gebhart/patrepeval huggingface dataset:
PAMAM Dendrimers Undergo pH Responsive Conformational Changes without Swelling (2009)

Atomistic molecular dynamics (MD) simulations of a G4-NH(2) PAMAM dendrimer were carried out in aqueous solution using explicit water molecules and counterions (with the Dreiding III force field optimized using quantum mechanics). Our simulations predict that the radius of gyration (R(g)) of the dendrimer changes little with pH from 21.1 A at pH approximately 10 (uncharged PAMAM) to 22.1 A at pH approximately 5 (charged with 126 protons), which agrees quantitatively with recent small angle neutron scattering (SANS) experiments (from 21.4 A at pH 10 to 21.5 A at pH 5). Even so we predict a dramatic change in the conformation. The ion pairing in the low pH form leads to a locally compact dense shell with an internal surface area only 37% of the high pH form with a dense core. This transformation from "dense core" at high pH to "dense shell" at low pH could facilitate the encapsulation and release of guest molecules (e.g., drugs) using pH as the trigger, making dendrimers a unique drug delivery vehicle.
The Preparation of Some Azo Boronic Acids (1948)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Preparation of Some Azo Boronic AcidsH. R. Snyder and Clay WeaverCite this: J. Am. Chem. Soc. 1948, 70, 1, 232–234Publication Date (Print):January 1, 1948Publication History Published online1 May 2002Published inissue 1 January 1948https://pubs.acs.org/doi/10.1021/ja01181a068https://doi.org/10.1021/ja01181a068research-articleACS PublicationsRequest reuse permissionsArticle Views404Altmetric-Citations14LEARN 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
Induction of cell differentiation in melanoma cells by inhibitors of IMP dehydrogenase: altered patterns of IMP dehydrogenase expression and activity. (1990)

To study the induction of differentiation in human melanoma cells, we treated 12 melanoma cell lines with mycophenolic acid and tiazofurin, inhibitors of IMP dehydrogenase (IMPDH). In all cell lines studied, both agents inhibited cell growth and increased melanin content. However, the degree of growth inhibition did not necessarily correspond to the increase in melanin content. A detailed analysis of the HO and SK-MEL-131 cell lines indicated that mycophenolic acid and tiazofurin caused a time- and dose-dependent increase in the expression of a series of other maturation markers, including formation of dendrite-like structures, tyrosinase activity, and reactivity with the CF21 monoclonal antibody. The growth inhibition and melanogenesis induced by the IMPDH inhibitors was abrogated by the addition of exogenous guanosine. No such effect was observed after treatment of the cells with phorbol 12-myristate 13-acetate or retinoic acid, two other inducers of differentiation in these cells. The mycophenolic acid- and tiazofurin-treated cells also showed an increased level of IMPDH mRNA and protein, perhaps because of compensation for the inhibitor-mediated decrease in IMPDH activity. In contrast, treatment with phorbol 12-myristate 13-acetate or retinoic acid resulted in decreased levels of IMPDH mRNA and protein. The lack of a consistent pattern of IMPDH expression in the cells treated with IMPDH inhibitors and phorbol 12-myristate 13-acetate or retinoic acid suggests that the altered expression of IMPDH is not a general requirement for the induction of cell differentiation in these cells. Our results also suggest that IMPDH inhibitors may provide a useful approach to circumvent the differentiation block in melanoma.
Protection against Methylation-induced Cytotoxicity by DNA Polymerase β-Dependent Long Patch Base Excision Repair (2000)

Using a plasmid-based uracil-containing DNA substrate, we found that the long patch base excision repair (BER) activity of a wild-type mouse fibroblast extract was partially inhibited by an antibody to DNA polymerase beta (beta-pol). This suggests that beta-pol participates in long patch BER, in addition to single-nucleotide BER. In single-nucleotide BER, the deoxyribose phosphate (dRP) in the abasic site is removed by the lyase activity of beta-pol. Methoxyamine (MX) can react with the aldehyde of an abasic site, making it refractory to the beta-elimination step of the dRP lyase mechanism, thus blocking single-nucleotide BER. MX exposure sensitizes wild-type, but not beta-pol null mouse embryonic fibroblasts, to the cytotoxic effects of methyl methanesulfonate (MMS) and methylnitrosourea. Expression of beta-pol in the null cells restores the ability of MX to modulate sensitivity to MMS. The beta-pol null cells are known to be hypersensitive to MMS and methylnitrosourea, and in the presence of MX (i.e. under conditions where single-nucleotide BER is blocked) the null cells are still considerably more sensitive than wild-type. The data are consistent with a role of beta-pol in long patch BER, which helps protect cells against methylation damage-induced cytotoxicity.
Atopic eczema: genetics or environment? (2007)

