gebhart/patrepeval huggingface dataset:
Purine Nucleoside Phosphorylase. 1. Structure−Function Studies (1997)

To probe the catalytic mechanism of human purine nucleoside phosphorylase (PNP), 13 active-site mutants were constructed and characterized by steady-state kinetics. In addition, microtiter plate assays were developed for both the phosphorolytic and synthetic reactions and used to determine the kinetic parameters of each mutant. Mutations in the purine binding site exhibited the largest effects on enzymatic activity with the Asn243Ala mutant resulting in a 1000-fold decrease in the kcat for inosine phosphorolysis. This result in combination with the crystallographic location of the Asn243 side chain suggested a potential transition state (TS) structure involving hydrogen bond donation by the carboxamido group of Asn243 to N7 of the purine base. Analogous to the oxyanion hole of serine proteases, this hydrogen bond was predicted to aid catalysis by preferentially stabilizing the TS as a consequence of the increase in negative charge on N7 that occurs during glycosidic bond cleavage and the associated increase in the N7-Asn243 hydrogen bond strength. Two residues in the phosphate binding site, namely His86 and Glu89, were also predicted to be catalytically important based on their alignment with phosphate in the X-ray structure and the 10-25-fold reduction in catalytic activity for the His86Ala and Glu89Ala mutants. In contrast, catalytic efficiencies for the Tyr88Phe and Lys244Ala mutants were comparable with wild-type, indicating that the hydrogen bonds predicted in the initial X-ray structure of PNP [Ealick, S. E., et al. (1990) J. Biol. Chem. 265, 1812-1820] were not essential for catalysis. These results provided the foundation for studies reported in the ensuing two manuscripts focused on the PNP catalytic mechanism [Erion, M. D., et al. (1997) Biochemistry 36, 11735-11748] and the use of mutagenesis to reverse the PNP substrate specificity from 6-oxopurines to 6-aminopurines [Stoeckler, J. D., et al. (1997) Biochemistry 36, 11749-11756].
Near-Infrared Studies of Glucose and Sucrose in Aqueous Solutions: Water Displacement Effect and Red Shift in Water Absorption from Water-Solute Interaction (2013)

We used near infrared spectroscopy to obtain concentration dependent glucose absorption spectra in aqueous solutions in the near-infrared range (3800-7500 cm(-1)). Here we introduce a new method to obtain reliable glucose absorption bands from aqueous glucose solutions without measuring the water displacement coefficients of glucose separately. Additionally, we were able to extract the water displacement coefficients of glucose, and this may offer a new general method using spectroscopy techniques applicable to other water-soluble materials. We also observed red shifts in the absorption bands of water in the hydration shell around solute molecules, which comes from the contribution of the interacting water molecules around the glucose molecules in solutions. The intensity of the red shift gets larger as the concentration increases, which indicates that as the concentration increases more water molecules are involved in the interaction. However, the red shift in frequency does not seem to depend significantly on the concentration. We also performed the same measurements and analysis with sucrose instead of glucose as solute and compared.
Tuning the mechanical properties of self‐assembled mixed‐peptide tubes (2013)

Summary In this study, nano‐ and microscale fibrillar and tubular structures formed by mixing two aromatic peptides known to self‐assemble separately, (diphenylalanine and di‐D‐2‐napthylalanine) have been investigated. The morphology, mechanical strength and thermal stability of the tubular structures formed have been studied. The tubes are shown to consist of both peptides with some degree of nanoscale phase separation. The ability of the mixed peptides to form structures, which display variable mechanical properties dependent on the percentage composition of the peptides is presented. Such materials with tuneable properties will be required for a range of applications in nanotechnology and biotechnology.
Factors Affecting the Adsorption of Complexed Heavy Metals on Hydrous Al2O3 (1985)

