gebhart/patrepeval huggingface dataset:
Nucleosides and nucleotides. 103. 2-Alkynyladenosines: a novel class of selective adenosine A2 receptor agonists with potent antihypertensive effects (1992)

The synthesis and receptor-binding activities at A1 and A2 adenosine receptors for a series of 2-alkynyladenosines are described. The palladium-catalyzed cross-coupling reaction of 2-iodoadenosine (4a) with various terminal alkynes in the presence of bis(triphenylphosphine)palladium dichloride and cuprous iodide in N,N-dimethylformamide containing triethylamine gives 2-alkynyladenosines (5a-r). An economical synthetic method for the preparation of 9-(2,3,5-tri-O-acetyl-1-beta-D-ribofuranosyl)-6-chloro-2-iodopurine++ + (2), which is a precursor of 4a, is also included. Several transformation reactions of 2-(1-octyn-1-yl)adenosine (5e) and 2-(1-ethyn-1-yl)adenosine (9) and a similar cross-coupling reaction of 6-chloropurine derivative 11 and 8-bromoadenosine (13) with 1-octyne are also reported. Many of these 2-alkynyladenosines tested for A1 and A2 adenosine receptor binding activities in rat brain are selective for the A2 adenosine receptor. Among them, 2-(1-hexyn-1-yl)adenosine (5c) has the highest affinity for both A1 and A2 receptors with Ki values of 126.5 and 2.8 nM, respectively. The structure-activity relationship of this series of compounds including 6- or 8-alkynylpurine nucleosides and 2-alkyl- and 2-alkenyladenosines is discussed in terms of potency at both receptor subtypes. Additionally, we describe how hypotensive activity and heart rate decrease brought on by 5 and some other compounds with spontaneously hypertensive rats are proportional to the order of the potency to both A1 and A2 binding affinities. Thus, 2-alkynyladenosines are interesting and promising as antihypertensive agents that should be considered for further detailed preclinical evaluation.
Deletion loop mutagenesis: a novel method for the construction of point mutations using deletion mutants (1982)

Deletion loop mutagenesis is a new, general method for site-directed mutagenesis that allows point mutations to the introduced within a sequence of DNA defined by a previously isolated deletion mutant. Wild type and deletion mutant DNA are cloned into a bacterial plasmid and each is cleaved with a different single cut restriction enzyme. Heteroduplexes are formed between the two DNAs to produce circular molecules containing a nick in each strand and a single-stranded deletion loop. The deletion loops are mutagenised using sodium bisulphite and the DNA transfected directly into a uracil repair deficient strain of Escherichia coli. Up to half of the resultant clones contain DNA produced by replication of the wild-type length strand and bear mutations exclusively within the target area. An example is given in which a deletion mutant lacking 21 nucleotides from the region coding for SV40 large-T was used. Eight of the possible nine target cytosine residues were mutagenised. The method described is specific, efficient and simple.
Controlled Precipitation of Dyes into Hollow Polyelectrolyte Capsules Based on Colloids and Biocolloids (2000)

Hollow polyelectrolyte capsules have been recently introduced as a novel type of artificial smart material. Here is reported the successful filling of polyelectrolyte capsules based on human erythrocytes with various dye compounds using a novel method of selective precipitation. Control of surface properties and conditions leads to preferential crystallization in the interior of the capsules, as shown schematically in the Figure.
Human glutaminyl cyclase and bacterial zinc aminopeptidase share a common fold and active site (2004)

We conclude that human pituitary glutaminyl cyclase and bacterial zinc aminopeptidase share a common fold and active site residues. In contrast to the aminopeptidase, however, QC does not appear to require zinc for enzymatic activity.
Type IIA Procollagen Containing the Cysteine-rich Amino Propeptide Is Deposited in the Extracellular Matrix of Prechondrogenic Tissue and Binds to TGF-β1 and BMP-2 (1999)

