gebhart/patrepeval huggingface dataset:
T cell Activation Is Driven by an ADP-Dependent Glucokinase Linking Enhanced Glycolysis with Mitochondrial Reactive Oxygen Species Generation (2012)

Mitochondria-originating reactive oxygen species (ROS) control T cell receptor (TCR)-induced gene expression. Here, we show that TCR-triggered activation of ADP-dependent glucokinase (ADPGK), an alternative, glycolytic enzyme typical for Archaea, mediates generation of the oxidative signal. We also show that ADPGK is localized in the endoplasmic reticulum and suggest that its active site protrudes toward the cytosol. The ADPGK-driven increase in glycolytic metabolism coincides with TCR-induced glucose uptake, downregulation of mitochondrial respiration, and deviation of glycolysis toward mitochondrial glycerol-3-phosphate dehydrogenase(GPD) shuttle; i.e., a metabolic shift to aerobic glycolysis similar to the Warburg effect. The activation of respiratory-chain-associated GPD2 results in hyperreduction of ubiquinone and ROS release from mitochondria. In parallel, mitochondrial bioenergetics and ultrastructure are altered. Downregulation of ADPGK or GPD2 abundance inhibits oxidative signal generation and induction of NF-κB-dependent gene expression, whereas overexpression of ADPGK potentiates them.
Enhanced Metastatic Potential of Tumor Cells Harvested From Spontaneous Metastases of Heterogeneous Murine Tumors<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref><xref ref-type="fn" rid="FN4">4</xref> (1982)

These studies demonstrated that cells populating spontaneous metastases are, in general, more metastatic than the cells populating the parent neoplasm, thereby providing direct evidence that the process of metastasis is selective and not random. The tumors used in these studies were the UV-2237 fibrosarcoma, an in vitro cloned line (C-40) from the UV-2237 tumor, and the K-1735 melanoma, all of which are syngeneic to the C3H/HeN (mammary tumor virus-negative) mouse strain; the M5076 reticulum cell sarcoma and the Lewis lung carcinoma 3LL, which are syngeneic to the C57BL/6 mouse strain, were also used. All tumors were implanted sc into the footpads of syngeneic mice, and several resulting spontaneous metastases were isolated and established in culture as individual cell lines. For each tumor system, comparison was made of the ability of parent tumor cells and cells isolated from several spontaneous metastases to produce either experimental or spontaneous metastases. Cells populating spontaneous metastases produced by heterogeneous and poorly metastatic tumors were significantly more metastatic than the cells of their respective parent tumors. In contrast, cells populating metastases produced by previously selected tumors did not differ significantly in metastatic potential from cells populating their parent tumors. In such systems, metastasis appeared to be random.
Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis: mechanisms of action. (2003)

Although the predominant mechanism of intra-articular hyaluronan (hyaluronic acid) (HA) and hylans for the treatment of pain associated with knee osteoarthritis (OA) is unknown, in vivo, in vitro, and clinical studies demonstrate various physiological effects of exogenous HA. HA can reduce nerve impulses and nerve sensitivity associated with the pain of OA. In experimental OA, this glycosaminoglycan has protective effects on cartilage, which may be mediated by its molecular and cellular effects observed in vitro. Exogenous HA enhances chondrocyte HA and proteoglycan synthesis, reduces the production and activity of proinflammatory mediators and matrix metalloproteinases, and alters the behavior of immune cells. Many of the physiological effects of exogenous HA may be a function of its molecular weight. Several physiological effects probably contribute to the mechanisms by which HA and hylans exert their clinical effects in knee OA.
Commentary: Three Decades of Folic Acid Antagonists in Dermatology (1983)

A little longer than 30 years ago, Gubner et al<sup>1</sup>made the serendipitous observation that the folic acid antagonist aminopterin had a beneficial effect in the treatment of psoriasis. In the early 1950s, the inhibitory effects of aminopterin on the inflammatory and proliferative responses of the connective tissue in mesenchymal disorders were being investigated.<sup>1</sup>Similar effects were being found with the administration of cortisone, also a newly used drug. Animal and clinical experiments showed that aminopterin was producing a greater inhibitory effect on epithelial tissues, whereas the major effects of cortisone therapy were appearing in mesenchymal tissues.<sup>2</sup>This unexpected finding occurred while Gubner et al1 were looking for an anti-inflammatory effect of aminopterin therapy in patients with rheumatoid arthritis, one of whom also had severe psoriasis. The beneficial response in this one patient (patient 3) led to the investigation of the use of aminopterin therapy in other
Protein Design, a Minimalist Approach (1989)

