gebhart/patrepeval huggingface dataset:
Chiral synthesis via organoboranes. 13. A highly diastereoselective and enantioselective addition of [(Z)-.gamma.-alkoxyallyl]diisopinocampheylboranes to aldehydes (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChiral synthesis via organoboranes. 13. A highly diastereoselective and enantioselective addition of [(Z)-.gamma.-alkoxyallyl]diisopinocampheylboranes to aldehydesHerbert C. Brown, Prabhakar K. Jadhav, and Krishna S. BhatCite this: J. Am. Chem. Soc. 1988, 110, 5, 1535–1538Publication Date (Print):March 1, 1988Publication History Published online1 May 2002Published inissue 1 March 1988https://pubs.acs.org/doi/10.1021/ja00213a029https://doi.org/10.1021/ja00213a029research-articleACS PublicationsRequest reuse permissionsArticle Views2674Altmetric-Citations189LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Protein Phosphorylation and Dephosphorylation in Physiologic and Oncologic Processes (1996)

Phosphorylation and dephosphorylation of proteins is an important regulatory mechanism of cell metabolism, proliferation and differentiation. The present review summarizes the known key players, their interactions, effects on physiological processes, and their role in pathology and neoplasia.
Aldehyde—Phenol Reaction Products and Derivatives (1950)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAldehyde—Phenol Reaction Products and DerivativesH. Eldridge FaithCite this: J. Am. Chem. Soc. 1950, 72, 2, 837–839Publication Date (Print):February 1, 1950Publication History Published online1 May 2002Published inissue 1 February 1950https://pubs.acs.org/doi/10.1021/ja01158a049https://doi.org/10.1021/ja01158a049research-articleACS PublicationsRequest reuse permissionsArticle Views1391Altmetric-Citations24LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Current Status of the Utilization of Antiepileptic Treatments in Mood, Anxiety and Aggression: Drugs and Devices (2004)

Interventions that have been utilized to control seizures in people with epilepsy have been employed by the psychiatric community to treat a variety of disorders. The purpose of this review will be to give an overview of the most prominent uses of antiepileptic drugs (AEDs) and devices like the Vagus Nerve Stimulator (VNS) and Transcranial Magnetic Stimulation (TMS) in the treatment of psychiatric disease states. By far, the most prevalent use of these interventions is in the treatment of mood disorders. AEDs have become a mainstay in the effective treatment of Bipolar Affective Disorder (BAD). The U.S. Food and Drug Administration has approved the use of valproic acid for acute mania, and lamotrigine for BAD maintenance therapy. AEDs are also effectively employed in the treatment of anxiety and aggressive disorders. Finally, VNS and TMS are emerging as possibly useful tools in the treatment of more refractory depressive illness.
The 131-Amino-Acid Repeat Region of the Essential 39-Kilodalton Core Protein of Fowlpox Virus FP9, Equivalent to Vaccinia Virus A4L Protein, Is Nonessential and Highly Immunogenic (1998)

The immunodominant, 39,000-molecular weight core protein (39K protein) of fowlpox virus (FP9 strain), equivalent to the vaccinia virus A4L gene product, contains highly charged domains at each end of the protein and multiple copies of a 12-amino-acid serine-rich repeat sequence in the middle of the protein. Similar repeats were also detected in other fowlpox virus strains, suggesting that they might confer a selective advantage to the virus. The molloscum contagiosum virus homolog (MC107L) also contains repeats, unlike the vaccinia virus protein. The number of repeats in the fowlpox virus protein does not seem to be crucial, since some strains have a different number of repeats, as shown by the difference in the size of the protein in these strains. The repeat region could be deleted, indicating that it is not essential for replication in vitro. It was not possible to delete the entire 39K protein, indicating that it was essential (transcriptional control signals for the flanking genes were left intact). The repeat region is partly responsible for the immunodominance of the protein, but the C-terminal part of the protein also contains highly antigenic linear epitopes. A role for the 39K protein in immune system modulation is discussed.
Waveform-preserving blind estimation of multiple independent sources (1993)

The problem of blind estimation of source signals is to estimate the source signals without knowing the characteristics of the transmission channel. It is shown that the minimum-variance unbiased estimates can be obtained if and only if the transmission channel can be identified blindly. It is shown that the channel can be blindly identified if and only if there is not more than one Gaussian source. This condition suggests that waveform-preserving blind estimation can be achieved over a wide range of signal processing applications, including those cases in which the source signals have identical nonGaussian distributions. The constructive proof of the necessary and sufficient condition serves as a foundation for the development of waveform-preserving blind signal estimation algorithms. Examples are presented to demonstrate the applications of the theoretical results.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Kinetic Mechanistic Studies of Cdk5/p25-Catalyzed H1P Phosphorylation: Metal Effect and Solvent Kinetic Isotope Effect (2010)