Type II procollagen is expressed as two splice forms. One form, type IIB, is synthesized by chondrocytes and is the major extracellular matrix component of cartilage. The other form, type IIA, contains an additional 69 amino acid cysteine-rich domain in the NH2-propeptide and is synthesized by chondrogenic mesenchyme and perichondrium. We have hypothesized that the additional protein domain of type IIA procollagen plays a role in chondrogenesis. The present study was designed to determine the localization of the type IIA NH2-propeptide and its function during chondrogenesis. Immunofluorescence histochemistry using antibodies to three domains of the type IIA procollagen molecule was used to localize the NH2-propeptide, fibrillar domain, and COOH-propeptides of the type IIA procollagen molecule during chondrogenesis in a developing human long bone (stage XXI). Before chondrogenesis, type IIA procollagen was synthesized by chondroprogenitor cells and deposited in the extracellular matrix. Immunoelectron microscopy revealed type IIA procollagen fibrils labeled with antibodies to NH2-propeptide at approximately 70 nm interval suggesting that the NH2-propeptide remains attached to the collagen molecule in the extracellular matrix. As differentiation proceeds, the cells switch synthesis from type IIA to IIB procollagen, and the newly synthesized type IIB collagen displaces the type IIA procollagen into the interterritorial matrix. To initiate studies on the function of type IIA procollagen, binding was tested between recombinant NH2-propeptide and various growth factors known to be involved in chondrogenesis. A solid phase binding assay showed no reaction with bFGF or IGF-1, however, binding was observed with TGF-beta1 and BMP-2, both known to induce endochondral bone formation. BMP-2, but not IGF-1, coimmunoprecipitated with type IIA NH2-propeptide. Recombinant type IIA NH2-propeptide and type IIA procollagen from media coimmunoprecipitated with BMP-2 while recombinant type IIB NH2-propeptide and all other forms of type II procollagens and mature collagen did not react with BMP-2. Taken together, these results suggest that the NH2-propeptide of type IIA procollagen could function in the extracellular matrix distribution of bone morphogenetic proteins in chondrogenic tissue.
Quantum dot strain engineering for light emission at 1.3, 1.4 and 1.5μm (2005)

We designed and prepared by molecular beam epitaxy strain-engineered InAs∕InGaAs∕GaAs quantum dot (QD) nanostructures where we separately controlled: (i) the mismatch f between QDs and confining layers (CLs), and, then, the QD strain, by changing the thickness of a partially relaxed InGaAs lower CL and (ii) the CL composition x. The appropriate values of f and x to tune the emission energies at wavelengths in the 1.3–1.55μm range were calculated by means of a simple model. Comparing model calculations and activation energies of photoluminescence quenching, we also concluded that quenching is due to both intrinsic and extrinsic processes; we show that the structures can be designed so as to maximize the activation energy of the intrinsic process, while keeping the emission energy at the intended value in the 1.3–1.55μm range.
LuxS: its role in central metabolism and the in vitro synthesis of 4-hydroxy-5-methyl-3(2H)-furanone (2002)

Many bacteria produce extracellular molecules which function in cell-to-cell communication. One of these molecules, autoinducer 2 (AI-2), was first described as an extracellular signal produced by Vibrio harveyi to control luciferase expression. Subsequently, a number of bacteria have been shown to possess AI-2 activity in their culture supernatants, and bear the luxS gene product, which is required for AI-2 synthesis. In Porphyromonas gingivalis, luxS and pfs, encoding a 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTA/SAH'ase), form an operon, suggesting that S-adenosylhomocysteine (SAH) or 5'-methylthioadenosine (MTA) serves as a substrate for AI-2 production. Cell-free extracts of Escherichia coli MG1655, but not DH5alpha (which carries a luxS frame-shift mutation) were capable of generating AI-2 activity upon addition of SAH, but not MTA. S-Ribosyl-homocysteine (RH) derived from SAH also served as a substrate in E. coli MG1655 extracts. RH-supplemented cell-free extracts of Pseudomonas aeruginosa, a bacterium that lacks luxS, only generated AI-2 activity following the introduction of a plasmid containing the Por. gingivalis pfs-luxS operon. In addition, defined in vitro systems consisting of the purified LuxS proteins from Por. gingivalis, E. coli, Neisseria meningitidis or Staphylococcus aureus converted RH to homocysteine and a compound that exhibits AI-2 activity.4-Hydroxy-5-methyl-3(2H)-furanone was identified by mass spectrometry analysis as a major product formed in this in vitro reaction. In E. coli MG1655, expression of T3SH [the bacteriophage T3 S-adenosylmethionine (SAM) hydrolase] significantly reduced AI-2 activity in culture supernatants, suggesting that AI-2 production is limited by the amount of SAH produced in SAM-dependent transmethylase reactions. The authors suggest that the LuxS protein has an important metabolic function in the recycling of SAH. They also show that Ps. aeruginosa is capable of removing AI-2 activity, implying that this molecule may act as a nutrient. In many bacteria AI-2 may in fact represent not a signal molecule but a metabolite which is released early and metabolized in the later stages of growth.
Techniques for non-linear magnification transformations (2002)

