gebhart/patrepeval huggingface dataset:
KlAft, the Kluyveromyces lactis Ortholog of Aft1 and Aft2, Mediates Activation of Iron-Responsive Transcription Through the PuCACCC Aft-Type Sequence (2009)

Iron homeostasis in fungi is regulated at the transcriptional level by two different mechanisms. It is mediated by a conserved GATA-type repressor in most fungi except in the yeast Saccharomyces cerevisiae, where it is controlled by the transcription activators Aft1 and Aft2. These activators are encoded by the paralogous genes AFT1 and AFT2, which result from the whole-genome duplication. Here, we explore regulation of iron homeostasis in the yeast Kluyveromyces lactis that diverged from S. cerevisiae before this event. We identify an ortholog of AFT1/AFT2, designated KlAFT, whose deletion leads to the inability to grow under iron limitation. We show with quantitative real-time PCR analysis that KlAft activates the transcription of all homologs of the Aft1-target genes involved in the iron transport at the cell surface in response to iron limitation. However, homologs of Aft2-specific target genes encoding intracellular iron transporters are regulated neither by KlAft nor by iron. Both bioinformatic and DNA binding and transcription analyses demonstrate that KlAft activates iron-responsive gene expression through the PuCACCC Aft-type sequence. Thus, K. lactis is the first documented species with a positive iron-transcriptional control mediated by only one copy of the Aft-type regulator. This indicates that this function was acquired before the whole-genome duplication and was then diversified into two regulators in S. cerevisiae.
Hydrocarbon-Stapled Peptides: Principles, Practice, and Progress (2014)

Protein structure underlies essential biological processes and provides a blueprint for molecular mimicry that drives drug discovery. Although small molecules represent the lion's share of agents that target proteins for therapeutic benefit, there remains no substitute for the natural properties of proteins and their peptide subunits in the majority of biological contexts. The peptide α-helix represents a common structural motif that mediates communication between signaling proteins. Because peptides can lose their shape when taken out of context, developing chemical interventions to stabilize their bioactive structure remains an active area of research. The all-hydrocarbon staple has emerged as one such solution, conferring α-helical structure, protease resistance, cellular penetrance, and biological activity upon successful incorporation of a series of design and application principles. Here, we describe our more than decade-long experience in developing stapled peptides as biomedical research tools and prototype therapeutics, highlighting lessons learned, pitfalls to avoid, and keys to success.
Respiratory Infections With Pseudomonas aeruginosa in Children With Cystic Fibrosis (2002)

In CF patients diagnosed through neonatal screening, P aeruginosa pulmonary infections occurred 6 to 12 months before the organism was isolated from respiratory secretions. The longitudinal monitoring of P aeruginosa antibody titers, in concert with WCXR score, should facilitate diagnosis and treatment of P aeruginosa pulmonary infections in young children with CF.
Analogs of 3-amino-7-chloro-1,2,4-benzotriazine 1-oxide as antimalarial agents (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAnalogs of 3-amino-7-chloro-1,2,4-benzotriazine 1-oxide as antimalarial agentsJ. Kenneth Horner and David W. HenryCite this: J. Med. Chem. 1968, 11, 5, 946–949Publication Date (Print):September 1, 1968Publication History Published online1 May 2002Published inissue 1 September 1968https://pubs.acs.org/doi/10.1021/jm00311a007https://doi.org/10.1021/jm00311a007research-articleACS PublicationsRequest reuse permissionsArticle Views294Altmetric-Citations29LEARN 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
Salts dramatically enhance activity of enzymes suspended in organic solvents (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSalts dramatically enhance activity of enzymes suspended in organic solventsYuri L. Khmelnitsky, Stephanie H. Welch, Douglas S. Clark, and Jonathan S. DordickCite this: J. Am. Chem. Soc. 1994, 116, 6, 2647–2648Publication Date (Print):March 1, 1994Publication History Published online1 May 2002Published inissue 1 March 1994https://pubs.acs.org/doi/10.1021/ja00085a066https://doi.org/10.1021/ja00085a066research-articleACS PublicationsRequest reuse permissionsArticle Views965Altmetric-Citations227LEARN 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
Real-Time Qualitative PCR for 57 Human Adenovirus Types from Multiple Specimen Sources (2011)