Atopic eczema (AE) is a multifactorial skin disease caused by a variety of factors such as genetic conditions, alterated skin structure, immunologic deviations and environmental factors, among others. There are two main subtypes of AE, i.e. the IgE-associated ("atopic eczema") and the non-IgE-associated type ("nonatopic eczema") with different prognosis concerning the development of respiratory diseases ("atopy march"). Recently, it was demonstrated that Filaggrin (=filament-aggregating protein, FL) is a major gene for atopic eczema. Filaggrin binds to and aggregates the keratin cytoskeleton in the epidermis. Homozygous FLG mutation leads to complete loss of filaggrin expression in skin. Half or more of children with moderate to severe AE carry FLG mutations. Moreover, filaggrin loss-of-function mutations predispose to phenotypes involved in the atopy march. The altered skin structure and a deficiency in antimicrobial peptides favour colonization with Staphylococcus aureus and yeasts (Malassezia sp.). Sensitization to the yeast occurs almost exclusively in AE patients. S. aureus enterotoxins with superantigenic activity stimulate activation of T cells and macrophages. So far, AE skin lesions are orchestrated by the local tissue expression of proinflammatory cytokines and chemokines with activation of T lymphocytes, dendritic cells, macrophages, keratinocytes, mast cells, and eosinophils which lead to the skin inflammatory responses. From the therapeutic point of view, besides emollients and local corticosteroids, topic immunomodulatory drugs (tacrolimus and pimecrolimus) have substantially improved the treatment of AE.
Genetic and molecular analysis of the tRNA-tufB operon of the myxobacterium Stigmatella aurantiaca (1995)

The tufB gene, encoding elongation factor Tu (EF-Tu), from the myxobacterium Stigmatella aurantiaca was cloned and sequenced. It is preceded by four tRNA genes, the first ever described in myxobacteria. The tRNA synthesized from these genes and the general organization of the locus seem identical to that of Escherichia coli, but differences of potential importance were found in the tRNA sequences and in the intergenic regions. The primary structure of EF-Tu was deduced from the tufB DNA sequence. The factor is composed of 396 amino acids, with a predicted molecular mass of 43.4 kDa, which was confirmed by expression of tufB in maxicells. Sequence comparisons between S.aurantiaca EF-Tu and other bacterial homologues from E.coli, Salmonella typhimurium and Thermus thermophilus displayed extensive homologies (75.9%). Among the variable positions, two Cys residues probably involved in the temperature sensitivity of E.coli and S.typhimurium EF-Tu are replaced in T.thermophilus and S.aurantiaca EF-Tu. Since two or even three tuf genes have been described in other bacterial species, the presence of multiple tuf genes was sought for. Southern and Northern analysis are consistent with two tuf genes in the genome of S.aurantiaca. Primer extension experiments indicate that the four tRNA genes and tufB are organized in a single operon.
Biology and Behaviour of the HoneybeeApis Florea, and Possibilities for Beekeeping (1981)

(1981). Biology and Behaviour of the Honeybee Apis Florea, and Possibilities for Beekeeping. Bee World: Vol. 62, No. 2, pp. 46-59.
Modulation of Transgene Expression in Retinal Gene Therapy by Selective Laser Treatment (2013)

Microsecond exposures produced by scanning laser destroyed RPE cells selectively, without damage to neural retina. Continuity of RPE layer is restored within days by migration and proliferation, but transgene not integrated into the nucleus is not replicated. Therefore, gene expression can be modulated in a precise manner by controlling the laser pattern density and further adjusted using repeated applications.
In Situ and Reactor Study of the Enantioselective Hydrogenation of Acetylacetone by Ruthenium Catalysis with the New Chiral Diphosphine Ligand (R)-(R)-3-Benzyl-2,4-bis(diphenylphosphino)pentane (2000)

