gebhart/patrepeval huggingface dataset:
β-Site Covalent Reactions Trigger Transitions between Open and Closed Conformations of the Tryptophan Synthase Bienzyme Complex (1996)

The tryptophan synthase bienzyme complex (alpha2beta2) from Salmonella tryphimurium catalyzes the final steps in the biosynthesis of L-Trp. To investigate the roles played by conformational change in tryptopthan synthase catalysis, the fluorophore 8-anilino-1-naphthalensulfonate (ANS) is used to identify conformational states. The binding of ANS to the alpha2beta2 bienzyme complex is accompanied by a dramatic enhancement of ANS fluorescence and a shift of the emission maximum from 520 to 482 nm. The ANS binding isotherm is biphasic and consists of a class of moderately high-affinity, noninteracting sites with a stoichiometry of 1 site/alpha beta dimeric unit (Kd' = 62 + or - 15 micrometer) and a much weaker set of non-specific interactions with K'd>1mM. Our findings show that the affinity of the enzyme for ANS is strongly decreased (> 10-fold) by interactions at two loci 30 angstroms apart: (i) the binding of the alpha-site ligands, 3-indole-D-glycerol 3'-phosphate or alpha-glycerol phosphate (GP) or (ii) reaction at the beta-subunit to form either the alpha-aminoacrylate Schiff base, E(A-A), or quinonoid species, E(Q). In contrast, formation of the L-Ser and L-Trp external aldimines E(Aex1) and E(Aex2) at the beta-site causes a 2-3 fold decrease in the affinity of the enzyme for ANS. The combination of E(A-A)or E(Q) with GP brings about almost complete displacement of ANS, indicating that these interactions drive a conformation change in alphabeta subunit pairs which prevents the binding of ANS. These results are consistent with a model which postulates that alphabeta subunit pairs undergo ligand-mediated transitions between open and closed conformations during the catalytic cycle. Consistent with the kinetic data showing that binding of alpha-site ligands increases the affinity of the beta site for L-Ser and that formation of E(A-A) activates the alpha reaction [Brzović, P. S., Ngo, K., & Dunn, M. F. (1992) Biochemistry 31, 3831-3839], while mutations in alpha subunit loops 2 and 6 prevent the ligand- mediated transition to a closed structure [Brzović, P.S., Hyde, C.C., Miles, E.W., & Dunn, M.F. (1993) Biochemistry 32, 10404-10413], we conclude that reciprocal ligand-mediated allosteric interactions between the heterologous subunits promote conformational transitions between open and closed structures in alphabeta subunit pairs which function to coordinate catalytic activities and facilitate the channeling of indole between the two catalytic sites.
A New Synthesis of Metathiazanone Derivatives via Intramolecular Pummerer Rearrangements (1975)

A new synthesis of metathiazanone derivatives is described.The synthesis involves a novel, intramolecular Pummerer rearrangement.
Effects of d,l-3-Phthalimidoglutarimide and N-Phthalyl-d,l-aspartimide on Rat Pregnancy (1963)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEffects of d,l-3-Phthalimidoglutarimide and N-Phthalyl-d,l-aspartimide on Rat PregnancyD. Misiti, V. Rosnath, G. Bignami, F. Bovet-Nitti, and D. BovetCite this: J. Med. Chem. 1963, 6, 4, 464–465Publication Date (Print):July 1, 1963Publication History Published online1 May 2002Published inissue 1 July 1963https://pubs.acs.org/doi/10.1021/jm00340a035https://doi.org/10.1021/jm00340a035research-articleACS PublicationsRequest reuse permissionsArticle Views117Altmetric-Citations12LEARN 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
Identification of a chemotactic epitope in human transforming growth factor‐β1 spanning amino acid residues 368–374 (1995)