Human adenoviruses (HAdVs) are ubiquitous double-stranded DNA viruses that cause a wide array of diseases in humans including pharyngitis, pneumonia, gastroenteritis, hemorrhagic cystitis, and keratoconjunctivitis. They also cause life-threatening opportunistic infections in immunocompromised individuals and are responsible for outbreaks in certain populations. Diagnosis is traditionally by cell culture or antigen detection methods. However, some HAdVs can take up to 4 weeks to isolate, and diarrheagenic types 40 and 41 will not grow in routine cell culture. Therefore, the goal of this study was to design a rapid, real-time PCR assay to detect all known 57 HAdV types from multiple different specimen sources. Primers and fluorescence resonance energy transfer hybridization probes were designed to target a 185-bp region of the penton base gene of HAdV. The analytical sensitivity was determined to be 10 copies/μl for HAdV types showing exact primer/probe homology in specimen matrix. Using whole-virus strains, the analytical sensitivity for representative HAdV types ranged from 10(-1) to 10(3) 50% tissue culture infective dose (TCID(50))/ml. The assay demonstrated 100% sensitivity and 99% specificity. This real-time PCR assay provides a rapid method for the detection of all 57 known HAdV types from respiratory specimens, blood, stool, urine, and ocular swabs.
Lipids and chronic central nervous system disease (2000)

Accumulating evidence has shown disturbances of lipid composition and function in several chronic disorders of the central nervous system. This paper reviews the recent progress towards elaborating specific abnormalities of the brain and peripheral lipids in three major neuropsychiatric disorders. Particular emphasis is placed on linking these advances with the most significant findings from the established literature.
Transcriptome analysis of the ischemia-reperfused remodeling myocardium: temporal changes in inflammation and extracellular matrix (2006)

cDNA microarray analysis was performed to screen 15,000 genes and expressed sequence tags (ESTs) to identify changes in the ischemia-reperfused (I-R) rat myocardial transcriptome in the early (day 2) and late (day 7) inflammatory phases of acute myocardial infarction. Lists of candidate genes that were affected by I-R transiently (2 or 7 days only) or on a more sustained basis (2 and 7 days) were derived. The candidate genes represented three major functional categories: extracellular matrix, apoptosis, and inflammation. To expand on the findings from microarray studies that dealt with the two above-mentioned time points, tissues collected from days 0, 0.25, 2, 3, 5, and 7 after reperfusion were examined. Acute myocardial infarction resulted in upregulation of IL-6 and IL-18. Genes encoding extracellular matrix proteins such as types I and III collagen were upregulated in day 2, and that response progressively grew stronger until day 7 after I-R. Comparable response kinetics was exhibited by the candidate genes of the apoptosis category. Caspases-2, -3, and -8 were induced in response to acute infarction. Compared with the myocardial tissue from the sham-operated rats, tissue collected from the infarct region stained heavily positive for the presence of active caspase-3. Laser microdissection and pressure catapulting technology was applied to harvest infarct and adjacent noninfarct control tissue from a microscopically defined region in the rat myocardium. Taken together, this work presents the first evidence gained from the use of DNA microarrays to understand the molecular mechanisms implicated in the early and late inflammatory phases of the I-R heart.
27.5% efficiency InGaP/InGaAs/Ge advanced triple junction (ATJ) space solar cells for high volume manufacturing (2003)

Results of improvements in Emcore's large-area ( a 26.6 cm/sup 2/) triple-junction (3J) space solar cells are presented. Volume production of this InGaP/InGaAs/Ge advanced triple-junction (ATJ) process shows an individual cell average conversion efficiency of 27.5% (AMO, 135.3 mW/cm, 28/spl deg/C) with observed lot average conversion efficiencies greater than 28.0%. The ATJ cells maintain a radiation hard design similar to that used in the first generation Emcore 3J solar cells. The power remaining factors after irradiation with 1-MeV electrons at fluences of 5E14, 1E15, and 5E15 e/ cm/sup 2/ are 0.89, 0.85,and 0.74 respectively. The realized improvements in the ATJ solar cell have resulted in part from an improved "blue" response in the Ge subcell, the addition of indium to the GaAs middle cell composition, and from improvements to the bulk material quality of the InGaP top cell.
Macrophage factors which enhance the mixed leukocyte reaction initiated by dendritic cells. (1989)

Stimulator cells for the allogeneic MLR are dendritic cells but not macrophages (M phi). M phi, however, enhance the MLR initiated by relatively low doses of dendritic cells. The present report demonstrates that the enhancement of the MLR is mediated by two factors produced by M phi. One is IL-1, inasmuch as it has a Mr approximately 15 kDa, and both partially purified IL-1 and rIL-1 also enhance the MLR. The other has been identified as granulocyte-macrophage (GM)-CSF. It had a Mr approximately 25 kDa, and is reproduced by rGM-CSF. Moreover, the MLR-enhancing activity of both the 25-kDa molecule and rGM-CSF have been neutralized by anti-GM-CSF antiserum. Both IL-1 and GM-CSF have autonomous enhancing activity, but they collaborate with each other in enhancing the MLR. Both factors act on DC to augment their stimulatory activity for allogeneic T lymphocytes.
Immune-mediated complications during interferon alpha therapy in chronic myelogenous leukemia. (2002)

