gebhart/patrepeval huggingface dataset:
Characterization of Reaper- and FADD-Induced Apoptosis in a Lepidopteran Cell Line (1997)

Expression of the reaper gene (rpr) correlates with the initiation of apoptosis in Drosophila melanogaster. Transient expression of rpr in the lepidopteran SF-21 cell line induced apoptosis displaying nuclear condensation and fragmentation, oligonucleosomal ladder formation, cell surface blebbing, and apoptotic body formation. Inhibitors of ICE-family proteases p35 and crmA, as well as members of the iap class of genes, Op-iap and D-iap2, but not bcl-2 family members, blocked rpr-induced apoptosis. Mutational analysis of rpr provided no support for the proposed sequence similarity of Reaper and death domain proteins. Mutations in the N-terminal region of Reaper, which displays sequence similarity to Hid and Grim, other Drosophila gene products correlated with the initiation of apoptosis, suggested that these residues might be functionally important. The mammalian cDNA encoding FADD (Fas-associating protein with a death domain) also induced cell death in SF-21 cells, but death progressed more slowly and with features which distinguished it from rpr-induced apoptosis. Several bcl-2 family members delayed or blocked FADD-induced cellular death. Thus, apoptosis initiated by Reaper progressed by a faster path which appeared to differ from that of FADD-induced apoptosis.
The Inflammatory Tumor Microenvironment and Its Impact on Cancer Development (2006)

The role of the immune system during cancer development is complex involving extensive reciprocal interactions between genetically altered cells, adaptive and innate immune cells, their soluble mediators and structural components present in the neoplastic microenvironment. Each stage of cancer development is regulated uniquely by the immune system; whereas full activation of adaptive immune cells at the tumor stage may result in eradication of malignant cells, chronic activation of innate immune cells at sites of premalignant growth may actually enhance tumor development. In addition, the balance between desirable antitumor immune responses and undesirable pro-tumor chronic inflammatory responses largely depends on the context in which a malignancy is developing. The following chapter focuses on the inflammatory components and processes engaged during cancer development and the impact of the inflammatory microenvironment.
Requirement for CD28 in Effector Regulatory T Cell Differentiation, CCR6 Induction, and Skin Homing (2015)

The skin, similar to most nonlymphoid tissues, contains substantial numbers of T cells. Among these, memory T cells serve a sentinel role to protect against pathogens, and regulatory T cells (Tregs) terminate immune responses as a check against unrestrained inflammation. Previously, we created conditional knockout mice with Treg-specific deletion of CD28. Although these mice have normal numbers of Tregs, these cells have lower levels of CTLA-4, PD-1, and CCR6, and the animals develop systemic autoimmunity characterized by prominent skin inflammation. In this study, we have performed a detailed analysis of the skin disease in these mice. Our data show that Treg-expressed CD28 is required for optimal maturation of CD44(lo)CD62L(hi) central Tregs into CD44(hi)CD62L(lo) effector Tregs (eTregs), as well as induction of CCR6 among the cells that do become eTregs. Although CD28-deficient Tregs are able to regulate inflammation normally when injected directly into the skin, they fail to home properly to inflamed skin. Collectively, these results suggest a key role for CD28 costimulation in promoting a central Treg to eTreg transition with appropriate upregulation of chemokine receptors such as CCR6 that are required for tissue homing.
Development of a Novel B-Cell Lymphoma 6 (BCL6) PROTAC To Provide Insight into Small Molecule Targeting of BCL6 (2018)