The question of how the amino acid sequence of a protein specifies its three-dimensional structure remains to be answered. Proteins are so large and complex that it is difficult to discern the features in their sequences that contribute to their structural stability and function. One approach to this problem is de novo design of model proteins, much simpler than their natural counterparts, yet containing sufficient information in their sequences to specify a given function (for example, folding in aqueous solution, folding in membranes, or formation of ion channels). Designed proteins provide simple model systems for understanding protein structure and function.
A collection of ordered tetranucleotide-repeat markers from the human genome (1995)

A collection of 1,069 human PCR-based genetic markers has been developed, and their distribution over the 22 autosomes and the X chromosome has been determined. Each marker was developed around a short-tandem-repeat DNA sequence. The majority (85%) of the markers described here were selected to contain tetranucleotide repeats, because these repeats show better stability during PCR than do dinucleotide repeats. Linkage maps constructed from genotypes collected with these markers in four CEPH pedigrees (1331, 1332, 1362, and 884) covered 3,419 cM of the human genome. More than 600 of the loci revealed heterozygosities >.70. Overall, 444 loci were ordered, with odds >100:1 against inversion of adjacent loci. The average distance between markers was 7.4 cM on the autosomes and 24.8 cM on the X chromosome. Likely locations (100:1 odds intervals) were assigned for the remaining 621 short-tandem-repeat polymorphisms, as well as for 160 other markers that are present on the framework maps published by the Cooperative Human Linkage Center. Four markers specific to the Y chromosome are also reported here. From our maps, 347 markers were chosen to define {open_quotes}index{close_quotes} maps for each of the 22 autosomes. The index markers detect loci with an average heterozygosity of .85 and covermore » 3,169 cM of the autosomes, with an average distance between markers of 9.2 cM. These polymorphic short tandem repeats will be highly useful as reagents for the ongoing genetic and physical mapping of the human genome and for characterization of genetic changes in cancer. 27 refs., 4 figs., 2 tabs.« less
Cough predicts prognosis in idiopathic pulmonary fibrosis (2011)

Cough in IPF is more prevalent in never-smokers and patients with more advanced disease. Cough is an independent predictor of disease progression and may predict time to death or lung transplantation.
A Genetically Encoded Photocaged Tyrosine (2006)

Activating proteins with light: A photocaged tyrosine was genetically encoded in E. coli in response to the amber codon TAG. Substitution of Tyr 503 in the active site of β-galactosidase allowed photoactivation of this enzyme in vitro or directly in bacteria with 360-nm light. This method should allow photoregulation of the activity of a variety of biological processes including transcription, signal transduction, and cellular trafficking.
Knockdown of ACAT‐1 reduces amyloidogenic processing of APP (2007)

Previous studies have shown that acyl-coenzyme A:cholesterol acyl transferase (ACAT), an enzyme that controls cellular equilibrium between free cholesterol and cholesteryl esters, modulates proteolytic processing of APP in cell-based and animal models of Alzheimer's disease. Here we report that ACAT-1 RNAi reduced cellular ACAT-1 protein by approximately 50% and cholesteryl ester levels by 22% while causing a slight increase in the free cholesterol content of ER membranes. This correlated with reduced proteolytic processing of APP and 40% decrease in Abeta secretion. These data show that even a modest decrease in ACAT activity can have robust suppressive effects on Abeta generation.
Birefringent omnidirectional reflector (2004)

Anisotropic optical coatings offer unique polarizing properties, unmatched by conventional isotropic devices. Here we demonstrate the fabrication of a birefringent omnidirectional reflector, a type of photonic crystal, which exhibits complete reflection of radiation at 1.1 microm for all incidence angles and polarizations. The thin-film device was deposited from electron-beam evaporated silicon, with refractive-index variation arising from atomic-scale porosity created with glancing-angle deposition. Birefringence was found to enhance the performance of the device compared with its isotropic counterpart by enlarging the photonic bandgap region of omnidirectional reflection.
Heritability of Mammographic Density, a Risk Factor for Breast Cancer (2002)

