gebhart/patrepeval huggingface dataset:
Cyclohexene Oxide/CO2 Copolymerization Catalyzed by Chromium(III) Salen Complexes and N-Methylimidazole:  Effects of Varying Salen Ligand Substituents and Relative Cocatalyst Loading (2004)

A detailed mechanistic study into the copolymerization of CO2 and cyclohexene oxide utilizing CrIII(salen)X complexes and N-methylimidazole, where H2salen = N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-ethylenediimine and other salen derivatives and X = Cl or N3, has been conducted. By studying salen ligands with various groups on the diimine backbone, we have observed that bulky groups oriented perpendicular to the salen plane reduce the activity of the catalyst significantly, while such groups oriented parallel to the salen plane do not retard copolymer formation. This is not surprising in that the mechanism for asymmetric ring opening of epoxides was found to occur in a bimetallic fashion, whereas these perpendicularly oriented groups along with the tert-butyl groups on the phenolate rings produce considerable steric requirements for the two metal centers to communicate and thus initiate the copolymerization process. It was also observed that altering the substituents on the phenolate rings of the salen ligand had a 2-fold effect, controlling both catalyst solubility as well as electron density around the metal center, producing significant effects on the rate of copolymer formation. This and other data discussed herein have led us to propose a more detailed mechanistic delineation, wherein the rate of copolymerization is dictated by two separate equilibria. The first equilibrium involves the initial second-order epoxide ring opening and is inhibited by excess amounts of cocatalyst. The second equilibrium involves the propagation step and is enhanced by excess cocatalyst. This gives the [cocatalyst] both a positive and negative effect on the overall rate of copolymerization.
Trends and racial/ethnic disparities in severe obesity among US children and adolescents, 1976–2006 (2010)

Abstract Introduction. This study aims to describe the trends and racial/ethnic differences in prevalence of severe obesity among US children. Methods. We examined height and weight measurements from US children and adolescents aged 2 to 19 years using three National Health and Nutrition Examination Surveys (NHANES II: 1976-1980, N = 7 201, NHANES III: 1988-1994, N = 10 600, and NHANES 1999-2006, N = 15 980). We estimated the prevalence of severe obesity, defined as having a body mass index (BMI) above 35 kg/m(2) or 120% of the age- and sex-specific 95(th) percentile on the CDC reference standards, stratified by sex and age groups (aged 2-5 years, 6-11 years, and 12-19 years). We compared prevalence estimates among non-Hispanic white, non-Hispanic black, and Hispanic children. Results. The age-standardized prevalence of severe obesity increased from 1.1%/1.3% (boys/girls) in NHANES II, to 2.9%/3.1% in NHANES III and 5.1%/4.7% in NHANES 1999-2006 (p-values for trend <0.001). We observed some differences in prevalence by race/ethnicity. Hispanic boys 6-11 years of age (9.0%, 95% CI: [6.4, 11.5]) and non-Hispanic black girls 12-19 years of age (12.6%, 95% CI: [10.6, 14.6]) had the highest prevalence of severe obesity in the most recent NHANES data. On average, obese youth were 9.7 kg (95% CI: [9.2, 10.2]) above the obesity standard, and severely obese youth were 21.3 kg (95% CI: [20.5, 22.3]) above. Conclusions. The prevalence of severe obesity among US youth is increasing, especially among Hispanic boys and non-Hispanic black girls. Our findings suggest that the degree of pediatric obesity is substantial and will likely have profound impact on adult morbid obesity and other morbidities.
Glucocorticoid regulation of transcription at an amplified, episomal promoter. (1983)

The mouse mammary tumor virus long terminal repeat (MMTV LTR) has been introduced into cultured murine cells, using the 69% transforming fragment of bovine papilloma virus type 1 (BPV). Transformed cells contain up to 200 copies of the chimeric molecules per diploid genome. The restriction endonuclease map of the acquired recombinants, as well as the physical structure of the DNA, indicates that the LTR-BPV molecules present in these cells occur exclusively as unintegrated, extrachromosomal episome. When a 72-base pair direct repeat "enhancer" element (derived from the Harvey sarcoma retrovirus) was included in the MMTV LTR-BPV chimeric plasmids, DNA acquired through transfection, with a single exception, was integrated or rearranged or both. The transcriptional potential of the episomal MMTV promoter present in these cells was tested in two ways. First, steady-state levels of MMTV-initiated RNA were measured by quantitative S1 mapping. Second, the relative number of transcription complexes initiated in vivo was determined by using a subnuclear fraction highly enriched for MMTV-BPV minichromosomes in an in vitro transcription extension assay. Both approaches showed that the MMTV LTR present in the episomal state was capable of supporting glucocorticoid hormone-regulated transcription. We have therefore demonstrated the hormone response for the first time in a totally defined primary sequence environment. Significant differences both in the basal level of MMTV-initiated transcription and in the extent of glucocorticoid induction were observed in individual cell lines with similar episomal copy numbers. These phenotypic variations suggest that epigenetic structure is an important component of the mechanism of regulation.
Small Molecule Interactions with Protein−Tyrosine Phosphatase PTP1B and Their Use in Inhibitor Design (1996)