TGF-beta 1 plays a critical role in inflammatory and repair processes due in part to its ability to provide a potent chemotactic stimulus for inflammatory cells such as neutrophils and monocytes and for fibroblasts which initiate the fibrogenic response. In the present study, we have used synthetic oligopeptides representing the amino acid sequence of the 12.1 kDa monomer of human TGF-beta 1 in an effort to identify a chemotactic epitope on the molecule. A seven residue peptide containing residues 368-374, Val Tyr Tyr Val Gly Arg Lys, was demonstrated to be capable of inducing chemotactic migration of human peripheral blood neutrophils, monocytes, monocyte leukemia cell line THP-1, and infant foreskin fibroblasts. Furthermore, larger peptides from the carboxy-terminal portion of TGF-beta 1 that contained residues 368-374 also induced migration of these cell types. None of the peptides representing the complete amino acid of TGF-beta 1 monomer were able to compete with [125I]hrTGF-beta 1 for binding to TGF-beta cell surface receptors or fibroblasts or THP-1 cells. Implications of these observations are discussed.
Enhancing humoral responses to a malaria antigen with nanoparticle vaccines that expand T fh cells and promote germinal center induction (2012)

For subunit vaccines, adjuvants play a key role in shaping immunological memory. Nanoparticle (NP) delivery systems for antigens and/or molecular danger signals are promising adjuvants capable of promoting both cellular and humoral immune responses, but in most cases the mechanisms of action of these materials are poorly understood. Here, we studied the immune response elicited by NPs composed of multilamellar "stapled" lipid vesicles carrying a recombinant Plasmodium vivax circumsporozoite antigen, VMP001, both entrapped in the aqueous core and anchored to the lipid bilayer surfaces. Immunization with these particles and monophosphoryl lipid A (MPLA), a US Food and Drug Administration-approved immunostimulatory agonist for Toll-like receptor-4, promoted high-titer, high-avidity antibody responses against VMP001, lasting more than 1 y in mice at 10-fold lower doses than conventional adjuvants. Compared to soluble VMP001 mixed with MPLA, VMP001-NPs promoted broader humoral responses, targeting multiple epitopes of the protein and a more balanced Th1/Th2 cytokine profile from antigen-specific T cells. To begin to understand the underlying mechanisms, we examined components of the B-cell response and found that NPs promoted robust germinal center (GC) formation at low doses of antigen where no GC induction occurred with soluble protein immunization, and that GCs nucleated near depots of NPs accumulating in the draining lymph nodes over time. In parallel, NP vaccination enhanced the expansion of antigen-specific follicular helper T cells (T(fh)), compared to vaccinations with soluble VMP001 or alum. Thus, NP vaccines may be a promising strategy to enhance the durability, breadth, and potency of humoral immunity by enhancing key elements of the B-cell response.
A Gaussian Process Guided Particle Filter for Tracking 3D Human Pose in Video (2013)

In this paper, we propose a hybrid method that combines Gaussian process learning, a particle filter, and annealing to track the 3D pose of a human subject in video sequences. Our approach, which we refer to as annealed Gaussian process guided particle filter, comprises two steps. In the training step, we use a supervised learning method to train a Gaussian process regressor that takes the silhouette descriptor as an input and produces multiple output poses modeled by a mixture of Gaussian distributions. In the tracking step, the output pose distributions from the Gaussian process regression are combined with the annealed particle filter to track the 3D pose in each frame of the video sequence. Our experiments show that the proposed method does not require initialization and does not lose tracking of the pose. We compare our approach with a standard annealed particle filter using the HumanEva-I dataset and with other state of the art approaches using the HumanEva-II dataset. The evaluation results show that our approach can successfully track the 3D human pose over long video sequences and give more accurate pose tracking results than the annealed particle filter.
Exclusive Transduction of Human CD4+ T Cells upon Systemic Delivery of CD4-Targeted Lentiviral Vectors (2015)