Factors influencing the adsorption behavior of heavy metals, viz Cu(II), Zn(II), Cd(II), Pb(II) and Ni(II), onto Al2O3 from aqueous solutions containing complexing ligands were investigated using batch adsoption experiments. For the Cu(II)/NTA/ γ-Al2O3, system, increasing the system ionic strength reduced Cu adsorption through activity coefficient and surface electrical double layer effects. The presence of alkaline earth cations (Ca(II) and Mg(II)) also reduced Cu removal from solution by lowering the ability of NTA to prevent Cu(OH)2 precipitation and through specific adsorption to the alumina surface. The adsorption of the heavy metals on Al2O3 from solutions containing NTA followed the sequence: Cu &amp;gt;Zn &amp;gt; Cd &amp;gt; Pb ≈ Ni. Increase in system temperature tended to decrease metal adsorption.
Genetic control of the murine immune response to cholera toxin. (1985)

This study was undertaken to determine whether previously noted differences in the immune response of inbred strains of mice to cholera toxin (CT) might be under immune response gene control. A series of inbred, congenic, and intra-H-2I region recombinant mouse strains were tested for responsiveness to CT after i.p. immunization with 0.1 micrograms CT in alum. Samples of plasma were collected at intervals before and after priming and boosting. IgG and IgA anti-CT were measured by ELISA. In three different sets of congenic strains, the level of IgG anti-CT clearly depended on the H-2 haplotype of the strain rather than on any background or Igh genes. Strains with the H-2b and H-2q haplotypes were high responders, and strains with the H-2k, H-2s and H-2d haplotypes were low responders. Within the H-2 complex, the IgG anti-CT response was mapped to the I-A subregion with the use of congenic intra-H-2I region recombinant strains. In contrast to these results with IgG anti-CT, plasma IgA anti-CT levels were uniformly low and indeterminate. We conclude that the murine IgG anti-CT response is controlled by a locus within the I-A subregion of H-2--a remarkable finding, considering the known abilities of this toxin to bind to and to directly stimulate lymphocytes.
A molecular basis for nonsecretory myeloma (2004)

The biosynthesis of aberrant immunoglobulin polypeptides by monoclonal plasma cells has been implicated in the pathogenesis of nonsecretory myeloma. Our studies of a patient with this disorder indeed have demonstrated the presence of abnormal kappa light chains that resulted from a frameshift mutation in nucleotides encoding the constant region of the molecule. As a consequence of a 2-base deletion in codon 187 and loss of the normal stop codon, this portion of the kappa chain was composed of 128 amino acids (rather than the expected 106), with a completely anomalous sequence after position 187 that included absence of the cysteines required for intrachain and interchain disulfide bonds. The unusual primary structure of this component was confirmed by mass spectrometric and amino acid sequence analyses of cytoplasmic protein extracts. Our studies provide the first evidence that human nonsecretory myeloma may result from an alteration in the light-chain constant region.
Techniques to enhance success in placement of tetracycline fibers as a periodontal therapy. (1998)

This article proposes specific clinical techniques as a component of periodontal therapy which can be used to enhance successful placement and retention of fibers containing tetracycline. Potential problems that may lead to clinical failure are also addressed and modalities to overcome these obstacles are suggested. This treatment technique need not be limited to the periodontal specialist. The general dentist, with clinical experience in restorations, may possess superior skills needed for optimal clinical success.
Superparamagnetic Clustering of Data (1996)

We present a new approach for clustering, based on the physical properties of an inhomogeneous ferromagnetic model. We do not assume any structure of the underlying distribution of the data. A Potts spin is assigned to each data point and short range interactions between neighboring points are introduced. Spin-spin correlations, measured (by Monte Carlo procedure) in a superparamagnetic regime in which aligned domains appear, serve to partition the data points into clusters. Our method outperforms other algorithms for toy problems as well as for real data.
Alterations of Single Molecule Fluorescence Lifetimes in Near-Field Optical Microscopy (1994)

Fluorescence lifetimes of single Rhodamine 6G molecules on silica surfaces were measured with pulsed laser excitation, time-correlated single photon counting, and near-field scanning optical microscopy (NSOM). The fluorescence lifetime varies with the position of a molecule relative to a near-field probe. Qualitative features of lifetime decreases are consistent with molecular excited state quenching effects near metal surfaces. The technique of NSOM provides a means of altering the environment of a single fluorescent molecule and its decay kinetics in a repeatable fashion.
1,2,4-Triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity. 1. Synthesis and biological properties of alkyl alcohol and statine derivatives (1990)