We have previously shown that a small peptide bearing the hydrolytically stable phosphotyrosyl (pTyr) mimetic, (difluorophosphonomethyl) phenylalanine (F2Pmp), is an extremely potent inhibitor of PTP1B, with an IC50 value of 100 nM [Burke, T. R., Kole, H. K., & Roller, P. P. (1994) Biochem. Biophys. Res. Commun. 204, 129-134]. We further demonstrated that removal of the peptide portion and incorporation of the difluorophosphonomethyl moiety onto a naphthalene ring system, but not a phenyl ring system, resulted in good inhibitory potency [Kole, H. K., Smyth, M. S., Russ, P. L., & Burke, T. R., Jr. (1995) Biochem, J. 311, 1025-1031]. In order to understand the structural basis for this inhibition, and to aid in the design of further analogs, we solved the X-ray structure of [1, 1-difluoro-1-(2-naphthalenyl)-methyl]phosphonic acid (6) complexed within the catalytic site of PTP1B, solved to 2.3 A resolution. In addition to showing the manner in which the phosphonate group is held within the catalytic site, the X-ray structure also revealed extensive hydrophobic interactions with the naphthalene ring system, beyond that possible with an analog bearing a single phenyl ring. It is further evident that, of the two fluorine atoms, the pro-R alpha-fluorine interacts with the enzyme to a significantly greater degree than the pro-S alpha-fluorine, forming a hydrogen bond to Phe 182. On the basis of a computer-assisted molecular modeling analysis, it was determined that addition of a hydroxyl to the naphthyl 4-position, giving [1, 1-difluoro-1-[2-(4-hydroxynaphthalenyl)] methyl]phosphonic acid (8), could potentially replace a water molecule situated in the PTP1B-6 complex, thereby allowing new hydrogen-bonding interactions with Lys 120 and Tyr 46. Compound 8 was therefore prepared and found to exhibit a doubling of affinity (Ki = 94 microM) relative to parent unsubstituted 6 (Ki = 179 microM), supporting, in principle, the development of high-affinity ligands based on molecular modeling analysis of the enzyme-bound parent.
Beta 2 integrin-dependent tyrosine phosphorylation of paxillin in human neutrophils treated with tumor necrosis factor. (1994)

The focal adhesion protein paxillin undergoes tyrosine phosphorylation in response to signals mediated by integrins, neuropeptides and oncogene products, possibly via activation of the focal adhesion-associated kinase, p125FAK. In the present work, tumor necrosis factor-alpha (TNF) stimulated tyrosine phosphorylation of paxillin in human neutrophils. Cell adhesion and participation of the beta 2 integrin CD18 were necessary, but not sufficient, for the response. Adherent neutrophils also tyrosine phosphorylated paxillin in response to phorbol ester, formylmethionyl-leucyl-phenylalanine and opsonized bacteria. In contrast, p125FAK was constitutively tyrosine phosphorylated in a manner unaffected by adherence and/or TNF. Thus, cytokines and microbial products are among the stimuli that can induce the tyrosine phosphorylation of paxillin, and kinases other than p125FAK may be responsible. This is the first identification of paxillin and p125FAK in human cells and neutrophils, and one of the few identifications of a specific protein that undergoes tyrosine phosphorylation in response to any agonist in neutrophils or in response to TNF in any cell.
50.3: Novel Write‐erasable Input Display with Memory Circuits and Photo‐sensors (2011)

Abstract We have developed a new conceptual LCD with a memory circuit and a photo‐sensor in each pixel. This LCD enables to display a still image in the low power consumption. In addition, direct writing and erasing a character in the LCD are available without calculating coordinates by using a light pen.
Accumulation of Dendritic Cells and Increased CCL20 Levels in the Airways of Patients with Chronic Obstructive Pulmonary Disease (2007)

