gebhart/patrepeval huggingface dataset:
The Role of Keap1 in Cellular Protective Responses (2005)

ADVERTISEMENT RETURN TO ISSUEReviewNEXTThe Role of Keap1 in Cellular Protective ResponsesAlbena T. Dinkova-Kostova, W. David Holtzclaw, and Thomas W. KenslerView Author Information The Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, School of Medicine, and Department of Environmental Health Sciences, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland 21205 Cite this: Chem. Res. Toxicol. 2005, 18, 12, 1779–1791Publication Date (Web):November 16, 2005Publication History Received2 August 2005Published online16 November 2005Published inissue 1 December 2005https://pubs.acs.org/doi/10.1021/tx050217chttps://doi.org/10.1021/tx050217creview-articleACS PublicationsCopyright © 2005 American Chemical SocietyRequest reuse permissionsArticle Views1755Altmetric-Citations305LEARN 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 SUBJECTS:Degradation,Genetics,Monomers,Peptides and proteins,Rodent models Get e-Alerts
Enabling domain experts to convey questions to a machine (2003)

In order for a knowledge capture system to be effective, it needs to not only acquire general domain knowledge from experts, but also capture the specific problem-solving scenarios and questions which those experts are interested in solving using that knowledge. For some tasks, this latter aspect of knowledge capture is straightforward. In other cases, in particular for systems aimed at a wide variety of tasks, the question-posing aspect of knowledge capture can be a challenge in its own right. In this paper, we present the approach we have developed to address this challenge, based on the creation of a catalog of domain-independent question types and the extension of question template methods with graphical tools. Our goal was that domain experts could directly convey complex questions to a machine, in a form which it could then reason with. We evaluated the resulting system over several weeks, and in this paper we report some important lessons learned from this evaluation, revealing several interesting strengths and weaknesses of the approach.
<p>Pharmacokinetics of hard micronized progesterone capsules via vaginal or oral route compared with soft micronized capsules in healthy postmenopausal women: a randomized open-label clinical study</p> (2019)

Pharmacokinetic parameters were different between Yimaxin and Utrogestan on vaginal and oral administration. By the oral route, the metabolism and absorption of Utrogestan was superior to Yimaxin, while by the vaginal route Yimaxin was superior.
The Regulation of Reactive Oxygen Species Production during Programmed Cell Death (1998)

Reactive oxygen species (ROS) are thought to be involved in many forms of programmed cell death. The role of ROS in cell death caused by oxidative glutamate toxicity was studied in an immortalized mouse hippocampal cell line (HT22). The causal relationship between ROS production and glutathione (GSH) levels, gene expression, caspase activity, and cytosolic Ca2+ concentration was examined. An initial 5-10-fold increase in ROS after glutamate addition is temporally correlated with GSH depletion. This early increase is followed by an explosive burst of ROS production to 200-400-fold above control values. The source of this burst is the mitochondrial electron transport chain, while only 5-10% of the maximum ROS production is caused by GSH depletion. Macromolecular synthesis inhibitors as well as Ac-YVAD-cmk, an interleukin 1beta-converting enzyme protease inhibitor, block the late burst of ROS production and protect HT22 cells from glutamate toxicity when added early in the death program. Inhibition of intracellular Ca2+ cycling and the influx of extracellular Ca2+ also blocks maximum ROS production and protects the cells. The conclusion is that GSH depletion is not sufficient to cause the maximal mitochondrial ROS production, and that there is an early requirement for protease activation, changes in gene expression, and a late requirement for Ca2+ mobilization.
Molecular Manipulation of G Protein coupled Receptors A New Avenue into Drug Discovery (2000)

