gebhart/patrepeval huggingface dataset:
Recurrent Fusion of TMPRSS2 and ETS Transcription Factor Genes in Prostate Cancer (2005)

Recurrent chromosomal rearrangements have not been well characterized in common carcinomas. We used a bioinformatics approach to discover candidate oncogenic chromosomal aberrations on the basis of outlier gene expression. Two ETS transcription factors, ERG and ETV1, were identified as outliers in prostate cancer. We identified recurrent gene fusions of the 5' untranslated region of TMPRSS2 to ERG or ETV1 in prostate cancer tissues with outlier expression. By using fluorescence in situ hybridization, we demonstrated that 23 of 29 prostate cancer samples harbor rearrangements in ERG or ETV1. Cell line experiments suggest that the androgen-responsive promoter elements of TMPRSS2 mediate the overexpression of ETS family members in prostate cancer. These results have implications in the development of carcinomas and the molecular diagnosis and treatment of prostate cancer.
Spontaneous abnormalities in normal fibroblasts from patients with Li-Fraumeni cancer syndrome: aneuploidy and immortalization. (1990)

Families of patients with the Li-Fraumeni cancer syndrome have an inherited pattern of sarcomas and various other types of cancers that follow a dominant mode of transmission, an early age of onset, and exhibit multiple primary tumors. As soft tissue sarcomas (including fibrosarcomas) are frequently observed with this syndrome, the in vitro growth characteristics of fibroblasts derived from skin biopsies of Li-Fraumeni syndrome patients were studied. Control fibroblasts maintained a normal morphology and eventually senesced in culture. Fibroblasts from seven of eight affected individuals developed changes in morphology, anchorage-independent growth, and chromosomal abnormalities. In a fashion similar to that of fibroblasts from normal donors they underwent a growth crisis during which their growth was slow, but they continued to grow past the point at which control samples had stopped dividing (35 population doublings). Fibroblasts from Li-Fraumeni cancer patients escape senescence, growing well beyond 35 population doublings with growth rates similar to early-passage cells. Patient fibroblasts maintain the morphology of a transformed cell but remain nontumorigenic in nude mice. These observations of the behavior of fibroblasts from patients with the Li-Fraumeni syndrome may have predictive value for the determination of gene carriers within these families who are at high risk of cancer.
Molecular heterogeneity of the vascular endothelium revealed by in vivo phage display. (1998)

Vascular beds are known to differ in structure and metabolic function, but less is known about their molecular diversity. We have studied organ-specific molecular differences of the endothelium in various tissues by using in vivo screening of peptide libraries expressed on the surface of a bacteriophage. We report here that targeting of a large number of tissues with this method yielded, in each case, phage that homed selectively to the targeted organ. Different peptide motifs were recovered from each of these tissues. The enrichment in homing to the target organs relative to an unselected phage was 3-35-fold. Peptide sequences that conferred selective phage homing to the vasculature of lung, skin, and pancreas were characterized in detail. Immunohistochemistry showed that the phage localized in the blood vessels of their target organ. When tested, the phage homing was blocked in the presence of the cognate peptide. By targeting several tissues and by showing that specific homing could be achieved in each case, we provide evidence that organ- and tissue-specific molecular heterogeneity of the vasculature is a general, perhaps even universal, phenomenon. Our results also show that these molecular differences can serve as molecular addresses.
Targeted VEGF (Vascular Endothelial Growth Factor) Therapy Induces Long-Term Renal Recovery in Chronic Kidney Disease via Macrophage Polarization (2019)

Chronic kidney disease (CKD) universally associates with renal microvascular rarefaction and inflammation, but whether a link exists between these 2 processes is unclear. We designed a therapeutic construct of VEGF (vascular endothelial growth factor) fused to an ELP (elastin-like polypeptide) carrier and show that it improves renal function in experimental renovascular disease. We test the hypothesis that ELP-VEGF therapy will improve CKD, and that recovery will be driven by decreasing microvascular rarefaction partly via modulation of macrophage phenotype and inflammation. CKD was induced in 14 pigs, which were observed for 14 weeks. At 6 weeks, renal blood flow and filtration were quantified using multidetector computed tomography, and then pigs received single intrarenal ELP-VEGF or placebo (n=7 each). Renal function was quantified again 4 and 8 weeks later. Pigs were euthanized and renal microvascular density, angiogenic and inflammatory markers, fibrosis, macrophage infiltration, and phenotype were quantified. Loss of renal hemodynamics in CKD was progressively recovered by ELP-VEGF therapy, accompanied by improved renal microvascular density, fibrosis, and expression of inflammatory mediators. Although renal macrophage infiltration was similar in both CKD groups, ELP-VEGF therapy distinctly shifted their phenotype from proinflammatory M1 to VEGF-expressing M2. Our study unravels potential mechanisms and feasibility of a new strategy to offset progression of CKD using drug-delivery technologies. The results indicate that renal recovery after ELP-VEGF therapy was largely driven by modulation of renal macrophages toward VEGF-expressing M2 phenotype, restoring VEGF signaling and sustaining improvement of renal function and microvascular integrity in CKD.
Site-specific transgene insertion: an approach (1994)

