gebhart/patrepeval huggingface dataset:
A molecular role for lysyl oxidase in breast cancer invasion. (2002)

We identified previously an up-regulation in lysyl oxidase (LOX) expression,an extracellular matrix remodeling enzyme, in a highly invasive/metastatic human breast cancer cell line, MDA-MB-231, compared with MCF-7, a poorly invasive/nonmetastatic breast cancer cell line. In this study, we demonstrate that the mRNA expression of LOX and other LOX family members [lysyl oxidase-like (LOXL), LOXL2, LOXL3, and LOXL4] was observed only in breast cancer cells with a highly invasive/metastatic phenotype but not in poorly invasive/nonmetastatic breast cancer cells. LOX and LOXL2 showed the strongest association with invasive potential in both highly invasive/metastatic breast cancer cell lines tested (MDA-MB-231 and Hs578T). To determine whether LOX is directly involved in breast cancer invasion, LOX antisense oligonucleotides were transfected into MDA-MB-231 and Hs578T cells, and found to inhibit invasion through a collagen IV/laminin/gelatin matrix in vitro compared with LOX sense oligonucleotide-treated and untreated controls. In addition, treatment of MDA-MB-231 and Hs578T cells with beta-aminopropionitrile (an irreversible inhibitor of LOX enzymatic activity) decreased invasive activity. Conversely, MCF-7 cells transfected with the murine LOX gene demonstrated a 2-fold increase in invasiveness that was reversible by the addition of beta-aminopropionitrile in a dose-dependent manner. In addition, endogenous LOX mRNA expression was induced when MCF-7 cells were cultured in the presence of fibroblast conditioned medium or conditioned matrix, suggesting a role for stromal fibroblasts in LOX regulation in breast cancer cells. Moreover, the correlation of LOX up-regulation and invasive/metastatic potential was additionally demonstrated in rat prostatic tumor cell lines, and human cutaneous and uveal melanoma cell lines. These results provide substantial new evidence that LOX is involved in cancer cell invasion.
Actaplanin, new glycopeptide antibiotics produced by Actinoplanes missouriensis. The isolation and preliminary chemical characterization of actaplanin. (1984)

Actaplanin (A4696), a new complex of broad spectrum Gram-positive antibiotics is produced by Actinoplanes missouriensis. High performance liquid chromatography was used to show that this complex is composed of several actaplanins. Hydrolytic experiments with acetaplanins A, B1, B2, B3, C1 and G showed that these actaplanins were composed of the same peptide core, an amino sugar and varying amounts of glucose, mannose and rhamnose. The neutral sugar content was determined for each actaplanin. A bioautographic study of aglycone formation during hydrolysis of the actaplanin complex showed that within a short time a simple mixture of two antimicrobially active hydrolysis products was obtained. These substances retained the antimicrobial spectrum and a high percentage of the antibiotic activity of the parent actaplanin complex. Methanolysis of the acetaplanin complex as well as the individual actaplanins resulted in the selective loss of the neutral sugar moieties and the isolation of actaplanin psi (pseudo)-aglycone--the core peptide which still retained an amino sugar group. The 1H NMR spectrum of this substance indicated a similarity to many features of ristocetin psi-aglycone. Hydrolytic studies showed that the amino sugar present in actaplanin was identical with L-ristosamine. It is concluded that the aglycone of actaplanin is a complex peptide composed of aromatic amino acids, and that the actaplanins each possess this aglycone and L-ristosamine but are differentiated by their neutral sugar composition.
Treatment success for overactive bladder with urinary urge incontinence refractory to oral antimuscarinics: a review of published evidence (2009)

A treatment success definition that encompasses the many components of underlying OAB with UUI symptoms is currently not practical as a consequence of difficulties in measuring urgency. The treatment success outcome of > or = 50% improvement in incontinence episodes was associated with a clinically meaningful improvement in disease-specific HRQoL for those with neurogenic OAB with UUI. The recommended success definition is less restrictive than a measure such as complete continence but includes patients who are satisfied with treatment and experience meaningful improvement in symptoms. A standardized measure of treatment success will be useful in clinical and health economic applications.
Usp9x- and Noxa-mediated Mcl-1 downregulation contributes to pemetrexed-induced apoptosis in human non-small-cell lung cancer cells (2014)