This paper presents efficient methods for implementing general non-linear magnification transformations. Techniques are provided for: combining linear and non-linear magnifications, constraining the domain of magnifications, combining multiple transformations, and smoothly interpolating between magnified and normal views. In addition, piecewise linear methods are introduced which allow greater efficiency and expressiveness than their continuous counterparts.
Regulation of Dendritic Cells and Macrophages by an Anti-Apoptotic Cell Natural Antibody that Suppresses TLR Responses and Inhibits Inflammatory Arthritis (2009)

Although natural Abs (NAbs) are present from birth, little is known about what drives their selection and whether they have housekeeping functions. The prototypic T15-NAb, first identified because of its protective role in infection, is representative of a special type of NAb response that specifically recognizes and forms complexes with apoptotic cells and which promotes cell-corpse engulfment by phagocytes. We now show that this T15-NAb IgM-mediated clearance process is dependent on the recruitment of C1q and mannose-binding lectin, which have known immune modulatory activities that also provide "eat me" signals for enhancing phagocytosis. Further investigation revealed that the addition of T15-NAb significantly suppressed in vitro LPS-induced TNF-alpha and IL-6 secretion by the macrophage-like cell line, RAW264.7, as well as TLR3-, TLR4-, TLR7-, and TLR9-induced maturation and secretion of a range of proinflammatory cytokines and chemokines by bone marrow-derived conventional dendritic cells. Significantly, high doses of this B-1 cell produced NAb also suppressed in vivo TLR-induced proinflammatory responses. Although infusions of apoptotic cells also suppressed such in vivo inflammatory responses and this effect was associated with the induction of high levels of IgM antiapoptotic cell Abs, apoptotic cell treatment was not effective at suppressing such TLR responses in B cell-deficient mice. Moreover, infusions of T15-NAb also efficiently inhibited both collagen-induced arthritis and anti-collagen II Ab-mediated arthritis. These studies identify and characterize a previously unknown regulatory circuit by which a NAb product of innate-like B cells aids homeostasis by control of fundamental inflammatory pathways.
CD4 ligands inhibit the formation of multifunctional transduction complexes involved in T cell activation (1997)

Ligands binding to the CD4 molecule can inhibit TCR-mediated T cell activation. We have previously reported that transcription factors regulating the expression of the IL-2 gene, NF-AT, NF-kappaB, and AP-1, are targets of this inhibitory effect in an in vitro model using peripheral human CD4+ T cells activated by a CD3 mAb. Two T cell activation pathways involved in the regulation of these transcription factors, calcium flux and the p21ras pathway, were investigated as potential targets. Binding of HIV envelope glycoprotein gp160/gp120 or a CD4 mAb to the CD4+ T cells, prior to TCR/CD3 activation, inhibited the intracellular calcium elevation. This event strongly suggested an inhibition of PLCgamma1 activity. Tyrosine phosphorylation of PLCgamma1, induced by CD3 activation, was not affected, but its association with tyrosine-phosphorylated proteins, including a 62-kDa protein, was disrupted. This PLCgamma1-associated p62 was found to be immunoreactive to p62-Sam68 Abs. The activation-induced phosphorylation of two p21ras effectors, Raf-1 and Erk2, was inhibited by the CD4 ligands, indirectly pointing to inhibition of the p21ras activation pathway. In addition, we demonstrate that TCR activation of normal CD4+ T cells induced the formation of p120GAP and PLCgamma1-containing complexes. These complexes also contain other unidentified proteins. CD4 ligand binding induced a defective formation of these transduction complexes. This may result in inefficient signaling, partially accounting for the inhibitory effects of the CD4 ligands on both p21ras and calcium-activation pathways.
A Practical Method for Preparation of Varicella-Zoster Immune Globulin (1978)

Outdated blood from blood banks in Massachusetts was screened for complement-fixing antibody to varicella-zoster virus (VZV). Approximately 15% of the plasma units had a titer greater than or equal to 16, and one-half of these had a titer of greater than or equal to 32. Plasma units with titers of CF antibody to VZV of greater than or equal to 16 were pooled. This pool had a CF antibody titer of 32 and a titer of fluorescent antibody of 64. Varicella-zoster immune globulin was prepared from the selected plasma pool by alcohol fractionation and analyzed for VZV-specific antibody. Varicella-zoster immune globulin had a fluorescent antibody titer of 2,048 and a neutralizing antibody titer of 1,024. This antibody concentration is equivalent to that in preparations of zoster immune globulin made from plasma of donors recovering from recent VZV infection.
Enzymatic formation of Glu-Xaa and Asp-Xaa bonds using Glu/Asp-specific endopeptidase from Bacillus licheniformis in frozen aqueous systems (2000)