Playing a central role in both innate and adaptive immunity, CD4(+) T cells are a key target for genetic modifications in basic research and immunotherapy. In this article, we describe novel lentiviral vectors (CD4-LV) that have been rendered selective for human or simian CD4(+) cells by surface engineering. When applied to PBMCs, CD4-LV transduced CD4(+) but not CD4(-) cells. Notably, also unstimulated T cells were stably genetically modified. Upon systemic or intrasplenic administration into mice reconstituted with human PBMCs or hematopoietic stem cells, reporter gene expression was predominantly detected in lymphoid organs. Evaluation of GFP expression in organ-derived cells and blood by flow cytometry demonstrated exclusive gene transfer into CD4(+) human lymphocytes. In bone marrow and spleen, memory T cells were preferentially hit. Toward therapeutic applications, we also show that CD4-LV can be used for HIV gene therapy, as well as for tumor therapy, by delivering chimeric Ag receptors. The potential for in vivo delivery of the FOXP3 gene was also demonstrated, making CD4-LV a powerful tool for inducible regulatory T cell generation. In summary, our work demonstrates the exclusive gene transfer into a T cell subset upon systemic vector administration opening an avenue toward novel strategies in immunotherapy.
High Quality Ultrathin CoTiO[sub 3] High-k Gate Dielectrics (1999)

A novel high‐k cobalt‐titanium oxide was formed by directly oxidizing sputtered film. capacitor structure was fabricated and measured. The effective dielectric constant with buffered layer for gate dielectric can reach as high as 40 while depicting excellent electrical properties at the same time. This novel metal oxide thus appears to be a promising high‐k gate dielectric for future ultralarge scale integrated devices. ©2000 The Electrochemical Society
Remarkably Broad Substrate Tolerance of Malonyl-CoA Synthetase, an Enzyme Capable of Intracellular Synthesis of Polyketide Precursors (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTRemarkably Broad Substrate Tolerance of Malonyl-CoA Synthetase, an Enzyme Capable of Intracellular Synthesis of Polyketide PrecursorsNicola L. Pohl, Marcus Hans, Hwan Young Lee, Yu Sam Kim, David E. Cane, and Chaitan KhoslaView Author Information Departments of Chemical Engineering and Chemistry and Biochemistry, Stanford University Stanford, California 94305-5025 Department of Biochemistry, College of Science Protein Network Research Center Yonsei University, Seoul, Korea 120-749 Department of Chemistry, Brown University Providence, Rhode Island 02912 Cite this: J. Am. Chem. Soc. 2001, 123, 24, 5822–5823Publication Date (Web):May 26, 2001Publication History Received1 August 2000Published online26 May 2001Published inissue 1 June 2001https://pubs.acs.org/doi/10.1021/ja0028368https://doi.org/10.1021/ja0028368rapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views1733Altmetric-Citations39LEARN 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:Biosynthesis,Metabolism,Peptides and proteins,Precursors,Reaction products Get e-Alerts
Estimate of overall treatment results in acute nonlymphocytic leukemia based on age-specific rates of incidence and of complete remission. (1985)

It is widely assumed that most patients with acute nonlymphocytic leukemia (ANLL) are less than 60 years old, that greater than 50% of all patients can now achieve a complete remission (CR), and that bone marrow transplantation (BMT) represents a significant therapeutic breakthrough in this disease. New epidemiological data, presented in this study, show that the median age of patients with ANLL is 62-64 years, with 54%-59% of the patients being greater than 60 years old. When combining age-specific incidence data with age-specific data on CR derived from the recent literature, it can be calculated that the cumulated rate of CR for all ages combined will be only between 35.3% and 49.2% with current therapy. It can also be calculated that BMT with its present limitations can at most cure 1.44%-2.5% of all patients with ANLL. These findings suggest that some of the accepted conceptions in ANLL regarding age distribution of patients, cumulated rates of CR, and value of BMT cannot stand up to closer scrutiny. Treatment priorities and resource allocation in ANLL should be reconsidered, and more attention should be given to solving the problems of treatment in elderly patients.
Induction of T helper cell hyporesponsiveness in an experimental model of autoimmunity by using nonmitogenic anti-CD3 monoclonal antibody. (1994)

