gebhart/patrepeval huggingface dataset:
Molecular Targets in Oncology: Implications of the Multidrug Resistance Gene (1993)

The curative potential of chemotherapy for a number of tumor types has been obscured by the fact that many patients initially have striking remissions but later relapse and die. At the time of relapse many patients manifest resistance to a wide array of structurally unrelated antineoplastic agents, hence the term multidrug resistance (MDR). Other tumor types, such as those arising in the colon, kidneys, liver, and lungs, tend to exhibit poor response to available cytotoxic drugs. The MDR phenomenon includes cross-resistance among the anthracyclines (doxorubicin, daunorubicin), the epipodophyllotoxins (etoposide, teniposide), the vinca alkaloids (vinblastine, vincristine), taxol, and other compounds. In vitro studies in cell culture indicate that this form of resistance is associated with amplification or overexpression of the mdr1 gene. The mdr1 gene codes for the expression of a cell surface protein, P-glycoprotein (P-gp), which acts as an energy-dependent efflux pump that transports drugs associated with MDR out of the cell before cytotoxic effects occur. The protein is expressed in normal human tissues such as the gastrointestinal tract, liver, and kidneys, where it is thought to serve as an excretory pathway for xenobiotic drugs and toxins. Preliminary studies demonstrated the presence of P-gp in tumor samples from patients with acute leukemia, multiple myeloma, lymphomas, and a variety of solid tumors. A number of drugs are able to reverse MDR, including calcium-channel blockers, phenothiazines, quinidine, antimalarial agents, antiestrogenic and other steroids, and cyclosporine. Limited results from clinical trials with small numbers of patients suggest that the addition of verapamil, diltiazem, quinine, trifluoperazine, or cyclosporine to chemotherapeutic regimens has the potential to reverse MDR; however, toxicities limit their clinical usefulness. A number of trials are under way to identify more active and less toxic modulators of MDR.
Efficient Incorporation of Nonnatural Amino Acids with Large Aromatic Groups into Streptavidin in In Vitro Protein Synthesizing Systems (1998)

Efficiencies of the incorporation of various nonnatural amino acids carrying aromatic side groups into streptavidin were examined. The aromatic amino acids were linked to a mixed dinucleotide, pdCpA, and the resulting aminoacyl pdCpAs were coupled with tRNAcccg(−CA) to afford chemically aminoacylated tRNAcccg's. Mutant streptavidin mRNA containing a CGGG 4 base codon at the Tyr83 site was prepared and added to an Escherichia coli in vitro translation system with the aminoacyl tRNAcccg. The expression of the full-length mutant streptavidins was confirmed by a Western blot analysis, and their biotin binding activity was examined by a dot blot analysis. The Western blot analysis indicated that the efficiencies of the incorporation were higher for aromatic groups with straight configurations than those with widely expanded or bend configurations. The incorporation efficiencies were also examined in a rabbit reticulocyte lysate. In the latter system, the efficiencies were markedly improved for nonnatural amino acids with large side groups such as pyrene and anthraquinone.
Deletions in vaccine strains of pseudorabies virus and their effect on synthesis of glycoprotein gp63 (1986)

The pseudorabies virus vaccine strains Norden and Bartha each have been reported to have deletions in the small unique component of the genome (B. Lomniczi, M. L. Blankenship, and T. Ben-Porat, J. Virol. 49:970-979, 1984). The deletion in Norden was shown to delete the entire coding region for gI but not any of the coding sequences for gp63. However, gp63 in Norden-infected cells was only 36 kilodaltons, and a 44-kilodalton form of gp63 was released into the medium. In Bartha, the deletion removed the coding region for all but 89 amino acids of gp63, and no gp63 was detected in either Bartha-infected cells or medium.
Hydrogen peroxide as a crystal growth modifier of CaCO3 (2012)

Using exclusively H2O2 as an additive, facile morphology control over CaCO3 crystal aggregation was realized readily by changing the concentrations of H2O2 and the pH values of the crystallization system. The ionization of H2O2 to [H–O–O]− and [O–O]2− and the generated gas molecules played significant roles in modifying the crystal morphologies. Based on the CaCO3 particles morphology through different aging times, a mechanism about the formation of CaCO3 crystals in the presence of H2O2 was proposed.
Gene Expression Analysis of Zebrafish Heart Regeneration (2006)