Pemetrexed, a folate antimetabolite, combined with cisplatin is used as a first-line therapy for malignant pleural mesothelioma (MPM) and locally advanced or metastatic non-small-cell lung cancer (NSCLC). Pemetrexed arrests cell cycle by inhibiting three enzymes in purine and pyrimidine synthesis that are necessary for DNA synthesis. Pemetrexed also promotes apoptosis in target cells, but little is known about its mechanism in cancer cells. We have previously shown that pemetrexed can result in endoplasmic reticulum (ER) stress, and it can lead to downstream apoptosis. In this study, we further elucidate this mechanism. Our data show that pemetrexed increases Noxa expression through activating transcription factor 4 (ATF4) and activating transcription factor 3 (ATF3) upregulation. Furthermore, pemetrexed induces apoptosis by activating the Noxa-Usp9x-Mcl-1 pathway. Inhibition of Noxa by small interfering RNA (siRNA) promotes Usp9x (ubiquitin-specific peptidase 9, X-linked) expression. Moreover, downregulation of the deubiquitinase Usp9x by pemetrexed results in downstream reduction of myeloid cell leukemia 1 (Mcl-1) expression. Mechanistically, Noxa upregulation likely reduces the availability of Usp9x to Mcl-1, thereby promoting its ubiquitination and degradation, leading to the apoptosis of neoplastic cells. Thus, our findings demonstrate that Noxa-Usp9x-Mcl-1 axis may contribute to pemetrexed-induced apoptosis in human lung cancer cells.
2-(2-Thienyl)-5,6-dihydroxy-4-carboxypyrimidines as Inhibitors of the Hepatitis C Virus NS5B Polymerase:  Discovery, SAR, Modeling, and Mutagenesis (2006)

Infections caused by hepatitis C virus (HCV) are a significant world health problem for which novel therapies are in urgent demand. The polymerase of HCV is responsible for the replication of viral RNA. We recently disclosed dihydroxypyrimidine carboxylates 2 as novel, reversible inhibitors of the HCV NS5B polymerase. This series was further developed into 5,6-dihydroxy-2-(2-thienyl)pyrimidine-4-carboxylic acids such as 34 (EC50 9.3 microM), which now show activity in the cell-based HCV replication assay. The structure-activity relationship of these inhibitors is discussed in the context of their physicochemical properties and of the polymerase crystal structure. We also report the results of mutagenesis experiments which support the proposed binding model, which involves pyrophosphate-like chelation of the active site Mg ions.
Polynomial splines and their tensor products in extended linear modeling: 1994 Wald memorial lecture (1997)

Analysis of variance type models are considered for a regression function or for the logarithm of a probability function, conditional probability function, density function, conditional density function, hazard function, conditional hazard function or spectral density function. Polynomial splines are used to model the main effects, and their tensor products are used to model any interaction components that are included. In the special context of survival analysis, the baseline hazard function is modeled and nonproportionality is allowed. In general, the theory involves the $L_2$ rate of convergence for the fitted model and its components. The methodology involves least squares and maximum likelihood estimation, stepwise addition of basis functions using Rao statistics, stepwise deletion using Wald statistics and model selection using the Bayesian information criterion, cross-validation or an independent test set. Publicly available software, written in C and interfaced to S/S-PLUS, is used to apply this methodology to real data.
Differential binding of drugs containing the NGR motif to CD13 isoforms in tumor vessels, epithelia, and myeloid cells. (2002)