B-cell lymphoma 6 (BCL6) inhibition is a promising mechanism for treating hematological cancers but high quality chemical probes are necessary to evaluate its therapeutic potential. Here we report potent BCL6 inhibitors that demonstrate cellular target engagement and exhibit exquisite selectivity for BCL6 based on mass spectrometry analyses following chemical proteomic pull down. Importantly, a proteolysis-targeting chimera (PROTAC) was also developed and shown to significantly degrade BCL6 in a number of diffuse large B-cell lymphoma (DLBCL) cell lines, but neither BCL6 inhibition nor degradation selectively induced marked phenotypic response. To investigate, we monitored PROTAC directed BCL6 degradation in DLBCL OCI-Ly1 cells by immunofluorescence and discovered a residual BCL6 population. Analysis of subcellular fractions also showed incomplete BCL6 degradation in all fractions despite having measurable PROTAC concentrations, together providing a rationale for the weak antiproliferative response seen with both BCL6 inhibitor and degrader. In summary, we have developed potent and selective BCL6 inhibitors and a BCL6 PROTAC that effectively degraded BCL6, but both modalities failed to induce a significant phenotypic response in DLBCL despite achieving cellular concentrations.
Effect of LTD4 on conjunctival vasopermeability and blood-aqueous barrier integrity. (1985)

The effect of leukotriene D4 (LTD4) on the microvascular permeability of selected ocular tissues of the guinea pig was evaluated quantitatively by utilizing 125I-albumin and 51Cr-erythrocytes. Topically applied LTD4 (1 ng-10 micrograms) produced a dose-related increase in conjunctival microvascular permeability. However, topical administration of such doses of LTD4 did not promote albumin leakage into the aqueous humor or iris-ciliary body. Intravitreal injection of graded doses of LTD4 also failed to increase the albumin content of the aqueous humor and iris-ciliary body. Thus, although LTD4 increased conjunctival microvascular permeability, it does not appear to disrupt the blood-aqueous barrier of the guinea pig eye.
The erythromycin-producing polyketide synthase (1993)

Conference Article| February 01 1993 The erythromycin-producing polyketide synthase P. F. Leadlay; P. F. Leadlay 1Cambridge Centre for Molecular Recognition, Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, U.K. Search for other works by this author on: This Site PubMed Google Scholar J. Staunton; J. Staunton *University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, U.K. Search for other works by this author on: This Site PubMed Google Scholar J. F. Aparicio; J. F. Aparicio 1Cambridge Centre for Molecular Recognition, Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, U.K. Search for other works by this author on: This Site PubMed Google Scholar D. J. Bevitt; D. J. Bevitt 1Cambridge Centre for Molecular Recognition, Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, U.K. Search for other works by this author on: This Site PubMed Google Scholar P. Caffrey; P. Caffrey 1Cambridge Centre for Molecular Recognition, Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, U.K. Search for other works by this author on: This Site PubMed Google Scholar J. Cortes; J. Cortes 1Cambridge Centre for Molecular Recognition, Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, U.K. Search for other works by this author on: This Site PubMed Google Scholar A. Marsden; A. Marsden 1Cambridge Centre for Molecular Recognition, Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, U.K. Search for other works by this author on: This Site PubMed Google Scholar G. A. Roberts G. A. Roberts 1Cambridge Centre for Molecular Recognition, Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1993) 21 (1): 218–222. https://doi.org/10.1042/bst0210218 Article history Received: October 01 1992 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation P. F. Leadlay, J. Staunton, J. F. Aparicio, D. J. Bevitt, P. Caffrey, J. Cortes, A. Marsden, G. A. Roberts; The erythromycin-producing polyketide synthase. Biochem Soc Trans 1 February 1993; 21 (1): 218–222. doi: https://doi.org/10.1042/bst0210218 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 Society Transactions Search Advanced Search Keywords: ACP, acyl carrier protein, DEBS, 6-deoxyerythronolide B synthase This content is only available as a PDF. © 1993 Biochemical Society1993 Article PDF first page preview Close Modal You do not currently have access to this content.
The distributed flight array (2009)

This paper introduces the Distributed Flight Array which is being developed at ETH Zurich. This multipropeller platform consists of autonomous single-propeller modules that are able to drive, dock with their peers, and fly in a coordinated fashion. These modules are organized as distributed computational units with minimal sensory input. This is a complex system that is rich in dynamics with plenty of room to explore various distributed estimation and control strategies. Experimental demonstrations in docking, driving, and flight have proven its feasibility.
Iron-regulatory proteins secure iron availability in cardiomyocytes to prevent heart failure (2016)

