gebhart/patrepeval huggingface dataset:
Microtubule-stabilizing agents based on designed laulimalide analogues (2004)

Laulimalide is a potent, structurally unique microtubule-stabilizing agent originally isolated from the marine sponge Cacospongia mycofijiensis. Laulimalide exhibits an activity profile different from other microtubule-binding agents, notably including effectiveness against paclitaxel-resistant cells, but it is intrinsically unstable. Five analogues of laulimalide were designed to exhibit enhanced chemical stability yet retain its exceptional biological activities. Evaluations of these analogues showed that all are effective inhibitors of cancer-cell proliferation yet differ substantially in potency with an IC(50) range of 0.12-16.5 microM. Although all of the analogues initiated cellular changes similar to laulimalide, including increased density of interphase microtubules, aberrant mitotic spindles, and ultimately apoptosis, differences among the analogues were apparent. The two most potent analogues, C(16)-C(17)-des-epoxy laulimalide and C(20)-methoxy laulimalide, appear to have a mechanism of action identical to laulimalide. The C(16)-C(17)-des-epoxy, C(20)-methoxy laulimalide derivative, which incorporates both chemical changes of the most potent analogues, was significantly less potent and initiated the formation of unique interphase microtubules unlike the parent compound and other analogues. Two C(2)-C(3)-alkynoate derivatives had lower potency, and they initiated abnormal microtubule structures but did not cause micronucleation or extensive G(2)/M accumulation. Significantly, paclitaxel- and epothilone-resistant cell lines were less resistant to the laulimalide analogues. In summary, analogues of laulimalide designed to minimize or eliminate its intrinsic instability have been synthesized, and some have been found to retain the unique biological activities of laulimalide.
Morphometric Tools for Landmark Data (1992)

Morphometrics is the statistical study of biological shape and shape change. Its richest data are landmarks, points such as 'the bridge of the nose' that have biological names as well as geometric locations. This book is the first systematic survey of morphometric methods for landmark data. The methods presented here combine conventional multivariate statistical analysis with themes from plane and solid geometry and from biomathematics to support biological insights into the features of many different organs and organisms. This book will be of value to applied statisticians and geometers, as well as to all biological and biomedical researchers who need quantitative analyses of information from biomedical images.
Prostaglandin D2, its metabolite 15‐d‐PGJ2, and peroxisome proliferator activated receptor‐γ agonists induce apoptosis in transformed, but not normal, human T lineage cells (2002)

Prostaglandin D(2) (PGD(2)) is abundantly produced by mast cells, platelets, and alveolar macrophages and has been proposed as a key immunoregulatory lipid mediator. 15-Deoxy-Delta(12,14)-PGJ(2) (15-d-PGJ(2)), a key PGD(2) metabolite, is under intense study as a potential anti-inflammatory mediator. Little is known about PGD(2) or the role of 15-d-PGJ(2), if any, in regulating the activities of human T lineage cells. In this report we demonstrate that both PGD(2) and 15-d-PGJ(2) have potent antiproliferative effects, and in fact kill human T lymphocyte lines derived from malignant cells by an apoptotic mechanism. Interestingly, normal human T cells were not similarly affected. Although the T lymphocyte lines express mRNA for the PGD(2) receptor (DP-R), a potent DP receptor agonist, BW245C, did not inhibit the proliferation or viability of the cells, suggesting an alternative mechanism of action. PGD(2) and 15-d-PGJ(2) can bind to the peroxisome proliferator activated receptor-gamma (PPAR-gamma) which is implicated in lipid metabolism and apoptosis. Exposure to synthetic PPAR-gamma ligands (e.g. ciglitazone, troglitazone) mimicked the inhibitory responses of PGD(2) and 15-d-PGJ(2), and induced apoptosis in the transformed T cells consistent with a PPAR-gamma-dependent mechanism. These observations suggest that PPAR-gamma ligands (which may include PGD2) provide strong apoptotic signals to transformed, but not normal T lymphocytes. Thus, the efficacy of utilizing PPAR-gamma and its ligands as therapeutics for human T cell cancers needs to be further evaluated.
Non-cell-autonomous control of vascular stem cell fate by a CLE peptide/receptor system (2008)

