gebhart/patrepeval huggingface dataset:
Recent advances in the discovery and design of multicomponent reactions for the generation of small-molecule libraries (2015)

Abstract: The current drug discovery process is dependent on the ability of synthetic chemistry to deliver libraries of small molecules with ever increasing levels of structural complexity and diversity. Sequencing multicomponent reactions (MCRs) with elaboration or cyclization steps represents an effective approach toward generating libraries of complex and diverse small molecules. This review highlights the most recent (2010–2015) examples of the application of reaction sequences including MCRs to the synthesis of diverse assemblies of small heterocycles. Sequences performed in multiple separate steps, or as one-pot operations, and including MCRs based on 1) carbonyl condensations; 2) isocyanide-based reactions; 3) cycloadditions; and 4) transition metal-mediated reactions are discussed. Keywords: multicomponent reactions, sequential reactions, tandem reactions, divergent reactions, heterocycles, diversity
Investigating the performance of smart antenna systems at the mobile and base stations in the down and uplinks (2002)

Future wireless communication systems are expected to support a wide range of services which will include video, data and voice. To achieve the necessary capacity for these systems, the use of adaptive antennas has been proposed at the base station. Further increases in capacity may be possible by including adaptive antennas at both the base and mobile stations in the up and down links. In this paper, we investigate the performance of such a system.
Concentrations and compositions of plasma lipoprotein subfractions of Lpb5-Lpu1 homozygous and heterozygous swine with hypercholesterolemia. (1990)

Pigs with two mutant epitopes, Lpb5 of apolipoprotein B (apoB) and Lpu1 of a yet undefined apolipoprotein, specified by a haplotype Lpb5-Lpu1 and fed a cholesterol-free low fat diet show hypercholesterolemia. The purpose of this study was to establish whether a direct relationship exists between the swine lipoprotein concentration/composition and the genotype for the Lpb5-Lpu1 haplotype; i.e., homozygote versus heterozygote. Lipoproteins of fasted plasma from hypercholesterolemic swine, homozygous (HmHC) and heterozygous (HtHC) for Lpb5-Lpu1, and from normolipidemic (NL) pigs of other Lpb-Lpu haplotypes were separated into five layers by density gradient ultracentrifugation. Layer 1 contained particles of d less than 1.019 g/ml and layer 5 particles of d greater than 1.073 g/ml. Layers 2, 3, and 4 represented subfractions of low density lipoproteins (LDL). The plasma total cholesterol (TC) of the HmHC group (300 +/- 84 mg/dl) was different (P less than 0.05) from the HtHC group (200 +/- 80 mg/dl) and in both HmHC and HtHC, TC was significantly higher (P less than 0.0005 and P less than 0.005, respectively) than that of the NL group (69 +/- 14 mg/dl). The elevation in plasma TC was due to the increased TC in layers 2 and 3: a 13- and 7-fold increase in HmHC and a 7- and 4-fold increase in HtHC in layers 2 and 3, respectively. Parallel increases in unesterified cholesterol were observed in these two layers. Marked increases in apoB were also observed in layers 2 and 3 of HmHC and intermediate increases in apoB in the same two layers of HtHC.(ABSTRACT TRUNCATED AT 250 WORDS)
Nucleation : basic theory with applications (2000)

Thermodynamics of Nucleation: First-Order Phase Transitions Driving Force for Nucleation Work for Cluster Formation Nucleus Size and Nucleation Work Nucleation Theorem Properties of Clusters Equilibrium Cluster Size Distribution Density-Functional Approach. Kinetics of Nucleation: Master Equation Transition Frequencies Nucleation Rate Equilibrium Stationary Nucleation First Application of the Nucleation Theorem Nonstationary Nucleation Second Application of the Nucleation Theorem Nucleation at Variable Supersaturation. Factors affecting Nucleation: Seed size Line Energy Strain Energy Electric Field Carrier-Gas Pressure Solution Pressure Preexisting Clusters Active Centres. Applications: Overall Crystallization Crystal Growth Third Application of the Nucleation Theorem Induction Time Fourth Application of the Nucleation Theorem Metastabiltiy Limit Maximum Number of Supernuclei Size Distribution of Supernuclei Growth of Thin Films Lifetime of Amphiphile Bilayers. Appendices References Author index Subject Index.
Late preconditioning enhances recovery of myocardial function after infarction in conscious rabbits (2000)

