gebhart/patrepeval huggingface dataset:
Altered chromatin structure associated with methylation-induced gene silencing in cancer cells: correlation of accessibility, methylation, MeCP2 binding and acetylation (2001)

Silencing of tumor-suppressor genes by hypermethylation of promoter CpG islands is well documented in human cancer and may be mediated by methyl-CpG-binding proteins, like MeCP2, that are associated in vivo with chromatin modifiers and transcriptional repressors. However, the exact dynamic between methylation and chromatin structure in the regulation of gene expression is not well understood. In this study, we have analyzed the methylation status and chromatin structure of three CpG islands in the p14(ARF)/p16(INK4A) locus in a series of normal and cancer cell lines using methylation-sensitive digestion, MspI accessibility in intact nuclei and chromatin immunoprecipitation (ChIP) assays. We demonstrate the existence of an altered chromatin structure associated with the silencing of tumor-suppressor genes in human cancer cell lines involving CpG island methylation, chromatin condensation, histone deacetylation and MeCP2 binding. The data showed that MeCP2 could bind to methylated CpG islands in both promoters and exons; MeCP2 does not interfere with transcription when bound at an exon, suggesting a more generalized role for the protein beyond transcriptional repression. In the absence of methylation, it is demonstrated that CpG islands located in promoters versus exons display marked differences in the levels of acetylation of associated histone H3, suggesting that chromatin remodeling can be achieved by methylation-independent processes and perhaps explaining why non-promoter CpG islands are more susceptible to de novo methylation than promoter islands.
Suspected Adverse Methylphenidate-lmipramine Interactions in Children (1986)

Two cases are presented which illustrate the dangers inherent in utilizing a polypharmacy approach in treating children with psychotropic medication. In each case, severe adverse effects, including cognitive and mood deterioration, were experienced by the child when treated with a combination of methylphenidate and imipramine. Possible mechanisms at the neurotransmitter level are described as postulated determinants for this pharmacological interaction.
Tissue Tregs (2016)

The immune system is responsible for defending an organism against the myriad of microbial invaders it constantly confronts. It has become increasingly clear that the immune system has a second major function: the maintenance of organismal homeostasis. Foxp3(+)CD4(+) regulatory T cells (Tregs) are important contributors to both of these critical activities, defense being the primary purview of Tregs circulating through lymphoid organs, and homeostasis ensured mainly by their counterparts residing in parenchymal tissues. This review focuses on so-called tissue Tregs. We first survey existing information on the phenotype, function, sustaining factors, and human equivalents of the three best-characterized tissue-Treg populations-those operating in visceral adipose tissue, skeletal muscle, and the colonic lamina propria. We then attempt to distill general principles from this body of work-as concerns the provenance, local adaptation, molecular sustenance, and targets of action of tissue Tregs, in particular.
Some Basic Properties of General Nonperfect Secret Sharing Schemes (2020)

Nonperfect secret sharing schemes (NSSs) have an advantage such that the size of shares can be shorter than that of perfect secret sharing schemes. This paper shows some basic properties of general NSS. First, we present a necessary and sufficient condition on the existence of an NSS. Next, we show two bounds of the size of shares, a combinatorial type bound and an entropy type bound. Further, we define a compact NSS as an NSS which meets the equalities of both our bounds. Then we show that a compact NSS has some special access hierarchy and it is closely related to a matroid. Verifiable nonperfect secret sharing schemes are also presented.
Development of Structures and Transport Functions in the Mouse Placenta (2005)

The placenta is essential for sustaining the growth of the fetus during gestation, and defects in its function result in fetal growth restriction or, if more severe, fetal death. Several molecular pathways have been identified that are essential for development of the placenta, and mouse mutants offer new insights into the cell biology of placental development and physiology of nutrient transport.
Efficient expression of influenza virus NS1 nonstructural proteins in Escherichia coli. (1983)