The capability of Glu/Asp-specific endopeptidase from Bacillus licheniformis to form Glu/Asp-Xaa bonds in frozen aqueous systems was investigated. Under frozen state conditions, the enzyme was able to catalyse peptide bond formation more effectively than in liquid reaction mixtures. The acceptance of amino components which were completely inefficient nucleophiles at room temperature indicates a changed specificity of Glu/Asp-specific endopeptidase under frozen state conditions. Protease-catalysed coupling of two acidic amino acids was demonstrated for the first time. The utilization of Glu/Asp-specific endopeptidase from Bacillus licheniformis in frozen aqueous systems offers new possibilities in enzyme-catalysed peptide synthesis. Copyright © 2000 European Peptide Society and John Wiley & Sons, Ltd.
Plant Sugar-Response Pathways. Part of a Complex Regulatory Web (2000)

In addition to playing a central role in metabolism, soluble sugars such as Glc and Suc help regulate many developmental and physiological processes in plants (for review, see [Koch, 1996][1]; [Smeekens, 1998][2]; [Sheen et al., 1999][3]; [Yu, 1999][4]). For example, sugar levels have been
Highly Effective Poly(Ethylene Glycol) Architectures for Specific Inhibition of Immune Receptor Activation (2003)

Architectural features of synthetic ligands were systematically varied to optimize inhibition of mast cell degranulation initiated by multivalent crossing of IgE-receptor complexes. A series of ligands were generated by end-capping poly(ethylene glycol) (PEG) polymers and amine-based dendrimers with the hapten 2,4-dinitrophenyl (DNP). These were used to explore the influence of polymeric backbone length, valency, and hapten presentation on binding to anti-DNP IgE and inhibition of stimulated activation of RBL cells. Monovalent MPEG(5000)-DNP (IC(50) = 50 nM), bivalent DNP-PEG(3350)-DNP (IC(50) = 8 nM), bismonovalent MPEG(5000)-DNP(2) (IC(50) = 20 nM), bisbivalent DNP(2)-PEG(3350)-DNP(2) (IC(50) = 3nM) and DNP(4)-dendrimer ligands (IC(50) = 50 nM) all effectively inhibit cellular activation caused by multivalent antigen, DNP-bovine serum albumin. For different DNP ligands, we provide evidence for more effective inhibition due to (i) preferential formation of intra-IgE cross-links by bivalent ligands of sufficient length, (ii) self-association of monovalent ligands with longer tails, and (iii) higher probability of binding for bisvalent ligands. We also show that larger DNP(16)-dendrimers of higher valency trigger degranulation by cross-linking IgE-receptor complexes, whereas smaller DNP-dendrimers are inhibitory. Thus, features of synthetic ligands can be manipulated to control receptor occupation, aggregation, and inhibition of the cellular response.
Application of Nanofluids in Heat Transfer (2012)

1. The particles settle rapidly, forming a layer on the surface and reducing the heat transfer capacity of the fluid. 2. If the circulation rate of the fluid is increased, sedimentation is reduced, but the erosion of the heat transfer devices, pipelines, etc., increases rapidly.
Effects of Intraventricular Encapsulated Hngf-Secreting Fibroblasts in Aged Rats (1996)

Exogenous NGF administered into the central nervous system (CNS) has been reported to improve cognitive function in aged rats. However, concerns have been expressed about the risks involved with supplying NGF to the CNS. In this study, baby hamster kidney cells (BHK) genetically modified to secrete human NGF (hNGF) were encapsulated in semipermeable membranes and implanted intraventricularly. ChAT/LNGFR-positive basal forebrain neurons were shown to atrophy and degenerate with age, especially in cognitively impaired rats. The encapsulated BHK-NGF cells produced less than 10% of doses previously reported to be effective, but this was sufficient to increase the size of ChAT/LNGFR-positive basal forebrain neurons in the aged and learning-impaired rats to the size of the neurons in young healthy rats. The hNGF from these encapsulated cells also improved performance in a repeated-acquisition version of the Morris water maze spatial learning task in learning-impaired 20.6- and 26.7- mo-old rats. Furthermore, there was no evidence that these doses of hNGF impaired Morris water maze performance in the youngest 3.3-5.4 mo rats, and analyses of mortality rates, body weights, somatosensory thresholds, potential hyperalgesia, and activity levels, suggested that these levels of exogenous hNGF are not toxic or harmful to aged rats. These results suggest that CNS-implanted semipermeable membranes, containing genetically modified xenogeneic cells continuously producing these levels of hNGF, attenuate age-related cognitive deficits in nonimmunosuppressed aged rats, and that both the surgical implantation procedure and long-term exposure to low doses of hNGF appear safe in aged rats.
Fitting optimal piecewise linear functions using genetic algorithms (2000)