Land plants evolved a long-distance transport system of water and nutrients composed of the xylem and phloem, both of which are generated from the procambium- and cambium-comprising vascular stem cells. However, little is known about the molecular mechanism of cell communication governing xylem-phloem patterning. Here, we show that a dodecapeptide (HEVHypSGHypNPISN; Hyp, 4-hydroxyproline), TDIF (tracheary element differentiation inhibitory factor), is secreted from the phloem and suppresses the differentiation of vascular stem cells into xylem cells through a leucine-rich repeat receptor-like kinase (LRR-RLK). TDIF binds in vitro specifically to the LRR-RLK, designated TDR (putative TDIF receptor), whose expression is restricted to procambial cells. However, the combined analysis of TDIF with a specific antibody and the expression profiles of the promoters of two genes encoding TDIF revealed that TDIF is synthesized mainly in, and secreted from, the phloem and its neighboring cells. The observation that TDIF is capable of promoting proliferation of procambial cells while suppressing xylem differentiation suggests that this small peptide functions as a phloem-derived, non-cell-autonomous signal that controls stem cell fate in the procambium. Our results indicate that we have discovered a cell communication system governing phloem-xylem cross-talk.
Stem cells in regenerative biology and medicine (2001)

Embryonic stem cells of the mammalian blastocyst give rise to all the tissue lineages that begin to emerge at gastrulation. They are pluripotent cells and can be propagated in vitro without loss of pluripotency. Many adult tissues harbor cells that do not complete their differentiation program. These cells serve as self-renewing stem cells whose normal fate is to regenerate site-specific tissue, in response to either physiological cell turnover or damage inflicted by injury or disease. Neural, muscle, and bone marrow stem cells possess developmental potency far greater than their normal lineage-restricted fate. The understanding of the biology of stem cells is leading us into an era of regenerative medicine. The growth potential and pluripotency of embryonic stem cells and the developmental plasticity of adult stem cells, particularly those of bone marrow, make them potentially useful for replacing tissues, via transplantation or construction of bioartificial tissues, that either do not regenerate naturally or are damaged beyond their natural capability for regeneration. In addition to these two ways of replacing tissue, a third strategy of regenerative medicine is to stimulate regeneration in vivo from resident stem cells. Before these approaches become clinical reality, however, a number of basic research issues must be resolved, including the revision of our concept of a regeneration-competent cell.
Functional expression of human cathepsin S in Saccharomyces cerevisiae. Purification and characterization of the recombinant enzyme. (1993)

A cDNA encoding the human lysosomal cysteine proteinase cathepsin S precursor has been expressed in yeast using the pVT100-U expression vector containing the alpha-factor promoter. The procathepsin S gene was expressed either as a fusion protein with the pre-region or with the prepro-region of the yeast alpha-factor precursor gene. Following in vitro processing both constructs gave an identical active mature enzyme with a molecular weight of 24,000. After prolonged cultivation of the cells the recombinant protein is also found as an active proteinase in the culture supernatant. The precursor can be activated in vitro at pH 4.5 and 40 degrees C under reducing conditions. The in vitro activated enzyme has a 6-amino acid NH2-terminal extension when compared with the native bovine enzyme. The purified enzyme displays a bell-shaped pH activity profile with a pH optimum of 6.5 and pK values of 4.5 and 7.8. The isoelectric point of the recombinant human cathepsin S is between 8.3 and 8.6 and about 1.5 pH units higher than for the bovine enzyme. The kinetic data for several synthetic substrates and inhibitors reveal a preference for smaller amino acid residues in the binding subsites S2 and S3 of cathepsin S. Like the bovine enzyme, the recombinant human cathepsin S is characterized by a broader range of pH stability (pH 5-7.5) than cathepsins B and L.
Eliminating the Renormalization Scale Ambiguity for Top-Pair Production Using the Principle of Maximum Conformality (2012)