Mammalian hearts cannot regenerate. In contrast, zebrafish hearts regenerate even when up to 20% of the ventricle is amputated. The mechanism of zebrafish heart regeneration is not understood. To systematically characterize this process at the molecular level, we generated transcriptional profiles of zebrafish cardiac regeneration by microarray analyses. Distinct gene clusters were identified based on temporal expression patterns. Genes coding for wound response/inflammatory factors, secreted molecules, and matrix metalloproteinases are expressed in regenerating heart in sequential patterns. Comparisons of gene expression profiles between heart and fin regeneration revealed a set of regeneration core molecules as well as tissue-specific factors. The expression patterns of several secreted molecules around the wound suggest that they play important roles in heart regeneration. We found that both platelet-derived growth factor-a and -b (pdgf-a and pdgf-b) are upregulated in regenerating zebrafish hearts. PDGF-B homodimers induce DNA synthesis in adult zebrafish cardiomyocytes. In addition, we demonstrate that a chemical inhibitor of PDGF receptor decreases DNA synthesis of cardiomyocytes both in vitro and in vivo during regeneration. Our data indicate that zebrafish heart regeneration is associated with sequentially upregulated wound healing genes and growth factors and suggest that PDGF signaling is required.
ChemInform Abstract: Reagents for Combinatorial Organic Synthesis: Development of a New o‐ Nitrobenzyl Photolabile Linker (I) for Solid Phase Synthesis. (1995)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Measures of distributional similarity (1999)

We study distributional similarity measures for the purpose of improving probability estimation for unseen cooccurrences. Our contributions are three-fold: an empirical comparison of a broad range of measures; a classification of similarity functions based on the information that they incorporate; and the introduction of a novel function that is superior at evaluating potential proxy distributions.
Blood-brain barrier derangement in uremic encephalopathy. (1982)

A disturbance of cerebral neurotransmitters and an accumulation of octopamine, a putative false neurotransmitter, have been found in patients with uremic encephalopathy who manifest disorientation, somnolence, asterixis, and coma--symptoms also seen in portal systemic encephalopathy (PSE). Altered plasma concentrations of the neutral amino acids (NAAs) and increased blood-brain NAA transport may play a role in PSE, and in the present study plasma amino acid concentrations and blood-brain barrier NAA transport were investigated in rats with acute and chronic uremia. Acute uremia was produced by unilateral nephrectomy and occlusion of the renal artery of the remaining kidney for 70 minutes; the animals were studied 24 hours later. Chronic uremia was produced by unilateral nephrectomy and 70% to 80% devascularization of the remaining kidney; these animals were studied 2 weeks later. Brain uptake was studied with the technique of Oldendorf, and blood and brain amino acids (AAs) were measured. The blood urea nitrogen (BUN) level in rats with acute uremia increased to 108 mg/dl, in rats with chronic uremic 54 mg/dl, and in sham-operated rats 22 mg/dl. In both uremic groups there was a decrease in plasma branched-chain AAs. In the brain these AA levels were normal, while levels of phenylalanine, tyrosine, and histidine were increased in uremic rats.
Relating rheological measurements to primary and secondary skin feeling when mineral‐based and Fischer–Tropsch wax‐based cosmetic emulsions and jellies are applied to the skin (2013)