A series of 1,2,4-triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity, which incorporate (1S,2S)-2-amino-1,3-dicyclohexyl-1-hydroxypropane, statine (Sta), and (3S,4S)-4-amino-5-cyclohexyl-3-hydroxy-pentanoic acid (ACHPA) transition-state mimetics, have been prepared. Structure-activity relationships for renin inhibitory activity in the series are consistent with the 2-[8-isobutyl-6-phenyl-1,2,4-triazolo[4,3-a]pyrazin-3-yl]-3-(3 pyridyl)propionic acid moiety 10b acting as a non-peptidic replacement for the P4-P2 (Pro-Phe-His) residues of the natural substrate angiotensinogen. Compounds 12m, 12o and 12q were potent inhibitors of partially purified human renin (IC50 values 1.7, 6.8, and 3.7 nM, respectively), and also effectively lowered blood pressure in anesthetized, sodium depleted marmosets following intravenous administration. On oral administration however, no blood pressure lowering activity could be detected, and absorption studies in bile duct cannulated rats indicate that this may be due primarily to poor oral absorption, rather than rapid biliary excretion. The reason for the observed poor oral activity is not clear, but it seems unlikely that poor aqueous solubility or metabolic instability to gut enzymes are rate-determining, and other factors such as high molecular weight may also be very important.
A Proposed Platform &amp;amp;amp; Performance Estimation of Digital-Home Service Delivery/Management Systems (2006)

Service delivery & management platforms give us how to manage home gateways and the life cycle of services downloaded to home gateways. When service providers register developed service applications to the service platform, the applications go through the operation of service delivery and are downloaded to the framework of home gateways. Upon the installation, the corresponding service application is activated to provide service users with services. This paper proposes the structure and functional models of a service delivery and management platform to work out the closeness found in the service provision and management system of home network when individual companies offer services, while presenting functional implementations and the results of system performance estimation
Monosized, magnetic polymer particles: Their use in separation of cells and subcellular components, and in the study of lymphocyte function<i>in vitro</i> (1988)

By employing the principles of "activated swelling", monosized, superparamagnetic polymer particles have been prepared ranging in size from 1-100 microns. Both during and after the swelling process, the particles can be modified to meet a series of specific demands making them potentially very interesting for many separation and assay purposes. Using monoclonal antibodies to direct the magnetic beads to their targets, immunomagnetic separation has turned out to be one of the most specific, reliable and, above all, the fastest technique available today to isolate particulate material for further studies. So far, most efforts have been concentrated on methodology for fractionation of cells in suspension, such as removal of tumour cells from bone marrow or isolation of lymphoid cells from peripheral blood. These studies have both established the parameters necessary for optimal performance and at the same time laid the groundwork for future developments making immunomagnetic separation an exciting new tool in many research areas. High speed and specificity are the most conspicuous features of immunomagnetic cell separation. These properties have been exploited in the successful development of a new technique for tissue typing of cells directly from peripheral blood specimens. Both higher sensitivity and specificity have been obtained. The same principles can be used for fast and safe quantification of cell populations and subpopulations in blood and cell suspensions. The functions of, and interactions between, peripheral blood cell populations or subpopulations in the immune response have also been studied with high precision. The significance of direct cell contact on the one hand, and soluble factors on the other, can now be established in detail. Immunomagnetic beads have also been used to study the interaction between various T lymphocyte membrane molecules in the early phases of the activation process. Finally, the usefulness of specially developed particles for the fractionation of subcellular components is described.
The generation of insulin-producing cells from embryonic stem cells - a discussion of controversial findings (2004)