ID in cardiomyocytes impairs mitochondrial respiration and adaptation to acute and chronic increases in workload. Iron supplementation restores cardiac energy reserve and function in iron-deficient hearts.
Scientific american molecular cardiovascular medicine (1995)

Arteriosclerosis - an overview lipoprotein receptors and atherosclerosis vascular endothelium in health and disease vascular cell growth and the arterial wall gene therapy for cardiovascular disease gene therapy fpr lipid disorder thrombosis thrombolytic agents antibody targeting - a strategy for improving thrombolytic therapy platelets in thrombosis and rethrombosis molecular mechanisms of cardiac hypertrophy gene mutations that cause familial hypertrphic cardiomyopathy ion channels and cardiac function molecular mechanisms in hypertension genetics of hypertension the renin-angiotensin system in human hypertension regulations of vascular tone immunobiology of transplantation the arteriosclerosis of cardiac transplantation.
Assembly of the Warfarin-sensitive Vitamin K 2,3-Epoxide Reductase Enzyme Complex in the Endoplasmic Reticulum Membrane (1997)

gamma-Carboxylation of vitamin K-dependent proteins requires a functional vitamin K cycle to produce the active vitamin K cofactor for the gamma-carboxylase which posttranslationally modifies precursors of these proteins to contain gamma-carboxyglutamic acid residues. The warfarin-sensitive enzyme vitamin K epoxide reductase (VKOR) of the cycle reduces vitamin K 2,3-epoxide to the active vitamin K hydroquinone cofactor. Because of the importance of warfarin as an anticoagulant in prophylactic medicine and as a poison in rodent pest control, numerous attempts have been made to understand the molecular mechanism underlying warfarin-sensitive vitamin K 2,3-epoxide reduction. In search for protein components that could be involved in this reaction we designed an in vitro gamma-carboxylation test system where the warfarin-sensitive VKOR produces the cofactor for the gamma-carboxylase. Dissection of this system by chromatographic techniques has identified a member(s) of the glutathione S-transferase gene family as one component of the VKOR enzyme complex in the endoplasmic reticulum membrane. The affinity-purified glutathione S-transferase(s) was sensitive to warfarin but lost its warfarin sensitivity and glutathione S-transferase activity upon association with lipids in the presence of Mn2+ or Ca2+. In the gamma-carboxylation test system, loss of warfarin-sensitive glutathione S-transferase activity coincided with formation of the VKOR enzyme complex. It is proposed that formation of VKOR in the endoplasmic reticulum membrane resembles formation of the lipoxygenase enzyme complex where the glutathione S-transferase-related FLAP protein binds cytosolic lipoxygenase to form a membrane enzyme complex.
Common acute lymphoblastic leukemia antigen (CALLA) is active neutral endopeptidase 24.11 ("enkephalinase"): direct evidence by cDNA transfection analysis. (1989)

The common acute lymphoblastic leukemia antigen (CALLA) is a 749-amino acid type II integral membrane protein expressed by most acute lymphoblastic leukemias, certain other lymphoid malignancies with an immature phenotype, and normal lymphoid progenitors. A computer search against the most recent GenBank release (no. 56) indicates that human CALLA cDNA encodes a protein nearly identical to the rat and rabbit neutral endopeptidase 24.11 ("enkephalinase;" EC 3.4.24.11). This zinc metalloendopeptidase, which has been shown to inactivate a variety of peptide hormones including enkephalin, chemotactic peptide, substance P, neurotensin, oxytocin, bradykinin, and angiotensins I and II, had not been identified in lymphoid cells. To determine whether CALLA cDNA derived from human acute lymphoblastic leukemia cells (Nalm-6 cell line) encodes functional neutral endopeptidase activity, we generated CALLA+ stable transfectants in the CALLA- murine myeloma cell line J558 and analyzed them for enzymatic activity in a fluorometric assay based upon cleavage of the substrate glutaryl-Ala-Ala-Phe 4-methoxy-2-naphthylamide at the Ala-Phe bond. Total lysates as well as whole-cell suspensions of the Nalm-6 line and of the CALLA+ transfectants, but not of the CALLA- J558 cells, possessed neutral endopeptidase activity. This enzymatic activity was associated with the cellular membrane fraction and was abrogated by the specific neutral endopeptidase inhibitor phosphoramidon. The unequivocal identification of CALLA as a functional neutral endopeptidase provides insight into its potential role in both normal and malignant lymphoid function.
Modulated expression of notch1 during thymocyte development (1996)

