gebhart/patrepeval huggingface dataset:
Sequencing and cloning of human prolylcarboxypeptidase (angiotensinase C). Similarity to both serine carboxypeptidase and prolylendopeptidase families (1993)

Prolylcarboxypeptidase, a lysosomal serine carboxypeptidase, cleaves COOH-terminal amino acids linked to proline, as in angiotensin II and III and [des-Arg9] bradykinin. About 25% of the enzyme protein was sequenced, and the complete sequence was deduced from its human kidney cDNA. The cDNA insert contained an open reading frame of 1488 base pairs coding for a protein of 496 residues. The authentic NH2-terminal sequence matched the deduced protein sequence starting with residue 46, suggesting the presence of both a signal and propeptide. The mature enzyme (451 residues) has a calculated M(r) = 51,043, whereas the M(r) of the purified glycoprotein is 58,000, indicating 12% carbohydrate. The overall sequence identity with serine peptidases is low (10-18%), but sequences around residues of the putative catalytic triad (Ser134, Asp333, His411) are similar (30-67%) to both the serine carboxypeptidases (e.g. deamidase or lysosomal protective protein, yeast carboxypeptidase Y, and KEX1 gene product) and the prolylendopeptidase family. Thus, prolylcarboxypeptidase links these two families, suggesting an evolutionary relationship. It is inhibited (Ki = 2.6 x 10(-7) M) by benzyloxycarbonyl-Pro-prolinal, a specific inhibitor of prolylendopeptidase, another angiotensin metabolizing enzyme. Prolylcarboxypeptidase contains serine or threonine residues repeated as the 26th residue 7 out of 9 times, with identical or similar amino acids in other positions in the repeats. The KEX1 gene product contains a similar motif, with serine or threonine as every 27th residue. The importance of prolylcarboxypeptidase is strongly suggested by its presence in various organs and cells and by the substrates it cleaves.
Development of Rechargeable Microbatteries for Autonomous MEMS Applications (1998)

This paper outlines fabrication and evaluation of a thin-film, rechargeable microbattery that provides sufficient power for many autonomous MEMS applications. Initial prototype microbattery 0-9640024-2-6/hh1998/$201998TRF
Effectiveness of cyproheptadine in the management of delayed vomiting after cisplatin-based chemotherapy and the assessment of the influence of cyproheptadine on ąuality of life (2000)

Introduction. Nausea and vomiting belong to the most frequently occurring side effects of chemotherapy, significantly worsening the quality of life of patients receiving cytostatics. The problem of treatment of delayed emesis occurring after administration of cytostatics with the highest emetic potential remains unsolved. Cyproheptadine is a non-specific blocker of serotonine and histamine receptors with a proven antiallergic, antiulcerous and appetite stimulating activity. Its non-specific influence on central and peripheral serotonine receptors suggests the possible influence of this drug on emesis in patients. The aim of this study was to assess the effectiveness of cyproheptadine in the management of delayed vomiting after the cisplatin-based multi-drug chemotherapy and to assess the influence of cyproheptadine on the quality of life of patients receiving chemotherapy. Material and methods. The study was prospective and randomized. Sixty chemotherapy-naive patients (44 women and 16 men), for whom at least three courses of cisplatine-based chemotherapy were planned, were entered. All patients received standard antiemetic treatment (ondansetron /8 mg iv/ or tropisetron /5 mg iv / with dexamethazone /8 mg iv / during the 1st day of treatment and also during the 2nd day when symptoms of nausea and vomiting ECOG grade 2 persisted). The patients belonging to one group additionally received cyproheptadine (Peritol – EGISTM) 12 mg per day for subsequent courses. To compare differences between studied groups according to intensity of nausea and vomiting, non-parametric Mann-Whitney’s and chi-square tests were applied. The remaining parameters (body weight, level of physical and psychological functioning) were analyzed with the use of t-Student test and F Snedecor’s test. Results. The study did not confirm the hypothesis about the influence of cyprohepatdine on the frequency and intensity of delayed vomiting after chemotherapy. However a positive influence of cyproheptadine administration on the occurrence of delayed nausea, body weight gain and quality of life in the aspect of physical functioning was observed.
Micromechanics-based wavelength-sensitive photonic beam control architectures and applications (2000)