The new optically pure C1-symmetric diphosphine ligand (R)-(R)-3-benzyl-2,4-bis(diphenylphosphino)pentane (BDPBzP) has been synthesized by enantioselective reduction of 3-benzyl-2,4-pentanedione with [((S)-BINAP)Ru(p-cymene)Cl]Cl, followed by the reaction of potassium diphenylphosphide with the bis(mesylate) intermediate (S)-(S)-PhCH2CH(CH(OMs)CH3)2. The Ru(II) complexes [(BDPBzP)Ru(p-cymene)I]I·2CH2Cl2 (5), [(BDPBzP)(DMSO)Ru(μ-Cl)3RuCl(BDPBzP)] (6a), and [(BDPBzP)RuCl(CH3CN)3]OTf (7) have been prepared and characterized by multinuclear NMR spectroscopy. The p-cymene complex 5 has been authenticated by a single-crystal X-ray analysis. All Ru(II) complexes are effective catalyst precursors for the enantioselective hydrogenation of acetylacetone to (R)-(R)-2,4-pentanediol. The best catalytic performance in terms of enantioselective discrimination (ee's up to 99%) has been observed for the dimer 6a. An in situ high-pressure NMR study in catalytic conditions has shown that the nonclassical polyhydride dimer [(BDPBzP)(η2-H2)ClRu(μ-H)2RuCl(η2-H2)(BDPBzP)] is the only species observed all over the catalytic cycle. The monohydrogenated intermediate (R)-4-hydroxypentan-2-one is obtained in appreciable yields only at low temperature or low conversion. The relative yields and ee's of the mono- and dihydrogenated products are consistent with the effect of a double stereodifferentiation process.
Ethanol Directly Excites Dopaminergic Ventral Tegmental Area Reward Neurons (1999)

These data provide strong evidence that ethanol directly excites dopaminergic VTA neurons, as this excitation still occurs in the absence of input from surrounding neurons.
Spin transport and spin torque in a magnetic nanowire with a non-collinear magnetic order (2007)

A theory is developed for the treatment of magneto transport properties and spin dynamics in magnetic nanowire that contains a domain wall (DW), i.e. a region of non-collinearity. The method is applicable when the wavelength of spin up and down electrons are larger than the DW width in which case the problem is solvable exactly as a spin-resolved scattering from a strongly localized spin-dependent effective potential created by DW. We present calculations for the current-induced spin density, the distribution of the spin currents, and the spin torque acting locally on the magnetic moments within DW. We also discuss an extension based on the weak gradient (adiabatic) perturbation arising after a local transformation to a uniform magnetization.
IgG-mediated enhancement of antibody responses is low in Fc receptor gamma chain-deficient mice and increased in Fc gamma RII-deficient mice. (1999)

Immunization with IgG/Ag or IgE/Ag complexes leads to a higher production of specific Abs than immunization with Ag alone. The enhancing effect of IgE is exclusively dependent upon the low-affinity receptor for IgE, Fc epsilon RII, whereas the mechanism behind IgG-mediated enhancement is unknown. We have investigated whether receptors for the Fc part of IgG are required for responses to IgG/Ag. Mice lacking the gamma subunit of Fc receptors (FcRs) (FcR gamma-/-), Fc gamma RII (Fc gamma RII-/-), or Fc gamma RIII (Fc gamma RIII-/-) were immunized with BSA-2,4,6-trinitrophenyl (TNP) alone or BSA-TNP complexed to monoclonal TNP-specific IgG1, IgG2a, or IgG2b. As expected, all subclasses enhanced the Ab-response to BSA in wild-type mice. Enhancement was in the same order of magnitude in Fc gamma RIII-/- mice (</=177-fold of controls administered Ag alone), whereas it was abrogated in FcR gamma-/- mice and augmented in Fc gamma RII-/- mice (</=5147-fold of controls). The response to IgE/Ag complexes in FcR gamma-/- and Fc gamma RII-/- mice was similar to that se for wild-type mice, demonstrating that non-Fc gamma R-dependent responses were normal. Our observations suggest that IgG/Ag complexes enhance Ab responses via Fc gamma Rs. Moreover, they reveal a strong negative regulation of Ab responses to IgG/Ag exerted by Fc gamma RII.
The Perfluoro-t-butyl Anion in the Synthesis of Organofluorine Compounds (1976)