RNA segment 8 of the influenza A virus genome codes for two nonstructural proteins, NS1 and NS2, for which the functions are unknown. Cloned cDNA copies of this gene from three different influenza A virus strains were inserted into an Escherichia coli plasmid expression vector, pAS1, carrying the strong regulatable lambda phage promoter, PL. After induction, the NS1 proteins were overproduced to levels of 20-25% of total cellular protein. This was surprising in that the codon composition for these eukaryotic genes is similar to that for weakly expressed proteins in E. coli. Thus, under the appropriate conditions, it appears that high level expression of genes containing a relatively large proportion of minor codons can be obtained. The NS1 protein produced in bacteria from a cloned cDNA copy of the A/PR/8/34 virus NS gene was purified to apparent homogeneity and used to generate a high-titer monospecific rabbit antiserum. Immunoprecipitation studies showed this antibody to be crossreactive against the NS1 proteins produced by several different influenza A virus strains. Immunofluorescence experiments in Madin-Darby canine kidney cells showed the NS1 proteins to be located in the nucleoplasm early in infection for all strains examined. With some of the strains, NS1-specific immunofluorescence was observed predominantly in the nucleoli later in infection. This technology can be used to obtain other viral proteins in pure form for structural, functional, and immunological studies.
Characterization and enzymatic degradation of PEG‐cross‐linked chitosan hydrogel films (2009)

Abstract In our previous study (Kiuch et al., J Appl Polym Sci 2008, 107, 3823), poly(ethylene glycol) (PEG) cross‐linked chitosan hydrogel films with various PEG to chitosan ratio and PEG molecular weight have been successfully prepared and their thermal, mechanical and swelling properties at acidic pH were studied. These films are potential biodegradable polymeric materials, because their constituents, that is, chitosan and PEG, are well known as biodegradable polymers. In this study, glass transition temperature ( T g ), contact angle, swelling behavior at physiological conditions and in vitro enzymatic degradation behavior were investigated for the PEG‐cross‐linked chitosan hydrogel films. These properties of chitosan hydrogel were found to change significantly upon introducing the PEG‐cross‐links. According to differential scanning calorimeter analysis, the T g value increased with the PEG content in the hydrogel films, indicating the densification of the film by PEG‐crosslinking. The contact angle was decreased with increasing the number of crosslinks, reflecting that introduction of the cross‐linked structure induced the reduction of chitosan ordered structure. The swelling behavior depended on the PEG to chitosan ratio and the cross‐linked structure. The water content was changed with the number of PEG‐crosslinks. The rate of lysozyme‐catalyzed degradation was also influenced by the introduction of PEG‐cross‐linked structure. The surface morphology of the film was observed by the scanning electron microscopy. It was confirmed that the PEG‐cross‐linked chitosan hydrogel film was degraded by lysozyme from its surface area. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Exchange Coupling in Niobocene Trihydrides, Nb(C5H3RR‘)2H3, and Their Adducts with Copper Triad Cations, [{Nb(C5H3RR‘)2H3}2M]+(R = R‘ = H; R = H, R‘= SiMe3; R = R‘ = SiMe3; M = Cu, Ag, Au) (1996)

The reactions of Nb(C5H3RR‘)2Cl2 with Red−Al followed by hydrolysis yield Nb(C5H3RR‘)2H3 (R = R‘ = H, 1; R = H, R‘ = SiMe3, 2; R = R‘ = SiMe3, 3). These compounds react with Lewis acidic coinage cationic species, namely, [Cu(MeCN)4]PF6, AgBF4, and “Au(THT)PF6”, prepared in situ from AuCl(THT) and TlPF6 in a 2 to 1 ratio to yield the adducts [{Nb(C5H3RR‘)2H3}2M]+ (M = Cu, R = R‘ = H, 7; R = H, R‘ = SiMe3, 8; R = R‘ = SiMe3, 9; M = Ag, R = H, R‘ = SiMe3, 10; R = R‘ = SiMe3, 11; M = Au, R = R‘ = H, 12; R = H, R‘ = SiMe3, 13; R = R‘ = SiMe3, 14). Like 1, but unlike the corresponding tantalum derivatives Ta(C5H3RR‘)2H3 (R = R‘ = H, 4; R = H, R‘ = SiMe3, 5; R = R‘ = SiMe3, 6), 2 and 3 show exchange couplings in their high-field 1H NMR spectra due to a hydride tunneling phenomenon. The magnitudes of exchange couplings are larger in the cases of 2 and 3 than in the case of 1 as a result of the decrease of electron density upon increasing the number of SiMe3 substituents on the Cp ring. The addition of a Lewis acidic cation results in the observation of an AB2 pattern for the hydrides at room temperature, which splits at low temperature into an ABC one in agreement with a fluxional behavior of the cation which binds to two hydrides of each niobium center. The activation energy of these fluxional processes are close to 42−45 kJ·mol-1 in the case of Cu adducts, 37 kJ·mol-1 in the case of Ag adducts, and 40 kJ·mol-1 in the case of Au adducts. The magnitude of exchange couplings is reduced upon addition of copper cation to 1−3, is of the same order of magnitude after addition of a silver cation, and is greatly increased by addition of a gold cation. A model is proposed to explain these variations which involves two isomeric states that are close in energy, one involving two bridging and one terminal hydrides on niobium and one involving one bridging hydride and a dihydrogen molecule. A line shape analysis experiment carried out on 14 allows determination of the parameters of the classical exchange, the coupling constants at various temperatures which reach 550 Hz at 347 K, and the parameters of the quantum mechanical exchange according to our proposed model. The structure of 14 has been studied by X-ray diffraction. The structure has been solved from diffractometer data by Patterson method and refined by blocked full-matrix least squares on the basis of 3082 observed reflections to R and Rw values of 0.0346 and 0.0381, respectively. The structure shows the presence of two bridging hydrides between the niobium and gold atoms; one of them is found close to the terminal hydride.
Inactivation of Apoe and Apoc1 by two consecutive rounds of gene targeting: effects on mRNA expression levels of gene cluster members (1995)