The Notch gene family encodes transmembrane proteins that have been implicated in control of diverse cellular differentiation events in the fly, frog, and mouse. Mammalian Notch1 is expressed at high levels in thymus and is mutated in a subset of human T-cell acute lymphoblastic neoplasms, suggesting a role in T-cell differentiation. To investigate the patterns of expression of NOTCH1 protein in thymocytes of the developing and mature thymus, antibodies raised against NOTCH1 were used to perform immunohistochemical and flow cytometric analyses. Strong staining for NOTCH1 within the fetal murine thymus was observed as early as 13.5 days postcoitum. By 17.5 days postcoitum, preferential staining of superficial cortical thymocytes was observed, with weak staining of developing medulla. Flow cytometric analysis and immunohistochemical staining of flow-sorted cells confirmed that the highest levels of NOTCH1 expression in adult murine thymus were present in immature cortical thymocytes (CD24high, CD4-CD8-). In contrast, NOTCH1 expression was low or absent in more mature cortical thymocytes (CD24low, CD4+CD8+), whereas intermediate levels of expression were observed in CD4+CD8- and CD4-CD8+ cells. These data indicate a dynamic pattern of NOTCH1 expression during T-cell differentiation and suggest that downregulation of NOTCH1 may be required for maturation of cortical thymocytes.
PTEN Deficiency in Endometrioid Endometrial Adenocarcinomas Predicts Sensitivity to PARP Inhibitors (2010)

PTEN (phosphatase and tensin homolog) loss of function is the most common genetic aberration in endometrioid endometrial carcinomas. In addition to its well-described role in cell signaling, PTEN is involved in the maintenance of genomic stability. Loss of PTEN function causes defects in repair of DNA double-strand breaks by homologous recombination and, therefore, sensitizes cells to inhibition of the poly(adenosine diphosphate ribose) polymerase (PARP). Here, we determined the PTEN status of eight endometrioid endometrial carcinoma cell lines and correlated it with in vitro sensitivity to the PARP inhibitor KU0058948. PTEN-deficient cells showed a significantly greater sensitivity to KU0058948 than the two endometrioid endometrial carcinoma cell lines with wild-type PTEN. The cell lines lacking PTEN expression were unable to elicit a homologous recombination damage response as assayed by RAD51 focus function (a marker of competent homologous recombination DNA repair) upon irradiation and treatment with PARP inhibitors. PTEN silencing in PTEN wild-type Hec-1b cells resulted in reduced RAD51 foci formation after DNA damage and increased sensitivity to PARP inhibition. PTEN reexpression in PTEN-null cell lines resulted in enhanced RAD51 foci formation and in relative resistance to KU0058948. Given that up to 80% of endometrioid endometrial cancers lack PTEN expression, our results suggest that PARP inhibitors may be therapeutically useful for a subset of endometrioid endometrial cancers.
Flexible bow-tie antennas with reduced metallization (2011)

This paper presents design, simulation, fabrication and measurement of a modified bow-tie antenna with reduced metallization. The antenna is mounted on a flexible substrate which is fabricated at the Flexible Display Center (FDC) of Arizona State University (ASU). The substrate is heat stabilized polyethylene naphthalate (PEN) which allows the antenna to be flexible. The antenna is fed by the aid of a microstrip-to-coplanar feed network balun. The reduction of the metallization is based on the observation that the majority of the current density is confined towards the edges of the regular bow-tie antenna. Hence, the centers of the triangular parts of the bow-tie antenna are removed. The radiation performance of the modified bow-tie is verified to be very close to the conventional bow-tie by simulations and measurements.
Reduction by Dissolving Metals (1955)