It is conventional to choose a typical momentum transfer of the process as the renormalization scale and take an arbitrary range to estimate the uncertainty in the QCD prediction. However, predictions using this procedure depend on the renormalization scheme, leave a nonconvergent renormalon perturbative series, and moreover, one obtains incorrect results when applied to QED processes. In contrast, if one fixes the renormalization scale using the principle of maximum conformality (PMC), all nonconformal {β(i)} terms in the perturbative expansion series are summed into the running coupling, and one obtains a unique, scale-fixed, scheme-independent prediction at any finite order. The PMC scale μ(R)(PMC) and the resulting finite-order PMC prediction are both to high accuracy independent of the choice of initial renormalization scale μ(R)(init), consistent with renormalization group invariance. As an application, we apply the PMC procedure to obtain next-to-next-to-leading-order (NNLO) predictions for the tt-pair production at the Tevatron and LHC colliders. The PMC prediction for the total cross section σ(tt) agrees well with the present Tevatron and LHC data. We also verify that the initial scale independence of the PMC prediction is satisfied to high accuracy at the NNLO level: the total cross section remains almost unchanged even when taking very disparate initial scales μ(R)(init) equal to m(t), 20m(t), and √s. Moreover, after PMC scale setting, we obtain A(FB)(tt)≃12.5%, A(FB)(pp)≃8.28% and A(FB)(tt)(M(tt)>450 GeV)≃35.0%. These predictions have a 1σ deviation from the present CDF and D0 measurements; the large discrepancy of the top quark forward-backward asymmetry between the standard model estimate and the data are, thus, greatly reduced.
MBX‐102/JNJ39659100, a Novel Non‐TZD Selective Partial PPAR‐γ Agonist Lowers Triglyceride Independently of PPAR‐α Activation (2009)

MBX-102/JNJ-39659100 (MBX-102) is a selective, partial PPAR-γ agonist that lowers glucose in the absence of some of the side effects, such as weight gain and edema, that are observed with the TZDs. Interestingly MBX-102 also displays pronounced triglyceride lowering in preclinical rodent models and in humans. Although in vitro reporter gene studies indicated that MBX-102 acid is a highly selective PPAR-γ agonist that lacks PPAR-α activity, we sought to determine if PPAR-α activation in vivo could possibly contribute to the triglyceride lowering abilities of MBX-102. In vivo studies using ZDF and ZF rats demonstrated that MBX-102 lowered plasma triglycerides. However in ZF rats, MBX-102 had no effect on liver weight or on hepatic expression levels of PPAR-α target genes. Further in vitro studies in primary human hepatocytes supported these findings. Finally, the ability of MBX-102 to lower triglycerides was maintained in PPAR-α knockout mice, unambiguously establishing that the triglyceride lowering effect of MBX-102 is PPAR-α independent. The in vivo lipid lowering abilities of MBX-102 are therefore mediated by an alternate mechanism which is yet to be determined.
Anemia in Heart Failure: an Overview of Current Concepts (2010)

Chronic heart failure is a substantial public health problem. Anemia is an important comorbidity frequently observed in patients with the disease and, in heart failure, anemia has only recently started to attract systematic epidemiological and therapeutical research endeavor. This article describes the many aspects of anemia in chronic heart failure, starting with the ongoing discussion of how to define anemia, which has important consequences for the estimation of its prevalence and incidence. Further, we discuss prognostic implications of anemia in patients with chronic or acute heart failure, the etiology of anemia in heart failure and treatment possibilities. Such therapeutic avenues embrace intravenous iron preparations and subcutaneous administration of erythropoietin and its derivatives, all of which have been extensively studied over the last several years. Finally, this article describes the potential costs incurred by treating anemic patients with heart failure.
Functional interaction between Epstein-Barr virus DNA polymerase catalytic subunit and its accessory subunit in vitro (1993)

