gebhart/patrepeval huggingface dataset:
Genetic Basis for Differential Activities of Fluconazole and Voriconazole against Candida krusei (2003)

Invasive infections caused by Candida krusei are a significant concern because this organism is intrinsically resistant to fluconazole. Voriconazole is more active than fluconazole against C. krusei in vitro. One mechanism of fluconazole resistance in C. krusei is diminished sensitivity of the target enzyme, cytochrome P450 sterol 14alpha-demethylase (CYP51), to inhibition by this drug. We investigated the interactions of fluconazole and voriconazole with the CYP51s of C. krusei (ckCYP51) and fluconazole-susceptible Candida albicans (caCYP51). We found that voriconazole was a more potent inhibitor of both ckCYP51 and caCYP51 in cell extracts than was fluconazole. Also, the ckCYP51 was less sensitive to inhibition by both drugs than was caCYP51. These results were confirmed by expressing the CYP51 genes from C. krusei and C. albicans in Saccharomyces cerevisiae and determining the susceptibility of the transformants to voriconazole and fluconazole. We constructed homology models of the CYP51s of C. albicans and C. krusei based on the crystal structure of CYP51 from Mycobacterium tuberculosis. These models predicted that voriconazole is a more potent inhibitor of both caCYP51 and ckCYP51 than is fluconazole, because the extra methyl group of voriconazole results in a stronger hydrophobic interaction with the aromatic amino acids in the substrate binding site and more extensive filling of this site. Although there are multiple differences in the predicted amino acid sequence of caCYP51 and ckCYP51, the models of the two enzymes were quite similar and the mechanism for the relative resistance of ckCYP51 to the azoles was not apparent.
Direction finding using an interpolated array (2002)

A direction-finding technique is developed which uses the outputs of a virtual array computed from the real array using a linear interpolation procedure. The geometry of the virtual array is under the control of the designer. Using a linear virtual array, an extension of the root-MUSIC algorithm to arbitrary array geometries is developed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Organic Photostimulated Luminescence (2020)

Photostimulated luminescence, which allows energy or data to be stored and released using electromagnetic waves as both the input and output, has attracted considerable interest in the fields of biomedical and informatics technologies, but this phenomenon is mostly limited to solid inorganic materials. Here, we report photostimulated luminescence from purely organic blend films composed of electron donor, acceptor, and trap/emitter molecules. In the films, charges are accumulated as radical ions by ultraviolet light irradiation and then extracted by near infrared light irradiation to produce visible light. Films are capable of multiple cycles (>10 times) of organic photostimulated luminescence, which was still observable from films left in the dark at room temperature for one week after excitation, and emission color could be varied by changing the trap/emitter molecules. These findings will broadly impact existing applications and provide new prospects for innovative flexible devices.
Interactions of Transforming Growth Factor-β and Angiotensin II in Renal Fibrosis (1998)

Overproduction of transforming growth factor-beta clearly underlies tissue fibrosis in numerous experimental and human diseases. Transforming growth factor-beta's powerful fibrogenic action results from simultaneous stimulation of matrix protein synthesis, inhibition of matrix degradation, and enhanced integrin expression that facilitates matrix assembly. In animals, overexpression of transforming growth factor-beta by intravenous injection, transient gene transfer, or transgene insertion has shown that the kidney is highly susceptible to rapid fibrosis. The same seems true in human disease, where excessive transforming growth factor-beta has been demonstrated in glomerulonephritis, diabetic nephropathy, and hypertensive glomerular injury. A possible explanation for the kidney's particular susceptibility to fibrosis may be the recent discovery of biologically complex interactions between the renin-angiotensin system and transforming growth factor-beta. Alterations in glomerular hemodynamics can activate both the renin-angiotensin system and transforming growth factor-beta. Components of the renin-angiotensin system act to further stimulate production of transforming growth factor-beta and plasminogen activator inhibitor leading to rapid matrix accumulation. In volume depletion, transforming growth factor-beta is released from juxtaglomerular cells and may act synergistically with angiotensin II to accentuate vasoconstriction and acute renal failure. Interaction of the renin-angiotensin system and transforming growth factor-beta has important clinical implications. The protective effect of inhibition of the renin-angiotensin system in experimental and human kidney diseases correlates closely with the suppression of transforming growth factor-beta production. This suggests that transforming growth factor-beta, in addition to blood pressure, should be a therapeutic target. Higher doses or different combinations of drugs that block the renin-angiotensin system or entirely new drug strategies may be needed to achieve a greater antifibrotic effect.
A Sulforaphane Analogue That Potently Activates the Nrf2-dependent Detoxification Pathway (2002)