It is unknown whether late preconditioning (PC) enhances the recovery of left ventricular (LV) function after a myocardial infarction. Thus 25 conscious rabbits were subjected to a 30-min coronary occlusion followed by 28 days of reperfusion after PC 24 h earlier with either ischemia or nitric oxide donor administration [S-nitroso-N-acetylpenicillamine (SNAP)]. The recovery of wall thickening (WTh) after reperfusion was significantly improved in the ischemic PC and SNAP PC groups compared with controls, both at rest and during dobutamine stress. Interestingly, neither ischemia- nor SNAP-induced late PC attenuated myocardial stunning from day 1 through day 14. Infarct size was smaller in the ischemic PC and SNAP PC groups compared with controls. In all groups, WTh at 28 days was positively and linearly related to the percentage of viable tissue in the region underlying the ultrasonic crystal (r = 0.90), indicating that the improvement in LV function after both ischemia-induced and NO donor-induced late PC can be fully explained by the reduction in infarct size; a separate effect of late PC on LV remodeling or LV contractility need not be invoked. In conclusion, in conscious rabbits late PC, induced either by ischemia or pharmacologically, not only limits infarct size but also enhances the recovery of LV function after myocardial infarction. This finding has important clinical implications and provides triphenyltetrazolium chloride-independent evidence that late PC limits myocellular death after sustained ischemia.
Computing the nearest correlation matrix--a problem from finance (2002)

Given a symmetric matrix what is the nearest correlation matrix, that is, the nearest symmetric positive semidefinite matrix with unit diagonal? This problem arises in the finance industry, where the correlations are between stocks. For distance measured in two weighted Frobenius norms we characterize the solution using convex analysis. We show how the modified alternating projections method can be used to compute the solution for the more commonly used of the weighted Frobenius norms. In the finance application the original matrix has many zero or negative eigenvalues; we show that for a certain class of weights the nearest correlation matrix has correspondingly many zero eigenvalues and that this fact can be exploited in the computation.
Internet E-Mail for Dummies (1996)

From the Publisher:
Is everyone in your office using e-mail but you? When someone asks you what your e-mail address is, do you wish you had an answer that's better than something or other dot com? With plenty of jargon-free explanations and easy-to-follow instructions, E-Mail For Dummies, 2nd Edition, has all the information you need to master the technology that has changed the way people communicate. Whether you use Netscape, Internet Explorer, Eudora, Microsoft Exchange, Pine, or even AOL or CompuServe, with this book you'll be communicating just like the pros in no time. 
Inside, find helpful advice on how to 
Exchange e-mail with anyone by using an online service or the Internet Keep your e-mail private and secure -- even on the Internet Use e-mail to improve communication within your company Discover how to use all of the major e-mail software, including Netscape Messenger, Internet Explorer, Eudora, America Online, and more Use smileys and e-mail acronyms like the pros Lower costs by attaching important documents to e-mail messages Decipher Internet e-mail addresses without getting a migraine
The repair of experimentally produced defects in rabbit articular cartilage by autologous chondrocyte transplantation (1989)

Using the knee joints of New Zealand White rabbits, a baseline study was made to determine the intrinsic capability of cartilage for healing defects that do not fracture the subchondral plate. A second experiment examined the effect of autologous chondrocytes grown in vitro on the healing rate of these defects. To determine whether any of the reconstituted cartilage resulted from the chondrocyte graft, a third experiment was conducted involving grafts with chondrocytes that had been labeled prior to grafting with a nuclear tracer. Results were evaluated using both qualitative and quantitative light microscopy. Macroscopic results from grafted specimens displayed a marked decrease in synovitis and other degenerative changes. In defects that had received transplants, a significant amount of cartilage was reconstituted (82%) compared to ungrafted controls (18%). Autoradiography on reconstituted cartilage showed that there were labeled cells incorporated into the repair matrix.
Orally and Nasally Induced Tolerance Studies in Ocular Inflammatory Disease: Guidance for Future Interventions (2004)