The Epstein-Barr virus (EBV) DNA polymerase catalytic subunit (BALF5 protein) and its accessory subunit (BMRF1 protein) have been independently overexpressed and purified (T. Tsurumi, A. Kobayashi, K. Tamai, T. Daikoku, R. Kurachi, and Y. Nishiyama, J. Virol. 67:4651-4658, 1993; T. Tsurumi, J. Virol. 67:1681-1687, 1993). In an investigation of the molecular basis of protein-protein interactions between the subunits of the EBV DNA polymerase holoenzyme, we compared the DNA polymerase activity catalyzed by the BALF5 protein in the presence or absence of the BMRF1 polymerase accessory subunit in vitro. The DNA polymerase activity of the BALF5 polymerase catalytic subunit alone was sensitive to high ionic strength on an activated DNA template (80% inhibition at 100 mM ammonium sulfate). Addition of the polymerase accessory subunit to the reaction greatly enhanced DNA polymerase activity in the presence of high concentrations of ammonium sulfate (10-fold stimulation at 100 mM ammonium sulfate). Optimal stimulation was obtained when the molar ratio of BMRF1 protein to BALF5 protein was 2 or more. The DNA polymerase activity of the BALF5 protein along with the BMRF1 protein was neutralized by a monoclonal antibody to the BMRF1 protein, whereas that of the BALF5 protein alone was not, suggesting a specific interaction between the BALF5 protein and the BMRF1 protein in the reaction. The processivity of nucleotide polymerization of the BALF5 polymerase catalytic subunit on singly primed M13 single-stranded DNA circles was low (approximately 50 nucleotides). Addition of the BMRF1 polymerase accessory subunit resulted in a strikingly high processive mode of deoxynucleotide polymerization (> 7,200 nucleotides). These findings strongly suggest that the BMRF1 polymerase accessory subunit stabilizes interaction between the EBV DNA polymerase and primer template and functions as a sliding clamp at the growing 3'-OH end of the primer terminus to increase the processivity of polymerization.
Biosynthesis of flavonoid and terphenyl metabolites by the fungus Aspergillus candidus (1973)

Chlorflavonin and two accompanying phenylalanine-derived metabolites, characterized from spectral evidence as dechlorochlorflavonin and 1,4-dimethoxy-2,4′,4″-trilhydroxy-p-terphenyl, are biosynthesized de novo by Aspergillus candidus.
Small-Molecule H-Bond Donors in Asymmetric Catalysis (2007)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSmall-Molecule H-Bond Donors in Asymmetric CatalysisAbigail G. Doyle and Eric N. JacobsenView Author Information Department of Chemistry & Chemical Biology, Harvard University, Cambridge, Massachusetts 02138 Cite this: Chem. Rev. 2007, 107, 12, 5713–5743Publication Date (Web):December 12, 2007Publication History Received28 March 2007Published online12 December 2007Published inissue 1 December 2007https://pubs.acs.org/doi/10.1021/cr068373rhttps://doi.org/10.1021/cr068373rresearch-articleACS PublicationsCopyright © 2007 American Chemical SocietyRequest reuse permissionsArticle Views40350Altmetric-Citations2297LEARN 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:Addition reactions,Aldehydes,Catalysts,Reaction products,Stereoselectivity Get e-Alerts
半经典分析、威顿-拉普拉斯和统计力学 (2005)

本书是新加坡世界科技出版公司出版的《偏微分方程及其应用》的系列丛书第1卷。此书论述威顿．拉普拉斯方法在统计力学中的应用，分析在统计力学中的相关性衰减问题并将威顿．拉普拉斯方法与传递矩阵法和半经典分析等其他技术进行比较，最后对均匀对数索波列夫不等式给出了完全的证明。
Adaptation of Prostatic-Group-Label Homogeneous Immunoassay to reagent-strip format. (1981)