Exposure of cells to a wide variety of chemoprotective compounds confers resistance to a broad set of carcinogens. For a subset of the chemoprotective compounds, protection is generated by an increase in the abundance of the protective phase II detoxification enzymes, such as glutathione S-transferase (GST). We have recently developed a cell culture system, using rat liver epithelial RL 34 cells, that potently responds to the phenolic antioxidants resulting in the induction of GST activity (Kawamoto, Y., Nakamura, Y., Naito, Y., Torii, Y., Kumagai, T., Osawa, T., Ohigashi, H., Satoh, K., Imagawa, M., and Uchida, K. (2000) J. Biol. Chem. 275, 11291-11299.) In the present study, we investigated the phase II-inducing potency of an isothiocyanate compound in vitro and in vivo and examined a possible induction mechanism. Based on an extensive screening of vegetable extracts for GST inducer activity in RL34 cells, we found Japanese horseradish, wasabi (Wasabia japonica, syn. Eutrema wasabi), as the richest source and identified 6-methylsulfinylhexyl isothiocyanate (6-HITC), an analogue of sulforaphane (4-methylsulfinylbutyl isothiocyanate) isolated from broccoli, as the major GST inducer in wasabi. 6-HITC potently induced both class alpha GSTA1 and class pi GSTP1 isozymes in RL34 cells. In animal experiments, we found that 6-MSHI was rapidly absorbed into the body and induced hepatic phase II detoxification enzymes more potently than sulforaphane. The observations that (i) 6-HITC activated the antioxidant response element (ARE), (ii) 6-HITC induced nuclear localization of the transcription factor Nrf2 that binds to ARE, and (iii) the induction of phase II enzyme genes by 6-HITC was completely abrogated in the nrf2-deficient mice, suggest that 6-HITC is a potential activator of the Nrf2/ARE-dependent detoxification pathway.
Self-Assembled Graphene Hydrogel via a One-Step Hydrothermal Process (2010)

Self-assembly of two-dimensional graphene sheets is an important strategy for producing macroscopic graphene architectures for practical applications, such as thin films and layered paperlike materials. However, construction of graphene self-assembled macrostructures with three-dimensional networks has never been realized. In this paper, we prepared a self-assembled graphene hydrogel (SGH) via a convenient one-step hydrothermal method. The SGH is electrically conductive, mechanically strong, and thermally stable and exhibits a high specific capacitance. The high-performance SGH with inherent biocompatibility of carbon materials is attractive in the fields of biotechnology and electrochemistry, such as drug-delivery, tissue scaffolds, bionic nanocomposites, and supercapacitors.
CERIAS educational outreach (2004)

This poster highlights recent CERIAS Educational Outreach activities, including faculty and curriculum development, continuing education efforts, train-the-trainer material, and self-paced learning options.
ChemInform Abstract: Synthesis and Biological Activity of Heterocyclic Derivatives Derived from Ethyl 2‐Hydroxyquinoxaline‐3‐carboxylate. (1987)

Abstract The thiosemicarbazides (V), which are synthesized from ethyl 2‐chloroquinoxaline‐3‐carboxylate (I), undergo cyclodehydration to give the thiadiazoles (VI).
Canstatin, a Novel Matrix-derived Inhibitor of Angiogenesis and Tumor Growth (2000)

We isolated and identified an endogenous 24-kDa human basement membrane-derived inhibitor of angiogenesis and tumor growth, termed canstatin. Canstatin, a fragment of the alpha2 chain of type IV collagen, was produced as a recombinant molecule in Escherichia coli and 293 embryonic kidneys cells. Canstatin significantly inhibited human endothelial cell migration and murine endothelial cell tube formation. Additionally, canstatin potently inhibited 10% fetal bovine serum-stimulated endothelial cell proliferation and induced apoptosis, with no inhibition of proliferation or apoptosis observed on non-endothelial cells. Inhibition of endothelial proliferation was not concomitant with a change in extracellular signal-regulated kinase activation. We demonstrate that apoptosis induced by canstatin was associated with a down-regulation of the anti-apoptotic protein, FLIP. Canstatin also suppressed in vivo growth of large and small size tumors in two human xenograft mouse models with histology revealing decreased CD31-positive vasculature. Collectively, these results suggest that canstatin is a powerful therapeutic molecule for suppressing angiogenesis.
Synthetic methods and reactions. 141. Fluoride-induced trifluoromethylation of carbonyl compounds with trifluoromethyltrimethylsilane (TMS-CF3). A trifluoromethide equivalent (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthetic methods and reactions. 141. Fluoride-induced trifluoromethylation of carbonyl compounds with trifluoromethyltrimethylsilane (TMS-CF3). A trifluoromethide equivalentG. K. Surya Prakash, Ramesh Krishnamurti, and George A. OlahCite this: J. Am. Chem. Soc. 1989, 111, 1, 393–395Publication Date (Print):January 1, 1989Publication History Published online1 May 2002Published inissue 1 January 1989https://pubs.acs.org/doi/10.1021/ja00183a073https://doi.org/10.1021/ja00183a073research-articleACS PublicationsRequest reuse permissionsArticle Views6365Altmetric-Citations469LEARN 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
An acute lymphoblastic leukemia (ALL) cell line with stem cell phenotype derived by long term co-culture with bone marrow stromal cells (2006)

