuron-Specific Gene Expression (1995)

L7 is expressed in all adult cerebellar Purkinje cells, although during development it appears in a stereotyped spatial and temporal pattern that is manifested as parasagittal domains of neurons. Mutations of the L7 promoter in transgenic mice have established that these domains represent functional compartments of Purkinje neurons. Therefore, it is hoped that by defining the transcriptional control of the L7 gene insights into the mechanisms that control functional fate and organization in the nervous system can be gained. Fragments of the L7 promoter were introduced into a selectable reporter gene in Saccharomyces cerevisiae, and these strains were used to select for cerebellar cDNAs encoding proteins that can bind to, and activate transcription from, these elements. This assay identified the c-Maf proto-oncogene as activating transcription from two sites in the L7 promoter. We did a functional domain analysis of vertebrate c-Maf based upon transcriptional activation in S. cerevisiae and showed the requirement for a transactivation domain, leucine zipper, and DNA-binding region in c-Maf. The c-Maf interaction site was mapped to the sequence G/TGG/CNG/TNCT CAGNN in the L7 promoter, which represents an atypical 12-O-tetradecanoate-13-acetate-responsive element-type Maf-responsive element. However, neither Fos nor Jun, either alone or in combination with each other or c-Maf, altered transcription from this element. In contrast, a Maf-related protein, Nrl, completely mimicked c-Maf actions. These data suggest that Maf may interact with additional basic-zipper proteins that determine a subtype of Maf-responsive element binding.
Insertional Inactivation of trpC in Cloned Bacillus trp Segments: Evidence for a Polar Effect on trpF (1979)

Plasmid pUB110 was previously used as a vector to clone fragments of deoxyribonucleic acid that complement the trpC2 mutation in Bacillus subtilis from endonuclease EcoRI digested B. licheniformis, B. pumilus, and B. subtilis cellular deoxyribonucleic acid. Each of several such trp plasmids was subsequently shown to contain a segment of the trp gene cluster on the basis of genetic complementing activity. In the present study, analysis of the Trp enzyme levels in B. subtilis harboring the constructed trp plasmids confirms the genetic constitution of the plasmids. Thus, plasmids that complement mutations in specific trp genes specify the corresponding enzyme activities. The levels of the plasmid-specified Trp enzymes in B. subtilis were generally above the repressed level of the chromosomally specified Trp enzymes and equal to or below the derepressed levels of the chromosomally specified Trp enzymes. Certain cloned trp segments contain a single HindIII-sensitive site. Insertion of HindIII-generated deoxyribonucleic acid fragments into these trp plasmids resulted in inactivation of trpC complementing activity, loss of the trpC-specified enzyme activity, and a 10-fold reduction in the specific activity of the plasmid-specified trpF product. The HindIII insertions had no detectable effect on the level of the trpD product, nor did the insertions detectably alter plasmid-specified complementing activity other than to abolish trpC complementation. Removal of the HindIII insertions was accompanied by recovery of trpC complementing activity and restoration of the trpC-and trpF-determined enzymes to the levels specified by the parent plasmids.
Activin A Is a Potent Activator of Renal Interstitial Fibroblasts (2004)

The present study was conducted to examine the involvement of the activin-follistatin system in the fibrotic process of the kidney. Immunoreactive activin A was upregulated in tubular cells in the kidneys with unilateral ureteral obstruction but not in normal and contralateral kidneys. Activin A promoted cell proliferation, enhanced the expression of type I collagen mRNA, and induced the production of alpha-smooth muscle actin in a rat kidney fibroblast cell line (NRK-49F cells) as well as in primary cultured renal interstitial fibroblasts. In contrast, activin A did not affect the expressions of alpha-smooth muscle actin and type I collagen in renal epithelial tubular cell lines LLC-PK1, and MDCK. Follistatin, an antagonist of activin A, significantly inhibited cell proliferation in NRK-49F cells. Blockade of activin signaling by overexpression of truncated type II activin receptor, which lacked the intracellular kinase domain, decreased cell proliferation and reduced the expression level of type I collagen mRNA in NRK-49F cells. The expression of activin A was induced by TGF-beta 1 or activin A itself. Induction of type I collagen expression by TGF-beta 1 was reduced by follistatin or by overexpression of truncated type II activin receptor. These results suggest that activin A produced by tubular cells acts as a paracrine factor that activates renal interstitial fibroblasts during the fibrotic processes of the kidney.
Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells (2003)