These results show that the population variation in the percentage of dense tissue on mammography at a given age has high heritability. Because mammographic density is associated with an increased risk of breast cancer, finding the genes responsible for this phenotype could be important for understanding the causes of the disease.
Neogenin Interacts with Matriptase-2 to Facilitate Hemojuvelin Cleavage (2012)

Hemojuvelin (HJV) and matriptase-2 (MT2) are co-expressed in hepatocytes, and both are essential for systemic iron homeostasis. HJV is a glycosylphosphatidylinositol-linked membrane protein that acts as a co-receptor for bone morphogenetic proteins to induce hepcidin expression. MT2 regulates the levels of membrane-bound HJV in hepatocytes by binding to and cleaving HJV into an inactive soluble form that is released from cells. HJV also interacts with neogenin, a ubiquitously expressed transmembrane protein with multiple functions. In this study, we showed that neogenin interacted with MT2 as well as with HJV and facilitated the cleavage of HJV by MT2. In contrast, neogenin was not cleaved by MT2, indicating some degree of specificity by MT2. Down-regulation of neogenin with siRNA increased the amount of MT2 and HJV on the plasma membrane, suggesting a lack of neogenin involvement in their trafficking to the cell surface. The increase in MT2 and HJV upon neogenin knockdown was likely due to the inhibition of cell surface MT2 and HJV internalization. Analysis of the Asn-linked oligosaccharides showed that MT2 cleavage of cell surface HJV was coupled to a transition from high mannose oligosaccharides to complex oligosaccharides on HJV. These results suggest that neogenin forms a ternary complex with both MT2 and HJV at the plasma membrane. The complex facilitates HJV cleavage by MT2, and release of the cleaved HJV from the cell occurs after a retrograde trafficking through the TGN/Golgi compartments.
Manipulation of a Hospital Antimicrobial Formulary to Control an Outbreak of Vancomycin-Resistant Enterococci (1996)

Infection control practices are not uniformly successful in limiting outbreaks of vancomycin-resistant enterococci (VRE). Despite the implementation of barrier precautions for VRE-infected patients, nearly one-half of the inpatients at our center were found to have gastrointestinal colonization by VRE. In an attempt to control the outbreak, we altered the antibiotic formulary by restricting the use of cefotaxime and vancomycin and adding beta-lactamase inhibitors to replace third-generation cephalosporins. The use of clindamycin was also restricted because of a concomitant outbreak of Clostridium difficile colitis. After 6 months, the average monthly use of cefotaxime, ceftazidime, vancomycin, and clindamycin had decreased by 84%, 55%, 34%, and 80%, respectively (P < .02). The point prevalence of fecal colonization with VRE decreased from 47% to 15% (P < .001), and the number of patients whose clinical specimens were culture positive also gradually decreased. A change in antibiotic use appears to have significantly affected our VRE outbreak when previous measures failed.
Partial characterization of Streptococcus suis type 2 hemolysin (1994)

Streptococcus suis type 2 was evaluated for hemolysin production. Supernatants of S. suis type 2 grown in Todd-Hewitt broth were assayed for hemolytic activity by a photometric assay. Twenty-two additional serotypes of S. suis (1,3 to 22, and 1/2) were evaluated for hemolysin production; nine of them (1/2, 1, 4, 5, 14, 15, 17, 19, and 20) were positive. The effects of temperature, atmosphere, centrifugation, sonication, chemicals, bovine serum albumin, fetal calf serum, and enzymes on S. suis type 2 hemolysin activity were studied. Maximum hemolysis occurred after incubation in RPMI 1640 medium at 40 degrees C in 6% CO2 and after growth in Todd-Hewitt broth at 37 degrees C under anaerobic conditions. Hemolytic activity was absent after the addition of fetal calf serum and decreased after the addition of trypsin or amylase. However, treatment of erythrocytes with amylase or trypsin prior to incubation with supernatant also resulted in a decrease in hemolytic activity. The addition of bovine serum albumin caused increased hemolytic activity. Dipyridyl and EDTA had negligible effects on hemolysis. Hemolytic S. suis type 2 culture supernatant injected intraperitoneally failed to cause death in BALB/c mice. Data from our study indicate that S. suis type 2 hemolysin is a secreted or loosely cell bound, thermolabile molecule whose activity is growth condition dependent.
Impact of Geomechanics on Microseismicity (2012)