The NGR peptide motif is an aminopeptidase N (CD13) ligand that targets angiogenic blood vessels. NGR-containing peptides have proven useful for delivering cytotoxic drugs, proapoptotic peptides, and tumor necrosis factor-alpha(TNF) to tumor vasculature. Given that CD13 is not only expressed in the angiogenic endothelium but also in other cell types, the mechanism(s) for the tumor-homing properties of NGR-drug conjugates remains elusive. We have examined the expression of CD13 in normal and neoplastic human tissues and cells by using two anti-CD13 monoclonal antibodies. The immunoreactivity patterns obtained with cultured cells and tissue sections from kidney, breast, and prostate carcinomas suggest that different CD13 forms are expressed in myeloid cells, epithelia, and tumor-associated blood vessels. Both, direct binding assays with a CNGRCG-TNF conjugate (NGR-TNF) and competitive inhibition experiments with anti-CD13 antibodies showed that a CD13 isoform expressed in tumor blood vessels could function as a vascular receptor for the NGR motif. In contrast, CD13 expressed in normal kidney and in myeloid cells failed to bind to NGR-TNF. Consistently with these results, neither murine(125)I-NGR-TNF nor (125)I-TNF accumulated in normal organs containing CD13-expressing cells after administration to mice. These findings may explain the selectivity and the tumor-homing properties of NGR-drug conjugates and may have important implications in the development of vascular-targeted therapies based on the NGR/CD13 system.
Polyamines found in gingival fluid enhance the secretory and oxidative function of human polymorphonuclear leukocytes in vitro (1995)

Many bacterial and host cells contain large amounts of polyamines that can be released at infection sites as a result of cell lysis. Consequently, the putrescine and spermidine content of gingival fluid from inflamed periodontal pockets (0.1 to 1 mM) is sharply elevated in comparison to peripheral blood. At these levels, polyamines potentiated fMet-Leu-Phe-induced Ca2+ signaling in polymorphonuclear leukocytes (PMNs) in vitro. Consistent with the essential role of Ca2+ signaling in PMN activation, secondary granule release and superoxide anion production by fMet-Leu-Phe-stimulated PMNs was enhanced in the presence of polyamines. Thus, polyamines may play a local role in modulating the antimicrobial activity of PMNs in periodontal disease.
Polyacrylamides Bearing Pendant α-Sialoside Groups Strongly Inhibit Agglutination of Erythrocytes by Influenza Virus:  The Strong Inhibition Reflects Enhanced Binding through Cooperative Polyvalent Interactions (1996)

An ELISA assay is described for measuring the binding of influenza virus A-X31 to α-sialoside groups that are linked to biotin-labeled polyacrylamides. The efficacy of these polymers in inhibiting the adhesion of influenza virus to erythrocytes (as measured by a hemagglutination assay) was shown to be directly related to the binding affinity of the polymers for the viral surface: the differences in inhibitory efficacy among the polymeric inhibitors and monomeric α-methyl sialoside, among fractions of a polymeric, polyvalent inhibitor with narrow molecular weight ranges, and among polymeric inhibitors prepared by copolymerization or modification of a preformed polymer chain, all correlated with differences in the affinity of the inhibitors for the surface of the virus. The polymeric inhibitors studied had affinities for the viral surface that ranged between 103 and >106 greater than α-methyl sialoside, on the basis of total sialic acid groups in solution. The role of steric stabilization in the mechanism by which these polymers inhibit hemagglutination was investigated. The ability of the polymeric, polyvalent inhibitors to inhibit the binding of a polyclonal antibody to the viral surface suggests that steric stabilization may also be an important effect in this system.
First-Trimester Sonographic Screening for Down Syndrome (2003)

In Brief Screening for Down syndrome is an important part of routine antenatal care. The most common screening method in the United States involves the assessment of a combination of factors: maternal age, multiple second-trimester serum markers, and second-trimester ultrasonography (as a so-called “genetic sonogram”). More recently, however, there has been significant interest in first-trimester methods of screening, including screening for first-trimester serum markers and the sonographic measurement of fetal nuchal translucency. Multiple studies have demonstrated that fetal nuchal translucency has the potential of being a very powerful predictor of fetal aneuploidy. However, for clinicians a large void remains between this knowledge and the practical issues that must be addressed prior to endorsing this form of screening for widespread use. This article provides an objective assessment of the literature describing nuchal translucency, as well as some adjunct first-trimester sonographic techniques, such as ductus venosus flow and nasal bone studies. Additionally, a detailed description of practical problems that might limit the implementation of this form of screening is presented. First-trimester nuchal translucency sonography represents a great advance in the field of Down syndrome screening, although many practical implementation issues remain to be clarified prior to recommending widespread utilization of this technique.
Entropy localization in magnetic compounds and thin-film nanostructures (2010)