Methods for the generation and reactions of the perfluoro-t-butyl anion — a convenient model for the investigation of the chemistry of perfluoroalkyl carbanions, are examined. Syntheses based on this anion lead to the formation of a wide variety of compounds containing the (CF3)3C group. The bibliography includes 76 references.
Noise Reduction of ECG by Averaging an Experimental Study of the Procedure and a Validated Method (1975)

Electrical noise often hampers the interpretation of ECG and other heart-synchronous signals. Time-coherent averaging is a commonly used method to reduce the noise. This method has been implemented on a computer with 12,000 12-bit words of core memory, suitable for on-line use in any clinical laboratory. An analysis was made of which demands apply to the exactness of synchronization of added heart cycles. The method was tested with respect to these demands and also, on a limited scale, for its efficiency in eliminating ectopic beats from the average.
Methionine adenosyltransferase 1A knockout mice are predisposed to liver injury and exhibit increased expression of genes involved in proliferation (2001)

Liver-specific and nonliver-specific methionine adenosyltransferases (MATs) are products of two genes, MAT1A and MAT2A, respectively, that catalyze the formation of S-adenosylmethionine (AdoMet), the principal biological methyl donor. Mature liver expresses MAT1A, whereas MAT2A is expressed in extrahepatic tissues and is induced during liver growth and dedifferentiation. To examine the influence of MAT1A on hepatic growth, we studied the effects of a targeted disruption of the murine MAT1A gene. MAT1A mRNA and protein levels were absent in homozygous knockout mice. At 3 months, plasma methionine level increased 776% in knockouts. Hepatic AdoMet and glutathione levels were reduced by 74 and 40%, respectively, whereas S-adenosylhomocysteine, methylthioadenosine, and global DNA methylation were unchanged. The body weight of 3-month-old knockout mice was unchanged from wild-type littermates, but the liver weight was increased 40%. The Affymetrix genechip system and Northern and Western blot analyses were used to analyze differential expression of genes. The expression of many acute phase-response and inflammatory markers, including orosomucoid, amyloid, metallothionein, Fas antigen, and growth-related genes, including early growth response 1 and proliferating cell nuclear antigen, is increased in the knockout animal. At 3 months, knockout mice are more susceptible to choline-deficient diet-induced fatty liver. At 8 months, knockout mice developed spontaneous macrovesicular steatosis and predominantly periportal mononuclear cell infiltration. Thus, absence of MAT1A resulted in a liver that is more susceptible to injury, expresses markers of an acute phase response, and displays increased proliferation.
Selective alpha IIb beta 3 receptor blockage with peptide TP9201 prevents platelet uptake on Dacron vascular grafts without significant effect on bleeding time. (1994)