Rheology measurements were correlated to skin sensations occurring when cream and petroleum jelly cosmetic products containing different amounts of synthetic Fischer-Tropsch wax were applied to the skin. A panel of 15 people with a background in cosmetic product development were asked to rate skin feelings when a range of petroleum jelly and cream samples are applied to the skin. Primary skin feel, or the spreadability of a cosmetic product, was correlated to the product's flow onset and maximum viscosity as measured by a Anton Paar rheometer, whereas secondary skin feel or the sensation occurring at the end of application when the product was completely rubbed into the skin was correlated to the product's viscosity measured at high shear rates. The cream samples prepared with a petroleum jelly containing 10% and 20% Fischer-Tropsch wax fell within the boundary of good primary skin feeling of cream products. Predominantly, synthetic petroleum jellies were given the best assessments in terms of primary skin feeling and were used with mineral-based petroleum jellies to determine the boundary of good primary skin feeling for petroleum jelly products. The further away a product falls from this rheological boundary the poorer the skin feeling assessment appears to be by the panel. Products containing Fischer-Tropsch waxes were given the best assessment by the panel for secondary skin feeling. Comments from the panel include that these products feel silky and light on the skin. The higher the Fischer-Tropsch wax content, the lower viscosity was at high shear rate (ϒ = 500 s(-1) ) and the higher the assessment by the panel. Rheological measurements can be used to objectively determine skin sensation when products are applied to the skin; this may shorten research and development times. A rheology boundary of certain product viscosity and shear stress applied is associated with good primary skin feeling for lotions, creams and petroleum jellies. Lower product viscosity at high shear rate seems to be associated with better secondary skin feeling. Products with higher Fischer-Tropsch wax content appear to be rated higher in terms of secondary skin feeling.
Multivariate Adaptive Regression Splines (1991)

A new method is presented for flexible regression modeling of high dimensional data. The model takes the form of an expansion in product spline basis functions, where the number of basis functions as well as the parameters associated with each one (product degree and knot locations) are automatically determined by the data. This procedure is motivated by the recursive partitioning approach to regression and shares its attractive properties. Unlike recursive partitioning, however, this method produces continuous models with continuous derivatives. It has more power and flexibility to model relationships that are nearly additive or involve interactions in at most a few variables. In addition, the model can be represented in a form that separately identifies the additive contributions and those associated with the different multivariable interactions.
Overexpression of TROP2 Predicts Poor Prognosis of Patients with Cervical Cancer and Promotes the Proliferation and Invasion of Cervical Cancer Cells by Regulating ERK Signaling Pathway (2013)

Overwhelming evidence has demonstrated that the aberrant expression of the human trophoblast cell-surface antigen (TROP2) was associated with tumor aggressiveness and poor prognosis in a variety of human cancers, however the roles of TROP2 in cervical cancer have not been investigated. The purpose of our study was to elucidate the prognostic significance of TROP2 expression in patients with cervical cancer and determine its effect on tumor progression. Immunohistochemistry assay showed that 88.7% (94/106 cases) of cervical cancer specimens were positively stained with TROP2, and the overexpression of TROP2 was closely related with FIGO stage, histological grades, lymphatic metastasis, invasive interstitial depth and high expression of Ki-67. Patients with TROP2-positive staining exhibited a significantly decreased overall survival and progression free survival; it was also an independent predictor for prognosis according to multivariate analysis. Moreover, down-regulation of TROP2 mediated by siRNA in Siha and CaSki cells resulted in a strong inhibition of proliferation and invasion, TROP2 abrogation also elevated the apoptotic ratio and caused G1 arrest. Conversely, enforced expression of TROP2 in HeLa and C33A cells remarkably promoted cell growth, migration and invasion. In addition, the tumorigenic function of TROP2 was associated with the increased expressions of cyclin D1, cyclin E, CDK2 and CDK4 but reduced expression of p27 and E-cadherin via the activation of Erk1/2 signaling pathway. Furthermore, the inhibition of TROP2 expression in cervical cancer cell lines enhances sensitivity to cisplatin. The present study suggest that overexpression of TROP2 may play crucial roles in the development and pathogenesis of human cervical cancer, therefore, TROP2 may represent a prospective prognostic indicator and a potential therapeutic target of cervical cancer.
Pneumococcal conjugate vaccine-induced regulatory T cells suppress the development of allergic airways disease (2010)

A currently available human conjugate vaccine suppresses the hallmark features of AAD through the induction of Tregs. Thus targeted administration may provide a novel immunoregulatory treatment for asthma.
Effects of Brown Midrib‐3 on Yields and Yield Components of Maize1 (1984)