During the past 10 years or so, associated with the introduction of molecular biology techniques to G protein-coupled receptor (GPCR) research, outstanding progress has been made in understanding the mechanisms of action of these key proteins and their physiological functions. in-vivo manipulation of levels of GPCRs using transgenic and gene knock-out approaches have been particularly successful in assessing the roles of specific GPCRs in animal physiology. Drug discovery is aiming to produce highly specific compounds based on subtle definition of receptor subtypes which can best be studied using heterologous expression of wild type or mutated forms of cDNA or genes encoding these proteins. Furthermore, new therapeutic opportunities may be provided by investigation of orphan receptors, the natural ligands for which remain unidentified. Some human diseases have been shown to be associated with rare mutations of GPCRs and the possibility that widely distributed polymorphisms in GPCR genes may allow selective therapeutic strategies for population subgroups is driving the development of the science of pharmacogenetics.
Prevalence of gastrointestinal symptoms in diabetic patients and non-diabetic subjects. (1994)

To determine the frequency of gastrointestinal symptoms in diabetic patients, 190 patients, consecutively referred to the Diabetes Research Institute, reported their gastrointestinal symptoms on a standardized symptom list. One hundred and eighty non-diabetic healthy subjects served as (matched) controls. Finally, 75 patients with Type 1 (insulin-dependent) diabetes mellitus (33 male, 43 female; age 34,1 (18-60) yrs, diabetes duration: 11,1 (0,3-41) yrs) and 68 patients with Type 2 (non-insulin-dependent) diabetes mellitus (31 male, 37 female, age: 61,4 (37-88) yrs, diabetes duration: 10,7 (0,3-40) yrs) were studied and compared with two cohorts of controls of the same size. There were no differences in prevalence of symptoms referrable to the upper and lower GI-tract in type 1 diabetic patients as compared with controls. Among patients with type 2 diabetes the main gastrointestinal complaint was constipation (22,1% vs 10,3%; p < 0.05). Upper gastrointestinal symptoms were also more frequent among Type 2 diabetic subjects (nausea 11,8% vs 2,9%, p < 0.05). There was a tendency for an increased symptom prevalence with higher age in both type 1 and type 2 diabetes. Presence of peripheral neuropathy was associated with a higher symptom prevalence in type 1 diabetes. After stratification, diabetes duration and glycaemic control (HbA1c) did not influence the frequency of symptoms. Thus, gastrointestinal symptoms occur frequently among both diabetic patients and non-diabetic subjects. However, significant differences were found only in type 2 (non-insulin-dependent) diabetes, the commonest symptom being constipation. These findings support the need of a nondiabetic control group in epidemiological studies evaluating symptom prevalence in diabetes mellitus.
The t(6;16)(p21;q22) chromosome translocation in the LNCaP prostate carcinoma cell line results in a tpc/hpr fusion gene. (1996)

Very little is known about the molecular and genetic mechanisms involved in prostate cancer. Previous studies have shown frequent loss of heterozygosity (40%) at chromosomal regions 8p, 10q, and 16q, suggesting the presence of tumor suppressor genes in these regions. The LNCaP cell line, established from a metastatic lesion of human prostatic adenocarcinoma, carries a t(6;16)(p21;q22) translocation. To determine whether this translocation involved genes important in the process of malignant transformation, we cloned and sequenced the t(6;16) breakpoint of this cell line. Sequence analysis showed that the breakpoint is within the haptoglobin gene cluster on chromosome 16, and that, on chromosome 6, the break occurs within a novel gene, tpc, similar to the prokaryotic S10 ribosomal protein gene. The translocation results in the production of a fusion transcript, tpc/hpr.
Resistance of SCID Mice to Candida albicans Administered Intravenously or Colonizing the Gut: Role of Polymorphonuclear Leukocytes and Macrophages (1993)