Methods to improve the production of transgenic animals are being developed. Conventional transgenesis, involving microinjection of DNA into fertilized eggs, has a number of limitations. These result from the inability to control both the site of transgene insertion and the number of gene copies inserted. The approach described seeks to overcome these problems and to allow single copy insertion of transgenes into a defined site in animal genomes. The method involves the use of embryonic stem cells, gene targeting and the FLP recombinase system.
Regulation of the RNA-dependent protein kinase by triple helix formation (2000)

The RNA-dependent protein kinase (PKR) is an interferon-induced, RNA-activated enzyme that phos-phorylates the alpha-subunit of the translation initiation factor eIF-2, inhibiting its function. PKR is activated in vitro by binding to double-stranded RNA (dsRNA) molecules of approximately 30 bp or longer. Here we show that triple helix forming oligonucleotides (TFOs) inhibit dsRNA binding to the isolated RNA binding domain of PKR. The inhibition is specific to the targeted RNA and dependent on TFO length. Binding to a 30 bp duplex is inhibited by a 28 nt TFO and a 20 nt TFO with an IC(50) of 35 +/- 2 and 210 +/- 22 nM, respectively. An 18 nt TFO partially inhibits binding. The activation of the kinase domain of PKR by a 30 bp RNA duplex is also inhibited by a 28 nt TFO. Inhibition of binding is most effective when the triple helix is formed prior to addition of the protein. These results indicate that triplex formation can be used to prevent the binding of an RNA binding protein with dsRNA-binding motifs.
A Haplotype-Based Haplotype Relative Risk&rsquo; Approach to Detecting Allelic Associations (1992)

A novel variation of the Haplotype Relative Risk (HRR) of Rubinstein et al. [Hum Immunol 1981;3:384] is proposed, in order to glean increased information about linkage disequilibrium or allelic associations by analyzing haplotype-based data rather than genotypic data. It is shown that statistical tests based on our design give much higher power than those based on the original HRR approach. Several additional nonparametric tests based on the same data are analyzed, and power is computed for each of them. Further, parametric likelihood methods are applied to testing linkage equilibrium, and estimating delta, the coefficient of linkage disequilibrium, from the same data.
Wine, Resveratrol and Health: A Review (2009)

Several studies have cited the Mediterranean diet as an example of healthy eating. In fact, the Mediterranean diet has become the reference diet for the prevention of cardiovascular disease. Red wine seems to be an essential component of the diet, since moderate consumption of wine is associated with lower risk and mortality from cardiovascular disease. Evidence is also accumulating that wine helps prevent the development of certain cancers. Of all the many components of wine, resveratrol, which is a natural component specifically present in wine, has been identified as being mainly responsible for these health-promoting properties. Many valuable properties such as cardioprotective and anticarcinogenic activity have been attributed to resveratrol; however, its bioavailability is quite low. The bioactivity of metabolites derived from resveratrol, and the accumulation of resveratrol in vital organs are still under study, but there are high expectations of positive results. Other stilbene compounds are also considered in this review, despite being present in undetectable or very small quantities in wine. The present paper reviews all aspects of the health properties of wine, bioactive compounds found in wine, and their concentrations, bioavailability and possible synergistic effects.
NF-κB- and AP-1-Mediated Induction of Human Beta Defensin-2 in Intestinal Epithelial Cells byEscherichia coliNissle 1917: a Novel Effect of a Probiotic Bacterium (2004)