This is the first description of airway infiltration by DC in COPD. Moreover, interaction between CCL20 and CCR6 provides a possible mechanism for accumulation of DC in the lungs in COPD.
Reduced contact sensitivity reactions in mice treated with monoclonal antibodies to leukocyte function-associated molecule-1 and intercellular adhesion molecule-1 (1993)

We have investigated the effect of the administration of mAb against leukocyte function-associated molecule-1 (CD11a/CD18) and intercellular adhesion molecule-1 (CD54) on the delayed-type hypersensitivity reaction in 2,4-dinitro-1-fluorobenzene-sensitized CD2F1 mice. An i.p. injection of the mAb FD441.8 against CD11a at the time of ear challenge led to an almost complete inhibition of ear swelling compared with control animals. Administration of anti-CD54 mAb, 3E2 or YN1/1.7.4, before challenge, resulted in approximately 50% reduction of the delayed-type hypersensitivity response. The decrease in ear swelling reflected a profound inhibition of the edema and the cell infiltration in ears from animals treated with anti-CD11a, and a partial inhibition with anti-CD54 treatment. In addition, the threefold increase in the number of cells recovered from the draining lymph nodes 24 h after challenge in sensitized mice injected with normal IgG was ablated in mice treated with anti-CD11a and partially reduced in anti-CD54-treated animals. Immunohistochemistry and flow cytometry analysis demonstrated that the in vivo administered anti-CD11a mAb was associated with the surface of the majority of the cells in the lymph nodes 24 h after injection and challenge, whereas the anti-intercellular adhesion molecule-1 mAb reacted preferentially with the vascular endothelium. It is concluded that leukocyte function-associated molecule-1 and intercellular adhesion molecule-1 contribute to the generation of an optimal delayed-type hypersensitivity response.
Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients (2012)

This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients.
The revised fundamental theorem of moment invariants (1991)

A revised fundamental theorem of moment invariants for pattern recognition which corrects the fundamental theorem proposed by M.K. Hu (1962), is presented. The correction affects neither similitude (scale) nor rotation invariants derived using the original theorem, but it does affect features invariant to general linear transformations. Four of the latter invariants were presented originally by Hu. These are revised to take the correction to the fundamental theorem into account. Furthermore, these four invariants are combined to yield three new invariants, which are additionally invariant to changes in the illumination of an image.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Canine Ehrlichiosis Caused Simultaneously by Ehrlichia canis and Ehrlichia platys (2000)

To identify the causative agent of canine ehrlichiosis that has occurred in the suburbs of Guangzhou, China, since 1998, the 16S rRNA gene was amplified and sequenced. Two sequences of 1,482 and 1,483 base pairs were obtained and named as Gzh981 and Gzh982, respectively. The level of similarity of these two was 91.50%, and Gzh981 closely resembled the 16S rRNA gene of Ehrlichia canis, whereas Gzh982 resembled Ehrlichia platys. We therefore conclude that E. canis and E. platys together caused recent outbreaks of canine ehrlichiosis in China.
Agonist-induced conformational changes in the G-protein-coupling domain of the β 2 adrenergic receptor (2001)

The majority of extracellular physiologic signaling molecules act by stimulating GTP-binding protein (G-protein)-coupled receptors (GPCRs). To monitor directly the formation of the active state of a prototypical GPCR, we devised a method to site specifically attach fluorescein to an endogenous cysteine (Cys-265) at the cytoplasmic end of transmembrane 6 (TM6) of the beta(2) adrenergic receptor (beta(2)AR), adjacent to the G-protein-coupling domain. We demonstrate that this tag reports agonist-induced conformational changes in the receptor, with agonists causing a decline in the fluorescence intensity of fluorescein-beta(2)AR that is proportional to the biological efficacy of the agonist. We also find that agonists alter the interaction between the fluorescein at Cys-265 and fluorescence-quenching reagents localized to different molecular environments of the receptor. These observations are consistent with a rotation and/or tilting of TM6 on agonist activation. Our studies, when compared with studies of activation in rhodopsin, indicate a general mechanism for GPCR activation; however, a notable difference is the relatively slow kinetics of the conformational changes in the beta(2)AR, which may reflect the different energetics of activation by diffusible ligands.
Fault diagnosis in discrete-event systems: Framework and model reduction (2003)

