gebhart/patrepeval huggingface dataset:
Tumor rejection requires a CTLA4 ligand provided by the host or expressed on the tumor: superiority of B7-1 over B7-2 for active tumor immunization (1996)

Although transfection to express any of a multitude of immunomodulatory molecules can lead to the rejection of murine tumors in vivo, it is not clear which of these cofactors are truly important for the induction of tumor-specific CTL. Examination of the costimuli used by the host immune response during the normal rejection of immunogenic tumors should reveal critical cofactors for CTL differentiation in vivo. The involvement of a host B7 family costimulator molecule in the rejection of immunogenic tum- variants of the mastocytoma P815 was explored. Rejection of immunogenic P815 variants was prevented by mCTLA4 gamma 3, a fusion protein between the extracellular domain of murine CTLA4 and the Fc portion of a murine IgG3 Ab, indicating the importance of a CTLA4 ligand provided by the host in the rejection of B7- tumors. Tumor rejection also was prevented by mCTLA4 gamma 3 in the absence of CD4+ cells, suggesting that CD8+ lymphocytes may receive direct costimulation by B7 in vivo. Finally, although living transfectants of poorly immunogenic P1.HTR cells expressing B7-1 or B7-2 were equally rejected by syngeneic mice, if delivered as multiple injections of irradiated cells, only B7-1 transfectants successfully induced CTL activity and protected against living tumor challenge. Our results indicate that a CTLA4 ligand is normally involved in the generation of CD8+ CTL against tumor Ag and suggest that immunization with irradiated B7-1-transfected tumor cells may be superior to immunization with irradiated B7-2 transfectants as an approach to tumor Ag vaccination in patients.
Substantial Alterations of the Cutaneous Bacterial Biota in Psoriatic Lesions (2008)

For psoriasis, an idiopathic inflammatory disorder of the skin, the microbial biota has not been defined using cultivation-independent methods. We used broad-range 16S rDNA PCR for archaea and bacteria to examine the microbiota of normal and psoriatic skin. From 6 patients, 19 cutaneous samples (13 from diseased skin and 6 from normal skin) were obtained. Extracted DNA was subjected to the broad range PCR, and 1,925 cloned products were compared with 2,038 products previously reported from healthy persons. Using 98% sequence identity as a species boundary, 1,841 (95.6%) clones were similar to known bacterial 16S rDNA, representing 6 phyla, 86 genera, or 189 species-level operational taxonomic unit (SLOTU); 84 (4.4%) clones with <98% identity probably represented novel species. The most abundant and diverse phylum populating the psoriatic lesions was Firmicutes (46.2%), significantly (P<0.001) overrepresented, compared to the samples from uninvolved skin of the patients (39.0%) and healthy persons (24.4%). In contrast, Actinobacteria, the most prevalent and diverse phylum in normal skin samples from both healthy persons (47.6%) and the patients (47.8%), was significantly (P<0.01) underrepresented in the psoriatic lesion samples (37.3%). Representation of Propionibacterium species were lower in the psoriatic lesions (2.9+/-5.5%) than from normal persons (21.1+/-18.2%; P<0.001), whereas normal skin from the psoriatic patients showed intermediate levels (12.3+/-21.6%). We conclude that psoriasis is associated with substantial alteration in the composition and representation of the cutaneous bacterial biota.
A secure and reliable bootstrap architecture (2002)

In a computer system, the integrity of lower layers is typically treated as axiomatic by higher layers. Under the presumption that the hardware comprising the machine (the lowest layer) is valid, the integrity of a layer can be guaranteed if and only if: (1) the integrity of the lower layers is checked and (2) transitions to higher layers occur only after integrity checks on them are complete. The resulting integrity "chain" inductively guarantees system integrity. When these conditions are not met, as they typically are not in the bootstrapping (initialization) of a computer system, no integrity guarantees can be made, yet these guarantees are increasingly important to diverse applications such as Internet commerce, security systems and "active networks". In this paper, we describe the AEGIS architecture for initializing a computer system. It validates integrity at each layer transition in the bootstrap process. AEGIS also includes a recovery process for integrity check failures, and we show how this results in robust systems.
A Single Amino Acid Substitution in the Envelope Protein of Chimeric Yellow Fever-Dengue 1 Vaccine Virus Reduces Neurovirulence for Suckling Mice and Viremia/Viscerotropism for Monkeys (2004)

