gebhart/patrepeval huggingface dataset:
STAT6 Inhibits TGF-β1-mediated Foxp3 Induction through Direct Binding to the Foxp3 Promoter, Which Is Reverted by Retinoic Acid Receptor (2008)

It has been shown that transforming growth factor beta1 (TGF-beta1) is critical in the generation of CD4(+)CD25(+)Foxp3(+)-inducible regulatory T cells (iTregs) from naïve CD4(+)T cells. However, in contrast to natural Tregs, TGF-beta1-induced iTregs rapidly lose both Foxp3 expression and suppression activity. We found that TGF-beta1-induced Foxp3 levels were maintained by the addition of the anti-interleukin 4 (IL-4) antibody or by STAT6 gene deletion. Thus, IL-4 is an important suppressor of Foxp3 induction, and T helper 2 development is a major cause for the disappearance of iTreg during long culture. Using promoter analysis in EL4 cells and primary T cells, we identified a silencer region containing a STAT6 binding site. STAT6 binding to this site reduced TGF-beta1-mediated Foxp3 promoter activation and chromatin modification. Retinoic acid has also been shown to suppress loss of Foxp3 induced by TGF-beta1. Retinoic acid in the presence of TGF-beta1 reduced STAT6 binding to the Foxp3 promoter and enhanced histone acetylation, thereby reverting the effect of IL-4. We propose that antagonistic agents for neutralizing IL-4 could be a novel strategy to facilitate inducible Treg cell generation and the promotion of tolerance in Th2-dominated diseases such as allergy.
Linkage Disequilibrium and Physical Mapping of Pas1 in Mice (1999)

By using linkage disequilibrium (LD) analysis in 21 strains of known susceptibility to lung cancer and by assembling a YAC contig, we mapped to a approximately 1.5-Mb region on distal mouse chromosome 6 the Pas1 locus, the major determinant of lung cancer predisposition in mice. Our results, on the basis of haplotype and phenetic analysis, suggest that the Pas1(s) susceptibility allele is shared by several mouse-inbred strains of independent origin, which show either high or intermediate predisposition to lung tumorigenesis. Therefore, the Pas1(s) allele is probably derived from an ancestral mouse rather than from independent mutations of the same gene. We showed the feasibility of LD in common inbred strains for the fine mapping of disease loci, and provided the biological basis and the reagents for the cloning of the Pas1 gene.
Twenty two novel mutations of the factor VII gene in factor VII deficiency (2000)

Factor VII is a vitamin K-dependent coagulation protease essential for the initiation phase of normal hemostasis. The human factor VII gene (FVII, also known as F7) spans 13 kb and is located on chromosome 13, 2.8 kb upstream of the factor X gene. In the Greifswald FVII deficiency study the molecular basis for inherited factor VII was investigated. All exons, exon-intron boundaries and the promotor of the FVII gene were amplified by PCR and directly sequenced. 87 unrelated probands with reduced or low FVII activities were investigated. Thirty-four different FVII gene lesions were analyzed in 101 FVII alleles of 77 unrelated probands. Twenty-two of these FVII gene lesions are novel FVII variations. The 34 different lesions comprise 31 point mutations and three small deletions. A transition in the CpG doublet accounted for 12 of the 34 different mutants. Sixteen mutations were noted only once. The missense mutation A294V and the double mutation A294V; 11128delC in exon 8 were by far the most common mutations found in this study. The haplotype of the different mutant FVII alleles were analyzed using six polymorphisms of the FVII gene. The haplotypes were identified in 29 mutant FVII alleles. Five different haplotypes are linked to the mutant FVII alleles. Except for one, the same haplotype was detected in FVII genes with an identical FVII gene mutation. Different haplotypes were identified in two patients with the mutant allele A206T. It is likely that identical mutant FVII alleles with the same haplotype share the same origin. Hum Mutat 15:489–496, 2000. © 2000 Wiley-Liss, Inc.
Recent developments in RNA-based strategies for cancer gene therapy. (2001)