This report describes an unbiased method for systematically determining gene function in mammalian cells. A total of 20,704 predicted human full-length cDNAs were tested for induction of the IL-8 promoter. A number of genes, including those for cytokines, receptors, adapters, kinases, and transcription factors, were identified that induced the IL-8 promoter through known regulatory sites. Proteins that acted through a cooperative interaction between an AP-1 and an unrecognized cAMP response element (CRE)-like site were also identified. A protein, termed transducer of regulated cAMP response element-binding protein (CREB) (TORC1), was identified that activated expression through the variant CRE and consensus CRE sites. TORC1 potently induced known CREB1 target genes, bound CREB1, and activated expression through a potent transcription activation domain. A functional Drosophila TORC gene was also identified. Thus, TORCs represent a family of highly conserved CREB coactivators that may control the potency and specificity of CRE-mediated responses.
Deterministic Localization and Analysis of Scan Hold-Time Faults (2008)

Abstract This paper presents a deterministic diagnosis analysis method for hold-time faults in scan chains. The defects discussed in this paper are primarily seen at low Vdd values, so called Vdd-min defects; Vdd -max defects can also be a problem. Traditional approaches require data collection, the creation of additional patterns, and an iterative trip back to the tester. This is a time consuming process and does not always lead to a closed end solution. This paper also presents a method to detect multiple hold-time faults in the chain using auto generated pattern, real-time on the tester. The approach includes validation of the hold-time fault model, characterization of the failure behavior in terms of Vdd and data dependencies and finally localization to a cone of logic including the data paths and the clock trees. This method of hold-time localization is organized into three steps. First, the chain integrity test is run at the safe voltage. Second, a set of new patterns is created and run at the failing voltage. Finally, the data is shifted out and compared with the simulation result. The data provides the locations of all of the hold-time faults for the selected failing voltage. Combined with silicon voltage probing, the technique allows the analysis to localize the faults and to measure timing slack on sub-nets in the failing circuitry. This allows very close correlation between timing models and silicon performance leading to more robust design/process matching.
Molecular characterization of ribonucleoprotein antigens bound by antinuclear antibodies. A diagnostic evaluation (1982)

The specificity of antinuclear antibodies in sera from 54 patients with various rheumatic diseases was analyzed by immunoprecipitation of 32P- or 35S-methionine-labeled HeLa cell extracts. Of 35 sera giving a speckled and/or homogeneous immunofluorescence pattern in rat liver nuclei, 20 contained antibodies to nuclear ribonucleoproteins, which are defined by their ribonucleic acid and protein components. Four sera reacted with a nuclear antigen (Ga) which has not been described so far. Of 19 sera with antinucleolar antibodies, 18 did not react with nuclear or nucleolar ribonucleoproteins. Correlation of these molecularly defined antinuclear antibody specificities with immunofluorescence patterns and rheumatic diseases is discussed.
3D approaches for non-volatile memory (2011)

The NAND flash market is continuously growing by the successive introduction of innovative devices and applications. To meet the market trend, 3-dimenstional (3D) non-volatile memories (NVMs) are expected to replace the planar one, especially for 10 nm-nodes and beyond. Therefore, the fundamentals and current status of the 3D NAND flash memory are reviewed and future directions are discussed.
Mutations in the LMNA gene encoding lamin A/C (2000)

Very recently, mutations within the LMNA gene on chromosome 1q21.2 were shown to result in forms of muscular dystrophy, conduction-system disease, cardiomyopathy, and partial lipodystrophy. The LMNA gene encodes for the nucleophilic A-type lamins, lamin A and lamin C. These isoforms are generated by different splicing within exon 10 of LMNA. Thus lamin A/C is, besides emerin, the first known nucleophilic protein which plays a role in human disease. To date, 41 different mutations, predominantly missense, in the LMNA gene are known causing variable phenotypes. Twenty-three different mutations of LMNA have so far been shown to cause autosomal-dominant Emery-Dreifuss muscular dystrophy (EDMD2), three mutations were reported to cause limb-girdle muscular dystrophy (LGMD1B), eight mutations are known to result in dilated cardiomyopathy (CMD1A), and seven mutations were reported to cause familial partial lipodystrophy (FPL). The reports of lamin mutations including the corresponding phenotype are of great interest in order to gain insights into the function of lamin A/C. Here we summarize the mutations published to date in LMNA encoding lamin A/C. Hum Mutat 16:451–459, 2000. © 2000 Wiley-Liss, Inc.
Blood group abh‐related antigens in normal and malignant bladder urothelium: Possible structural basis for the deletion of type‐2 chain abh antigens in invasive carcinomas (1989)