A chimeric yellow fever-dengue 1 (ChimeriVax-DEN1) virus was produced by the transfection of Vero cells with chimeric in vitro RNA transcripts. The cell culture supernatant was subjected to plaque purification for the identification of a vaccine candidate without mutations. Of 10 plaque-purified clones, 1 containing no mutation (clone J) was selected for production of the vaccine virus. During subsequent cell culture passaging of this clone for vaccine production, a single amino acid substitution (K to R) occurred in the envelope (E) protein at residue 204 (E204) (F. Guirakhoo, K. Pugachev, Z. Zhang, G. Myers, I. Levenbook, K. Draper, J. Lang, S. Ocran, F. Mitchell, M. Parsons, N. Brown, S. Brandler, C. Fournier, B. Barrere, F. Rizvi, A. Travassos, R. Nichols, D. Trent, and T. Monath, J. Virol. 78:4761-4775, 2004). The same mutation was observed in another clone (clone E). This mutation attenuated the virus in 4-day-old suckling mice inoculated by the intracerebral (i.c.) route and led to reduced viremia in monkeys inoculated by the subcutaneous or i.c. route. The histopathology scores of lesions in the brain tissue of monkeys inoculated with either the E204K or E204R virus were reduced compared to those for monkeys inoculated with the reference virus, a commercial yellow fever 17D vaccine (YF-VAX). Both viruses grew to significantly lower titers than YF-VAX in HepG2, a human hepatoma cell line. After intrathoracic inoculation into mosquitoes, both viruses grew to a similar level as YF-VAX, which was significantly lower than that of their wild-type DEN1 parent virus. A comparison of the E-protein structures of nonmutant and mutant viruses suggested the appearance of new intramolecular bonds between residues 204R, 261H, and 257E in the mutant virus. These changes may be responsible for virus attenuation through a change in the pH threshold for virus envelope fusion with the host cell membrane.
Tumor suppressor activity of the human consensus type I interferon gene. (1995)

Type I interferons have potent antiproliferative activity both in vitro and in vivo, and their tumor suppressor activity has been suggested. A series of eukaryotic vectors containing a synthetic human consensus type I interferon gene (IFN-con1) under the control of different promoters (cytomegalovirus early promoter, murine metallothionein promoter and the Rous sarcoma virus LTR) were constructed and stably transfected into type I IFN-deficient myelogenous leukemic K562 cells. Constitutive expression of IFNcon1 reverted the malignant phenotype, as indicated by loss of tumorgenicity in nude mice. When stably transformed cells were mixed with parental tumor cells, there was retardation of tumor growth. Constitutive expression of IFNcon1 reverted the malignant phenotype in vitro, as indicated by growth inhibition in culture, and reduction in colony formation on soft agar. Furthermore, IFNcon1 gene expression resulted in elevated erythroid differentiation, growth arrest in S phase and induced apoptosis. Thus the presence of an active IFNcon1 gene overcomes the oncogenic potential of K562 by coordinated modulation of cell proliferation, differentiation and programmed cell death, and it acts as a tumor suppressor in vivo.
Intraocular DHODH-inhibitor PP-001 suppresses relapsing experimental uveitis and cytokine production of human lymphocytes, but not of RPE cells (2018)

For the first time, intravitreal injection of PP-001 demonstrated an effective, but transient reduction of relapses in the rat EAU model. In vitro PP-001 suppressed proliferation and cytokine/chemokine secretion of human lymphocytes, while neither human RPE cell line ARPE-19 nor primary RPE cells were affected.
Detection of pancreatic cancer using antibody microarray‐based serum protein profiling (2008)

The driving force behind oncoproteomics is to identify protein signatures that are associated with a particular malignancy. Here, we have used a recombinant scFv antibody microarray in an attempt to classify sera derived from pancreatic adenocarcinoma patients versus healthy subjects. Based on analysis of nonfractionated, directly labeled, whole human serum proteomes we have identified a protein signature based on 19 nonredundant analytes, that discriminates between cancer patients and healthy subjects. Furthermore, a potential protein signature, consisting of 21 protein analytes, could be defined that was shown to be associated with cancer patients having a life expectancy of <12 months. Taken together, the data suggest that antibody microarray analysis of complex proteomes will be a useful tool to define disease associated protein signatures.
Role of Endogenous Endonucleases and Tissue Site in Transfection and CpG-Mediated Immune Activation after Naked DNA Injection (1999)