The effect of nanostructuring on the magnetic entropy of materials for room-temperature magnetic cooling is investigated by model calculations. The materials are structurally inhomogeneous with a large number of nonequivalent crystallographic sites. In the mean-field Heisenberg model, the entropy density is a unique function of the local magnetization so that the coupled set of nonlinear mean-field equations yields not only the magnetization but also the entropy density. Since most of the entropy is localized near grain boundaries, nanomagnetic cooling requires small feature sizes. Magnetic anisotropy is a substantial complication, even on a mean-field level, but the corresponding corrections are often very small.
Mechanisms of allergy CpG-oligodeoxynucleotides inhibit airway remodeling in a murine model of chronic asthma (2002)

Background: We have previously demonstrated that CpG oligodeoxynucleotides (CpG-ODNs) protect against eosinophilia and airway hyperresponsiveness in murine models of allergeninduced asthma. Acute inflammation is hypothesized to induce chronic airway responses, but no previous studies have evaluated the effects of CpG-ODNs on allergen-induced airway remodeling. Because remodeling is thought to be responsible for many of the long-term adverse effects on asthmatic patients, we evaluated whether CpG-ODNs might similarly prevent these changes using a murine model of recurrent allergen exposure. Objective: The purpose of this study was to evaluate the effect of CpG-ODNs on chronic inflammatory changes and airway remodeling by using a murine model of chronic allergeninduced asthma. Methods: C57BL/6 mice were sensitized to ovalbumin (OVA) and subsequently exposed to nebulized OVA by means of inhalation 3 times weekly for 6 weeks. Some mice received CpG-ODNs by means of intraperitoneal injection at the time of sensitization. At the end of the exposure period, mice were evaluated for the development of airway inflammation, airway hyperresponsiveness, and airway remodeling. Results: OVA-sensitized mice exposed to recurrent airway challenge with OVA have chronic inflammation, persistent airway hyperresponsiveness, and evidence of airway remodeling, including subepithelial collagen deposition and goblet cell hyperplasia-metaplasia. These changes are significantly reduced in mice treated with CpG-ODNs. Interestingly, mice treated with CpG-ODNs exhibit increased levels of bronchoalveolar lavage transforming growth factor β, suggesting that regulatory T cells might be responsible for some of these protective effects. Conclusion: CpG-ODNs are effective not only in preventing acute inflammation but also appear to reduce markers of airway remodeling that develop after chronic allergen exposure. (J Allergy Clin Immunol 2002;110:867-72.)
Theory of the hydrophobic effect (1977)

A microscopic theory is developed which can describe many of the structural and thermodynamic properties of infinitely dilute solutions of apolar solutes in liquid water. The theory is based on an integral equation for the pair correlation functions associated with spherical apolar species dissolved in water. It requires as input the experimentally determined oxygen–oxygen correlation function for pure liquid water. The theory is tested by computing thermodynamic properties for aqueous solutions of apolar solute species. The predictions of both the Henry’s Law constant and the entropy of solution are in good agreement with experiment. The calculation of the latter quantity is essentially independent of any adjustable parameters. It is shown how the correlation functions we have calculated can be used to predict the solubility of more complicated, aspherical, and nonrigid solutes in liquid water. For the more complex molecules it is convenient to study the difference between the excess chemical potential of the molecule and the chemical potentials of its separated components (Ben-Naim’s measure of the hydrophobic interaction strength δA(HI)M). A generalized formula for δA(HI)M is presented which reduces to Ben-Naim’s result in the special case of a rigid solute. The calculations of δA(HI)M for normal alkanes through n-decane are independent of unknown and adjustable mean field parameters. For ethane, the theoretical results for δA(HI)M are in good agreement with experimental data. To treat longer alkanes multipoint correlation functions are required. It is shown that the standard superposition approximation for the multipoint correlation functions predicts qualitatively incorrect results. A correction to the superposition approximation is developed. Its use yields theoretical values for δA(HI)M which agree well with experiment. We also calculate free energies of transfer of n-alkane solutes from a hydrocarbon solvent to liquid water. Here, too, our results are in good agreement with experiment. After testing the theory against experiment, several experimentally inaccessible aspects of the hydrophobic effect are discussed. Analysis of pair correlation functions between spherical apolar species indicates that the hydrophobic interaction becomes more attractive as the solute size is increased at constant temperature, or as the temperature is decreased. The solute–solute correlations in liquid water are compared with those in a nonassociated (hard-spherelike) solvent. Plots are presented which indicate that the insertion of an apolar species increases the intermolecular structure of water in the vicinity of the apolar solute. The effects of solvent environments on the conformations of small chain molecules are discussed. It is shown that hydrocarbon solvents as well as water tend to reduce the spatial extension of the chain molecules from what is found in the gas phase. However, calculations which take cognizance of the detailed structure of the solvent liquids reveal that the average conformational structure of some n-alkanes may be more compact in some nonassociated solvents than in water.
Graphene/carbon aerogels derived from graphene crosslinked polyimide as electrode materials for supercapacitors (2014)