A complete panel of mouse monoclonal antibodies (MAbs) against Type-2 chain (GaI beta I-4GlcNAc-R) blood-group antigens (N-acetyl-lactosamine, Lex, H, Ley, A monofucosylated, Aley, repetitive A) was used in a detailed immunohistological study of the modulation of these carbohydrate antigens in transitional-cell carcinomas. The histological and cellular locations of these antigens were studied in 19 normal bladder biopsies and 53 transitional-cell carcinomas with as well as without neuraminidase treatment of tissue sections in order to uncover potential sialylated antigens. The antigen expression was correlated to individual A1A2BO, Lewis, and secretor status. Several alterations of blood group expression were found: (1) loss of A and H antigens with accumulation of Ley antigens; (2) loss of correlation between antigen expression and secretor status; (3) disruption of the orderly stratification of blood-group antigen expression in relation to cell layers; and (4) changes in subcellular location of antigen expression. The present data indicate that deletion of Type-2 chain ABH antigens in transitional-cell carcinomas is associated with alpha 1-3 fucosylation of the H antigen leading to accumulation of Ley antigens.
Eucharist: Symbol of Transformation. By William R. Crockett. New York, Pueblo Publishing Company, 1989. Pp. x + 286. £12.95. (1993)

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Correlations Between Cancer Incidence Rates From the Canadian National Cancer Incidence Reporting System, 1969–78 (1984)

Incidence rates for 19 cancers in females and 16 cancers in males have been computed from data reported by 8 Canadian provinces to the National Cancer Incidence Reporting System between 1969 and 1978. The rates, very similar in absolute and relative magnitude to those reported by the U.S. Third National Cancer Survey, have been used to examine patterns of correlation between various cancers within the 8 provinces. There is strong evidence of positive associations between a number of cancers, including a number of associations that have been reported in other similar correlational studies. Correlations that may be of particular interest in suggesting etiologic factors in common include clusters of smoking-related cancers (buccal cavity with pharynx, larynx, lung, and bladder), female sexual cancers (breast, corpus uteri, and ovary), and a group of cancers that have shown correlation in other studies (i.e., cancers of the pancreas and kidney, leukemias, lymphomas, and cancer of the prostate gland). Organs in the gastrointestinal tract (esophagus, stomach, colon, and rectum) anatomically close to each other show a high positive correlation in both females and males, but the further apart the organs are the lower is the correlation; these observations are consistent with other evidence of varying dietary etiologies. Two individual correlations of particular interest are those between female brain tumors and female bladder cancer (two cancers for which little is known of the etiology for a large percentage of them) and those between female breast cancer and female lung cancer. This study, the largest correlational study of incidence data reported to date, demonstrates the utility of such simple correlational analyses.
Evolution of supercontraction in spider silk: structure–function relationship from tarantulas to orb-weavers (2010)

Spider silk is a promising biomaterial with impressive performance. However, some spider silks also 'supercontract' when exposed to water, shrinking by up to ∼50% in length. Supercontraction may provide a critical mechanism to tailor silk properties, both for future synthetic silk production and by the spiders themselves. Several hypotheses are proposed for the mechanism and function of supercontraction, but they remain largely untested. In particular, supercontraction may result from a rearrangement of the GPGXX motif within the silk proteins, where G represents glycine, P proline and X is one of a small subset of amino acids. Supercontraction may prevent sagging in wet orb-webs or allow spiders to tailor silk properties for different ecological functions. Because both the molecular structures of silk proteins and how dragline is used in webs differ among species, we can test these hypotheses by comparing supercontraction of silk across diverse spider taxa. In this study we measured supercontraction in 28 spider taxa, ranging from tarantulas to orb-weaving spiders. We found that silk from all species supercontracted, except that of most tarantulas. This suggests that supercontraction evolved at least with the origin of the Araneomorphae, over 200 million years ago. We found differences in the pattern of evolution for two components of supercontraction. Stress generated during supercontraction of a restrained fiber is not associated with changes in silk structure and web architecture. By contrast, the shrink of unrestrained supercontracting fibers is higher for Orbiculariae spiders, whose silk contains high ratios of GPGXX motifs. These results support the hypothesis that supercontraction is caused by a rearrangement of GPGXX motifs in silk, and that it functions to tailor silk material properties.
Delta-like ligand 4 (Dll4) is critical for tumor growth and angiogenesis. (2006)