Little is known about the defensive mechanisms induced in epithelial cells by pathogenic versus probiotic bacteria. The aim of our study was to compare probiotic bacterial strains such as Escherichia coli Nissle 1917 with nonprobiotic, pathogenic and nonpathogenic bacteria with respect to innate defense mechanisms in the intestinal mucosal cell. Here we report that E. coli strain Nissle 1917 and a variety of other probiotic bacteria, including lactobacilli--in contrast to more than 40 different E. coli strains tested--strongly induce the expression of the antimicrobial peptide human beta-defensin-2 (hBD-2) in Caco-2 intestinal epithelial cells in a time- and dose-dependent manner. Induction of hBD-2 through E. coli Nissle 1917 was further confirmed by activation of the hBD-2 promoter and detection of the hBD-2 peptide in the culture supernatants of E. coli Nissle 1917-treated Caco-2 cells. Luciferase gene reporter analyses and site-directed mutagenesis experiments demonstrated that functional binding sites for NF-kappaB and AP-1 in the hBD-2 promoter are required for induction of hBD-2 through E. coli Nissle 1917. Treatment with the NF-kappaB inhibitor Helenalin, as well as with SP600125, a selective inhibitor of c-Jun N-terminal kinase, blocked hBD-2 induction by E. coli Nissle 1917 in Caco-2 cells. SB 202190, a specific p38 mitogen-activated protein kinase inhibitor, and PD 98059, a selective inhibitor of extracellular signal-regulated kinase 1/2, were ineffective. This report demonstrates that probiotic bacteria may stimulate the intestinal innate defense through the upregulation of inducible antimicrobial peptides such as hBD-2. The induction of hBD-2 may contribute to an enhanced mucosal barrier to the luminal bacteria.
Macrocyclic metal complexes built on polyethylenimine (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMacrocyclic metal complexes built on polyethylenimineJunghun Suh, Younghee Cho, and Kyung Joo LeeCite this: J. Am. Chem. Soc. 1991, 113, 11, 4198–4202Publication Date (Print):May 1, 1991Publication History Published online1 May 2002Published inissue 1 May 1991https://pubs.acs.org/doi/10.1021/ja00011a022https://doi.org/10.1021/ja00011a022research-articleACS PublicationsRequest reuse permissionsArticle Views298Altmetric-Citations47LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Near-Surface Characterization from Remote Sensing Data (2006)

The understanding of near-surface elastic properties is among the biggest challenges in onshore surface seismic technology. Effects related to the coupling of sources and receivers to the surface, as well as the propagation of the seismic waves in the near-surface, result in significant degradation of the recorded seismic signal. &lt;br&gt; &lt;br&gt;Optical remote sensing using visible, near-infrared, and shortwave infrared data allows mapping of the surface covering, including land-use, vegetation, and surface rock types. Thermal infrared data also provide information about the shallow near surface through conversion of sunlight into heat radiation. Volcanic and highly weathered rocks are characterized by a high thermal infrared signal, whereas, buried drainage systems and surface faults appear cool on the thermal infrared data. Radar remote sensing using microwave scattering from the surface and the shallow near surface provides information about the texture, and about the size of boulders in dry, rough, areas. Remote sensing data can be interpreted for elastic properties of the surface with application to seismic data quality estimation, and logistical planning. They can also assist in surface velocity model building and interpolation of surface velocity models obtained from sparse seismic data. &lt;br&gt;
Recent developments in glycoconjugates (1999)

B. G. Davis, J. Chem. Soc., Perkin Trans. 1, 1999, 3215 DOI: 10.1039/A809773I
Poly(ethylene glycols) are extraordinary catalysts in liquid-liquid two-phase dehydrohalogenation (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPoly(ethylene glycols) are extraordinary catalysts in liquid-liquid two-phase dehydrohalogenationYoshikazu Kimura and Steven L. RegenCite this: J. Org. Chem. 1982, 47, 12, 2493–2494Publication Date (Print):June 1, 1982Publication History Published online1 May 2002Published inissue 1 June 1982https://pubs.acs.org/doi/10.1021/jo00133a056https://doi.org/10.1021/jo00133a056research-articleACS PublicationsRequest reuse permissionsArticle Views744Altmetric-Citations67LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
A methodology for quantitation and characterization of oligonucleotides in albumin microspheres (2009)

A fluorescence assay was developed to quantify oligonucleotides (ODNs) encapsulated in bovine serum albumin (BSA) microspheres using antisense to Nuclear Factor-kappaB (NF-kappaB) as a model ODN and employing Oligreen as the fluorescent dye. Methodologies were optimized for the suspension of the microspheres as well as release of the encapsulated ODN using protease digestion. This was followed by the detection and quantitation of the ODN using the Oligreen dye. The Oligreen fluorescence assay gave a concentration-dependent fluorescent interaction with the ODN. Further characterization of the ODN with respect to their structural integrity in non-irradiated and gamma-irradiated antisense encapsulated in BSA microspheres was performed using HPLC, infrared spectroscopy and polyacrylamide gel electrophoresis. Results showed no structural modification of antisense in the BSA microspheres as determined by HPLC retention times for the pure antisense and microsphere-encapsulated ODN. The migration pattern of the antisense in polyacrylamide gels confirmed the absence of significant alterations as a result of the encapsulation process or due to gamma-irradiation. The infrared spectra of non-irradiated and gamma-irradiated antisense to NF-kappaB microspheres also displayed peaks characteristic of the functional groups. The fluorescence assay could also detect NF-kappaB antisense in the serum of rats administered with encapsulated antisense by oral and intravenous routes. This methodology should be valuable for the analysis of BSA-encapsulated antisense ODN and for pharmacokinetic studies during antisense therapy.
Improved Histogram Equalzaiton (HEQ) for Robust Speech Recogntion (2007)

