gebhart/patrepeval huggingface dataset:
Identification of 11 novel mutations in eight BBS genes by high-resolution homozygosity mapping (2009)

Thus, in the presence of extreme genetic locus heterogeneity, homozygosity mapping provides a valuable approach to the molecular genetic diagnosis of BBS and will facilitate the discovery of novel pathogenic mutations.
Generation of cytotoxic T lymphocytes against immunorecessive epitopes after multiple immunizations with adenovirus vectors is dependent on haplotype (1997)

Currently, adenovirus (Ad) is being considered as a vector for the treatment of cystic fibrosis as well as other diseases. However, the cytotoxic T lymphocyte (CTL) response to Ad could limit the effectiveness of such approaches. Since the CTL response to virus infection is often focused on one or a few immunodominant epitopes, one approach to circumvent this response is to create vectors that lack these immunodominant epitopes. The effectiveness of this approach was tested by immunizing mice with human group C adenoviruses. Three mouse strains (C57BL/10SnJ [H-2b], C3HeB/FeJ [H-2k], and BALB/cByJ [H-2d]) were immunized with wild-type Ad or Ad vectors lacking the immunodominant antigen(s), and the CTL responses were measured. In C57BL/10 (B10) mice, a single inoculation intraperitoneally (i.p.) led to the recognition of an immunodominant antigen in E1A. When B10 mice were inoculated multiple times either i.p. or intranasally with wild-type Ad or an Ad vector lacking most of the E1 region, subdominant epitopes outside this region were recognized. In contrast, C3H mice inoculated with wild-type Ad recognized an epitope mapping within E1B. When inoculated twice with Ad vectors lacking both E1A and E1B, no immunorecessive epitopes were recognized. The immune response to Ad in BALB/c mice was more complex. CTLs from BALB/c mice inoculated i.p. with wild-type Ad recognized E1B in the context of the major histocompatibility complex (MHC) class I Dd allele and a region outside E1 associated with the Kd allele. When BALB/c mice were inoculated with E1-deleted Ad vectors, only the immunodominant Kd-restricted epitope was recognized, and Dd-restricted CTLs did not develop. This report indicates that the emergence of CTLs against immunorecessive epitopes following multiple administrations of Ad vectors lacking immunodominant antigens is dependent on haplotype and could present an obstacle to gene therapy in an MHC-diverse human population.
Chemical Methods for Peptide and Protein Production (2013)

Since the invention of solid phase synthetic methods by Merrifield in 1963, the number of research groups focusing on peptide synthesis has grown exponentially. However, the original step-by-step synthesis had limitations: the purity of the final product decreased with the number of coupling steps. After the development of Boc and Fmoc protecting groups, novel amino acid protecting groups and new techniques were introduced to provide high quality and quantity peptide products. Fragment condensation was a popular method for peptide production in the 1980s, but unfortunately the rate of racemization and reaction difficulties proved less than ideal. Kent and co-workers revolutionized peptide coupling by introducing the chemoselective reaction of unprotected peptides, called native chemical ligation. Subsequently, research has focused on the development of novel ligating techniques including the famous click reaction, ligation of peptide hydrazides, and the recently reported α-ketoacid-hydroxylamine ligations with 5-oxaproline. Several companies have been formed all over the world to prepare high quality Good Manufacturing Practice peptide products on a multi-kilogram scale. This review describes the advances in peptide chemistry including the variety of synthetic peptide methods currently available and the broad application of peptides in medicinal chemistry.
Accurate and efficient image intensifier distortion correction algorithm for volume tomographic angiography (1998)