The reduction by sodium and ethanol, with or without liquid ammonia as solvent, of various amidines followed by acid hydrolysis, leads in many cases to a good yield of the corresponding aldehyde. Further reduction in liquid ammonia of several 2-aryl-imidazolines or imidazolidines followed by acid hydrolysis leads to the 2,5-dihydro-benzaldehyde derivative. The reduction of some acid amides by sodium and proton sources in liquid ammonia has been examined. Under the right conditions this process is of preparative value for aldehydes.
Level set based segmentation with intensity and curvature priors (2002)

A method is presented for segmentation of anatomical structures that incorporates prior information about the intensity and curvature profile of the structure from a training set of images and boundaries. Specifically the authors model the intensity distribution as a function of signed distance from the object boundary, instead of modeling only the intensity of the object as a whole. A curvature profile acts as a boundary regularization term specific to the shape being extracted, as opposed to simply penalizing high curvature. Using the prior model, the segmentation process estimates a maximum a posteriori higher dimensional surface whose zero level set converges on the boundary of the object to be segmented. Segmentation results are demonstrated on synthetic data and magnetic resonance imagery.
Universal mobile electrochemical detector designed for use in resource-limited applications (2014)

This paper describes an inexpensive, handheld device that couples the most common forms of electrochemical analysis directly to "the cloud" using any mobile phone, for use in resource-limited settings. The device is designed to operate with a wide range of electrode formats, performs on-board mixing of samples by vibration, and transmits data over voice using audio--an approach that guarantees broad compatibility with any available mobile phone (from low-end phones to smartphones) or cellular network (second, third, and fourth generation). The electrochemical methods that we demonstrate enable quantitative, broadly applicable, and inexpensive sensing with flexibility based on a wide variety of important electroanalytical techniques (chronoamperometry, cyclic voltammetry, differential pulse voltammetry, square wave voltammetry, and potentiometry), each with different uses. Four applications demonstrate the analytical performance of the device: these involve the detection of (i) glucose in the blood for personal health, (ii) trace heavy metals (lead, cadmium, and zinc) in water for in-field environmental monitoring, (iii) sodium in urine for clinical analysis, and (iv) a malarial antigen (Plasmodium falciparum histidine-rich protein 2) for clinical research. The combination of these electrochemical capabilities in an affordable, handheld format that is compatible with any mobile phone or network worldwide guarantees that sophisticated diagnostic testing can be performed by users with a broad spectrum of needs, resources, and levels of technical expertise.
Ray-based approach to integrated 3D visual communication (2001)

For a high sense of reality in the next-generation communications, it is very important to realize three-dimensional (3D) spatial media, instead of existing 2D image media. In order to comprehensively deal with a variety of 3D visual data formats, the authors first introduce the concept of ”Integrated 3D Visual Communication,” which reflects the necessity of developing a neutral representation method independent of input/output systems. Then, the following discussions are concentrated on the ray-based approach to this concept, in which any visual sensation is considered to be derived from a set of light rays. This approach is a simple and straightforward to the problem of how to represent 3D space, which is an issue shared by various fields including 3D image communications, computer graphics, and virtual reality. This paper mainly presents the several developments in this approach, including some efficient methods of representing ray data, a real-time video-based rendering system, an interactive rendering system based on the integral photography, a concept of virtual object surface for the compression of tremendous amount of data, and a light ray capturing system using a telecentric lens. Experimental results demonstrate the effectiveness of the proposed techniques.
Use of a Microcavity Mode in Porous Silicon Superlattice to Enhance Band Intensities in Vibrational Spectra (1999)

We have used a Fabry-Perot type microcavity in porous silicon layered structures to enhance vibrational band intensities in infrared (IR) and Raman spectra. Parameters of the layers in the structure were chosen to have the cavity mode in the spectral region of adsorbate vibrational bands for the IR measurements and near a visible laser wavelength in the Raman experiment. In the IR spectra the enhancement achieved more than one order of magnitude due to photon confinement in the microcavity acting like a multipass cell. In the Raman experiment the enhancement factor of the band intensity was larger than 30. The obtained enhancement was due to the coupling of both laser radiation and Stokes photons of porous silicon with the cavity mode at optimal laser beam incidence and scattering angles.