SCID mice, which lack functional T and B cells, and their immunocompetent counterparts were treated with a monoclonal antibody to murine granulocytes (anti-Gr-1), silica, or carrageenan to assess the role of phagocytic cells (Polymorphonuclear leukocytes and macrophages) in resistance to candidiasis. SCID mice treated with anti-Gr-1 showed enhanced susceptibility to acute systemic candidiasis, disseminated candidiasis of endogenous origin, and orogastric candidiasis. Immunocompetent CB.17 and BALB/c mice treated with anti-Gr-1 showed enhanced susceptibility to acute systemic candidiasis but not to either orogastric or disseminated candidiasis of endogenous origin. Impairment of phagocytic cell functions with silica or carrageenan also enhanced the susceptibility of SCID mice to acute systemic candidiasis. These data in SCID and CB.17 mice support clinical studies in patients that point out the important role that granulocytes play in resistance to candidiasis. The resistance of granulocyte-depleted CB.17 mice to orogastric and disseminated candidiasis of endogenous origin also demonstrates that functional T and B cells play a role in controlling candidiasis.
Biosynthesis of Silicon–Germanium Oxide Nanocomposites by the Marine Diatom Nitzschia frustulum (2005)

The biomineralization capacity of the photosynthetic marine diatom Nitzschia frustulum was harnessed to fabricate Si-Ge oxide nanocomposite materials. Germanium was incorporated into the diatom cell by a two-stage cultivation process. In stage 1, the N. frustulum cell suspension was grown up to cell density of 3 x 10(6) cells/mL in 0.35 mM silicic acid within a bubble-column photobioreactor. In stage 2, when all of the soluble silicon was consumed, 0.10 mM Ge(OH)4 or a mixture of 0.020 mM Ge(OH)4 and 0.25 mM Si(OH)4 were added to Si-starved cells. The cells assimilated soluble germanium by a surge uptake mechanism. The cell mass was thermally annealed in air at 800 degrees C for 6 h to oxidize carbonaceous materials. The thermally annealed cell biomass was characterized by TEM-EDS, FT-IR, and XRD. These measurements confirmed the formation nanostructured Ge-Si oxides composed of CaSiO3 and Ca3GeO5.
A sensitive method for measuring ATP-formation in rat muscle mitochondria (1990)

A sensitive method for the measurement of the ATP production rate in isolated skeletal muscle mitochondria is presented. Mitochondrial suspensions were prepared by differential centrifugation from approximately 80 mg of soleus muscle. ATP production rates were measured luminometrically, utilizing a reagent based upon firefly luciferase, which emits light proportional to the ATP concentration. In a group of 10 rats the ATP production rates were measured with the following substrate combinations: pyruvate + malate, palmitoyl-L-carnitine + malate, alpha-ketoglutarate, succinate + rotenone and succinate alone. The variance of the method including tissue preparation, protein determination and the luminometric determination of ATP production was estimated to be 10-14% for the various substrates. Compared to values in the literature, the present results show a good agreement for the substrates pyruvate + malate and palmitoyl-L-carnitine + malate, but lower rates were obtained in our study for alpha-ketoglutarate and succinate + rotenone. The advantage of the luminometric method is its high sensitivity. Only 30-40 mg of tissue is required for a complete determination, compared to 1-2 g for a similar assay of oxygen consumption. The method is intended for use in human subjects and will facilitate studies of mitochondrial respiration both in patients of different age groups and in healthy subjects.
Correction of Presbyopia with Contact Lenses: Comparative Success Rates with Three Systems (1989)

In a study designed to compare subjective success rates of three presbyopic contact lens systems, 200 presbyopes were fitted with monovision (MV), a pair of concentric center-near lenses (CN pair), or a combination of center-near/center-distance concentric lenses (CNCD). Overall, 112 subjects (56% of those fitted) successfully wore at least one lens system for a minimum of 3 months. MV was the most successful system (67% success); disrupted stereopsis was not a significant reason for failure with this system. The lower success rates with the two concentric bifocal systems (CN pair 42%, CNCD 37%) could be attributed to the greater visual compromise required with these lenses.
DNA Tunneling Detector Embedded in a Nanopore (2010)