The recent advance in image intensifier based volume tomog- raphic angiography has stirred a significant interest in the development of accurate and efficient algorithms to correct image intensifier distor- tions. An algorithm and its calibration protocol are developed to correct the distortion caused by the image intensifier-CCD camera imaging chain in a single step regardless of distortion sources. This algorithm first partitions a distorted image into small quadrilateral regions, then maps each region individually to the corrected image using the corresponding bilinear functions. The general applicable parameters of these bilinear functions can be obtained using a specially designed grid phantom. The algorithm and the calibration protocol are tested using this grid phantom on a newly built image intensifier based volume tomographic angiogra- phy imaging system. The maximum distortion error is reduced from 5.96 mm before correction to 0.05 mm after correction. Further validation of the proposed algorithm is performed through three-dimensional tomog- raphic reconstructions of a vascular phantom and animal studies. The reconstruction results indicate that the accuracy of the algorithm and the calibration protocol is acceptable for volume tomographic angiography. This algorithm can also be applied to radiation therapy and stereosurgi- cal treatment planning where image intensifier distortions must be cor- rected. © 1998 Society of Photo-Optical Instrumentation Engineers. (S0091-3286(98)03603-4)
Nuclear accumulation of the E2F heterodimer regulated by subunit composition and alternative splicing of a nuclear localization signal (1996)

The cellular transcription factor E2F plays a critical role in integrating cell cycle progression with the transcription apparatus by virtue of a physical interaction and control by key regulators of the cell cycle, such as pRb, cyclins and cyclin-dependent kinases. Generic E2F DNA binding activity arises when a member of two families of proteins, E2F and DP, form heterodimeric complexes, an interaction which results in co-operative transcriptional and DNA binding activity. Here, we characterise a new and hitherto unexpected mechanism of control influencing the activity of E2F which is mediated at the level of intracellular location through a dependence on heterodimer formation for nuclear translocation. Nuclear accumulation is dramatically influenced by two distinct processes: alternative splicing of a nuclear localization signal and subunit composition of the E2F heterodimer. These data define a new level of control in the E2F transcription factor whereby interplay between subunits dictates the levels of nuclear DNA binding activity.
CD47 in the Tumor Microenvironment Limits Cooperation between Antitumor T-cell Immunity and Radiotherapy (2014)

Although significant advances in radiotherapy have increased its effectiveness in many cancer settings, general strategies to widen the therapeutic window between normal tissue toxicity and malignant tumor destruction would still offer great value. CD47 blockade has been found to confer radioprotection to normal tissues while enhancing tumor radiosensitivity. Here, we report that CD47 blockade directly enhances tumor immunosurveillance by CD8(+) T cells. Combining CD47 blockade with irradiation did not affect fibrosarcoma growth in T cell-deficient mice, whereas adoptive transfer of tumor-specific CD8(+) T cells restored combinatorial efficacy. Furthermore, ablation of CD8(+) T cells abolished radiotherapeutic response in immunocompetent syngeneic hosts. CD47 blockade in either target cells or effector cells was sufficient to enhance antigen-dependent CD8(+) CTL-mediated tumor cell killing in vitro. In CD47-deficient syngeneic hosts, engrafted B16 melanomas were 50% more sensitive to irradiation, establishing that CD47 expression in the microenvironment was sufficient to limit tumor radiosensitivity. Mechanistic investigations revealed increased tumor infiltration by cytotoxic CD8(+) T cells in a CD47-deficient microenvironment, with an associated increase in T cell-dependent intratumoral expression of granzyme B. Correspondingly, an inverse correlation between CD8(+) T-cell infiltration and CD47 expression was observed in human melanomas. Our findings establish that blocking CD47 in the context of radiotherapy enhances antitumor immunity by directly stimulating CD8(+) cytotoxic T cells, with the potential to increase curative responses.
Synthesized Synchronous Sampling Technique for Differential Bearing Damage Detection (2010)

The differential bearing between the low-pressure turbine (LPT) and high-pressure turbine (HPT) shafts is one of the most vulnerable parts in a turbomachinery engine. Unfortunately, it is also one of the most difficult parts to monitor for damage existence signatures, because the signal-to-noise ratio at the normal sensor locations is extremely low. In addition, the speed variations in both the LPT and HPT can further deteriorate the damage signature extracted by conventional analysis methods. In this paper, we developed a “synthesized synchronous sampling” technique to enhance the detection of differential bearing damage signature. Combining this technique together with the conventional acceleration enveloping technique, we are able to detect differential bearing damage at a much earlier stage, thus providing early warnings of the machinery health conditions.
TRU-015, a fusion protein derived from an anti-CD20 antibody, for the treatment of rheumatoid arthritis. (2010)