DNA degradation is a fundamental problem for any gene therapy or genetic immunization approach, since destruction of incoming genes translates into loss of gene expression. To characterize the biology of DNA degradation after naked DNA injection, the location and levels of tissue nucleases were assessed. Extracts from the serum, kidney, and liver of mice had high levels of calcium-dependent endonuclease activity. High levels of acidic endonuclease activity were identified in the spleen, liver, kidney, and skin with little activity in skeletal or cardiac muscle. Relatively little exonuclease activity was observed in any tissue. The presence of endonucleases in the skin and muscle mediated degradation of 99% of naked DNA within 90 min of injection. This degradation most likely occurred in the extracellular space upstream of other cellular events. Despite this massive destruction, gross tissue nuclease levels did not determine skin-to-muscle transfection efficiency, or site-to-site transfection efficiency in the skin. While gross tissue nuclease levels do not appear to determine differences in transfection efficiency, the presence of robust tissue nuclease activity still necessitates that massive amounts of DNA be used to overcome the loss of 99% of expressible DNA. In addition to destroying genes, the nucleases may play a second role in genetic immunization by converting large plasmids into small oligonucleotides that can be taken up more easily by immune cells to stimulate CpG-dependent Th1 immune responses. For genetic immunization, vaccine outcome may depend on striking the right balance of nuclease effects to allow survival of sufficient DNA to express the antigen, while concomitantly generating sufficient amounts of immunostimulatory DNA fragments to drive Th1 booster effects. For gene therapy, all nuclease effects would appear to be negative, since these enzymes destroy gene expression while also stimulating cellular immune responses against transgene-modified host cells.
Interaction of metal ions with polynucleotides and related compounds. XII. The relative effect of various metal ions on DNA helicity (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInteraction of metal ions with polynucleotides and related compounds. XII. The relative effect of various metal ions on DNA helicityGunther L. Eichhorn and Yong Ae ShinCite this: J. Am. Chem. Soc. 1968, 90, 26, 7323–7328Publication Date (Print):December 1, 1968Publication History Published online1 May 2002Published inissue 1 December 1968https://pubs.acs.org/doi/10.1021/ja01028a024https://doi.org/10.1021/ja01028a024research-articleACS PublicationsRequest reuse permissionsArticle Views1824Altmetric-Citations490LEARN 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
Technology of silicon nano- and microelectrode arrays for pollution control (2002)

A very simple fabrication technology for a new electrode array architecture with metal/dielectric pyramidal nanostructures and disk microstructures on silicon is described. This working electrode is intended for measurements and detection of metallic traces in liquid media.
Multimodal chromatography: An efficient tool in downstream processing of proteins (2012)

Chromatography has become an indispensable tool for the purification of proteins. Since the regulatory demands on protein purity are expected to become stricter, the need for generating improved resins for chromatographic separations has increased. More advanced scientific investigations of protein structure/function relationships, in particular, have also been a driving force for generating more sophisticated chromatographic materials for protein separations. As a consequence, the development of alternative chromatographic strategies has been very rapid during the past decade and several new ligands have been designed and explored both in the laboratory and in large-scale industrial settings. This review describes some of these efforts using multimodal chromatography, where two or more physicochemical properties are used to enhance the specificity of the interactions between the protein and the ligand on the chromatographic matrix. In addition to experimental studies, computer modeling of ligand-protein binding has improved the design of ligands for protein recognition. The use of descriptors as well as in silico docking methods have been implemented to design multimodal resins in several instances.
Modeling hippocampal and neocortical contributions to recognition memory: A complementary-learning-systems approach. (2003)

The authors present a computational neural-network model of how the hippocampus and medial temporal lobe cortex (MTLC) contribute to recognition memory. The hippocampal component contributes by recalling studied details. The MTLC component cannot support recall, but one can extract a scalar familiarity signal from MTLC that tracks how well a test item matches studied items. The authors present simulations that establish key differences in the operating characteristics of the hippocampal-recall and MTLC-familiarity signals and identify several manipulations (e.g., target-lure similarity, interference) that differentially affect the 2 signals. They also use the model to address the stochastic relationship between recall and familiarity and the effects of partial versus complete hippocampal lesions on recognition.
Incremental validation of XML documents (2004)

We investigate the incremental validation of XML documents with respect to DTDs, specialized DTDs, and XML Schemas, under updates consisting of element tag renamings, insertions, and deletions. DTDs are modeled as extended context-free grammars. "Specialized DTDs" allow the decoupling of element types from element tags. XML Schemas are abstracted as specialized DTDs with limitations on the type assignment. For DTDs and XML Schemas, we exhibit an O ( m log n ) incremental validation algorithm using an auxiliary structure of size O ( n ), where n is the size of the document and m the number of updates. The algorithm does not handle the incremental validation of XML Schema wrt renaming of internal nodes, which is handled by the specialized DTDs incremental validation algorithm. For specialized DTDs, we provide an O ( m log 2 n ) incremental algorithm, again using an auxiliary structure of size O ( n ). This is a significant improvement over brute-force re-validation from scratch.We exhibit a restricted class of DTDs called local that arise commonly in practice and for which incremental validation can be done in practically constant time by maintaining only a list of counters. We present implementations of both general incremental validation and local validation on an XML database built on top of a relational database.Our experimentation includes a study of the applicability of local validation in practice, results on the calibration of parameters of the auxiliary data structure, and results on the performance comparison between the general incremental validation technique, the local validation technique, and brute-force validation from scratch.
Regular expressions for language engineering (1996)