The introduction of RNA into mammalian cells is a relatively straightforward procedure with many therapeutic applications. An advantage of using mRNA is that protein expression can be achieved in post-mitotic or quiescent cells where there is usually little or no gene expression with non-viral DNA delivery systems. Furthermore, the cleavage of mRNA by catalytic RNA molecules, or ribozymes, is a useful strategy to downregulate aberrant gene expression. The purpose of this review is to provide an update of current applications that use RNA molecules such as mRNA and ribozymes as a basis for gene therapy strategies targeting the initiation and progression of cancer. In particular, we focus on recent developments that improve the delivery and stability of RNA molecules to achieve therapeutic efficacy.
Thermal decomposition of three crystalline modifications of anhydrous copper(II) formate (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThermal decomposition of three crystalline modifications of anhydrous copper(II) formateA. K. Galwey, D. Jamieson, and M. E. BrownCite this: J. Phys. Chem. 1974, 78, 26, 2664–2670Publication Date (Print):December 19, 1974Publication History Published online16 June 2008Published inissue 19 December 1974https://pubs.acs.org/doi/10.1021/j100619a006https://doi.org/10.1021/j100619a006research-articleACS PublicationsRequest reuse permissionsArticle Views815Altmetric-Citations83LEARN 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 options Get e-Alerts
Photodamage to human RPE cells by A2-E, a retinoid component of lipofuscin. (2000)

A2-E is detrimental to RPE cell function by a variety of mechanisms: inhibition of lysosomal degradative capacity, loss of membrane integrity, and phototoxicity. Such mechanisms could contribute to retinal aging as well as retinal diseases associated with excessive lipofuscin accumulation-for example, age-related macular degeneration and Stargardt's disease.
Aequorea green fluorescent protein (1994)

Expression of the cDNA for Aequorea green fluorescent protein in E. coli yielded a fused protein with fluorescence excitation and emission spectra virtually identical to those of the native green fluorescent protein. Further, a solution of the protein, when mixed with aequorin and calcium ion, emitted a greenish luminescence characteristic of the in vivo luminescence of the animal, indicating a radiationless energy transfer to the protein.
Attenuated Shigella as a DNA Delivery Vehicle for DNA-Mediated Immunization (1995)

Direct inoculation of DNA, in the form of purified bacterial plasmids that are unable to replicate in mammalian cells but are able to direct cell synthesis of foreign proteins, is being explored as an approach to vaccine development. Here, a highly attenuated Shigella vector invaded mammalian cells and delivered such plasmids into the cytoplasm of cells, and subsequent production of functional foreign protein was measured. Because this Shigella vector was designed to deliver DNA to colonic mucosa, the method is a potential basis for oral and other mucosal DNA immunization and gene therapy strategies.
Endoplasmic Reticulum-Localized Human Papillomavirus Type 16 E5 Protein Alters Endosomal pH but Not trans -Golgi pH (2005)

The human papillomavirus type 16 (HPV-16) E5 protein is a small, hydrophobic polypeptide that is expressed in virus-infected keratinocytes and alters receptor signaling pathways, apoptotic responses, and endosomal pH. Despite its ability to inhibit endosomal acidification, the HPV-16 E5 protein is found predominantly in the endoplasmic reticulum (ER), suggesting that its effect may be indirect and perhaps global. To determine whether E5 alters the pHs of additional intracellular compartments, we transduced human keratinocytes with a codon-optimized E5 vector and then quantified endosomal and trans-Golgi pHs using sensitive, compartment-specific, ratiometric pHluorin constructs. E5 protein increased endosomal pH from 5.9 to 6.9 but did not affect the normal trans-Golgi pH of 6.3. Confirming the lack of alteration in trans-Golgi pH, we observed no alterations in the acidification-dependent processing of the proH3 protein. C-terminal deletions of E5, which retained normal expression and localization in the ER, were defective for endosomal alkalization. Thus, E5 does not uniformly alkalinize intracellular compartments, and its C-terminal 10 amino acids appear to mediate interactions with critical ER targets that modulate proton pump function and/or localization.
A prototype computer system for de novo protein design (1994)