TRU-015, being developed by Trubion Pharmaceuticals Inc and Pfizer Inc, is an intravenously administered anti-CD20 IgG fusion protein for the treatment of rheumatoid arthritis. TRU-015 depletes B-cells from the peripheral blood in vitro, and can mediate complement-and antibody-dependent cellular cytotoxicity. TRU-015 was well tolerated in patients with rheumatoid arthritis in phase I and II clinical trials, and demonstrated an efficacy profile similar to other biological agents approved for rheumatoid arthritis. At the time of publication, phase II trials were ongoing in patients with rheumatoid arthritis. TRU-015 could represent a novel therapy for the treatment of rheumatoid arthritis, although the efficacy, safety profile and advantages of this compound compared with existing therapeutic options would need to be established in phase III trials. In addition, this agent also may be useful to the treatment of B-cell neoplasms and autoimmune diseases.
Function of GATA Transcription Factors in Induction of Endothelial Vascular Cell Adhesion Molecule-1 by Tumor Necrosis Factor-α (2001)

Endothelial vascular cell adhesion molecule-1 (VCAM-1) is expressed in response to cytokine stimulation and plays a critical role in inflammatory reactions. Previously, we developed a novel VCAM-1 inhibitor that acts through a mechanism independent of nuclear factor-kappaB activity. It suppresses the binding activity of GATA proteins in cytokine-stimulated endothelial cells, which may be related to the anti-VCAM-1 induction effect of this drug. In this study, we investigated the role of GATA proteins in the induction of VCAM-1 by tumor necrosis factor-alpha (TNF-alpha) in human endothelial cells. The mRNA expression of GATA-6 was increased, whereas GATA-3 mRNA was decreased by TNF-alpha stimulation. Electrophoretic mobility shift assay showed that TNF-alpha stimulation increased the DNA binding of GATA-6 but decreased that of GATA-3. Experiments using protein overexpression or antisense oligonucleotides revealed that GATA-6 potently acts as a positive regulator of VCAM-1 gene transcription. In contrast, overexpression of GATA-3 was able to suppress TNF-alpha-induced VCAM-1 expression. Our results provide evidence of the importance of GATA proteins in the induction of VCAM-1 by TNF-alpha in vascular endothelial cells. The switch from GATA-3 to GATA-6 is taken to be an important transcriptional control event in TNF-alpha induction of VCAM-1.
Two CD95 tumor classes with different sensitivities to antitumor drugs (2003)

CD95 type I and II cells differ in their dependence on mitochondria to execute apoptosis, because antiapoptotic members of the Bcl-2 family render only type II cells resistant to death receptor-induced apoptosis. They can also be distinguished by a more efficient formation of the death-inducing signaling complex in type I cells. We have identified a soluble form of CD95 ligand (S2) that is cytotoxic to type II cells but does not kill type I cells. By testing 58 tumor cell lines of the National Cancer Institute's anticancer drug-screening panel for apoptosis sensitivity to S2 and performing death-inducing signaling complex analyses, we determined that half of the CD95-sensitive cells are type I and half are type II. Most of the type I cell lines fall into a distinct class of tumor cells expressing mesenchymal-like genes, whereas the type II cell lines preferentially express epithelium-like markers. This suggests that type I and II tumor cells represent different stages of carcinogenesis that resemble the epithelial-mesenchymal transition. We then screened the National Cancer Institute database of >42,000 compounds for reagents with patterns of growth inhibition that correlated with either type I or type II cell lines and found that actin-binding compounds selectively inhibited growth of type I cells, whereas tubulin-interacting compounds inhibited growth of type II cells. Our analysis reveals fundamental differences in programs of gene expression between type I and type II cells and could impact the way actin- and microtubule-disrupting antitumor agents are used in tumor therapy.
Activation of human platelets by a stimulatory monoclonal antibody. (1990)