The induction of both oral and nasal tolerance has been used in both experimental models of ocular disease and clinically. Initial work centered around the abrogation of experimental autoimmune uveitis using either one or two whole uveitogenic antigens. Other models of ocular disease have included a corneal transplant model, demonstrating that feeding splenocytes from the donor strain of rats enhanced corneal engraftment. Fragments of pertinent antigens have been shown to alter the expression of experimental uveitis and possibly human disease. A randomized, masked study in uveitis provided valuable information for future studies, demonstrating that single antigen feeding provided far better protection than the feeding of multiple antigens. This review will deal with animal and human studies in the treatment of ocular inflammatory disease with the goal of extracting from past experience how to construct a future study in humans.
Bifrontal transcranial direct current stimulation slows reaction time in a working memory task (2005)

Intermittent tDCS over lateral prefrontal cortex during a working memory task impairs central nervous processing related to response selection and preparation. We conclude that this decrease in performance by our protocol of intermittent stimulation results from an interference mainly with the temporal dynamics of cortical processing as indexed by event-related sustained and oscillatory EEG activity such as theta.
Enhancement of tumor radioresponse by combined treatment with gefitinib (Iressa, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, is accompanied by inhibition of DNA damage repair and cell growth in oral cancer (2003)

Molecular blockade of EGFR with either an EGFR MAb or an EGFR TKI enhances the radiosensitivity of human SCCs. In the present study, we investigated whether treatment with the EGFR TKI gefitinib (Iressa, ZD1839) improves the response to radiotherapy in the OSCC cell lines HSC2 and HSC3. We examined potential mechanisms that may contribute to the enhanced radiation response induced by gefitinib. Growth inhibition was observed in vitro with radiation or gefitinib. A cooperative antiproliferative effect was obtained when cancer cells were treated with radiation followed by gefitinib. Cells treated with a combination of radiation and gefitinib arrested in G(1) and G(2)-M phases, with a decrease in the S-phase population. While radiation alone did not significantly affect MEK1/2 and p38 MAPK autophosphorylation, the combination of gefitinib and radiation completely inhibited the downstream signaling of EGFR. Results from DNA damage repair analysis in cultured OSCC cells demonstrated that gefitinib had a strong inhibitory effect on DNA-PKc pathways after radiation. Tumor xenograft studies demonstrated that the combination of gefitinib and radiation caused growth inhibition and tumor regression of well-established OSCC tumors in athymic mice; tumor volume was reduced from 1,008.2 to 231.4 mm(3) in HSC2 cells (p < 0.01) and from 284.2 to 12.4 mm(3) in HSC3 cells (p < 0.01). Immunohistochemical analysis of OSCC xenografts revealed that gefitinib caused a striking decrease in tumor cell proliferation when combined with radiotherapy. Overall, we conclude that gefitinib enhances tumor radioresponse by multiple mechanisms that may involve antiproliferative growth inhibition and effects on DNA repair after exposure to radiation.
Diels−Alder Bioconjugation of Diene-Modified Oligonucleotides (2001)

In an effort to offer complementary technology for covalent biomolecule modification (bioconjugation), we have developed a method that exploits the aqueous acceleration of Diels--Alder reactions for this purpose. Three different diene phosphoramidite reagents have been synthesized that enable diene modification of synthetic oligonucleotides prepared by the phosphoramidite method. Clean and efficient Diels--Alder cycloaddition of these diene oligonucleotides with maleimide dieneophiles was carried out, and the labeled oligonucleotide bioconjugates were characterized by HPLC and electrospray mass spectrometry. Dieneophile stoichiometry, temperature, and pH are all parameters that were shown to influence the efficiency of the process.
Rapid serological detection of autoantibodies associated with Sjögren's syndrome (2009)