Synthetic vascular prostheses lack the uniquely low thrombogenicity provided by the endothelial cell lining of autogenous saphenous vein or artery grafts. The thrombogenic nature of the synthetic graft surface becomes a major determinant of early prosthetic graft patency. We demonstrate in a baboon ex vivo synthetic graft model that modification of the host's platelet interaction with the graft surface results in inhibition of platelet thrombus formation and thereby, a possible enhancement of early prosthetic graft patency. This was achieved by selective blockage of the platelet alpha IIb beta 3 receptor by the arginine-glycine-aspartic acid-containing synthetic peptide TP9201. Platelet thrombus formation on a Dacron graft indicated by accumulation of indium III-oxine-labeled autologous platelets was measured by gamma camera imaging. After 60 minutes of circulation, TP9201 at a bolus of 125 micrograms/kg; infusion of 3 micrograms/kg/min, bolus of 190 micrograms/kg; infusion of 5 micrograms/kg/min, bolus of 250 micrograms/kg; infusion of 6 micrograms/kg/min, and bolus of 500 micrograms/kg; infusion of 12 micrograms/kg/min decreased platelet uptake on the graft to 50%, 40%, 30%, and 10% of control uptake, respectively. Forelimb template bleeding times were not found to be significantly prolonged at doses that effectively inhibit ex vivo platelet aggregation. As a result of drug treatment, no changes in hemodynamic parameters or hematologic profile, including platelet number and clotting time, were observed. We demonstrate here that the arginine-glycine-aspartic acid-containing peptide TP9201, which competitively inhibits the alpha IIb beta 3 integrin-fibrinogen interaction, significantly decreased the accumulation of platelets on a Dacron vascular graft. Molecules like peptide TP9201, because of its unique activity profile, may represent a superior approach to the control of platelet accumulation on thrombogenic surfaces.
A hypothesis for the HLA-B27 immune dysregulation in spondyloarthropathy: contributions from enteric organisms, B27 structure, peptides bound by B27, and convergent evolution. (1993)

Several human rheumatic diseases occur predominantly in persons who carry the histocompatibility (HLA) class I allele B27. They have also been related to Gram-negative enteric microorganisms. In addition, the recent recovery of peptides bound to B27 has allowed an understanding of the structural requirements for their binding. Using the accumulated data base of protein sequences, we have tested a series of hypotheses. First, we have asked whether the primary amino acid sequence of the hypervariable regions of HLA-B27 shares short sequences with the proteins of Gram-negative enteric bacteria. The data demonstrate that, unique among the HLA-B molecules, the hypervariable regions of HLA-B27 unexpectedly share short peptide sequences with proteins from these bacteria. Second, we have asked whether the enteric proteins tend to satisfy the structural requirements for peptide binding to B27 in those regions of the sequence shared with B27. This hypothesis also tends to be true, especially in an allelically variable part of the B27 sequence which is predicted to bind B27 if it were to be presented as a free peptide. We conclude that HLA-B27 and enteric Gram-negative bacteria have undergone a previously unappreciated form of convergent evolution which may be important in the process leading to these rheumatic diseases. Moreover, the regions of the enteric bacterial proteins which are contiguous with the short sequences shared with B27 tend to have structures which are also predicted to bind B27. These observations suggest a mechanism for autoimmunity and lead to the prediction that the B27-associated diseases are mediated by a subset of T-cell receptors, B27, and the peptides bound by B27.
Synergistic interactions between interferon-γ and TRAIL modulate c-FLIP in endothelial cells, mediating their lineage-specific sensitivity to thrombotic thrombocytopenic purpura plasma–associated apoptosis (2008)

Microvascular endothelial cell (MVEC) injury coupled to progression of platelet microthrombi facilitated by ADAMTS13 deficiency is characteristic of idiopathic and HIV-linked thrombotic thrombocytopenic purpura (TTP). Cytokines capable of inducing MVEC apoptosis in vitro are up-regulated in both TTP and HIV infection. However, the concentrations of these cytokines required to elicit EC apoptosis in vitro are 2- to 3-log-fold greater than present in patient plasmas. We report that clinically relevant levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interferon (IFN)-gamma act in synergy to induce apoptosis in dermal MVECs, but have no effect on large-vessel ECs or pulmonary MVECs. This reflects the tissue distribution of TTP lesions in vivo. Sensitivity to TTP plasma or TRAIL plus IFN-gamma is paralleled by enhanced ubiquitination of the caspase-8 regulator cellular FLICE-like inhibitory protein (c-FLIP), targeting it for proteasome degradation. c-FLIP silencing with anti-FLIP short interfering RNA (siRNA) in pulmonary MVECs rendered them susceptible to TTP plasma- and cytokine-mediated apoptosis, while up-regulation of c-FLIP by gene transfer partially protected dermal MVECs from such injury. TTP plasma-mediated apoptosis appears to involve cytokine-induced acceleration of c-FLIP degradation, sensitizing cells to TRAIL-mediated caspase-8 activation and cell death. Suppression of TRAIL or modulation of immunoproteasome activity may have therapeutic relevance in TTP.