The clinical significance of the interaction of antibodies with circulating platelets is well documented, but the mechanisms underlying these interactions are not fully known. Here we describe the characterization of anti-human platelet membrane protein monoclonal antibody (mAb) termed F11. Interaction of mAb F11 with human platelets resulted in dose-dependent granular secretion, measured by [14C]serotonin and ATP release, fibrinogen binding and aggregation. Analysis of the specific binding of mAb F11 to platelets revealed a high affinity site with 8,067 +/- 1,307 sites per platelet with a dissociation constant (Kd) of 2.7 +/- 0.9 x 10(-8) M. Two membrane proteins of 32,000 and 35,000 daltons, identified by Western blotting, were recognized by mAb F11. Incubation of 32Pi-labeled platelets with mAb F11 resulted in rapid phosphorylation of intracellular 40,000- and 20,000-dalton proteins, followed by dephosphorylation of these proteins. Monovalent Fab fragments or Fc fragments of mAb F11 IgG did not induce platelet aggregation or secretion; however, Fab fragments of mAb F11 IgG blocked mAb F11-induced platelet aggregation and the binding of 125I-mAb F11 to platelets. The addition of an anti-GPIIIa monoclonal antibody (mAb G10), which inhibits 125I-fibrinogen binding and platelet aggregation, completely blocked mAb F11-induced [14C]serotonin secretion and aggregation but not the binding of 125I-mAb F11 to platelets. mAb G10 also inhibited the increase in the phosphorylation of the 40,000- and 20,000-dalton proteins induced by mAb F11. These results implicate the involvement of the GPIIIa molecule in the chain of biochemical events involved in the induction of granular secretion.
Oxidation of 1-aminopyrazoles and synthesis of 1,2,3-triazines (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOxidation of 1-aminopyrazoles and synthesis of 1,2,3-triazinesAkio Ohsawa, Heihachiro Arai, Hidefumi Ohnishi, Takashi Itoh, Terumitsu Kaihoh, Mamiko Okada, and Hiroshi IgetaCite this: J. Org. Chem. 1985, 50, 26, 5520–5523Publication Date (Print):December 1, 1985Publication History Published online1 May 2002Published inissue 1 December 1985https://pubs.acs.org/doi/10.1021/jo00350a017https://doi.org/10.1021/jo00350a017research-articleACS PublicationsRequest reuse permissionsArticle Views1140Altmetric-Citations43LEARN 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
Inflammatory Cytokines Released from the Facet Joint Tissue in Degenerative Lumbar Spinal Disorders (2004)

There are inflammatory cytokines in facet joint tissue at high levels in degenerative lumbar spinal disorders. Inflammatory cytokines have a higher concentration rate in lumbar spinal canal stenosis than in lumbar disc herniation. This finding suggests that inflammatory cytokines in degenerated facet joints may have some relation to the cause of pain in degenerative lumbar disorders.
A Dual-Function DNA Vaccine Encoding Carcinoembryonic Antigen and CD40 Ligand Trimer Induces T Cell-Mediated Protective Immunity Against Colon Cancer in Carcinoembryonic Antigen-Transgenic Mice (2001)

A carcinoembryonic Ag (CEA)-based DNA vaccine encoding both CEA and CD40 ligand trimer achieved effective tumor-protective immunity against murine colon carcinoma in CEA-transgenic mice by activating both naive T cells and dendritic cells. Peripheral T cell tolerance to CEA was broken in a prophylactic model by this novel, dual-function DNA vaccine, whose efficacy was further enhanced by boosts with a recombinant Ab-IL-2 fusion protein (huKS1/4-IL-2). These conclusions are supported by four lines of evidence. First, a lethal challenge of MC38-CEA-KS Ag murine colon carcinoma cells was for the first time completely rejected in 100% of experimental animals treated by oral gavage of this DNA vaccine carried by attenuated Salmonella typhimurium, followed by five boosts with huKS1/4-IL-2. Second, specific activation of dendritic cells was indicated by their marked up-regulation in expression of costimulatory molecules B7.1 (CD80), B7.2 (CD86), and ICAM-1. Third, a decisive increase over control values was observed in both MHC class I Ag-restricted cytotoxicity of CTLs from successfully vaccinated mice and secretion of proinflammatory cytokines IFN-gamma and IL-12. Fourth, activation of CTLs was augmented, as indicated by up-regulation of activity markers LFA-1, CD25, CD28, and CD69. Taken together, these results suggest that a dual-function DNA vaccine encoding CEA and CD40 ligand trimer combined with tumor-targeted IL-2 may be a promising strategy for the rational development of DNA-based cancer vaccines for future clinical applications.
Metabolomic Analysis and Visualization Engine for LC−MS Data (2010)