The brown midrib‐3 ( bm3 ) gene associated with low lignin in corn ( Zea mays L.) was evaluated for its effects on yield and yield components in Hawaii. Fifteen bm3 hybrids representing a sixparent diallel and their 15 isogenic normal counterpart hybrids were planted as paired rows in two trials. Yields of the bm3 hybrids were significantly lower than normals in both trials, with average reductions of 20% (range 7 to 29%) for grain and 17% (range 8 to 25%) for stover. Traits also affected negatively by bm3 included kernel number per row (−;12%), filled ear length (−10%), ear height (−7%), plant height (−5%), and five other measured traits. Correlation matrices of yields and all measured traits revealed few consistent differences among normal and bm3 hybrids. Grain yields correlated highly with leaf area index for normal hybrids, but not for the isogenic bm3 hybrids. Mean square values for general and specific combining ability (GCA, SCA) were significant for grain and stover yields and plant height, and GCA effects were significant for kernel number per row and ear length. The GCA/SCA ratios were higher for bm3 hybrids than for normals for grain and stover yield. The gains in stover digestibility of bm3 through lowered lignin content did not offset yield losses enough to justify separate breeding programs with bm3 . Linkage of the bm3 gene with yield‐reducing genes was virtually excluded in this study as a cause for the yield reduction, and a role of colored lignins in reducing photosynthates is postulated.
Intercellular adhesion molecule 1 is induced on isolated endocrine islet cells by cytokines but not by reovirus infection. (1989)

The selective destruction of the pancreatic islet beta cells in type 1 diabetes mellitus is thought to be mediated by a cellular autoimmune process, possibly triggered by virus infection in genetically susceptible individuals. Because of the potentially important role of cell-cell adhesion in the immune response, we investigated whether cytokine products of mononuclear cells, or virus infection, induced the expression of intercellular adhesion molecule 1 (ICAM-1) on human endocrine islet cells. By flow cytofluorimetry, control islet cells did not express detectable ICAM-1. However, after a 72-hr exposure of islets to interferon gamma (IFN-gamma) and/or tumor necrosis factor alpha (TNF-alpha) (each at 250 units/ml), ICAM-1 was induced on greater than 85% of islet cells. IFN-gamma was 50% more potent than TNF-alpha; together, their effects were additive. Class I major histocompatibility complex (MHC) protein expression, detected on control islet cells, was also stimulated by IFN-gamma and/or TNF-alpha. In contrast, infection with reovirus type 3 did not induce ICAM-1 on islet cells, although it stimulated the expression of class I MHC proteins. By double-label indirect immunofluorescence microscopy, ICAM-1 expression was identified on both beta (insulin-secreting) and delta (somatostatin-secreting) islet cells. Monoclonal antibody to ICAM-1 precipitated protein of Mr 97,000 from [35S]methionine-labeled islets exposed to IFN-gamma and TNF-alpha, but not from control islets. RNA blot analysis revealed a major species of 3.3 kilobases and a minor species of 2.2 kilobases induced in islets exposed to the cytokines. These findings have implications for the molecular mechanisms of beta-cell destruction in type 1 diabetes, in that expression of ICAM-1 by beta cells may facilitate adhesion of antigen-targeted immune cells.
Methods for site-specific drug conjugation to antibodies (2013)

Antibody drug conjugates (ADCs) are an emerging class of targeted therapeutics with the potential to improve therapeutic index over traditional chemotherapy. Drugs and linkers have been the current focus of ADC development, in addition to antibody and target selection. Recently, however,the importance of conjugate homogeneity has been realized. The current methods for drug attachment lead to a heterogeneous mixture, and some populations of that mixture have poor in vivo performance. New methods for site-specific drug attachment lead to more homogeneous conjugates and allow control of the site of drug attachment. These subtle improvements can have profound effects on in vivo efficacy and therapeutic index. This review examines current methods for site-specific drug conjugation to antibodies, and compares in vivo results with their non-specifically conjugated counterparts. The apparent improvement in pharmacokinetics and the reduced off target toxicity warrant further development of this site-specific modification approach for future ADC development.
Wound-inducible expression of a potato inhibitor II-chloramphenicol acetyltransferase gene fusion in transgenic tobacco plants (1987)