5705 The Delta-like/Notch signaling pathway is necessary to establish an organized and hierarchical vasculature during development. Targeted deletions of various Delta-like/Notch genes result in mice that die during development due to severe vascular defects. Using microarray analysis, we previously identified Delta-like ligand 4 (Dll4) as a VEGF-regulated gene in mouse xenograft tumor models. In addition, we found that in these tumor models, Dll4 expression was significantly higher in tumor vessels compared to those in adjacent normal skin. To explore the effects of blocking Dll4/Notch signaling in tumors, we performed xenograft studies in mice, where a soluble Dll4-Fc molecule was delivered locally by retrovirally mediated overexpression in tumor cells or was delivered systemically using an adenoviral approach. We found that both methods of delivering Dll4-Fc resulted in reduced tumor growth compared to controls. Additionally, Dll4-Fc treated tumor vessels were more highly branched than controls, forming fine networks with dense vascular sprouting. As revealed by expression analysis, these effects were apparently associated with a decrease in Notch signaling. These findings show that Dll4 plays a key role in tumor angiogenesis, and suggest that Dll4 may be an attractive potential target for the development of anti-angiogenic therapies.
Characterization of the 2-(α-Carbolinyl)nitrenium Ion and Its Conjugate Base Produced during the Decomposition of the Model Carcinogen 2-N-(Pivaloyloxy)-2-amino-α-carboline in Aqueous Solution (2000)

The kinetics of the decomposition of the model ultimate carcinogen 2-N-(pivaloyloxy)-2-amino-α-carboline (4a), and its 9-methyl analogue (4b), in 20 vol % CH3CN−H2O, μ = 0.5 (NaClO4) at 20 °C, are consistent with the uncatalyzed N−O bond heterolysis of the neutral esters. The protonated ester 4aH+ (pKa = 1.6), detected kinetically and by spectrophotometric titration, is unreactive under these conditions. Spectrophotometric titration of 4b also indicates that a protonated species, 4bH+ (pKa = 0.9), is formed under acidic conditions. Both 4a and 4b produce electrophilic intermediates, identified as the nitrenium ions 5a and 5b, that are efficiently trapped by N3-, Br-, and 2‘-deoxyguanosine, d-G, without an increase in the overall rate of decomposition of the esters. N3- and d-G trapping efficiencies, kaz+/ks+ and kd-G+/ks+, for 5a and 5b are very similar to each other and are within a factor of 4 of the trapping efficiencies with N3- and d-G previously measured for the 2-fluorenylnitrenium ion (6). The trapping efficiencies for 5a, but not 5b, decrease with increasing pH. These results indicate that 5a is deprotonated at the indolyl nitrogen to produce a neutral intermediate (7a) that retains reduced reactivity with Br-, N3-, and d-G in an aqueous environment. The neutral 7a undergoes reduction and dimerization reactions in the absence of nonsolvent nucleophiles much more efficiently than its conjugate acid. Microscopic rate constants for trapping of 5a and 7a by the three nucleophiles and the pKa for ionization of 5a to produce 7a have been estimated from experimental data, from the assumption of diffusion control of the reaction of 5a with N3-, and by analogy to the reactions of structurally related species. The relatively low mutagenicity and carcinogenicity of the parent amine, 2-amino-α-carboline (3a), may be related to the fact that the less selective neutral species 7a is responsible for the reaction with nucleophiles at neutral pH.
Electroluminescence from an Organic−Inorganic Perovskite Incorporating a Quaterthiophene Dye within Lead Halide Perovskite Layers (1999)