With the rapid development of intelligent transportation systems (ITS), how to provide users with a natural and efficient human-machine interface is now becoming a crucial issue for driver safety. It is no doubt that speech will be one of the best mediators of human-machine interaction; however, the performance of automatic speech recognition (ASR) always radically degrades when the input speech is corrupted by varying noises. In this paper, we consider the use of histogram equalization (HEQ) for robust ASR. A novel data fitting scheme was presented to efficiently approximate the inverse of the cumulative density function of training speech for HEQ, which has the merits of lower storage and time consumption compared to the conventional table-lookup or quantile based HEQ approaches. Moreover, a more elaborate attempt of using multiple inverse functions for different noise conditions was investigated as well. All experiments were carried out on the Aurora-2 standard database and task. Very encouraging results were obtained. The proposed robustness technique has also been properly integrated into our prototype system for in-vehicle traffic information retrieval using spoken queries.
Two of three promoter elements identified in a rice gene for proliferating cell nuclear antigen are essential for meristematic tissue‐specific expression (1995)

Proliferating cell nuclear antigen (PCNA) is an auxiliary protein of DNA polymerase delta, and it is highly conserved among eukaryotes. The rice PCNA promoter, truncated to position -263, was previously shown to confer meristematic tissue-specific expression in transgenic plants. By DNasel footprinting and gel retardation analysis, three cis-acting elements were defined in this truncated promoter, which designated site I (-201 to -194, CCAGGTGG), site IIa (-197 to -188, TGGGCCCGT) and site IIb (-178 to -169, TGGTCCCAC). Site I resembles the G-box, and sites IIa and IIb resemble the conserved motif (T/GGTCCCAT) that is found in promoter regions of auxin-regulated genes. Functional analysis of expression of a PCNA-GUS gene fusion in transgenic tobacco plants revealed that a mutation in site I in the full-length 2.0 kb promoter had no significant effect on the activity. However, the mutation in site I in the truncated -263 promoter, which had 14% of the activity of the full-length promoter, caused a considerable decrease in the activity, suggesting that site I contributes in part to transcriptional activation. Simultaneous disruption of sites IIa and IIb in the full-length promoter caused about 80-85% loss of promoter activity, while separate disruption of site IIa or site IIb resulted in no marked change on the activity. These observations suggest that site IIa and site IIb play an important role in the meristematic tissue-specific expression of the rice PCNA gene, presumably by mediating putative enhancer activities dependent on the far-upstream region.
Molecular Cloning and Characterization of the Porcine Calcitonin Gene-Related Peptide Receptor (1998)

Calcitonin gene-related peptide (CGRP) receptors (CGRP-Rs) are widely distributed throughout the central and peripheral nervous systems. A novel CGRP-R was identified from a porcine lung complementary DNA library. Sequence analysis indicated that the CGRP-R is 462 amino acids in length and shares 93% sequence identity with the human CGRP-R. Northern blot analysis indicated a messenger RNA species of 5.4 kilobases, which is abundantly expressed in the lung. Ligand binding studies of the cloned CGRP-R expressed in human embryonic kidney (HEK-293) cells showed the presence of high affinity receptor for CGRP with a Kd of 38.5 pm. The pharmacological profiles of various ligands competing for [125I]CGRP binding to the expressed receptor were in accordance with those for the natural receptor. Binding of [125I]CGRP to the expressed receptor was decreased in the presence of a nonhydrolyzable analog of GTP, guanosine 5′ (γ-thio)-triphosphate. In functional studies, CGRP stimulated the activation of adenylyl cyclase with an EC50 of 2.5 nm. The linear analog of CGRP, diacetoamidomethyl cysteine CGRP, did not affect adenylyl cyclase activity on its own or in the presence of CGRP. Furthermore, the CGRP receptor antagonists, CGRP-(8–37)α, inhibited the CGRP-mediated response in a competitive manner. Collectively, the binding and functional data demonstrate that we have cloned a porcine CGRP type 1 receptor. The availability of the CGRP-R complementary DNA will allow us to examine its participation in pathophysiological processes.