Cdk5/p25 is a member of the cyclin-dependent, Ser/Thr kinase family and has been identified as one of the principle Alzheimer's disease-associated kinases that promote the formation of hyperphosphorylated tau, the major component of neurofibrillary tangles. We and others have been developing inhibitors of cdk5/p25 as possible therapeutic agents for Alzheimer's disease (AD). In support of these efforts, we examine the metal effect and solvent kinetic isotope effect on cdk5/p25-catalyzed H1P (a histone H-1-derived peptide) phosphorylation. Here, we report that a second Mg(2+) in addition to the one forming the MgATP complex is required to bind to cdk5/p25 for its catalytic activity. It activates cdk5/p25 by demonstrating an increase in k(cat) and induces a conformational change that favors ATP binding but has no effect on the binding affinity for the H1P peptide substrate. The binding of the second Mg(2+) does not change the binding order of substrates. The reaction follows the same rapid equilibrium random mechanism in the presence or absence of the second Mg(2+) as evidenced by initial velocity analysis and substrate analogue and product inhibition studies. A linear proton inventory with a normal SKIE of 2.0 +/- 0.1 in the presence of the second Mg(2+) was revealed and suggested a single proton transfer in the rate-limiting phosphoryl transfer step. The pH profile revealed a residue with a pK(a) of 6.5 that is most likely the general acid-base catalyst facilitating the proton transfer.
Photonic analog-to-digital conversion (2005)

Potentially THz-regime optical quantizing and coding for ultrafast analog-to-digital conversion using fiber-optic nonlinear loop mirror is presented. Emerging applications would be in high bit rate (<40 Gb/s) optical communications. 3-bit AD conversion at 10-Giga-sample-per-second is experimentally demonstrated.
MinK-Related Peptide 1 Associates With Kv4.2 and Modulates Its Gating Function (2001)

Inherited mutations and a polymorphism in minK-related peptide 1 (MiRP1) have been linked to congenital or acquired long-QT syndrome, pointing to the importance of MiRP1 in maintaining the cardiac electrical stability. We tested whether MiRP1 could affect the function of Kv4.x (x=2 and 3), the major pore-forming (alpha) subunits of transient outward (I(to)) channels in the heart. We used the Xenopus oocyte expression system to examine the effects of MiRP1 on Kv4.x channel gating kinetics and current amplitude and correlated these effects with MiRP1 expression level. MiRP1 slowed the rates of Kv4.2 activation and inactivation and shifted the voltage dependence of channel gating in the positive direction. These effects had a similar "dose" dependence: they plateaued at a cRNA ratio (MiRP1:Kv4.2) of 13:1, with half-maximum effects at estimated cRNA ratios of 2 to 4. On the other hand, MiRP1 had no significant effects on Kv4.2 current amplitude in the same range of expression level. When expressed at a comparable low level, MiRP1 had similar (although smaller) effects on Kv4.3 but could not modulate Kv1.4 (another alpha subunit of I(to) channels in the heart). Kv4.2 could be coimmunoprecipitated with epitope-tagged MiRP1, indicating that the 2 could form a stable complex. Our data suggest that MiRP1 may serve as a regulatory (beta) subunit of I(to) channels in the heart. This is supported by the observation that MiRP1 induced an "overshoot" of Kv4.2 current amplitude during channel recovery from inactivation, similar to the overshoot of I(to) described for human epicardial myocytes.
Join synopses for approximate query answering (1999)

In large data warehousing environments, it is often advantageous to provide fast, approximate answers to complex aggregate queries based on statistical summaries of the full data. In this paper, we demonstrate the difficulty of providing good approximate answers for join-queries using only statistics (in particular, samples) from the base relations. We propose join synopses as an effective solution for this problem and show how precomputing just one join synopsis for each relation suffices to significantly improve the quality of approximate answers for arbitrary queries with foreign key joins. We present optimal strategies for allocating the available space among the various join synopses when the query work load is known and identify heuristics for the common case when the work load is not known. We also present efficient algorithms for incrementally maintaining join synopses in the presence of updates to the base relations. Our extensive set of experiments on the TPC-D benchmark database show the effectiveness of join synopses and various other techniques proposed in this paper.
Genetic Characterization of Strain Differences in the Ability to Mediate CD40/CD28-Independent Rejection of Skin Allografts (2000)