Micromechanics-based wavelength-sensitive photonic delay and amplitude control modules are introduced for multiwavelength photonic applications such as hardware-compressed beam forming in phased-array antennas, timing-error compensation in high-speed long-haul fiber-optic communication networks, and pulse synchronization in photonic analog-to-digital converters and space-time code division multiplexed decoders. The basic delay structure relies on a single-circulator compact reflective parallel path design that features polarization insensitivity, independently controllable optical time-delay and amplitude settings, and fiber compatibility. Switched fiber time delays are proposed that use various micromechanical mechanisms such as mechanically stretched fiber Bragg gratings with comb-drive translational stages or magnetic levitation-based stretchers. Additional, shorter-duration variable time delays are obtained by means of the translational motion of external mirrors and the inherent delays in the zigzag reflective path geometry of the bulk-optic thin-film interference filter-based wavelength multiplexer used in our proposed design. Experiments are performed to test these concepts.
DNA-Templated Nanotube Localization (2003)

Carbon nanotubes are nanometer-scale materials with important properties, but their use in nanofabrication will require further development of methods for controlled positioning at well-defined locations on surfaces. We have devised an approach for specifically localizing single-walled carbon nanotubes (SWNTs) onto 1-pyrenemethylamine (PMA)-decorated lambda-DNA molecules aligned on Si surfaces. PMA is used as a bridging compound because its amine group is attracted electrostatically to the negatively charged phosphate backbone of DNA, while the pyrenyl group in PMA interacts with SWNT surfaces through pi-stacking forces. From a total of 60 atomic force microscopy images obtained on three different substrates, we determined that 63% of SWNTs observed on the surfaces were anchored along DNA, and these nanotubes covered approximately 5% of the total DNA length. DNA-templated nanopositioning offers intriguing possibilities for the bottom-up assembly of materials at the nanometer scale.
Oxazolines. XI. Synthesis of functionalized aromatic and aliphatic acids. Useful protecting group for carboxylic acids against Grignard and hydride reagents (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOxazolines. XI. Synthesis of functionalized aromatic and aliphatic acids. Useful protecting group for carboxylic acids against Grignard and hydride reagentsA. I. Meyers, Davis L. Temple, Dan Haidukewych, and Edward D. MihelichCite this: J. Org. Chem. 1974, 39, 18, 2787–2793Publication Date (Print):September 1, 1974Publication History Published online1 May 2002Published inissue 1 September 1974https://pubs.acs.org/doi/10.1021/jo00932a024https://doi.org/10.1021/jo00932a024research-articleACS PublicationsRequest reuse permissionsArticle Views3029Altmetric-Citations130LEARN 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
Research Resource: Transcriptional Profiling in a Cellular Model of Breast Cancer Reveals Functional and Mechanistic Differences Between Clinically Relevant SERM and Between SERM/Estrogen Complexes (2012)

Exploitation of the relationship between estrogen receptor (ER) structure and activity has led to the development of 1) selective ER modulators (SERM), compounds whose relative agonist/antagonist activities differ between target tissues; 2) selective ER degraders (SERD), compounds that induce a conformational change in the receptor that targets it for proteasomal degradation; and 3) tissue-selective estrogen complexes (TSEC), drugs in which a SERM and an ER agonist are combined to yield a blended activity that results in distinct clinical profiles. In this study, we have performed a comprehensive head-to-head analysis of the transcriptional activity of these different classes of ERM in a cellular model of breast cancer. Not surprisingly, these studies highlighted important functional differences and similarities among the existing SERM, selective ER degraders, and TSEC. Of particular importance was the identification of genes that were regulated by various TSEC combinations but not by an estrogen or SERM alone. Cumulatively, the findings of this analysis are informative with respect to the mechanisms by which ER is engaged by different enhancers/promoters and highlights how promoter context influences the pharmacological activity of ER ligands.
Computer-assisted analysis of envelope protein sequences of seven human immunodeficiency virus isolates: prediction of antigenic epitopes in conserved and variable regions (1987)