Together these results suggest that the QLIPS format for Ro52 yields both a more rapid and more discriminating test for detecting Ro52 autoantibodies than existing immunoassays and has the potential to be adapted for point-of-care evaluation of patients with SjS and other rheumatologic diseases.
Functional Replacement of the Mouse E2A Gene with a Human HEB cDNA (1998)

The mammalian E2A, HEB, and E2-2 genes encode a unique class of basic helix-loop-helix (bHLH) transcription factors that are evolutionarily conserved and essential for embryonic and postnatal development. While the structural and functional similarities among the gene products are well demonstrated, it is not clear why deletion of E2A, but not HEB or E2-2, leads to a complete arrest in B-lymphocyte development. To understand the molecular basis of the functional specificity between E2A and HEB/E2-2 in mammalian development, we generated and tested a panel of E2A knockin mutations including subtle mutations in the E12 and E47 exons and substitution of both E12 and E47 exons with a human HEB cDNA. We find that the alternatively spliced E12 and E47 bHLH proteins of the E2A gene play similar and additive roles in supporting B lymphopoiesis. Further, we find that HEB driven by the endogenous E2A promoter can functionally replace E2A in supporting B-cell commitment and differentiation toward completion. Finally, the postnatal lethality associated with E2A disruption is fully rescued by the addition of HEB. This study suggests that the functional divergence among E12, E47, and HEB in different cell types is partially defined by the context of gene expression.
Plant adaptation to fluctuating environment and biomass production are strongly dependent on guard cell potassium channels (2008)

At least four genes encoding plasma membrane inward K+ channels (K(in) channels) are expressed in Arabidopsis guard cells. A double mutant plant was engineered by disruption of a major K(in) channel gene and expression of a dominant negative channel construct. Using the patch-clamp technique revealed that this mutant was totally deprived of guard cell K(in) channel (GCK(in)) activity, providing a model to investigate the roles of this activity in the plant. GCK(in) activity was found to be an essential effector of stomatal opening triggered by membrane hyperpolarization and thereby of blue light-induced stomatal opening at dawn. It improved stomatal reactivity to external or internal signals (light, CO2 availability, and evaporative demand). It protected stomatal function against detrimental effects of Na+ when plants were grown in the presence of physiological concentrations of this cation, probably by enabling guard cells to selectively and rapidly take up K+ instead of Na+ during stomatal opening, thereby preventing deleterious effects of Na+ on stomatal closure. It was also shown to be a key component of the mechanisms that underlie the circadian rhythm of stomatal opening, which is known to gate stomatal responses to extracellular and intracellular signals. Finally, in a meteorological scenario with higher light intensity during the first hours of the photophase, GCK(in) activity was found to allow a strong increase (35%) in plant biomass production. Thus, a large diversity of approaches indicates that GCK(in) activity plays pleiotropic roles that crucially contribute to plant adaptation to fluctuating and stressing natural environments.
PARE: a power-aware hardware data prefetching engine (2005)

Aggressive hardware prefetching often significantly increases energy consumption in the memory system. Experiments show that a major fraction of prefetching energy degradation is due to the hardware history table related energy costs. In this paper, the authors presented PARE, a power-aware prefetching engine that uses a newly designed indexed hardware history table. Compared to the conventional single table design, the new prefetching table consumes 7-11X less power per access. With the help of compiler-based location-set analysis, it is shown that the proposed PARE design improves energy consumption by as much as 40% in the data memory systems in 70nm processor designs.
Optical all-pass filters for phase response design with applications for dispersion compensation (1998)

Lossless all-pass optical filters are introduced, which can approximate any desired phase response while maintaining a constant, unity amplitude response. Architectures using cascade and lattice structures based on ring resonators and cavities defined by reflectors are discussed. Two applications are presented: 1) for fiber dispersion compensation and 2) for compensation of the nonlinear phase response of narrow bandpass optical filters such as thin-film or Bragg grating filters. All orders of dispersion can be compensated in principle, and the filters are periodic so multiple channels can be compensated with a single device. The architectures are very compact compared to alternatives such as chirped Bragg gratings.
Stem Cells from the Mammalian Blastocyst (2001)