Constructing a model for data in R/sup 2/ is a common problem in many scientific fields, including pattern recognition, computer vision, and applied mathematics. Often little is known about the process which generated the data or its statistical properties. For example, in fitting a piecewise linear model, the number of pieces, as well as the knot locations, may be unknown. Hence, the method used to build the statistical model should have few assumptions, yet, still provide a model that is optimal in some sense. Such methods can be designed through the use of genetic algorithms. We examine the use of genetic algorithms to fit piecewise linear functions to data in R/sup 2/. The number of pieces, the location of the knots, and the underlying distribution of the data are assumed to be unknown. We discuss existing methods which attempt to solve this problem and introduce a new method which employs genetic algorithms to optimize the number and location of the pieces. Experimental results are presented which demonstrate the performance of our method and compare it to the performance of several existing methods, We conclude that our method represents a valuable tool for fitting both robust and nonrobust piecewise linear functions.
CdS Nanoclusters: Synthesis, Characterization, Size Dependent Oscillator Strength, Temperature Shift of the Excitonic Transition Energy, and Reversible Absorbance Shift (1994)

Improved synthetic routes and size-selective precipitation have enabled the preparation of almost monodisperse CdS clusters. Six samples of 1-thioglycerol stabilized clusters with diameters of approximately 13, 14, 16, 19, 23, and 39 Å have been prepared as fully redispersible powders and were characterized by elemental analysis, powder X-ray diffraction, electron microscopy, thermogravimetric analysis, and UV-vis spectroscopy. Small-angle X-ray scattering was used to determine the mean cluster size. The well-structured UV-vis spectra reveal that the size-dependent shift of the 1s-1s excitonic transition is in agreement with the tight-binding theory and the pseudopotential theory. Moreover, as expected by quantum mechanical calculations the oscillator strength of the transition increases proportional to 1/r3. UV-vis spectra taken at various temperatures between 4 and 295 K have shown that the temperature shift of the excitonic transition energy becomes stronger with decreasing particle size. Strong, reversible absorbance shifts were observed, upon transferring the clusters from their solutions onto quartz plates and vice versa.
An unusual antibody that blocks tissue factor/factor VIIa function by inhibiting cleavage only of macromolecular substrates (1992)

Tissue factor (TF), the cell surface receptor and cofactor for factor VIIa (FVIIa), is considered the major physiologic trigger of the coagulation cascade. Most monoclonal antibodies to TF have been reported to inhibit TF activity by blocking association of FVII(a) with TF. Using solution-phase kinetic analyses, we have reexamined two strongly inhibitory anti-TF monoclonal antibodies (TF8–11D12 and TF9–9C3) previously reported to block FVII binding in cell-binding assays. Kinetic analysis of TF9–9C3 was consistent with direct competition with FVIIa for binding to TF. However, antibody TF8–11D12 did not block FVIIa binding to TF as measured by ability of the TF:FVIIa complex to cleave a small peptide substrate or by enhanced reactivity of FVIIa with a tripeptidyl-chloromethylketone. Interestingly, TF8–11D12 strongly inhibited cleavage of all three known macromolecular substrates (factors VII, IX, and X) of the TF:FVIIa complex. We hypothesize that TF8–11D12 blocks access of macromolecular substrates to the active site of FVIIa by steric hindrance. This study identifies a useful probe for TF function and provides insights into the inhibitory mechanism of an unusual class of antibody proposed for therapeutic intervention in thrombotic disease.
Identifying Quality-Based Requirements (2004)

Abstract This article proposes a model for identifying quality requirements based on three different views of quality. By specifying quality requirements in this manner, the framework establishes quailty requirements that can be quanitfied and measured as part of an overall quality assurance program. This results in two levels of quality: one at the system level that ensures a quality software product and another at the process level that mitigates project risk.