The genes encoding apolipoprotein (apo) E and apoC1 are, together with the gene for apoC2, located in a conserved gene cluster on human chromosome 19q12-13.2 and mouse chromosome 7. Although the significance of apoE as a ligand for receptor-mediated uptake of lipoprotein remnant particles is undisputed, the in vivo function of apoC1 and the possible interaction between apoE and apoC1 in the modulation of plasma cholesterol and triglyceride levels is far from understood. Our strategy to unravel the metabolic relationship between apoE and apoC1 in vivo is to first generate mice deficient in both apolipoproteins, enabling future production of transgenic mice with variable ratios of normal and mutant apoE and apoC1 on a null background. Here we report the creation and characterization of mice deficient in both apoE and apoC1. As these genes are tightly genetically linked, double-deficient mice were obtained by two consecutive rounds of gene targeting in mouse embryonic stem cells. Surprisingly, double inactivation of the Apoe and Apoc1 gene loci as well as single inactivations at either one of these loci were found to affect also the RNA expression levels of the other gene members in the Apoe-c1-c2 cluster. This indicates that targeted insertions are not necessarily neutral for the expression of nearby gene members in a given gene cluster. Homozygous Apoe-c1 knockout mice are hypercholesterolemic, with serum cholesterol levels of 12.5 +/- 4.3 mM compared with 2.9 +/- 0.5 mM in control mice, resembling mice solely deficient in apoE.
Cementomimetics—constructing a cementum-like biomineralized microlayer via amelogenin-derived peptides (2012)

Cementum is the outer-, mineralized-tissue covering the tooth root and an essential part of the system of periodontal tissue that anchors the tooth to the bone. Periodontal disease results from the destructive behavior of the host elicited by an infectious biofilm adhering to the tooth root and left untreated, may lead to tooth loss. We describe a novel protocol for identifying peptide sequences from native proteins with the potential to repair damaged dental tissues by controlling hydroxyapatite biomineralization. Using amelogenin as a case study and a bioinformatics scoring matrix, we identified regions within amelogenin that are shared with a set of hydroxyapatite-binding peptides (HABPs) previously selected by phage display. One 22-amino acid long peptide regions referred to as amelogenin-derived peptide 5 (ADP5) was shown to facilitate cell-free formation of a cementum-like hydroxyapatite mineral layer on demineralized human root dentin that, in turn, supported attachment of periodontal ligament cells in vitro. Our findings have several implications in peptide-assisted mineral formation that mimic biomineralization. By further elaborating the mechanism for protein control over the biomineral formed, we afford new insights into the evolution of protein-mineral interactions. By exploiting small peptide domains of native proteins, our understanding of structure-function relationships of biomineralizing proteins can be extended and these peptides can be utilized to engineer mineral formation. Finally, the cementomimetic layer formed by ADP5 has the potential clinical application to repair diseased root surfaces so as to promote the regeneration of periodontal tissues and thereby reduce the morbidity associated with tooth loss.
Effects of Dietary L-Arginine Intake on Cardiorespiratory and Metabolic Adaptation in Athletes (2009)