Independent isolates of human immunodeficiency virus (HIV) exhibit a striking genomic diversity, most of which is located in the viral envelope gene. Since this property of the HIV group of viruses may play an important role in the pathobiology of the virus, we analyzed the predicted amino acid sequences of the envelope proteins of seven different HIV strains, three of which represent sequential isolates from a single patient. By using a computer program that predicts the secondary protein structure and superimposes values for hydrophilicity, surface probability, and flexibility, we identified several potential antigenic epitopes in the envelope proteins of the seven different viruses. Interestingly, the majority of the predicted epitopes in the exterior envelope protein (gp120) were found in regions of high sequence variability which are interspersed with highly conserved regions among the independent viral isolates. A comparison of the sequential viral isolates revealed that changes concerning the secondary structure of the protein occurred only in regions which were predicted to be antigenic, predominantly in highly variable regions. The membrane-associated protein gp41 contains no highly variable regions; about 80% of the amino acids were found to be conserved, and only one hydrophilic area was identified as likely to be accessible to antibody recognition. These findings give insight into the secondary and possible tertiary structure of variant HIV envelope proteins and should facilitate experimental approaches directed toward the identification and fine mapping of HIV envelope proteins.
llβ-Hydroxysteroid Dehydrogenase Activity in the Renal Target Cells of Aldosterone* (1991)

Aldosterone selectivity in mineralocorticoid target tissues has been suggested to be due to 11 beta-hydroxysteroid dehydrogenase (11-OHSD), which, by inactivating the endogenous glucocorticoids cortisol and corticosterone (CS), would allow aldosterone to bind to the mineralocorticoid receptor that has equal affinity for aldosterone and natural glucocorticoids. However, a recent immunohistochemical study failed to colocalize 11-OHSD and mineralocorticoid receptors in the kidney. The goal of this study was to determine 1) whether metabolism of CS occurs in the renal target cells of aldosterone, i.e. in cortical collecting duct cells, and 2) if it does so, whether this activity is sufficient to reduce intracellular CS levels to allow binding of aldosterone to the mineralocorticoid receptor. Cortical collecting duct cells were isolated by solid phase immunoadsorption, with a cell purity of approximately 98%. Metabolism of CS was studied in both freshly isolated cells and primary cultures grown as monolayers on permeable supports. Freshly isolated cells rapidly converted CS to 11-dehydro-CS, which was the only major metabolite detected. In intact collecting duct cells 11-OHSD had an apparent Km for CS of approximately 60 nM, a value more than 100-fold lower than the Km of 11-OHSD in the rat liver, and a maximum velocity of approximately 1.7 x 10(-14) mol/min.1000 cells. In cultured cells, when [3H]CS was applied to one side of the monolayer, almost all radioactivity on the opposite side was 11-dehydro-CS. The cells were able to almost completely metabolize CS passing through them for up to a concentration of 2.5 x 10(-7) M. Carbenoxolone, an inhibitor of 11-OHSD, reduced CS degradation by 88%. Neither freshly isolated nor cultured collecting duct cells converted [3H]11-dehydro-CS back to CS in a significant amount (less than 1%). These data provide functional evidence for 11-OHSD activity in renal aldosterone target cells and indicate that this enzyme might be a collecting duct-specific isoform of 11-OHSD which can sufficiently reduce intracellular CS concentrations to contribute to the apparent mineralocorticoid selectivity of the collecting duct.
Glial Fibrillary Acidic Protein in Serum After Traumatic Brain Injury and Multiple Trauma (2004)

The findings showed that GFAP is released after TBI, that GFAP is related to brain injury severity and outcome after TBI, and that GFAP is not released after multiple trauma without brain injury.
Estrogen Modulates Microglial Inflammatory Mediator Production via Interactions with Estrogen Receptor β (2004)