Conference Article| November 01 1994 A prototype computer system for de novo protein design A. Berry; A. Berry ‡ *Cambridge Centre for Molecular Recognition, Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, U.K. *To whom correspondence should be addressed. Present address: Department of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, U.K. Search for other works by this author on: This Site PubMed Google Scholar S. E. Brenner S. E. Brenner *Cambridge Centre for Molecular Recognition, Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, U.K.†M.R.C. Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1994) 22 (4): 1033–1036. https://doi.org/10.1042/bst0221033 Article history Received: July 07 1994 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 A. Berry, S. E. Brenner; A prototype computer system for de novo protein design. Biochem Soc Trans 1 November 1994; 22 (4): 1033–1036. doi: https://doi.org/10.1042/bst0221033 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 © 1994 Biochemical Society1994 Article PDF first page preview Close Modal You do not currently have access to this content.
Biotechnology of Antibiotics (1997)

Introduction and Approaches for Improvement in Antibiotic Production Aminoglycosides Template-Biosynthesized Peptide and b-Lactam Antibiotics Ribosomally Synthesized Peptide Antibiotics Polyketide Antibiotics Produced by Type-I Multifunctional Enzymes Polyketide Antibiotics Produced by Type-II Polyketide Synthase Systems Peptydil Nucleoside Antibiotics Recombinant Bioconversions of Bioactive Molecules
pH and brain function (1998)

Partial table of contents: INTRODUCTION TO PH. Principles and Practical Aspects of pH Buffering (M. Chesler). Cerebral Energy Metabolism and pH (P. Mellergard & B. Siesjo). METHODS OF STUDYING PH. Absorbance pH Indicators (J. LaManna & K. Lauro). Fluorescence Indicators (M. Bevensee & W. Boron). CELLULAR MECHANISMS OF PH REGULATION. pH Regulation in Invertebrate Glia (J. Deitmer). pH Regulation in Mammalian Glia (C. Rose & B. Ransom). ACTIVITY--INDUCED CHANGES IN PH. Activity--Evoked Changes in Intracellular pH (K. Ballanyi & K. Kaila). pH Changes Associated with Glutamate Uptake (A. Amato, et al.). PH MODULATION OF NEURAL ACTIVITY. Proton--Gated Ion Channels in Neurons (S. Bevan). Modulation of Vertebrate Retinal Function by pH (S. Barnes). PH CONTROL OF RESPIRATION. Central Chemoreceptors, pH, and Respiratory Control (E. Nattie). PH AND PATHOPHYSIOLOGY OF THE NERVOUS SYSTEM. Acid--Base Metabolism in Ischemia (K. Katsura & B. Siesjo). Brain Edema and pH (H. Kimelberg & P. Feustel). Index.
On the security of multiple encryption (1981)

Double encryption has been suggested to strengthen the Federal Data Encryption Standard (DES). A recent proposal suggests that using two 56-bit keys but enciphering 3 times (encrypt with a first key, decrypt with a second key, then encrypt with the first key again) increases security over simple double encryption. This paper shows that although either technique significantly improves security over single encryption, the new technique does not significantly increase security over simple double encryption. Cryptanalysis of the 112-bit key requires about 2 56 operations and words of memory, using a chosen plaintext attack. While DES is used as an example, the technique is applicable to any similar cipher.
CFTR Chloride Channel Drug Discovery - Inhibitors as Antidiarrheals and Activators for Therapy of Cystic Fibrosis (2006)