Graphene/carbon aerogels with hierarchical pores have been facilely prepared by carbonization of graphene/polyimide aerogels.
Stress-activated martensitic transformation and transformation plasticity (1988)

On etudie les caracteristiques morphologiques et cristallographiques de la transformation, ainsi que l'influence des contraintes mecaniques sur la transformation. On etudie le cas de certains aciers, des ceramiques MgO-ZrO 2 et des ceramiques de zircone quadratique polycristalline
Genetic control of cobalamin binding in normal and mutant cells: Assignment of the gene for 5-methyltetrahydrofolate:L-homocysteine S -methyltransferase to human chromosome 1 (1979)

When extracts prepared from cultured human or rodent fibroblasts grown in medium containing [(57)Co]cobalamin were analyzed by polyacrylamide gel electrophoresis, most of the intracellular radioactivity migrated with the activity of the cobalamin-dependent enzyme 5-methyltetrahydrofolate:L-homocysteine S-methyltransferase (EC 2.1.1.13). Because the rodent and human forms of this enzyme are electrophoretically different, we used the binding of [(57)Co]cobalamin to detect the presence of the human methyltransferase isozyme in rodent-human somatic cell hybrids. As expected, binding and methyltransferase activities were found to cosegregate, thus confirming genetically their electrophoretic identity. Accordingly, we examined the [(57)Co]cobalamin-binding patterns and human chromosome contents of a panel of 12 rodent-human hybrid clones, and concluded that the gene for the methyltransferase (designated Mtr) is located on human chromosome 1. Using this information, we probed the nature of the molecular defect exhibited by fibroblasts cultured from patients expressing the cbl C mutation. Although these cells are unable to associate newly taken up [(57)Co]cobalamin with the methyltransferase, hybrids of mouse L-cells and cbl C cells containing chromosome 1 show a "reappearance" of the human [(57)Co]cobalamin-methyltransferase. These results indicate that the cbl C mutation does not affect the methyltransferase apoprotein, but rather some metabolic step that must convert cobalamin to a chemical form capable of attaching to the enzyme.
Inherited interleukin 12 deficiency in a child with bacille Calmette-Guérin and Salmonella enteritidis disseminated infection. (1998)

Interferon-gamma receptor ligand-binding chain (IFN-gammaR1) or signaling chain (IFN-gammaR2) deficiency, like interleukin 12 receptor beta1 chain (IL-12Rbeta1) deficiency, predispose to severe infections due to poorly virulent mycobacteria and salmonella. A child with bacille Calmette-Guérin and Salmonella enteritidis infection was investigated. Mutations in the genes for IFN-gammaR1, IFN-gammaR2, IL-12Rbeta1, and other molecules implicated in IL-12- or IFN-gamma-mediated immunity were sought. A large homozygous deletion within the IL-12 p40 subunit gene was found, precluding expression of functional IL-12 p70 cytokine by activated dendritic cells and phagocytes. As a result, IFN-gamma production by lymphocytes was markedly impaired. This is the first discovered human disease resulting from a cytokine gene defect. It suggests that IL-12 is essential to and appears specific for protective immunity to intracellular bacteria such as mycobacteria and salmonella.