Estrogens are well known to exert antiinflammatory effects outside the central nervous system (CNS). They have also been shown to exert neuroprotective effects in the CNS after several types of injury, including neurodegeneration. However, the molecular mechanisms by which these effects occur remain unclear. Because microglial hyperactivation and their production of neurotoxins is associated with many types of brain injury for which estrogens are beneficial, we sought to investigate the ability of estrogen to modulate microglial function. Furthermore, because little is known regarding the role of each of the two known estrogen receptors (ERs) in microglia, our studies were designed to test the hypothesis that 17beta-estradiol (E(2)) exerts antiinflammatory effects in microglia, specifically via interactions with ERbeta. We tested this hypothesis using the murine microglial cell line BV-2, which naturally expresses only ERbeta. Our results indicate that not only does E(2) decrease lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression, it also reduces the expression of cyclooxygenase-2, a target for estrogen that has not previously been reported for ERbeta. We also observed that LPS-stimulated TNFalpha mRNA was increased by estrogen. E(2) exerts these effects within 30 min compared with typical estrogen transcriptional responses. Tamoxifen and ICI 182,780 differentially blocked the inhibitory effects of E(2) on LPS-stimulated iNOS and cyclooxygenase-2. In addition, we show that E(2) alters LPS-stimulated MAPK pathway activation, supporting the idea that alterations in the MAPKs may be a potential mechanism by which ERbeta mediates decreased microglial activation.
Design and Characterization of an HIV-Specific Ribonuclease Zymogen (2008)

Ribonucleases are evoking medical interest because of their intrinsic cytotoxic activity. Most notably, ranpirnase, which is an amphibian ribonuclease, is in advanced clinical trials as a chemotherapeutic agent for the treatment of cancer. Here, we describe a strategy to create a novel antiviral agent based on bovine pancreatic ribonuclease (RNase A), a mammalian homologue of ranpirnase. Specifically, we have linked the N- and C-termini of RNase A with an amino acid sequence that is recognized and cleaved by human immunodeficiency virus (HIV) protease. This linkage obstructs the active site, forming an HIV-specific RNase A zymogen. Cleavage by HIV-1 protease increases ribonucleolytic activity by 50-fold. By relying on the proper function of HIV-1 protease, rather than its inhibition, our approach will not engender known mechanisms of resistance. Thus, we report an initial step toward a new class of agents for the treatment of HIV/AIDS.
Automatic text summarization with neural networks (2004)

A novel technique for summarizing news articles using neural networks is presented. A neural network is trained to learn the relevant features of sentences that should be included in the summary of the article. The neural network is then modified to generalize and combine the relevant features apparent in summary sentences. Finally, the modified neural network is used as a filter to summarize news articles.
Pro- and antiinflammatory cytokine balance in rheumatoid arthritis. (1996)

High levels of proinflammatory cytokines such as IL-1, TNF-alpha and IL-6 are produced by the rheumatoid synovitis. These cytokines, mainly produced by monocytes/macrophages, are thought to play a major role in chronic inflammation and in the final joint degradation. IL-4, IL-10, and IL-13 have been classified as antiinflammatory cytokines as they inhibit the production of the proinflammatory cytokines by monocytes. Acting on the balance between these two groups of cytokines may lead to new therapeutic approaches to controlling chronic inflammation without interfering at the level of the antigen.
CRISPR/Cas9-Mediated Targeted Mutagenesis in the Liverwort Marchantia polymorpha L. (2014)