The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a cAMP-activated chloride channel expressed in epithelia in the lung, intestine, pancreas, testis and other tissues, where it facilitates transepithelial fluid transport. In the intestine CFTR provides the major route for chloride secretion in certain diarrheas. Mutations in CFTR cause the hereditary disease cystic fibrosis, where chronic lung infection and deterioration in lung function cause early death. CFTR is a well-validated targeted for development of inhibitors for therapy of secretory diarrheas and activators for therapy in cystic fibrosis. Our lab has identified and optimized small molecule inhibitors of CFTR, as well as activators of DeltaF508-CFTR, the most common mutant CFTR causing cystic fibrosis. High-throughput screening of small molecule collections utilizing a cell-based fluorescence assay of halide transport yielded thiazolidinone and glycine hydrazide CFTR inhibitors that block enterotoxin-mediated secretory diarrhea in rodent models, including a class of non-absorbable inhibitors that target the CFTR pore at its external entrance. Benzothiophene, phenylglycine and sulfonamide potentiators were identified that correct the defective gating of DeltaF508-CFTR chloride channels, and other small molecules that correct its defective cellular processing. Small molecule modulators of CFTR function may be useful in the treatment of cystic fibrosis, secretory diarrhea and polycystic kidney disease.
Modulation of Gut Microbiota–Brain Axis by Probiotics, Prebiotics, and Diet (2015)

There exists a bidirectional communication system between the gastrointestinal tract and the brain. Increasing evidence shows that gut microbiota can play a critical role in this communication; thus, the concept of a gut microbiota and brain axis is emerging. Here, we review recent findings in the relationship between intestinal microbes and brain function, such as anxiety, depression, stress, autism, learning, and memory. We highlight the advances in modulating brain development and behavior by probiotics, prebiotics, and diet through the gut microbiota-brain axis. A variety of mechanisms including immune, neural, and metabolic pathways may be involved in modulation of the gut microbiota-brain axis. We also discuss some future challenges. A deeper understanding of the relationship between the gut bacteria and their hosts is implicated in developing microbial-based therapeutic strategies for brain disorders.
Critical Role of Interleukin-11 in Isoflurane-mediated Protection against Ischemic Acute Kidney Injury in Mice (2013)

In this study, the authors suggest that isoflurane induces renal tubular IL-11 via TGF-β1 signaling to protect against ischemic acute kidney injury.
Claudins upregulation in human colorectal cancer (2005)

In colorectal cancer tight junction molecular and morphological alterations are poorly understood. In this study, adenocarcinoma tissues and their paired normal mucosa (n = 12) were analyzed for tight junction alterations molecular. The expression of claudin-1, -3 and -4 was upregulated 5.7-, 1.5- and 2.4-fold, respectively, in colorectal tumor tissues in comparison to the normal ones. Although tight junction remains in the cancerous epithelium, its barrier function was altered. Despite claudins overexpression, paracellular permeability to ruthenium red was increased and a significant disorganization of tight junction strands was observed in freeze fracture replicas. Whereas the functional significance of claudin overexpression in colorectal cancer is unclear, these proteins can become potential markers and targets in colorectal cancer.
The Stochastic Nature of Cardiac Propagation at a Microscopic Level (1995)

The object of this study is to present evidence that the myocardial architecture creates inhomogeneities of electrical load at the cellular level that cause cardiac propagation to be stochastic in nature; ie, the excitatory events during propagation are constantly changing and disorderly in the sense of varying intracellular events and delays between cells. At a macroscopic level, however, these stochastic events become averaged and appear consistent with a continuous medium. We examined this concept in a two-dimensional (2D) model of myocardial architecture by exploring whether experimentally observed Vmax variability reflected different patterns of intracellular excitation events and junctional delays. The patterns of Vmax variability at randomly chosen intracellular sites were similar experimentally and in the 2D model. The 2D cellular model produced marked variability in gap junction delays; however, on the average, different gap junctions were used for cell-to-cell charge flow during conduction in different directions. During longitudinal propagation (LP), the velocity increased from the proximal to the distal end of each myocyte, and Vmax was lowest proximally, increased to a maximum at the distal fourth of the cell, and decreased distally. Transverse propagation (TP) produced rapid intracellular conduction with variable intracellular excitation sequences. TP Vmax was greater than LP Vmax in most subcellular regions, but near the ends of some myocytes, a reversed "TP > LP Vmax" relation occurred. Total charge carried by the sodium current varied inversely with Vmax, demonstrating feedback effects of cellular loading on the subcellular sodium current and the kinetics of the sodium channels. The results suggest that the stochastic nature of normal propagation at a microscopic level provides a considerable protective effect against arrhythmias by reestablishing the general trend of wave-front movement after small variations in excitation events occur.
Further additions to MolScript version 1.4, including reading and contouring of electron-density maps (1999)