Simultaneous blockade of the CD40 and CD28 T cell costimulatory pathways effectively promotes skin allograft survival in C3H/HeJ mice, extending median survival times (MSTs) beyond 100 days. This strategy is markedly less effective in C57BL/6 mice, with MSTs ranging between 20 and 30 days. In this study, we investigate the underlying genetic causes of these distinct phenotypes. Using H-2 congenic mice, we show that the genetic basis for the varied responses between these two strains is independent of the H-2 locus and T cell precursor frequency. C57BL/6 mice treated with costimulation blockade are able to generate allospecific CTL- and IFN-gamma-producing T cells within 3-4 wk posttransplant, whereas mice with a C3H background generate neither CTL- nor IFN-gamma-producing cells. Thus, differences appear to be in the generation of the immune response and not T cell homing. Strain differences in costimulation blockade-induced hyporesponsiveness persist in the absence of CD4(+) T cells, implying a direct effect on CD8(+) T cells. We demonstrate that genetic differences are important in cells of hemopoietic origin and that the costimulation blockade-resistant phenotype is dominant. Analysis of BXH recombinant inbred strains indicates that multiple loci contribute to the phenotype, and that the blockade resistance loci are preliminarily linked to 17 markers on four chromosomes. We conclude that strain variation in allograft MSTs following CD40/CD28 blockade results from the ability of CD8(+) T cells in some strains to use alternative modes of costimulation to mount an effective alloresponse.
Adipose-derived stromal/stem cells (2013)

Until recently, the complexity of adipose tissue and its physiological role was not well appreciated. This changed with the discovery of adipokines such as leptin. The cellular composition of adipose tissue is heterogeneous and changes as a function of diabetes and disease states such as diabetes. Tissue engineers view adipose tissue as a rich source of adult stromal/stem cells isolated by collagenase digestion. In vitro and in vivo studies have documented that adipose stromal/stem cells are multipotent, with the ability to differentiate along the adipocyte, chondrocyte, osteoblast and other lineage pathways. The adipose stromal/stem cells secrete a wide range of cytokines and growth factors with potential paracrine actions. Furthermore, adipose stromal/stem cells exert immunomodulatory functions when added to mixed lymphocyte reactions, suggesting that they can be transplanted allogeneically. This review article focuses on these mechanisms of adipose stromal/stem cell action and their potential utility as cellular therapeutics.
Reactivity-Dependent PCR: Direct, Solution-Phase in Vitro Selection for Bond Formation (2009)

In vitro selection is a key component of efforts to discover functional nucleic acids and small molecules from libraries of DNA, RNA, and DNA-encoded small molecules. Such selections have been widely used to evolve RNA and DNA catalysts and, more recently, to discover new reactions from DNA-encoded libraries of potential substrates. While effective, current strategies for selections of bond-forming and bond-cleaving reactivity are generally indirect, require the synthesis of biotin-linked substrates, and involve multiple solution-phase and solid-phase manipulations. In this work we report the successful development and validation of reactivity-dependent PCR (RDPCR), a new method that more directly links bond formation or bond cleavage with the amplification of desired sequences and that obviates the need for solid-phase capture, washing, and elution steps. We show that RDPCR can be used to select for bond formation in the context of reaction discovery and for bond cleavage in the context of protease activity profiling.
STUDIES ON THE DEVELOPMENT OF MOUSE EMBRYOS IN VITRO (1965)

Summary. The interactions of a number of possible energy sources for in-vitro development of 2-cell mouse ova were examined using statistical experimental designs. These experiments indicated that glucose has no beneficial effect on development when employed with the optimum concentration of pyruvate. Optimum concentrations of pyruvate and oxaloacetate when employed together resulted in a significantly lower response than when either compound was employed alone. It was found that the best medium for the development of 2-cell mouse ova into blastocysts contained 2·5 to 5·0 × 10-4 m-pyruvate + 2·5 to 5·0 × 10-2 m-lactate.
3D reconstruction using labeled image regions (2003)

In this paper we present a novel algorithm for reconstructing 3D scenes from a set of images. The user defines a set of polygonal regions with corresponding labels in each image using familiar 2D photo-editing tools. Our reconstruction algorithm computes the 3D model with maximum volume that is consistent with the set of regions in the input images. The algorithm is fast, uses only 2D intersection operations, and directly computes a polygonal model. We implemented a user-assisted system for 3D scene reconstruction and show results on scenes that are difficult or impossible to reconstruct with other methods.
Overcoming Multidrug Resistance in Cancer: Clinical Studies of P-Glycoprotein Inhibitors (2009)