To assess the effect of diet enrichment with L-arginine or supplementation at high doses on physiological adaptation during exercise, 9 athletes followed 3 different diets, each over 3 consecutive days, with a wash-out period of 4 d between training sessions: control diet (CD), 5.5 +/- 0.3 g/d of L-arginine; Diet 1 (rich in L-arginine food), 9.0 +/- 1.1 g/d of L-arginine; and Diet 2 (the same as CD but including an oral supplement of 15 g/d), 20.5 +/- 0.3 g/d of L-arginine. Plasma nitrate levels of each participant were determined on the day after each treatment. Participants performed a submaximal treadmill test (initial speed 10-11 km/hr, work increments 1 km/hr every 4 min until 85-90% VO2max, and passive recovery periods of 2 min). Oxygen uptake and heart rate were monitored throughout the test. Blood lactate concentration ([La-]b) was determined at the end of each stage. Repeated-measures ANOVA and paired Student's t tests were used to compare the various physiological parameters between diets. The level of significance was set at p < .05. [La-]b showed a significant effect at the 5-min time point between CD and Diet 2 (CD 3.0 +/- 0.5 mM, Diet 2 2.5 +/- 0.5 mM, p = .03), but this tendency was not found at higher exercise intensities. No significant differences were observed in any of the cardiorespiratory or plasma nitrate levels. In conclusion, dietary L-arginine intake on the days preceding the test does not improve physiological parameters during exercise.
Monoclonal antibodies to vascular endothelial growth factor‐D block its interactions with both VEGF receptor‐2 and VEGF receptor‐3 (2000)

Vascular endothelial growth factor-D (VEGF-D), the most recently discovered mammalian member of the VEGF family, is an angiogenic protein that activates VEGF receptor-2 (VEGFR-2/Flk1/KDR) and VEGFR-3 (Flt4). These receptor tyrosine kinases, localized on vascular and lymphatic endothelial cells, signal for angiogenesis and lymphangiogenesis. VEGF-D consists of a central receptor-binding VEGF homology domain (VHD) and N-terminal and C-terminal propeptides that are cleaved from the VHD to generate a mature, bioactive form consisting of dimers of the VHD. Here we report characterization of mAbs raised to the VHD of human VEGF-D in order to generate VEGF-D antagonists. The mAbs bind the fully processed VHD with high affinity and also bind unprocessed VEGF-D. We demonstrate, using bioassays for the binding and cross-linking of VEGFR-2 and VEGFR-3 and biosensor analysis with immobilized receptors, that one of the mAbs, designated VD1, is able to compete potently with mature VEGF-D for binding to both VEGFR-2 and VEGFR-3 for binding to mature VEGF-D. This indicates that the binding epitopes on VEGF-D for these two receptors may be in close proximity. Furthermore, VD1 blocks the mitogenic response of human microvascular endothelial cells to VEGF-D. The anti-(VEGF-D) mAbs raised to the bioactive region of this growth factor will be powerful tools for analysis of the biological functions of VEGF-D.
Inhibition of platelet function with synthetic peptides designed to be high-affinity antagonists of fibrinogen binding to platelets. (1986)

We have constructed synthetic peptides modeled on the sequences of (i) Arg-Gly-Asp, present in fibrinogen, fibronectin, and von Willebrand factor, and of (ii) the fibrinogen gamma chain (gamma 400-411) His-His-Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val. The concentration of each peptide that inhibits 50% of 125I-labeled fibrinogen binding to thrombin-stimulated platelets (IC50) was then determined. The IC50 for (gamma 400-411) was 48-180 microM at a fibrinogen concentration of 60 micrograms/ml. A substitution of arginine for alanine at position 9 decreased the IC50 to 14.5 microM. Arginine substitutions for all other residues on the amino-terminal side of the peptide Arg9-Gly-Asp-Val resulted in an IC50 of 0.4-0.8 microM, and the IC50 of the peptide Arg13-Gly-Asp-Val was 0.2-0.3 microM. This contrasts with an IC50 of 200 microM for Arg5-Gly-Asp-Val-Arg4 and an IC50 greater than 1 mM for the peptide Arg12. The inhibitory effect resulted primarily in a decreased affinity of fibrinogen binding to platelets, although the number of available binding sites had also decreased. Binding was completely inhibited. At concentrations between 10 and 18 microM, Arg9-Gly-Asp-Val blocked all ADP-induced aggregation in citrated platelet-rich plasma. The peptide Tyr-His-His-Lys-Arg-Lys-Arg-Lys-Gln-Arg-Gly-Asp-Val was labeled with 125I to quantitate its binding to thrombin-stimulated platelets; at saturation, 59,990 molecules were bound per cell (Kd = 3.8 X 10(-7) M). These modified synthetic peptides bind to platelets with the same affinity as does intact fibrinogen and inhibit platelet function. The increased affinity of these modified peptides is greater than 20-fold that of peptides comprised of only native sequences and is a prerequisite for the potential antithrombotic use of these agents.
Influence of Erroneous Data on the Results of Calculations From Acid–Base Surface Free Energy Theories. IV. Solution of an Overdetermined Set in the Case of Homoscedastic Error (2009)