Room-temperature electroluminescence was realized from an OILED (organic−inorganic light-emitting device) by employing a hybrid organic−inorganic perovskite as the emission layer. The hybrid perovskite consists of a specially modified quaterthiophene dye incorporated within infinite, lead halide perovskite sheets. Relatively efficient (0.1 lm/W) green emission (λmax = 530 nm), with low turn-on voltages (5.5 V), was obtained from a device with a 3000-Å-thick emission layer.
Isolation of Dimeric Forms of Human Pituitary Growth Hormone (1989)

A procedure is described which for the first time allows the isolation of noncovalently-linked dimeric human pituitary growth hormone. Isomers of this dimeric species were prepared as were also, for the first time, isomers of covalently-linked dimers. Chromatography on DEAE-Sepharose CL-6B revealed the existence of noncovalently-linked dimers composed of monomers of 22K hGH, 20K hGH and 20K1 hGH (the latter is a new form of 20K hGH with a scission in the peptide chain) and covalent dimers containing 22K hGH and 24K hGH (the latter a 22K hGH with a scission). The different dimers all occurred as charge isomers and subsequent HPLC on an anion exchanger followed by zone electrophoresis in agarose suspension made possible the isolation of four noncovalently-linked isomers: one form of (20K-20K)hGH, two forms of (20K-22K)hGH and one form of (22K-22K)hGH; and of three covalently-linked isomers: one form of (22K-22K)hGH and two forms of (22K-24K)hGH.
Automated inference of molecular mechanisms of disease from amino acid substitutions (2009)

predrag@indiana.edu; smooney@buckinstitute.org.
The 13C NMR spectra of poly(1‐pentenylene) and poly(1,3‐cyclopentylenevinylene) (1977)

Abstract 13 C NMR spectra were obtained for polymers made by ring‐opening polymerization of cyclopentene and bicyclo[2.2.1]hept‐2‐ene respectively. The fraction of cis double bonds could be determined with much greater precision from 13 C NMR spectra than from IR spectra and varied from 0,66 to 0,31 for the samples of poly(1‐pentenylene), ( 2 ), and from 1,0 to 0,14 for the samples of poly(1,3‐cyclopentylenevinylene), ( 4 ). This is the first time an all‐cis polymer of 4 has been reported. The spectra of 2 showed a cis (upfield) and trans (downfield) peak for each of  C H and α‐CH 2 , but only one peak for β‐CH 2 . The spectra of 4 showed multiple fine structure, the main splittings corresponding to a cis (upfield) and trans (downfield) peak for α‐CH, and a reverse line order for the other three carbons; subsidiary splittings were observed for all but the olefinic carbons, interpreted in terms of sensitivity of the chemical shifts to the cis/trans structure at the next nearest double bond. A complete interpretation of the line orders in 4 is given in terms of steric compression effects. The possibility that ring tacticity accounts for some of the fine structure cannot be entirely discounted. The stereochemistry of 4 is discussed in relation to the four possible modes of addition of monomer to a carbene chain carrier during polymerization.
Increase of protein tyrosine phosphorylation in rat retina after ischemia-reperfusion injury. (1996)

Ischemia-reperfusion injury in the rat retina leads to activation of the tyrosine kinase pathway, increasing the amounts of angiogenic growth factors. The resultant activation of signal proteins PLC gamma, SHC, MAPK, PI3K, and PDGF-beta receptor may play an important role in ischemia-induced retinal changes such as cell proliferation.
Banked multiported register files for high-frequency superscalar microprocessors (2003)

Multiported register files are a critical component of high-performance superscalar microprocessors. Conventional multiported structures can consume significant power and die area. We examine the designs of banked multiported register files that employ multiple interleaved banks of fewer ported register cells to reduce power and area. Banked register files designs have been shown to provide sufficient bandwidth for a superscalar machine, but previous designs had complex control structures that would likely limit cycle time and add to design complexity. We develop a banked register file with much simpler and faster control logic while only slightly increasing the number of ports per bank. We present area, delay, and energy numbers extracted from layouts of the banked register file. For a four-issue superscalar processor, we show that we can reduce area by a factor of three, access time by 20%, and energy by 40%, while decreasing IPC by less than 5%.