Abstract The proper interpretation of microseismic event patterns to estimate hydraulic-fracture geometries is critical for understanding well performance in unconventional reservoirs. Besides factors such as microseismic event location uncertainty, advanced interpretations should also include a proper understanding of the geomechanical context in which these events take place and the underlying mechanisms that link the hydraulic fracture to the microseismic events. In this paper we investigate the different mechanisms that can cause microseismic activity around a hydraulic fracture from the viewpoint of a 3D elasto-static model to explain the behavior of microseismic event patterns. Stress perturbations caused by the opening of hydraulic fractures, opening of extensional branch fractures, and leakoff-related effects are considered. Multiple transverse fractures as well as dilated natural fractures orthogonal to the hydraulic-fracture direction are modeled under different sets of reservoir and treatment conditions to gain insight into the importance of different mechanisms. An important observation is that stress changes alone caused by tensile opening behind the hydraulic-fracture tip cannot cause microseismic events under any set of reservoir conditions normally encountered in practice. The results indicate that tip effects, propagation of extensional branch fractures, and activation of natural fractures upon intersection should be the main drivers of microseismic activity in shale-gas plays. The modeling shows that microseismic events are expected to occur very close to the hydraulically activated fractures or planes, thus enhancing the value of microseismic monitoring. The modeling also showed that under certain conditions (critically stressed formations), the shear zone caused by tip effects can extend fairly far ahead of the fracture tip, which needs to be considered in the interpretation of fracture geometry. The presented results help to constrain and enhance the interpretation of microseismic data, from a geomechanical perspective.
Anti‐Transforming Growth Factor Beta as a Treatment for Laryngotracheal Stenosis in a Canine Model (2008)

Anti-TGFB appears to be a useful adjunct in the treatment of LTS. Further study regarding the optimal dosing, route of administration, and timing of delivery is needed to understand the role of anti-TGFB in the treatment for laryngotracheal stenosis.
Prevention of transmission of Babesia canis by Dermacentor reticulatus ticks to dogs treated orally with fluralaner chewable tablets (Bravecto™) (2015)

A single oral administration of fluralaner chewable tablets effectively prevented the transmission of B. canis by infected D. reticulatus ticks over a 12-week period.
Highly practical, enantiospecific synthesis of the cyclohexyl fragment of the immunosuppressant FK-506 (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHighly practical, enantiospecific synthesis of the cyclohexyl fragment of the immunosuppressant FK-506Hiyoshizo Kotsuki, Hideyuki Nishikawa, Yumi Mori, and Masamitsu OchiCite this: J. Org. Chem. 1992, 57, 18, 5036–5040Publication Date (Print):August 1, 1992Publication History Published online1 May 2002Published inissue 1 August 1992https://pubs.acs.org/doi/10.1021/jo00044a051https://doi.org/10.1021/jo00044a051research-articleACS PublicationsRequest reuse permissionsArticle Views387Altmetric-Citations20LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Mechanistic Relationships Between DNA Adducts, Oncogene Mutations, and Lung Tumorigenesis in Strain A Mice (1998)