Several prospective randomized studies have shown that the treatment of chronic myeloid leukemia with interferon alpha (IFNalpha) prolongs the survival by comparison with conventional chemotherapy. However, long-term treatment with Interferon alpha can produce or exacerbate immune-mediated complications (IMC). The purpose of this study was to analyze the experience with IMC in patients with chronic myelogenous leukemia (CML) undergoing IFNalpha treatment. The occurrence of IMC was evaluated in 76 patients (47 male; 29 female) with Philadelphia chromosome (Ph)-positive CML. Diagnostic criteria of IMC were performed in patients with symptoms suggestive of particular disorders. Well-documented and clinically evident complications developed in 7 patients after a median of 19 months (range 1-84) of IFNalpha treatment. These included 9.2% patients with Ph-positive CML treated with IFNalpha-containing regimens. Hypothyroidism (H) occurred in 1 patient (1.3%), immune-mediated hemolysis (HEM) in 2 patients (2.6%) and connective tissue disorders (CTD) in 4 patients (5.3%) (2 systemic lupus erythematosus--SLE, 1 Raynaud's phenomena and 1 mixed connective tissue disease--MCTD). IFNalpha was discontinued in 3 patients and the dose was reduced in 2 patients. Five of 7 patients (75%) with immune-mediated complications had some degree of cytogenetic response at the time of the event. The association with female sex was strong and significant (86% vs 33.6%, x2; 48; p = 0.02). The frequency of IMC of clinical relevance with interferon alpha therapy in CML increased (long-term therapy). The patients treated with interferon alpha should be monitored for signs and symptoms of autoimmunity.
Seamless mobile computing on fixed infrastructure (2004)

The term mobile computing typically evokes images of a laptop, handheld, or wearable computer. However, the plummeting cost of hardware suggests that pervasive computing infrastructure could minimize the need to carry such devices in the near future. Personal computing will be available anywhere on demand, like light at the flip of a switch. Only when a user starts to use a computer will it acquire unique customization and state. When the user finishes using the computer, this customization and state will disappear from it. Thus, a user could travel hands-free yet be confident of making productive use of slivers of free time anywhere. For this to be a compelling vision from a user's viewpoint, the customization and state acquisition process must be accurate and nearly instantaneous. For it to be a viable business model, the management and system administration costs of pervasive deployments of machines must be low. Internet Suspend/Resume is a thick-client approach to mobility in which hardware virtualization and file caching are the keys to rapid personalization of anonymous hardware for transient use.
Abstract 271: Targeting PD-1, TIM-3 and LAG-3 in combination for improved immunotherapy combinations (2015)

Abstract Antibodies that inhibit the CTLA-4 and PD-1 checkpoint pathways have shown significant activity as either single agents or in combination in both mouse models and clinical studies. TIM-3 and LAG-3 have been reported to function as additional immune checkpoints which limit anti-tumor T cell responses and represent an opportunity for additional combination approaches to improve patient response to immunotherapy. To explore the potential for targeting other immune checkpoints in combination with anti-PD-1, studies were conducted in syngeneic mouse models and in human in vitro assays. A series of surrogate mouse specific reagents targeting TIM-3, LAG-3 and PD-1 have been generated to improve understanding of combination checkpoint therapy in several syngeneic models. Mouse tumor models were characterized by IHC and FACS for relevant markers including PD-L1, Foxp3, TIM3and LAG3, to identify those most likely to be subject to immunosuppressive mechanisms contributing to tumor growth and immune evasion. Initial syngeneic studies in MC38 and Colon 26 demonstrated that combinations of antibodies to murine PD-1, TIM-3 and LAG-3 improved efficacy over single agent therapy, suggesting that combinations of these checkpoint inhibitors might have therapeutic potential in the clinic. The results of ongoing studies to evaluate the dose response of the combinations as well as the contribution of the antibody isotype will be reported. Potent anti-human PD-1, -TIM-3 and LAG-3 clinical candidates have been identified using SHM-XEL™, which combines mammalian cell display of human IgG with somatic hypermutation in vitro to select and mature antibodies with desired biological activities. In a DC/T cell MLR assay, combination of the anti-LAG-3 antibody with a novel anti-PD-1 antibody could further increase T cell secretion of IL-2 up to 30-fold compared to anti-LAG-3 alone. Anti-TIM-3 in combination with anti-PD-1 also improved the EC50 up to 6-fold. Staining of activated purified CD4+ or CD8+ T-cells demonstrate that co-expression of PD-1 and LAG-3 increases upon activation compared to naïve T-cells, suggesting combination therapy may be particularly effective against activated or exhausted T-cells. These in vitro data and in vivo pre-clinical model results support evaluating combination immunotherapy with anti-LAG-3, anti-TIM-3, and anti-PD-1 in cancer patients. Citation Format: Marilyn Kehry, Robert Horlick, Peter Bowers, Toni Jun, Jean da Silva Correia, Jonathan Graves, Yan Wang, Haley Laken, David J. King. Targeting PD-1, TIM-3 and LAG-3 in combination for improved immunotherapy combinations. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 271. doi:10.1158/1538-7445.AM2015-271
Effect of N-Acetylcysteine on Acetaminophen Toxicity in Mice: Relationship to Reactive Nitrogen and Cytokine Formation (2003)