MolScript is one of the most popular programs for the generation of publication-quality figures and the recent re-working of the program should ensure its continued popularity. However, some functionality of particular interest to crystallographers is not part of the standard program. A modified MolScript version 1.4 has been described previously, with more flexible colouring schemes among its new features. This report describes further enhancements to MolScript version 1.4, including facilities for drawing rods for helices and ribbons for oligonucleotides and allowing several formats of electron-density maps to be read and contoured using either lines or smoothed triangulated surfaces.
The v-Src SH3 domain binds phosphatidylinositol 3'-kinase. (1993)

Fibroblasts transformed by v-src or by related oncogenes encoding activated tyrosine kinases contain elevated levels of polyphosphoinositides with phosphate at the D-3 position of the inositol ring, as a result of the activation of phosphatidylinositol (PI) 3'-kinase. v-src-transformed cells also contain increased levels of PI 3'-kinase activity immunoprecipitable with anti-phosphotyrosine antibodies; furthermore, PI 3'-kinase can be detected in association with the v-Src tyrosine kinase. To identify regions of v-Src that can interact with PI 3'-kinase, the v-Src SH2 and SH3 domains were expressed in bacteria and incubated with lysates of normal chicken embryo fibroblasts. In vitro, the v-Src SH3 domain, but not the SH2 domain, bound PI 3'-kinase in lysates of uninfected chicken embryo fibroblasts. Substitutions of two highly conserved SH3 residues implicated in ligand binding abolished the ability of the v-Src SH3 domain to associate with PI 3'-kinase. Furthermore, the v-Src SH3 domain bound in vitro to the amino-terminal region of the p85 alpha subunit of PI 3'-kinase. These results suggest that the v-Src SH3 domain may mediate an interaction between the v-Src tyrosine kinase and PI 3'-kinase, by direct binding to p85.
Microchannel-pinhole parameters investigation for cells visualization in holographic microscopy (2011)

Here we propose a compact system built around a microchannel aiming to analyze individual blood cells (BCs), using digital in-line holographic microscopy (DIHM). Under the constraints of achieving maximum resolution for BC images, the study is focused on analytical investigations of the main elements constructive dimensions and the distances between them. In the simulations, we used models of oblate spheroids for BC shapes. The iso-intensity curves in the diffraction pattern of the BCs which flow in the microchannel at different distances are studied and the technically possible dimensions were selected to record the signal from one BC.
Laser skin resurfacing (1996)

There has always been interest in looking younger, but recently there seems to have been an explosion of public interest in facial rejuvenation. Physicians have been treating photodamaged skin for many years by removing the epidermis and a variable thickness of dermis with dermabrasion or chemical peels, with the expectation that reepithialization and collagen remodeling will result in a more youthful appearance. With the recent development of short-pulsed high-peak power and rapidly scanned carbon dioxide (CO2) lasers, the ability to remove photodamaged skin in a precise and reproducible manner while leaving behind a narrow zone of thermal damage has been achieved. This development has generated tremendous interest in laser skin resurfacing as a technique to reverse photoaging.
<title>Video I/O interface for wearable computers</title> (1999)

This paper is a report of work in progress toward the development and testing of a computer interface mounted in eyewear, and capable of both input and output functions. The unique feature of this interface is the use of advanced embedded optical techniques to form eyeglass lenses capable of relaying images internally, without significant optical components in front of the user's face. These optical techniques make possible the incorporation of both a camera and display within eyeglasses. The interface also includes audio input and output. The paper discusses methods of constructing such an interface, design considerations, and will describe work in progress to realize working models.