Chemotherapy remains the mainstay in the treatment and management of many cancers. However, this treatment modality is fraught with difficulties associated with toxicity and also the emergence of chemotherapy resistance is a considerable problem. Cancer scientists and oncologists have worked together for some time to find ways of understanding anticancer drug resistance and also to develop pharmacological strategies to overcome that resistance. The greatest focus has been on the reversal of the multidrug resistance (MDR) phenotype by inhibition of the ATP-binding cassette (ABC) drug transporters. Inhibitors of ABC transporters--termed MDR modulators--have in the past been numerous and have occupied industry and academia in drug discovery programs. The field has been fraught with difficulties and disappointments but, nonetheless, we are currently considering the fourth generation of MDR modulator development with much data pending from the clinical trials with the third-generation modulators. First-generation MDR modulator compounds were very diverse and broad spectrum pharmacological agents which fuelled the excitement surrounding the research into the MDR phenotype in cancer at the time. Second-generation agents were very heavily evaluated in mechanistic studies and formed the basis for a number of oncology portfolios of big pharmaceutical companies. Given this input, a number of clinical trials were carried out, the results of which were somewhat disappointing. Even with the modest evidence of active combinations, trial data were considered promising enough to warrant development of the third-generation of modulators. A number of key molecules have been identified with potent, long lasting MDR reversal properties, and minimal pharmacokinetic interaction with the co-administered cytotoxic agent. The results from a number of these trials are eagerly awaited and there are many in the cancer research community who remain committed to this area of anticancer drug discovery.
Structural and ICAM-1-Docking Properties of a Cyclic Peptide from the I-domain of LFA-1: An inhibitor of ICAM-1/LFA-1-mediated T-cell adhesion (2002)

The purpose of this work was to study the conformation of cyclic peptide 1, cyclo(1,12)-Pen1-Ile2-Thr3-Asp4-Gly5-Glu6-Ala7- Thr8-Asp9-Ser10-Gly11-Cys12-OH, derived from the I-domain of the LFA-1 alpha-subunit. We found that cyclic peptide 1 can bind to the D1-domain of ICAM-1 and inhibit ICAM-1/LFA-1-mediated homotypic and heterotypic T-cell adhesion. To understand the bioactive conformation and binding requirements for cyclic peptide 1, its solution structure was studied using NMR, CD, and molecular dynamics simulations. Furthermore, possible binding properties between the cyclic peptide and the D1-domain of ICAM-1 were evaluated using docking experiments. This cyclic peptide has a stable betaII -turn at Asp4- Gly5-Glu6-Ala7 and a betaI-turn at Pen1-Ile2-Thr3-Asp4; a less stable betaV-turn is found at the C-terminal region. The beta-turn at Asp4- Gly5-Glu6-Ala7 was also found in the X-ray structure of the I-domain of LFA-1. Our CD studies showed that the peptide binds to calcium/magnesium and forms a 1:1 (peptide:calcium/magnesium) complex with low cation concentrations and multiple types of complexes with higher cation concentrations. Binding to divalent cations causes a conformational change in peptide 1; this is consistent with our previous study that binding of peptide 1 to ICAM-1 was influenced by divalent cations. Docking studies show the interaction between cyclic peptide 1 and the D1-domain of ICAM-1; it indicates that the Ile2-Thr3-Asp4-Gly4-Glu6-Ala7-Thr8 sequence interacts with the F and C strands of the D1-domain. Finally, these studies will help us design a new generation of selective peptides that may bind better to the D1-domain of ICAM-1.
A robust type I interferon gene signature from blood RNA defines quantitative but not qualitative differences between three major IFN drugs in the treatment of multiple sclerosis (2015)

We analysed gene expression microarray data from whole blood samples from 228 multiple sclerosis (MS) patients either untreated or treated with one of three alternative commonly used interferon beta (IFNβ) disease modifying drugs: Avonex (×1 weekly), Betaseron (every second day) or Rebif (×3 weekly). Patient injections were not timed to coordinate sample collections, thus providing a global transcriptomic profile for each population of patients studied. Three hundred and fifty one genes were significantly differentially expressed by at least one of the IFNβ drugs. Despite the different drug sources with distinct injection and dosage protocols, a striking similarity was found in the identity and functional classes of the differentially expressed genes induced. Using the 25 most-upregulated genes, we defined a robust IFNβ gene expression signature that quantifies the IFN activation state per blood sample collected irrespective of the type of IFNβ therapy. This 25-gene signature also defined basal IFN activation states among untreated MS patients, which differed among individuals but remained relatively constant per patient with time. The maximum drug-induced IFN-activation state was similar for all three drugs despite a 1.7-2.0-fold diminished average effect for Avonex. This and a more erratic effect of Avonex per patient across longitudinal measurements is likely a result of its reduced injection frequency. In summary, we have defined a robust blood-derived type I IFN gene signature from MS patients. This signature could potentially serve to generically quantify the systemic Type I IFN activation status for any other clinical manifestation, inclusive of other autoimmune diseases.