Targeted genome modification technologies are key tools for functional genomics. The clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease Cas9 system (CRISPR/Cas9) is an emerging technology for targeted genome modification. The CRISPR/Cas9 system consists of a short guide RNA (gRNA), which specifies the target genome sequence, and the Cas9 protein, which has endonuclease activity. The CRISPR/Cas9 system has been applied to model animals and flowering plants, including rice, sorghum, wheat, tobacco and Arabidopsis. Here, we report the application of CRISPR/Cas9 to targeted mutagenesis in the liverwort Marchantia polymorpha L., which has emerged as a model species for studying land plant evolution. The U6 promoter of M. polymorpha was identified and cloned to express the gRNA. The target sequence of the gRNA was designed to disrupt the gene encoding auxin response factor 1 (ARF1) in M. polymorpha. Using Agrobacterium-mediated transformation, we isolated stable mutants in the gametophyte generation of M. polymorpha. CRISPR/Cas9-based site-directed mutagenesis in vivo was achieved using either the Cauliflower mosaic virus 35S or M. polymorpha EF1α promoter to express Cas9. Isolated mutant individuals showing an auxin-resistant phenotype were not chimeric. Moreover, stable mutants were produced by asexual reproduction of T1 plants. Multiple arf1 alleles were easily established using CRIPSR/Cas9-based targeted mutagenesis. Our results provide a rapid and simple approach for molecular genetics in M. polymorpha, and raise the possibility that CRISPR/Cas9 may be applied to a wide variety of plant species.
ICAM-1, GRP-78, and NFkB gene polymorphisms and clinical outcome in patients (pts) with metastatic colorectal cancer (mCRC) treated with first line 5-FU or capecitabine in combination with oxaliplatin and bevacizumab (FOLFOX/BV or XELOX/BV) (2008)

4134 Background: We evaluated polymorphisms of genes involved in angiogenesis, cell proliferation, and cell-cell or cell-matrix adhesion as potential predictors of clinical outcome in pts with mCRC who received BV as part of their frontline therapy. These genes included: VEGF, VEGF receptor 2, neuropilin 1, Interleukin 6 and 8, adrenomedullin, leptin, fibroblast growth factor receptor 4, tissue factor, matrix metalloproteinases 2,7,9, intracellular adhesion molecule-1 (ICAM1), glucose regulated protein 78 (GRP78), epidermal growth factor receptor, and nuclear factor kappa b (NFkB). Methods: PCR-RFLP assays were performed on genomic DNA extracted from the blood of pts with mCRC treated with first-line FOLFOX/BV or XELOX/BV at USC. Results: There were 59 pts (36 males, 23 females), median age: 56 years (range: 29–81). 38 pts received XELOX/BV and 21 pts FOLFOX/BV. Radiologic response: 2/59 (3%) complete response (CR), 35/59 (59%) partial response (PR), 18/59 (30.5%) stable disease and 4/59 (6%) progressive disease. At a median follow-up of 17.9 months (mo), 36/59 pts progressed with a median progression free survival (PFS) of 13.7 mo. Single nucleotide polymorphisms (SNP) C/T in ICAM1 (codon K469E, exon 6) and C/T in the 3’UTR region of GRP78 (rs12009 were significantly associated with response (CR+PR). Pts homozygous for the T allele in ICAM1 were found to have a lower probability of response (41%) compared to pts with the C/C (73%) or C/T (71%) genotypes (p=0.032). Pts with any C allele in the GRP78 gene (C/C; C/T) had a higher probability of response (89%; 64%) compared to pts homozygous for the T allele (T/T; 52%) (p=0.027). Significantly improved PFS was found in pts who had >24 CA repeats on at least one of the NFkB1 alleles located at 4q23–24 (15.5 mo [95% CI: 8.3–20.9+] for ≥24/≥24 genotype vs. 13.9 mo for <24/≥24 [95% CI: 13.0–38.6] vs. 7.2 mo [95% CI: 5.3–15.4] for <24/<24, p=0.023). Conclusions: This pilot study demonstrated, in a preliminary fashion, the potential predictive and prognostic value of ICAM-1, GRP78 and NFkB genomic polymorphisms in pts with mCRC treated with FOLFOX/BV or XELOX/BV. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, Genentech™ BioOncology, ImClone Systems Incorporated, Merck, Pfizer Oncology, Response Genetics Genentech™ BioOncology, Merck, Pfizer Oncology, Roche, sanofi-aventis