We report on the fabrication and characterization of a DNA nanopore detector with integrated tunneling electrodes. Functional tunneling devices were identified by tunneling spectroscopy in different solvents and then used in proof-of-principle experiments demonstrating, for the first time, concurrent tunneling detection and ionic current detection of DNA molecules in a nanopore platform. This is an important step toward ultrafast DNA sequencing by tunneling.
Instantaneous Non-Local Computation of Low T-Depth Quantum Circuits (1998)

Instantaneous non-local quantum computation requires multiple parties to jointly perform a quantum operation, using pre-shared entanglement and a single round of simultaneous communication. We study this task for its close connection to position-based quantum cryptography, but it also has natural applications in the context of foundations of quantum physics and in distributed computing. The best known general construction for instantaneous non-local quantum computation requires a pre-shared state which is exponentially large in the number of qubits involved in the operation, while efficient constructions are known for very specific cases only. We partially close this gap by presenting new schemes for efficient instantaneous non-local computation of several classes of quantum circuits, using the Clifford+T gate set. Our main result is a protocol which uses entanglement exponential in the T-depth of a quantum circuit, able to perform non-local computation of quantum circuits with a (poly-)logarithmic number of layers of T gates with quasi-polynomial entanglement. Our proofs combine ideas from blind and delegated quantum computation with the garden-hose model, a combinatorial model of communication complexity which was recently introduced as a tool for studying certain schemes for quantum position verification. As an application of our results, we also present an efficient attack on a recently-proposed scheme for position verification by Chakraborty and Leverrier.
Brown Recluse Spider Bites (1985)

In a prospective study, 31 patients with brown recluse spider bites were treated by either immediate surgical excision or with the leukocyte inhibitor, dapsone, followed by delayed surgical excision. Patients were matched for age, gender, and lesion size and were excluded if the typical history and physical findings were not present. In patients treated with immediate surgical excision (N = 14), delayed wound healing (N = 5) and objectional scarring (N = 7) were common complications. However, pretreatment treatment with dapsone reduced the incidence of wound complications (N = 1) and objectional scarring (N = 1) (p less than 0.05), while reducing the need for surgical excision (N = 1). There were no severe drug reactions due to dapsone, although one patient had persistent G.I. upset. Pretreatment with dapsone not only reduced surgical complications but also improved the outcome of patients bitten by the brown recluse spider.
Antiplatelet Activity of Clopidogrel in Coronary Artery Bypass Graft Surgery Patients (1999)

Clopidogrel is a recently introduced platelet ADP receptor antagonist, belonging to the thienopyridine derivatives, like its analogue ticlopidine. Its potential advantage is to be safer than ticlopidine. At 75 mg/od clopidogrel significantly inhibits platelet aggregation in ambulatory patients with symptomatic atherosclerotic disease and it prevents the recurrence of ischemic events more efficiently than aspirin. Its adequate dose in more acute situations remained to be determined. Therefore, sixty two patients with coronary artery disease were randomly assigned in four groups treated, within 24 h after coronary artery bypass graft, by clopidogrel 50 mg/od, 75 mg/od or 100 mg/od or by ticlopidine 250 mg/bid which was considered as the reference. The tolerance of clopidogrel was fairly good during the whole period of the study. Bleeding time and ex-vivo platelet aggregation induced by ADP 2 microM and 5 microM were performed at day -1, +9 and +28 after surgery. Like ticlopidine, the three dose levels of clopidogrel significantly inhibited ex-vivo platelet activity and prolonged the bleeding time at day 28. However, unlike ticlopidine, the inhibitory effects of clopidogrel were not significant at day 9, especially with 75 mg/od, a dose which was found to significantly protect patients in a chronic situation. Hence, although the clinical outcome for patients included in this limited study was the same in the four groups, these results suggest that the dose regime of clopidogrel should be more extensively investigated during the early period following coronary artery bypass graft, facing an overproduction of young and hyperreactive platelets. By analogy, the dose regime should be also investigated in other situations with an acute risk of arterial thrombotic occlusion.
MERS coronavirus: diagnostics, epidemiology and transmission (2015)