This paper describes a series of studies on the lung tumorigenic activities of polycyclic aromatic hydrocarbons (PAHs) in strain A/J mice, their ability to form PAH-DNA adducts in lung tissues, and their ability to mutate the Ki-ras oncogene in PAH-induced tumors. Seven PAHs were studied: cyclopenta[cd]pyrene (CPP), benzo[a]pyrene (B[a]P), benzo[b]fluoranthene (B[b]F), dibenz[a,h] anthracene (DBA), 5-methylchrysene (5MC), benz[j]aceanthrylene (B[j]A), and dibenzo[a,l]pyrene (DB[a,l]P). The dose-response data for the PAHs revealed 100-fold differences in tumor potency based on dose, with the order of activity DB[a,l]P, DBA > B[j]A > 5MC > CPP B[a]P > B[b]F. Large differences in tumor multiplicity were also observed between the PAHs. DNA adducts were measured by 32P-postlabeling techniques on DNA from lungs of mice treated with these PAH's. DB[a,l]P gave syn- and anti-fjord-region diol-epoxide adducts of dAdo and dGuo; DBA gave both bay-region diol-epoxide-dGuo and bisdihydrodiol-epoxide adducts; CPP gave cyclopenta-ring-dGuo adducts; B[j]A gave a mixture of cyclopenta-ring-dGuo and -dAdo adducts; 5MC gave anti-bay-region diol-epoxide-dGuo adducts; B[a]P gave bay-region diol-epoxide-dGuo adducts; and B[b]F gave 5-hydroxy-B[b]F-diol-epoxide-dGuo adducts. Ki-ras codon 12 and 61 mutation analysis of PAH induced tumors was performed using PCR and dideoxy sequencing methods. DB[a,l]P gave both codon 12 and codon 61 mutations. High proportions of codon 12 TGT mutations from B[a]P-, B[b]F- and 5MC-, induced tumors and CGT mutations from CPP- and B[j]A-induced tumors were observed. DBA produced no mutations in Ki-ras codons 12 or 61 by direct sequencing. The interrelationships between the tumorigenesis, DNA adduct, and oncogene mutation data are discussed.
Two members of a widely expressed subfamily of hormone-stimulated adenylyl cyclases. (1992)

cDNA encoding a hormone- and guanine nucleotide-stimulated adenylyl cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] (type 6) from rat liver and kidney has been cloned and expressed. This enzyme is stimulated by forskolin, guanosine 5'-[gamma-thio]triphosphate, and isoproterenol plus GTP but is not stimulated by beta gamma subunits of guanine nucleotide-binding proteins. A second form (type 5), which is 75% similar to type 6, has also been cloned. Both types 5 and 6 cDNAs have multiple messages. PCR-based detection of the mRNA for the type 5 and 6 enzymes indicates that both are widely distributed. Homology analyses indicate at least four distinct subfamilies of guanine nucleotide stimulatory protein-regulated adenylyl cyclases. Types 5 and 6 enzymes define one distinct subfamily of mammalian adenylyl cyclases. Diversity of one guanine nucleotide-binding protein-regulated effector may allow different modes of regulation of cell-surface signal transmission.
Ebola Outbreak in Kikwit, Democratic Republic of the Congo: Discovery and Control Measures (1999)

The Ebola epidemic in Kikwit, Democratic Republic of the Congo, was recognized because of a nosocomial outbreak in Kikwit General Hospital. Initially, a diagnosis of shigella infection was suspected because many patients presented with bloody diarrhea. On 4 May 1995, blood samples from 14 acutely ill patients were sent to the Centers for Disease Control and Prevention (Atlanta), and on 9 May, a diagnosis of Ebola hemorrhagic fever was confirmed. The major disease control measures that were undertaken were the isolation of patients in a quarantine ward at Kikwit General Hospital, the distribution of protective equipment to health care workers and family members caring for Ebola patients, the use of barrier nursing techniques, the distribution of health education material, active and passive case finding, and the burying of the deceased in plastic bags by a trained team of Red Cross volunteers who wore gloves and protective clothing.
Physical uncloneable function hardware keys utilizing Kirchhoff-law-Johnson-noise secure key exchange and noise-based logic (2013)

Weak physical uncloneable function (WPUF) encryption key means that the manufacturer of the hardware can clone the key but anybody else is unable to so that. Strong physical uncloneable function (SPUF) encryption key means that even the manufacturer of the hardware is unable to clone the key. In this paper, first we introduce a "ultra"-strong PUF with intrinsic dynamical randomness, which is not only not cloneable but it also gets renewed to an independent key (with fresh randomness) during each use via the unconditionally secure key exchange. The solution utilizes the Kirchhoff-law-Johnson-noise (KLJN) method for dynamical key renewal and a one-time-pad secure key for the challenge/response process. The secure key is stored in a flash memory on the chip to provide tamper-resistance and non-volatile storage with zero power requirements in standby mode. Simplified PUF keys are shown: a strong PUF utilizing KLJN protocol during the first run and noise-based logic (NBL) hyperspace vector string verification method for the challenge/response during the rest of its life or until it is re-initialized. Finally, the simplest PUF utilizes NBL without KLJN thus it can be cloned by the manufacturer but not by anybody else.