A state-based approach for online passive fault diagnosis in systems modeled as finite-state automata is presented. In this framework, the system and the diagnoser (the fault detection system) do not have to be initialized at the same time. Furthermore, no information about the state or even the condition (failure status) of the system before the initiation of diagnosis is required. The design of the fault detection system, in the worst case, has exponential complexity. A model reduction scheme with polynomial time complexity is introduced to reduce the computational complexity of the design. Diagnosability of failures is studied, and necessary and sufficient conditions for failure diagnosability are derived.
The NF-kappa B and Sp1 motifs of the human immunodeficiency virus type 1 long terminal repeat function as novel thyroid hormone response elements. (1993)

We report that thyroid hormone (T3) receptor (T3R) can activate the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR). Purified chick T3R-alpha 1 (cT3R-alpha 1) binds as monomers and homodimers to a region in the LTR (nucleotides -104 to -75 [-104/-75]) which contains two tandem NF-kappa B binding sites and to a region (-80/-45) which contains three Sp1 binding sites. In contrast, human retinoic acid receptor alpha (RAR-alpha) and mouse retinoid X receptor beta (RXR-beta) do not bind to these elements. However, RXR-beta binds to these elements as heterodimers with cT3R-alpha 1 and to a lesser extent with RAR-alpha. Gel mobility shift assays also revealed that purified NF-kappa B p50/65 or p50/50 can bind to one but not both NF-kappa B sites simultaneously. Although the binding sites for p50/65, p50/50, and T3R, or Sp1 and T3R, overlap, their binding is mutually exclusive, and with the inclusion of RXR-beta, the major complex is the RXR-beta-cT3R-alpha 1 heterodimer. The NF-kappa B region of the LTR and the NF-kappa B elements from the kappa light chain enhancer both function as T3 response elements (TREs) when linked to a heterologous promoter. The TREs in the HIV-1 NF-kappa B sites appear to be organized as a direct repeat with an 8- or 10-bp gap between the half-sites. Mutations within the NF-kappa B motifs which eliminate binding of cT3R-alpha 1 also abolish stimulation by T3, indicating that cT3R-alpha 1 binding to the Sp1 region does not independently mediate activation by T3. The Sp1 region, however, is converted to a functionally strong TRE by the viral tat factor. These studies indicate that the HIV-1 LTR contains both tat-dependent and tat-independent TREs and reveal the potential for T3R to modulate other genes containing NF-kappa B- and Sp1-like elements. Furthermore, they indicate the importance of other transcription factors in determining whether certain T3R DNA binding sequences can function as an active TRE.
The PIM kinases in hematological cancers (2012)

The PIM genes represent a family of proto-oncogenes that encode three different serine/threonine protein kinases (PIM1, PIM2 and PIM3) with essential roles in the regulation of signal transduction cascades, which promote cell survival, proliferation and drug resistance. PIM kinases are overexpressed in several hematopoietic tumors and support in vitro and in vivo malignant cell growth and survival, through cell cycle regulation and inhibition of apoptosis. PIM kinases do not have an identified regulatory domain, which means that these proteins are constitutively active once transcribed. They appear to be critical downstream effectors of important oncoproteins and, when overexpressed, can mediate drug resistance to available agents, such as rapamycin. Recent crystallography studies reveal that, unlike other kinases, they possess a hinge region, which creates a unique binding pocket for ATP, offering a target for an increasing number of potent small-molecule PIM kinase inhibitors. Preclinical studies in models of various hematologic cancers indicate that these novel agents show promising activity and some of them are currently being evaluated in a clinical setting. In this review, we profile the PIM kinases as targets for therapeutics in hematologic malignancies.
Inhibition of Vascular Nitric Oxide after Rat Chronic Brain Hypoperfusion: Spatial Memory and Immunocytochemical Changes (2005)