The first known cases of Middle East respiratory syndrome (MERS), associated with infection by a novel coronavirus (CoV), occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia (KSA). Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels (DC). MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. In humans, MERS is mostly known as a lower respiratory tract (LRT) disease involving fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20% to 40% of those infected. However, MERS-CoV has also been detected in mild and influenza-like illnesses and in those with no signs or symptoms. Older males most obviously suffer severe disease and MERS patients often have comorbidities. Compared to severe acute respiratory syndrome (SARS), another sometimes- fatal zoonotic coronavirus disease that has since disappeared, MERS progresses more rapidly to respiratory failure and acute kidney injury (it also has an affinity for growth in kidney cells under laboratory conditions), is more frequently reported in patients with underlying disease and is more often fatal. Most human cases of MERS have been linked to lapses in infection prevention and control (IPC) in healthcare settings, with approximately 20% of all virus detections reported among healthcare workers (HCWs) and higher exposures in those with occupations that bring them into close contact with camels. Sero-surveys have found widespread evidence of past infection in adult camels and limited past exposure among humans. Sensitive, validated reverse transcriptase real-time polymerase chain reaction (RT-rtPCR)-based diagnostics have been available almost from the start of the emergence of MERS. While the basic virology of MERS-CoV has advanced over the past three years, understanding of the interplay between camel, environment, and human remains limited.
MHC Class II Derived Recombinant T Cell Receptor Ligands Protect DBA/1LacJ Mice from Collagen-Induced Arthritis (2008)

We previously demonstrated the therapeutic effects of MHC class II derived recombinant T cell receptor ligands (RTL), single-chain two domain complexes of the alpha1 and beta1 domains of MHC class II molecules genetically linked with an immunodominant peptide, in experimental autoimmune encephalomyelitis. In the current study, we produced a monomeric murine I-Aq-derived RTL construct covalently linked with bovine collagen type II peptide (bCII257-270) suitable for use in DBA/1LacJ mice that develop collagen-induced arthritis (CIA), an animal model of human rheumatoid arthritis, after immunization with bCII protein in CFA. In this study, we demonstrate that the I-Aq-derived RTLs reduced the incidence of the disease, suppressed the clinical and histological signs of CIA and induced long-term modulation of T cells specific for arthritogenic Ags. Our results showed that the I-Aq/bCII257-270 molecule could systemically reduce proinflammatory IL-17 and IFN-gamma production and significantly increase anti-inflammatory IL-10, IL-13, and FoxP3 gene expression in splenocytes. Moreover, I-Aq/bCII257-270 molecule could also selectively inhibit IL-1beta, IL-6, and IL-23 expression in local joint tissue. This is the first report demonstrating effective prevention of joint inflammation and clinical signs of CIA with an I-Aq-derived RTL, thus supporting the possible clinical use of this approach for treating rheumatoid arthritis in humans.
Dynamic DNA devices and assemblies formed by shape-complementary, non–base pairing 3D components (2015)

We demonstrate that discrete three-dimensional (3D) DNA components can specifically self-assemble in solution on the basis of shape-complementarity and without base pairing. Using this principle, we produced homo- and heteromultimeric objects, including micrometer-scale one- and two-stranded filaments and lattices, as well as reconfigurable devices, including an actuator, a switchable gear, an unfoldable nanobook, and a nanorobot. These multidomain assemblies were stabilized via short-ranged nucleobase stacking bonds that compete against electrostatic repulsion between the components' interfaces. Using imaging by electron microscopy, ensemble and single-molecule fluorescence resonance energy transfer spectroscopy, and electrophoretic mobility analysis, we show that the balance between attractive and repulsive interactions, and thus the conformation of the assemblies, may be finely controlled by global parameters such as cation concentration or temperature and by an allosteric mechanism based on strand-displacement reactions.