A potato inhibitor II gene (IIK) was isolated from a library of potato genes in lambda bacteriophage. An 8-kilobase-pair (kbp) insert was identified using a tomato inhibitor II cDNA as a hybridization probe, and a 2.6-kbp fragment containing the gene was subcloned into the plasmid pUC13 and characterized. The nucleotide sequence of the isolated gene exhibited 87% identity with the wound-inducible tomato inhibitor II cDNA sequence. The amino acid sequence of inhibitor IIK, deduced from the potato gene, exhibited 84% identity with the tomato inhibitor II protein. A 1000-bp restriction fragment from the 5' flanking region of the gene was fused to the open reading frame of the chloramphenicol acetyltransferase (CAT) gene. This fusion was terminated in two ways: (i) with a terminator sequence from the potato inhibitor II gene and (ii) with a terminator from the 6b gene of Ti plasmid pTiA6. These chimeric genes were transferred into tobacco cells via a binary Ti vector system, and transgenic plants were regenerated. The CAT gene was expressed in leaves of transformed plants in response to wounding when fused with the inhibitor IIK promoter and terminator regions. The chimeric gene containing the 6b terminator did not express CAT in response to wounding. The wound-inducible expression of CAT activity was systemic and was induced in tissues distal to the wounded tissues. The time course of wound induction of CAT activity in transgenic tobacco leaves is similar to that found for wound-inducible inhibitor I and II mRNAs in tomato leaves. These results demonstrate that sequences necessary and sufficient for wound inducibility are present within approximately 1000 bp of the control regions of the inhibitor IIK genes and that wound-inducible components of tobacco leaf cells can regulate these sequences.
Sensory Peptides as Neuromodulators of Wound Healing in Aged Rats (1996)

An intact nociceptor system of primary afferent sensory nerves is important for the initiation of the inflammatory process and successful tissue repair. Dysfunction of this system with age could be a contributing factor for delayed wound healing in the elderly. This study was designed to examine the role of sensory nerves (using capsaicin-pretreated rats) and the effect of aging on the healing of a thermal wound induced on the interscapular region (using a CO2 laser). The healing endpoint was the time when full wound contraction had occurred. The ability of the sensory peptides, substance P (SP) and calcitonin gene-related peptide (CGRP), in modulating wound healing in aged rats was examined by taking into account the modulatory interaction effects between these peptides. A blister model in the rat hind footpad combined with a laser Doppler flowmeter was used initially to establish these vascular interaction effects. The results showed a significant delay in thermal wound healing in both the capsaicin-treated and aged rats. Using the blister model, we demonstrated the ability of SP and CGRP to induce a limited and a prolonged vasodilator response, respectively. When tested together, SP attenuated the vascular effect of CGRP, an effect that was reversed using the tachykinin antagonist spantide II. When injected at the wound site, SP and CGRP were equally potent in promoting wound healing in aged rats. The beneficial effect of taking the interaction effects into account was most evident in a group of rats that received the tachykinin antagonist as part of their initial treatment with CGRP and 6 h later, an injection of SP; the time to complete wound closure was 11.3 +/- 0.6 days compared to 21.0 +/- 0.9 days in aged controls. We contend that would healing in aged rats can be accelerated by exogenous administration of sensory peptides. Furthermore, modulatory interaction effects between sensory peptides should be taken into consideration when designing any treatment protocol that purports to accelerate wound healing.
Derivation of Xeno-Free and GMP-Grade Human Embryonic Stem Cells – Platforms for Future Clinical Applications (2012)

Clinically compliant human embryonic stem cells (hESCs) should be developed in adherence to ethical standards, without risk of contamination by adventitious agents. Here we developed for the first time animal-component free and good manufacturing practice (GMP)-compliant hESCs. After vendor and raw material qualification, we derived xeno-free, GMP-grade feeders from umbilical cord tissue, and utilized them within a novel, xeno-free hESC culture system. We derived and characterized three hESC lines in adherence to regulations for embryo procurement, and good tissue, manufacturing and laboratory practices. To minimize freezing and thawing, we continuously expanded the lines from initial outgrowths and samples were cryopreserved as early stocks and banks. Batch release criteria included DNA-fingerprinting and HLA-typing for identity, characterization of pluripotency-associated marker expression, proliferation, karyotyping and differentiation in-vitro and in-vivo. These hESCs may be valuable for regenerative therapy. The ethical, scientific and regulatory methodology presented here may serve for development of additional clinical-grade hESCs.