An aging rat model of chronic brain hypoperfusion (CBH) that mimics human mild cognitive impairment (MCI) was used to examine the role of nitric oxide synthase (NOS) isoforms on spatial memory function. Rats with CBH underwent bilateral common carotid artery occlusion (2-vessel occlusion (2-VO)) for either 26 or 8 weeks and were compared with nonoccluded sham controls (S-VO). The neuronal and endothelial (nNOS/eNOS) constitutive inhibitor nitro-L-arginine methyl ester (L-NAME) 20 mg/kg was administered after 26 weeks for 3 days to 2-VO and S-VO groups and spatial memory was assessed with a modified Morris watermaze test. Only 2-VO rats worsened their spatial memory ability after L-NAME. Electron microscopic immunocytochemical examination using an antibody against eNOS showed 2-VO rats had significant loss or absence of eNOS-containing positive gold particles in hippocampal endothelium and these changes were associated with endothelial cell compression, mitochondrial damage and heavy amyloid deposition in hippocampal capillaries and perivascular region. In the 8-week study, three groups of 2-VO rats were administered an acute dose of 7-NI, aminoguanidine or L-NIO, the relatively selective inhibitors of nNOS, inducible NOS and eNOS. Only rats administered the eNOS inhibitor L-NIO worsened markedly their watermaze performance (P = 0.009) when compared with S-VO nonoccluded controls. We conclude from these findings that vascular nitric oxide derived from eNOS may play a critical role in spatial memory function during CBH possibly by keeping cerebral perfusion optimal through its regulation of microvessel tone and cerebral blood flow and that disruption of this mechanism can result in spatial memory impairment. These findings may identify therapeutic targets for preventing MCI and treating Alzheimer's disease.
Coamplification and Coexpression of Human Tissue-Type Plasminogen Activator and Murine Dihydrofolate Reductase Sequences in Chinese Hamster Ovary Cells (1985)

Expression of human tissue-type plasminogen activator (t-PA) at high levels has been achieved in Chinese hamster ovary (CHO) cells by cotransfection and subsequent coamplification of the transfected sequences. Expression vectors containing the t-PA cDNA gene and dihydrofolate reductase (DHFR) cDNA gene were cotransfected into CHO DHFR-deficient cells. Transformants expressing DHFR were selected by growth in media lacking nucleosides and contained low numbers of t-PA genes and DHFR genes. Stepwise selection of the DHFR+ transformants in increasing concentrations of methotrexate generated cells which had amplified both DHFR genes and t-PA genes over 100-fold. These cell lines expressed elevated levels of enzymatically active t-PA. To optimize both t-PA sequence amplification and t-PA expression, various modifications of the original procedure were used. These included alterations to the DHFR expression vector, optimization of the molar ratio of t-PA to DHFR sequences in the cotransfection, and modification of the methotrexate resistance selection procedure. The structure of the amplified DNA, its chromosomal location, and its stability during growth in the absence of methotrexate are reported.
Genome Sequence Diversity and Clues to the Evolution of Variola (Smallpox) Virus (2006)

Comparative genomics of 45 epidemiologically varied variola virus isolates from the past 30 years of the smallpox era indicate low sequence diversity, suggesting that there is probably little difference in the isolates' functional gene content. Phylogenetic clustering inferred three clades coincident with their geographical origin and case-fatality rate; the latter implicated putative proteins that mediate viral virulence differences. Analysis of the viral linear DNA genome suggests that its evolution involved direct descent and DNA end-region recombination events. Knowing the sequences will help understand the viral proteome and improve diagnostic test precision, therapeutics, and systems for their assessment.
Poly(ether urethane) and poly(ether urethane urea) membranes with high H2S/CH4 selectivity (1997)

The objective of this study was to synthesize rubbery polymers with a high H2S/CH4 selectivity for possible use as membrane materials for the separation of H2S from ‘low-quality’ natural gas. Two poly(ether urethanes), designated hereafter PU1 and PU3, and two poly(ether urethane ureas), designated PU2 and PU4, were synthesized and cast in the form of ‘dense’ (homogeneous) membranes. PU1 and PU2 contained poly(propylene oxide) whereas PU3 and PU4 contained poly(ethylene oxide) as the polyether component. The permeability of these membranes to two ternary mixtures of CH4, CO2, and H2S was measured at 35°C, and for a PU4 membrane also at 20°C, in the pressure range from 4 to 13.6 atm (4.05–13.78×105 Pa). PU4 is a very promising membrane material for H2S separation from mixtures with CH4 and CO2, having a H2S/CH4 selectivity greater than 100 at 20°C as well as a very high permeability to H2S. Permeability measurements were also made with commercial PEBAXTM membranes for comparison. The possibility of upgrading low-quality natural gas to US pipeline specifications for H2S and CO2 by means of membrane processes utilizing both highly H2S-selective and CO2-selective polymer membranes is discussed.