Metabolomic analysis by liquid chromatography-high-resolution mass spectrometry results in data sets with thousands of features arising from metabolites, fragments, isotopes, and adducts. Here we describe a software package, Metabolomic Analysis and Visualization ENgine (MAVEN), designed for efficient interactive analysis of LC-MS data, including in the presence of isotope labeling. The software contains tools for all aspects of the data analysis process, from feature extraction to pathway-based graphical data display. To facilitate data validation, a machine learning algorithm automatically assesses peak quality. Users interact with raw data primarily in the form of extracted ion chromatograms, which are displayed with overlaid circles indicating peak quality, and bar graphs of peak intensities for both unlabeled and isotope-labeled metabolite forms. Click-based navigation leads to additional information, such as raw data for specific isotopic forms or for metabolites changing significantly between conditions. Fast data processing algorithms result in nearly delay-free browsing. Drop-down menus provide tools for the overlay of data onto pathway maps. These tools enable animating series of pathway graphs, e.g., to show propagation of labeled forms through a metabolic network. MAVEN is released under an open source license at http://maven.princeton.edu.
New Forms of International Migration: In Search of Which Europe? (2001)

International migration has provided one of the important preconditions for economic growth in post-1945 Europe. Yet a regulatory system based on the implicit assumption that migration would be temporary, legal and for work purposes has largely failed to address changes in the meanings of boundaries and citizenship in Europe and, moreover, in the very nature of international mobility. In the mid 1990s there were an estimated 15 million immigrants in Europe who are foreigners, without legal citizenship, in their countries of residence (Soysal, 1996). The majority do have permanent resident status which provides most of the same rights as national citizens in terms of social and welfare provision, and access to legal justice, but only limited electoral rights. However, across Europe, the pattern of national provision has produced a bricolage of territories with differentiated rights for different migrant groups.
A Convenient Synthesis of Orthoformic Esters (1952)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA Convenient Synthesis of Orthoformic EstersElliot R. Alexander and Hirsh M. BuschCite this: J. Am. Chem. Soc. 1952, 74, 2, 554–555Publication Date (Print):January 1, 1952Publication History Published online1 May 2002Published inissue 1 January 1952https://pubs.acs.org/doi/10.1021/ja01122a502https://doi.org/10.1021/ja01122a502research-articleACS PublicationsRequest reuse permissionsArticle Views349Altmetric-Citations31LEARN 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
Chemical Reactor Analysis and Design (1979)

CHEMICAL ENGINEERING KINETICS Elements of Reaction Kinetics Kinetics of Heterogeneous Catalytic Reactions Transport Processes with Reactions Catalyzed by Solids Noncatalytic Gas-Solid Reactions Catalyst Deactivation Gas-Liquid Reactions ANALYSIS AND DESIGN OF CHEMICAL REACTORS The Fundamental Mass, Energy, and Momentum Balance Equations The Batch and Semibatch Reactors The Plug Flow Reactor The Perfectly Mixed Flow Reactor Fixed Bed Catalytic Reactors Nonideal Flow Patterns and Population Balance Models Fluidized Bed and Transport Reactors Multiphase Flow Reactors Author Index Subject Index.
Predicting multiple organ failure in patients with severe trauma. (2008)

According to the results of our study, it is possible to create predictive models with a high level of accuracy for the development of organ failure in traumatized patients. The most important parameters of MOF development are serum IL-6 concentration on the first day of hospitalization and the number of positive SIRS criteria on the fourth day of hospitalization.