Many of the processing steps in natural language engineering can be performed using finite state transducers. An optimal way to create such transducers is to compile them from regular expressions. This paper is an introduction to the regular expression calculus, extended with certain operators that have proved very useful in natural language applications ranging from tokenization to light parsing. The examples in the paper illustrate in concrete detail some of these applications.
Focal Subnuclear Distribution of Progesterone Receptor Is Ligand Dependent and Associated with Transcriptional Activity (2006)

The progesterone receptor (PR) is a critical mediator of progesterone action in the female reproductive system. Expressed in the human as two proteins, PRA and PRB, the receptor is a ligand-activated nuclear transcription factor that regulates transcription by interaction with protein cofactors and binding to specific response elements in target genes. We previously reported that PR was located in discrete subnuclear foci in human endometrium. In this study, we investigated the role of ligand in the formation of PR foci and their association with transcriptional activity. PR foci were detected in mouse uterus and normal human breast tissues and were more abundant when circulating progesterone was high. In human malignant tissues, PR foci were aberrant: foci were larger in endometrial cancers than in normal endometrium, and in breast cancers hormone-dependence was decreased. Chromatin disruption also increased foci size and decreased ligand dependence, suggesting that altered nuclear architecture may contribute to the aberrant PR foci observed in endometrial and breast cancers. In breast cancer cells, movement of PR into foci required exposure to ligand and was blocked by transcriptional inhibitors and by prolonged inhibition of proteasomal degradation. Foci contained PR dimers, and fluorescence resonance energy transfer demonstrated that PR foci contained the highest concentration of receptor dimers in the nucleus. PR in foci colocalized with transcription factors and nascent RNA transcripts only in the presence of ligand, and inhibition of coactivator recruitment inhibited PR foci formation. The demonstration that focal distribution of PR within the nucleus is associated with transcription suggests a link between the subnuclear distribution of PR and its transcriptional activity that is likely to be important for normal cellular function of PR.
Effectiveness of a topical salve (Dynexan) on pain sensitivity and early wound healing following nonsurgical periodontal therapy. (2007)

The purpose of the present study was to evaluate clinically the effect of an anaesthetic gel (lidocaine 20 mg/g as active agent) on pain sensitivity and early wound healing following nonsurgical periodontal therapy. A total of 40 patients with chronic periodontitis were enrolled in this randomized, split-mouth, double-blind, placebo-controlled clinical trial. Each subject had 3 sites in each of 2 contra-lateral jaw quadrants with a probing pocket depth (PPD) of > or = 5 mm and bleeding on probing (BOP+). All experimental sites received scaling and root planing without local anesthesia followed by irrigation with sterile saline and assessment of pain sensitivity using a standardized Visual Analogue Scale (VAS). After treatment, the patients randomly received the active or placebo gel into the periodontal pockets and overall pain was again assessed immediately after debridement and after 10, 20 and 30 minutes. The VAS showed a statistically significant (p < or = 0.0001) reduction in reported pain, favoring the active gel over the placebo at all 3 different points in time. After 30 minutes the median VAS score was 0.3 in the Dynexan group as opposed to 1.7 in the placebo-treated group (p < or = 0.0001). In terms of wound healing no differences were found between the test and control sites after 1 week. The results of the study showed that the anaesthetic gel was statistically more effective than the placebo in reducing pain following nonsurgical periodontal therapy. However, in terms of early wound healing no significant differences were seen between the two treatment sites.
Acute arterial thrombosis due to platelet aggregation in a patient receiving granulocyte colony‐stimulating factor (1996)

We describe a 44-year-old man with non-Hodgkin's lymphoma receiving granulocyte colony-stimulating factor (G-CSF) who developed an acute arterial thrombosis. The removed thrombus contained large amounts of platelet aggregation. A rapid increase of platelets and increased adenosine diphosphate (ADP)- and collagen-induced platelet aggregation were observed at the time of the thrombotic event. A challenge test of G-CSF showed an increase in the platelet count and an augmentation of ADP- and collagen-induced platelet aggregation. In the use of GCSF. patients who produce a rapid increase in platelet levels could be at greater risk for thrombotic events and need to be followed-up carefully.