The derivation of insulin-producing cells from embryonic stem (ES) cells has been controversially described. Whereas several authors showed successful differentiation of mouse ES cells into islet-like clusters, others could not confirm the results. Here, we present a detailed comparison of the various strategies used to generate pancreatic cells with respect to protocols and differentiation factors and give an explanation of the contradictory findings. It is suggested that the selection or enrichment of ES-derived nestin-positive cells should be avoided, since these cells are already committed to a neural fate before pancreatic differentiation is induced.
SIRT1: A Novel Target for the Treatment of Muscular Dystrophies (2016)

Muscular dystrophies are inherited myogenic disorders accompanied by progressive skeletal muscle weakness and degeneration. Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy and is caused by mutations in the gene that encodes the cytoskeletal protein dystrophin. The treatment for DMD is limited to glucocorticoids, which are associated with multiple side effects. Thus, the identification of novel therapeutic targets is urgently needed. SIRT1 is an NAD(+)-dependent histone/protein deacetylase that plays roles in diverse cellular processes, including stress resistance and cell survival. Studies have shown that SIRT1 activation provides beneficial effects in the dystrophin-deficient mdx mouse, a model of DMD. SIRT1 activation leads to the attenuation of oxidative stress and inflammation, a shift from the fast to slow myofiber phenotype, and the suppression of tissue fibrosis. Although further research is needed to clarify the molecular mechanisms underlying the protective role of SIRT1 in mdx mice, we propose SIRT1 as a novel therapeutic target for patients with muscular dystrophies.
A basophil-activating factor from human T lymphocytes. (1984)

Human T lymphocytes stimulated with phytohaemagglutinin (PHA) or streptokinase-streptodornase (SK-SD) generate an activity which elicits non-cytotoxic histamine release from human basophils. Filtration of the T lymphocyte-derived activity on columns of Sephadex G-100 and Fractogel 55F sequentially revealed one predominant basophil-activating factor of mol. wt. 70,000-90,000, that was designated BAF-T. BAF-T was composed of two acidic proteins of approximate pI 4.4 and 5.2-5.5, as assessed by isoelectric focusing. The distinction of BAF-T from IgE was confirmed by the failure of BAF-T to bind to an anti-IgE affinity column and the capacity of BAF-T to release histamine maximally from basophils desensitized to IgE-dependent stimuli. The inability of BAF-T to release histamine from human lung mast cells and dog cutaneous mastocytoma cells suggests target cell specificity. The source and activity of BAF-T are consistent with a specific contribution of this mediator to human cellular immune and hypersensitivity responses involving T lymphocytes and basophils.
DNA technology for Corynebacterium glutamicum : isolation and characterization of amino acid biosynthetic genes (1989)

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Applied Biological Sciences, 1989.
Bone characterization with ultrasound: state of the art and new proposal. (1994)

Ultrasound transmission measurement through the os calcis is an emerging technique and a promising clinical tool for early assessment of osteoporosis. In this paper we first present a short discussion on the physical meaning of ultrasound velocity and attenuation, the methods of measurements and the potential contribution of ultrasound compared to photon absorptiometry. After analysing the various results in vivo published up to now we shall present some new perspectives of ultrasonic bone characterization: broadband ultrasonic attenuation imaging (BUAI) and pulse-echo measurement.
Performance of Hybrid Reinforcements in PVC Composites: III. Use of Surface-Modified Glass Fiber and Wood Pulp as Reinforcements (1992)

This paper reports on the effect of the composition of hardwood aspen (CTMP) filled with surface-treated glass fibers, and the different treatment of CTMP on the mechanical properties of PVC composites. The properties of composites filled with glass fiber are superior to those submitted to non-treated CTMP Most of the properties (except modulus) of the composites filled with non-treated CTMP or its hybrid combina tions with glass fiber are inferior to those of unfilled polymer. When surface-coated CTMP was used alone or along with glass fiber, most of the properties (except modulus) improved in comparison with those of non-coated CTMP/glass fiber-filled composites. The compositions as well as concentrations of the reinforcement are sensitive to prior treatments of CTMP and individual mechanical properties.
Binding Affinities of Oligonucleotides and PNAs Containing Phenoxazine and G-Clamp Cytosine Analogues Are Unusually Sequence-Dependent (2007)