Autoimmune diseases can be characterized by increases in Th cell activities, suggesting that inhibition of Th cell function might ameliorate autoimmunity. We have recently reported that administration of nonmitogenic anti-CD3 mAb (nmCD3) to nonautoimmune mice can induce long-term Th cell hyporesponsiveness, reflected by reduced IL-2 secretion upon re-exposure to Ag. This study was designed to determine the effects of nmCD3 on autoimmunity by using the murine collagen-induced arthritis model. Treatment of DBA/1 mice with nmCD3 delayed the onset and reduced the severity of arthritis in mice immunized with type II collagen (CII). This effect was not caused by depletion of T cells or modulation of TCR. The observed inhibition of arthritis was not caused by decreased Ab production, as anti-CII titers were not affected. Rather, lymph node cells from CII-immunized mice treated with nmCD3 were hyporesponsive to in vitro stimulation with CII. This hyporesponsiveness was reflected by a marked decrease in secretion of IL-2 and IFN-gamma, but not of IL-4, which suggests that nmCD3 had its principal effect on Th1 cells. The hyporesponsiveness was not Ag-specific, because IL-2 and IFN-gamma production in response to a pan-T cell mitogen was also reduced. These results demonstrate that induction of Th1 cell hyporesponsiveness with nmCD3 can significantly alter the course of CIA and suggest that IL-2 and/or IFN-gamma play a crucial role in disease pathogenesis.
遠隔醫療(Telemedizin)에서의 醫療過誤責任과 準據法 (2004)

이 논문은 인터넷 등의 첨단통신기술의 발달로 인하여 현실화되고 있는 원격의료에 있어 수반되어 지는 법률적 문제, 특히 의료과오에서의 책임소재 문제와 아울러 국내외를 넘나들며 이루어지는 원격 의료에서의 국제사법적인 재판관할과 준거법의 적용문제를 심도있게 논술하였다. 국내에서도 이미 이러한 원격의료의 현실화로 인하여 발생되는 법적 분쟁에 대비하여 의료법을...
Ischemic Preconditioning at a Distance (1997)

Remote ischemia of a skeletal muscle induced by muscle stimulation combined with restriction of blood flow preconditioned the myocardium. The combination of muscle stimulation with reduction of femoral arterial blood flow but not muscle stimulation without blood flow restriction or of flow restriction without muscle stimulation reduced myocardial infarct size considerably.
Continuous Production of Ethylene-Based Diblock Copolymers Using Coordinative Chain Transfer Polymerization (2007)

ADVERTISEMENT RETURN TO ISSUECommunication to the...Communication to the EditorNEXTContinuous Production of Ethylene-Based Diblock Copolymers Using Coordinative Chain Transfer PolymerizationPhillip D. Hustad, Roger L. Kuhlman, Daniel J. Arriola, Edmund M. Carnahan, and Timothy T. WenzelView Author Information The Dow Chemical Company, 2301 N. Brazosport Blvd., Freeport, Texas 77541, and The Dow Chemical Company, Building 1776, Midland, Michigan 48674 Cite this: Macromolecules 2007, 40, 20, 7061–7064Publication Date (Web):September 5, 2007Publication History Received7 August 2007Revised10 August 2007Published online5 September 2007Published inissue 1 October 2007https://pubs.acs.org/doi/10.1021/ma0717791https://doi.org/10.1021/ma0717791rapid-communicationACS PublicationsCopyright © 2007 American Chemical SocietyRequest reuse permissionsArticle Views2444Altmetric-Citations142LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Catalysts,Copolymers,Living polymerization,Monomers,Polymers Get e-Alerts
Flavopiridol disrupts STAT3/DNA interactions, attenuates STAT3-directed transcription, and combines with the Jak kinase inhibitor AG490 to achieve cytotoxic synergy (2006)