Early differentiation of the mammalian embryo leads to the development of two distinct lineages-the inner cell mass (ICM) and the trophectoderm. Cells of the ICM are pluripotent and give rise to all tissues of the fetus, while trophectoderm cells are restricted in their potential to the trophoblast cell layers of the placenta. In the mouse, apparently immortal stem cell lines can be obtained from both cell types. These cell lines, embryonic stem (ES) cells and trophoblast stem (TS) cells, are morphologically and molecularly distinct and depend on different signaling pathways for their maintenance. They also show different cell fates when introduced into early embryos to generate chimeras. However, a change in the levels of expression of a key regulator of pluripotency, Oct4, can push ES cells towards the TS phenotype, when grown in TS cell conditions. Stem cell potential in the early embryo thus appears to depend on a combination of the levels of expression of key intrinsic regulators and the appropriate extrinsic environmental factors. Manipulation of both intrinsic and extrinsic regulators may be needed to reveal the full potential of stem cells from other stages of development and the adult.
Generation of three different fragments of bound C3 with purified factor I or serum. II. Location of binding sites in the C3 Fragments for Factors B and H, complement receptors , and bovine conglutinin (1983)

The many different recognized functions of C3 are dependent upon the ability of the activated C3 molecule both to bind covalently to protein and carbohydrate surfaces and to provide binding sites for as many as eleven different proteins. The location of the binding sites for six of these different proteins (factors B and H, complement receptors CR(1), CR(2) and CR(3) and conglutinin) was examined in the naturally occurring C3-fragments generated by C3 activation (C3b) and degradation by Factor I (iC3b, C3c, C3d,g) and trypsin (C3d). Evidence was obtained for at least four distinct binding sites in C3 for these six different C3 ligands. One binding site for B was detectable only in C3b, whereas a second binding site for H and CR(1) was detectable in both C3b and iC3b. The affinity of the binding site for H and CR(1) was charge dependent and considerably reduced in iC3b as compared to C3b. H binding to iC3b-coated sheep erythrocytes (EC3bi) was measurable only in low ionic strength buffer (4 mS). The finding that C3c-coated microspheres bound to CR(1), indicated that this second binding site was still intact in the C3c fragment. However, H binding to C3c was not examined. A third binding site in C3 for CR(2) was exposed in the d region by factor I cleavage of C3b into iC3b, and the activity of this site was unaffected by the further I cleavage of iC3b into C3d,g. Removal of the 8,000-dalton C3g fragment from C3d,g with trypsin forming C3d, resulted in reduced CR2 activity. However, because saturating amounts of monoclonal anti-C3g did not block the CR(2)-binding activity of EC3d,g, it appears unlikely that the g region of C3d,g or iC3b forms a part of the CR(2)-binding site. In addition, detergent-solubilized EC3d (C3d-OR) inhibited the CR(2)-binding activity of EC3d,g. Monocytes and neutrophils, that had been previously thought to lack CR(2) because of their inability to form EC3d rosettes, did bind EC3d,g containing greater than 5 x 10(4) C3d,g molecules per E. The finding that monocyte and neutrophil rosettes with EC3d,g were inhibited by C3d-OR, suggested that these phagocytic cells might indeed express very low numbers of CR(2), and that these CR(2) were detectable with EC3d,g and not with EC3d because C3d,g had a higher affinity for CR2 than did C3d. A fourth C3 binding site for CR(3) and conglutinin (K) was restricted to the iC3b fragment. Because of simultaneous attachment of iC3b to phagocyte CR3 and CR(3), the characteristics of iC3b binding to CR3 could only be examined with phagocytes on which the CR(1) had been blocked with anti-CR(1). Inhibition studies with EDTA and N-acetyl-D-glucosamine demonstrated a requirement for both calcium cations and carbohydrate in the binding of EC3bi to CR3 and to K. However, CR(3) differed from K in that magnesium cations were required in addition to calcium for maximum CR(3) binding activity, and NADG produced less inhibition of CR(3) activity than of K activity.