The van Oss–Chaudhury–Good theory (vOCGT) was checked for a large artificial set of the work of adhesion input data calculated for 15 solids and 300 liquids. Numerical values of LW component and acid (A) and base (B) parameters were assigned to 15 solids. These 15 solids were grouped in 5 sets of 3 solids each. Also numerical values of LW component and A and B parameters were assigned to 300 liquids (three sets of 100 liquids each). Data for these solids and liquids were especially selected to present real types of materials encountered in practice. For all 15 solids and 300 liquids the values of the work of adhesion were calculated and these values were assumed to be error-free. Next, new values of the work of adhesion were obtained by adding a random homoscedastic error of normal distribution (also called the Gaussian distribution — it is continuous probability distribution defined by two parameters: the mean and variance (standard deviation squared, σ 2)) belonging to 8 distributions of a mean value equal to the error-free work of adhesion value and standard deviations of 0.5, 1, 2, 5, 7, 10, 15 and 20 mJ/m2. The LW components and A and B parameters for these solids were back-calculated for each solid and error level. Liquids were grouped in sets of 10 liquids and overdetermined set of equations was solved for the 3 solids. It was found, that there existed a linear correlation between the RMSE (root mean square error) of the solution and the standard deviation of the work of adhesion data. This correlation was highly significant (with correlation coefficient higher than 0.9998) and existed separately for LW component, A and B parameters as well as for the total solution vector. The RMSE values of the total solution as well as separately for LW component and A and B parameters were correlated with the condition number of a given 10-equation overdetermined set. A very good correlation was found only for the total solution and worse for A parameter, and practically there was no correlation for B parameter and the LW component. Based on the correlation between the RMSE and the standard deviation of the work of adhesion it was possible to determine what should have been the maximal standard deviation of the work of adhesion when a calculated value of a given LW component or A or B parameter differed no more than 1 mJ/m2 from an error-free (true) value.
Mechanisms of antibody-mediated protection against lymphocytic choriomeningitis virus infection: mother-to-baby transfer of humoral protection (1992)

The role of antiviral antibodies in resistance to lymphocytic choriomeningitis virus (LCMV) infection was explored. Immune serum and monoclonal antibodies prevented fatal T-cell-mediated immunopathology following acute LCMV infections. In addition, 10- and 14-day-old mice that received maternally derived anti-LCMV antibodies through nursing were protected from an otherwise lethal LCMV challenge. Detailed investigation of the mechanism(s) by which these antiviral antibodies provided was carried out by using anti-LCMV monoclonal antibodies. Protection correlated directly with the ability of the antibodies to reduce viral titers in the tissues of conventional (K. E. Wright and M. J. Buchmeier, J. Virol. 65:3001-3006, 1991) and nude mice. However, this reduction was not simply a reflection of virus neutralizing activity, since not all antibodies which neutralized in vitro were protective. A correlation was also found between immunoglobulin isotype and protection: all of the protective antibodies were immunoglobulin G2a (IgG2a), while IgG1 antibodies mapping to the same epitopes were not. Protection appeared to be associated with events controlled by the Fc region. Functional F(ab')2 fragments which retained in vitro neutralizing activity were not protective in vivo. Furthermore, this Fc-associated function was not related to complement-mediated cell lysis, since C5-deficient mouse strains were also protected. These results suggest a role for antibody in protection from arenavirus infections and indicate that a distinct immunoglobulin subclass, IgG2a, may be essential for this protection.