Up-regulated signal transducers and activators of transcription (STAT)-mediated signaling is believed to contribute to the pathogenesis of a variety of solid and hematologic cancers. Consequently, inhibition of STAT-mediated signaling has recently been proposed as a potential new therapeutic approach to the treatment of cancers. Having shown previously that the pan-cyclin-dependent kinase inhibitor flavopiridol binds to DNA and seems to kill cancer cells via that process in some circumstances, we evaluated the hypothesis that flavopiridol might consequently disrupt STAT3/DNA interactions, attenuate STAT3-directed transcription, and down-regulate STAT3 downstream polypeptides, including the antiapoptotic polypeptide Mcl-1. SDS-PAGE/immunoblotting and reverse transcription-PCR were used to assess RNA and polypeptide levels, respectively. DNA cellulose affinity chromatography and a nuclear elution assay were used to evaluate the ability of flavopiridol to disrupt STAT3/DNA interactions. A STAT3 luciferase reporter assay was used to examine the ability of flavopiridol to attenuate STAT3-directed transcription. Colony-forming assays were used to assess cytotoxic synergy between flavopiridol and AG490. Flavopiridol was found to (a) disrupt STAT3/DNA interactions (DNA cellulose affinity chromatography and nuclear elution assay), (b) attenuate STAT3-directed transcription (STAT3 luciferase reporter assay), and (c) down-regulate the STAT3 downstream antiapoptotic polypeptide Mcl-1 at the transcriptional level (reverse transcription-PCR and SDS-PAGE/immunoblotting). Furthermore, flavopiridol, but not the microtubule inhibitor paclitaxel, could be combined with the STAT3 pathway inhibitor AG490 to achieve cytotoxic synergy in A549 human non-small cell lung cancer cells. Collectively, these data suggest that flavopiridol can attenuate STAT3-directed transcription in a targeted fashion and may therefore be exploitable clinically in the development of chemotherapy regimens combining flavopiridol and other inhibitors of STAT3 signaling pathways.
Large-area chromogenics: Materials and devices for transmittance control. Volume IS 4 (1990)

Chromogenic materials can alter their optical properties in a persistent yet reversible manner when subjected to a change in external conditions such as irradiation intensity, temperature, or electric-field strength. In the future chromogenic materials may be used on large scale to regulate the throughput of radiant energy for windows in buildings and cars, so that comfortable lighting and temperature are maintained without excessive air conditioning. The purpose of this book is to give a broad coverage of large-area chromogenics and to discuss their applications. The book is divided into the following areas: applications; photochromic materials; thermochromic materials; inorganic electrochromic materials; inorganic electrochromic materials; organic electrochromic materials; conductors for ions and electrons in electrochromic devices; electrochromic devices; and liquid crystals materials and devices. Separate abstracts were prepared for 33 papers in this book.
160 nm continuous tuning of an MQW laser in an external cavity across the entire 1.3 μm communications window (1991)

A tuning range of 160 nm has been demonstrated with an InGaAsP/InP MQW laser in a grating extended cavity across the 1.3 μm optical fibre communications window. The device tuned continuously from 1.255 μm to 1.417 μm with a CW power output of over 40 mW at 1.336 μm.
Enantioselective construction of quaternary carbon centre catalysed by bifunctional organocatalyst (2006)

The bifunctional thiourea-tertiary amine derivatives of simple chiral diamines serve as highly enantioselective catalysts for the Michael addition of alpha-substituted cyanoacetates to vinyl sulfones, giving an efficient protocol for the construction of an all-carbon substituted quaternary stereocentre.
Wetting: statics and dynamics (1985)

The wetting of solids by liquids is connected to physical chemistry (wettability), to statistical physics (pinning of the contact line, wetting transitions, etc.), to long-range forces (van der Waals, double layers), and to fluid dynamics. The present review represents an attempt towards a unified picture with special emphasis on certain features of "dry spreading": (a) the final state of a spreading droplet need not be a monomolecular film; (b) the spreading drop is surrounded by a precursor film, where most of the available free energy is spent; and (c) polymer melts may slip on the solid and belong to a separate dynamical class, conceptually related to the spreading of superfluids.