Melting temperatures of DNA duplexes containing the phenoxazine (P) and G-clamp (X) cytosine analogues exhibited a strong and unusual dependence on the nucleoside flanking the modified nucleobase, and the same trend was observed in PNA-DNA duplexes incorporating X in the PNA chain. Molecular dynamics simulations of the DNA duplexes show that generalized stacking (including secondary interactions of the ammonium group of X) and hydrogen bonding are good descriptors of the different duplex stabilities.
Selective p38α Inhibitors Clinically Evaluated for the Treatment of Chronic Inflammatory Disorders (2009)

ADVERTISEMENT RETURN TO ISSUEPREVPerspectiveNEXTSelective p38α Inhibitors Clinically Evaluated for the Treatment of Chronic Inflammatory DisordersDavid M. Goldstein*, Andreas Kuglstatter, Yan Lou, and Michael J. SothView Author Information Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, California 94304*To whom correspondence should be addressed. Phone: +1 (973) 235-4008. Fax: +1 (973) 235-6263. E-mail: [email protected]Cite this: J. Med. Chem. 2010, 53, 6, 2345–2353Publication Date (Web):December 1, 2009Publication History Received27 August 2009Published online1 December 2009Published inissue 25 March 2010https://pubs.acs.org/doi/10.1021/jm9012906https://doi.org/10.1021/jm9012906review-articleACS PublicationsCopyright © 2009 American Chemical SocietyRequest reuse permissionsArticle Views4834Altmetric-Citations156LEARN 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 SUBJECTS:Inflammation,Inhibition,Inhibitors,Peptides and proteins,Selectivity Get e-Alerts
Efficient Generation of Germ Line Transmitting Chimeras from C57BL/6N ES Cells by Aggregation with Outbred Host Embryos (2010)

Genetically modified mouse strains derived from embryonic stem (ES) cells have become essential tools for functional genomics and biomedical research. Large scale mutagenesis projects are producing libraries of mutant C57BL/6 (B6) ES cells to enable the functional annotation of every gene of the mouse genome. To realize the utility of these resources, efficient and accessible methods of generating mutant mice from these ES cells are necessary. Here, we describe a combination of ICR morula aggregation and a chemically-defined culture medium with widely available and accessible components for the high efficiency generation of germline transmitting chimeras from C57BL/6N ES cells. Together these methods will ease the access of the broader biomedical research community to the publicly available B6 ES cell resources.
Recognition of Gonadotroph Adenomas in Women (1991)

Most apparently nonsecreting pituitary macroadenomas in women arise from gonadotroph cells. The majority of these can be recognized, even in postmenopausal women, by the serum LH beta responses to TRH, and some can be recognized by the responses of serum FSH and LH.
Tick-borne parasitic diseases in cattle: Current knowledge and prospective risk analysis related to the ongoing evolution in French cattle farming systems (2002)

Parasitic diseases, like babesiosis and theileriosis are transmitted by ticks: their occurrence is therefore linked to the size of the tick stock and the seasonality of the vectors. Babesia divergens bovine babesiosis transmitted by Ixodes ricinus is widespread and often reported in France. Serological prevalence is high, ranging from 20 to 80% according to the farms. Clinical incidence is low: around 0.4% for the whole cattle population. The endemic situation is unstable and clinical cases occur more frequently with farming system modifications. L. ricinus is a tick essentially found in woodlands and so, for the most part, is found in closed rural areas. The situation of the other bovine babesiosis (Babesia major) and theileriosis (Theileria orientalis) is not well documented in France. However, the epidemiology of parasitic diseases is changing, especially because of changes in the environmental characteristics, i.e. both farm and herd management conditions and also climatic conditions. These modifications can provoke an increase in the tick stocks, an increase in the contact rate between cattle and ticks, and an increase in the contact rate between cattle and the wild fauna, especially deer. This results in likely modifications of the endemic situation, with a higher risk of clinical babesiosis in the medium term.