The Prostatic-Group-Label Immunoassay (PGLIA) technique has been incorporated into a reagent-strip format. We report use of flavin N6-(N'-2,4-dinitrophenyl-6-aminohexyl)adenine dinucleotide (DNP-FAD) as the prosthetic group derivative and 6-N-(2,4-dinitrophenyl)aminohexanoic acid (DNP-caproate) as the competing ligand. DNP-FAD not bound by antibody combines with glucose oxidase apoenzyme, which then reacts with glucose and oxygen, and gives color through a peroxidase-linked system. The rate of color generation is thus a function of the DNP-caproate concentration. PGLIA reagent strips are prepared by sequential impregnations of filter paper with an acetone solution of indicator (3,3',5,5'-tetramethylbenzidine); an aqueous solution containing glucose oxidase apoenzyme, the rest of the color generation system, stabilizers, and antibody to DNP; and a solution of DNP-FAD in n-propanol. This preparation permits effective antibody binding, and prevents premature interaction of immunoassay components. A quantitative color response to concentrations of DNP-caproate in the range of 1 to 8 mumol/L was demonstrated with these reagent strips. Prototype PGLIA reagent strips for theophylline and phenytoin have been successfully developed by substituting the appropriate FAD derivative and antibody for the corresponding reagents in the DNP model system.
Microbial Evasion of the Immune System:  Structural Modifications of Enterobactin Impair Siderocalin Recognition (2006)

The mammalian protein siderocalin binds and inactivates the ferric complex of the bacterial siderophore enterobactin with a Kd value similar to that of the bacterial receptor FepA. However, microorganisms can evade this immune response by structural modifications of the siderophore. The binding of siderophores by siderocalin relies in part on electrostatic interactions and does not depend greatly on what metal is in the complex. It is also sterically limited by the rigid conformation of the protein calyx; methylation of the three catecholate rings of enterobactin hinders siderocalin recognition. The siderocalin binding has been probed for a series of enterobactin analogues in order to investigate in detail the specificity of siderocalin recognition.
Effect of rule weights in fuzzy rule-based classification systems (2001)

This paper examines the effect of rule weights in fuzzy rule-based classification systems. Each fuzzy IF-THEN rule in our classification system has antecedent linguistic values and a single consequent class. We use a fuzzy reasoning method based on a single winner rule in the classification phase. The winner rule for a new pattern is the fuzzy IF-THEN rule that has the maximum compatibility grade with the new pattern. When we use fuzzy IF-THEN rules with certainty grades, the winner is determined as the rule with the maximum product of the compatibility grade and the certainty grade. In this paper, the effect of rule weights is illustrated by drawing classification boundaries using fuzzy IF-THEN rules with/without certainty grades. It is also shown that certainty grades play an important role when a fuzzy rule-based classification system is a mixture of general rules and specific rules. Through computer simulations, we show that comprehensible fuzzy rule-based systems with high classification performance can be designed without modifying the membership functions of antecedent linguistic values when we use fuzzy IF-THEN rules with certainty grades.
Absorption spectra of substances derived from vitamin A (1932)

Research Article| January 01 1932 Absorption spectra of substances derived from vitamin A Joseph Ratcliffe Edisbury; Joseph Ratcliffe Edisbury 1The Department of Chemistry, University of Liverpool Search for other works by this author on: This Site PubMed Google Scholar Albert Edward Gillam; Albert Edward Gillam 1The Department of Chemistry, University of Liverpool Search for other works by this author on: This Site PubMed Google Scholar Isidor Morris Heilbron; Isidor Morris Heilbron 1The Department of Chemistry, University of Liverpool Search for other works by this author on: This Site PubMed Google Scholar Richard Alan Morton Richard Alan Morton 1The Department of Chemistry, University of Liverpool Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1932) 26 (4): 1164–1173. https://doi.org/10.1042/bj0261164 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation Joseph Ratcliffe Edisbury, Albert Edward Gillam, Isidor Morris Heilbron, Richard Alan Morton; Absorption spectra of substances derived from vitamin A. Biochem J 1 January 1932; 26 (4): 1164–1173. doi: https://doi.org/10.1042/bj0261164 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1932 LONDON: CAMBRIDGE UNIVERSITY PRESS1932 Article PDF first page preview Close Modal You do not currently have access to this content.