The relationship between acetaminophen (APAP) reactive metabolite formation, nitrotyrosine (NT) production, and cytokine elevation in APAP toxicity was investigated. Mice were dosed with 300 mg/kg of APAP and sacrificed at 1, 2, 4, 8, and 12 h. Serum aspartate aminotransferase (AST) was elevated by 4 h. The relative amount of NT correlated with toxicity and was localized in the necrotic cells. IL-1b was increased at 1 h, whereas IL-6, MIP-2, and MCP-1 were increased by 4-8 h. To determine the importance of reversible versus toxic events, N-acetylcysteine (NAC) was administered to mice either before APAP or 1, 2, or 4 h after APAP. The animals were sacrificed at 12 h. NAC treatment before APAP resulted in serum AST, serum nitrate plus nitrite as a measure of nitric oxide (NO) production, and hepatic cytokine levels that were similar to the controls. No APAP protein adducts or NT was present in these animals. In mice treated with NAC at 1 h, cytokines and serum AST were normal at 12 h, but APAP protein adducts were present in the hepatic centrilobular areas. No NT was present in these animals. In mice treated with NAC at 2 h and sacrificed at 12 h, serum AST was reduced by 80%. APAP adducts and NT were present in the centrilobular areas. Mice receiving NAC at 4 h had no protection from toxicity and serum nitrate plus nitrite. The NT and cytokine levels were similar to those of mice receiving APAP alone. The data suggest a relationship between metabolic events in APAP toxicity and the upregulation of NO, and IL-1b. IL-6, MIP-2, and MCP-1 appear to follow the toxicity. While it is a pre-requisite event, covalent binding per se does not appear to be a toxic event in the development of toxicity.
Deep UV Photochemistry of Chemisorbed Monolayers: Patterned Coplanar Molecular Assemblies (1991)

Deep ultraviolet (UV) irradiation is shown to modify organosilane self-assembled monolayer (SAM) films by a photocleavage mechanism, which renders the surface amenable to further SAM modification. Patterned UV exposure creates alternating regions of intact SAM film and hydrophilic, reactive sites. The exposed regions can undergo a second chemisorption reaction to produce an assembly of SAMs in the same molecular plane with similar substrate attachment chemistry. The UV-patterned films are used as a template for selective buildup of fluorophores, metals, and biological cells.
Synthesis of luminescent Si Nanoparticles using the laser-induced pyrolysis (2011)

The synthesis of silicon nanoparticles in the reaction of the silane pyrolysis is presented. The reaction of the silane decomposition is performed in a flow reactor in the presence of the cw CO2-laser irradiation. As-prepared Si nanoparticles are studied with the aid of transmission electron microscope, fiber spectrometer, and FTIR spectrometer. Spherical Si nanoparticles with a diameter of about 15 nm are produced. The luminescence of the as-prepared nanoparticles is virtually absent. The nanoparticles are etched in acid vapor and are oxidized to increase the luminescence quantum yield. After the chemical treatment, the mean size of the crystalline core of nanoparticles decreases to 5 nm and the luminescence spectrum exhibits the band peaked at 730 nm.
Bacillus and relatives in foodborne illness (2011)

Species of Bacillus and related genera have long been troublesome to food producers on account of their resistant endospores. These organisms have undergone huge taxonomic changes in the last 30 years, with numbers of genera and species now standing at 56 and over 545, respectively. Despite this expansion, relatively few new species have been isolated from infections, few are associated with food and no important new agents of foodborne illness have been reported. What has changed is our knowledge of the established agents. Bacillus cereus is well known as a cause of food poisoning, and much more is now understood about its toxins and their involvement in infections and intoxications. Also, although B. licheniformis, B. subtilis and B. pumilus have occasionally been isolated from cases of food-associated illness, their roles were usually uncertain. Much more is now known about the toxins that strains of these species may produce, so that their significances in such episodes are clearer; however, it is still unclear why such cases are so rarely reported. Another important development is the use of aerobic endosporeformers as probiotics, as the potentials of such organisms to cause illness or to be sources of antibiotic resistance need to be borne in mind.
Expressions of angiopoietins and Tie2 in human choroidal neovascular membranes. (1999)

Present findings that Ang2 and VEGF are co-upregulated and that Tie2 is expressed in a variety of cell types in CNVMs further support a crucial role of the interaction between VEGF and Ang2 in pathologic angiogenesis of CNVM formation.