1022 Accumulating evidence suggests that a sub-population of tumor cells that contribute to relapse of leukemia may be comprised of leukemic stem cells (LSC) characterized by their ability to self-renewal and differentiate to multiple lineages. Their significant proliferative potential emphasizes the need to understand the signals that regulate LSC survival during treatment, include cues provided by bone marrow stromal cells. This information is critical for the development of novel treatment strategies that target LSCs to reduce the potential contribution to relapse of disease. In the current study we sought to determine whether acute lymphoblastic leukemia cells with a LSC phenotype are protected by bone marrow stromal cells during chemotherapy. Further, we investigated the mechanisms underlying stromal cell protection of ALL LSCs. A LSC population with expression of markers consistent with that of a hemangioblast, VE-cadherin+Flk-1+CD31+CD34+CD38+CD19+, was isolated following long term co-culture of the ALL cell line Sup-B15 with murine bone marrow stromal cells. Sup-B15 cells that were maintained in culture with adherent stroma for greater than 2 months formed colonies morphologically comparable to human embryonic stem cell colonies grown on mouse embryonic feeder layers. Consistent with their morphological similarity to human embryonic stem cell derived colonies grown in our laboratory, the tumor cells expressed the stem cell markers SSEA-3, SSEA-4, Oct-4, Tra-1-60 and Tra-1-81. Microarray analysis indicated that Sup-B15 cells with the LSC phenotype had a gene expression profile that was clearly distinguishable from the parent population of Sup-B15 cells grown in media alone. Long term co-culture with stromal cells, as well as exposure to the stromal cell derived growth factor TGF-β up-regulated a variety of molecules involved in the Wnt signaling pathway including Wnt 10a and Wnt16. TGF-β1 treatment of Sup-B15 LSCs also resulted in elevated VE-cadherin expression and stabilization of nuclear beta-catenin, while TGF-β2 or TGF-β3 had no effect on cellular distribution of beta-catenin. These data demonstrate a subpopulation of ALL tumor cells, derived by sustained co-culture with bone marrow stromal cells, may be influenced by factors released from the bone marrow microenvironment. The availability of Sup-B15 sustained in media alone, which does not express stem cell markers, will allow unique comparisons between the “bulk” tumor population and a matched “tumor stem cell” with identical genetic make-up as we strive to understand regulation of the survival of each by the bone marrow microenvironment.
Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo (2003)

Erythropoietin (EPO) is a tissue-protective cytokine preventing vascular spasm, apoptosis, and inflammatory responses. Although best known for its role in hematopoietic lineages, EPO also affects other tissues, including those of the nervous system. Enthusiasm for recombinant human erythropoietin (rhEPO) as a potential neuroprotective therapeutic must be tempered, however, by the knowledge it also enlarges circulating red cell mass and increases platelet aggregability. Here we examined whether erythropoietic and tissue-protective activities of rhEPO might be dissociated by a variation of the molecule. We demonstrate that asialoerythropoietin (asialoEPO), generated by total enzymatic desialylation of rhEPO, possesses a very short plasma half-life and is fully neuroprotective. In marked contrast with rhEPO, this molecule at doses and frequencies at which rhEPO exhibited erythropoiesis, did not increase the hematocrit of mice or rats. AsialoEPO appeared promptly within the cerebrospinal fluid after i.v. administration; intravenously administered radioiodine-labeled asialoEPO bound to neurons within the hippocampus and cortex in a pattern corresponding to the distribution of the EPO receptor. Most importantly, asialoEPO exhibits a broad spectrum of neuroprotective activities, as demonstrated in models of cerebral ischemia, spinal cord compression, and sciatic nerve crush. These data suggest that nonerythropoietic variants of rhEPO can cross the blood-brain barrier and provide neuroprotection.
Patterns of Drug Use Amongst Police Detainees: 1999-2000 (2000)

Drug Use Monitoring in Australia is the only project in Australia that is routinely monitoring the use of illicit drugs by people detained by police. The results presented in this paper describe the extent of illicit drug use every three months in four sites across Australia.
Evolution scenario of broadband services based on granulated broadband network concept (2003)

An evolution scenario of broadband services is proposed with a new asynchronous transfer mode (ATM) platform concept named granulated broadband network (GBN). High-speed LAN interconnection service will be the first ATM broadband application, followed by ATM public switched services for medium-sized customers providing a flexible information outlet with several megabits-per-second capacity. These ATM private network and public switched services can be achieved economically by constructing a GBN platform on which all information carried by existing public switched telephone network (PSTN) services as well as broadband services is transformed into ATM cells at subscriber line terminals or at customer premises.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Naturally formed or artificially reconstituted non-covalent alpha2-macroglobulin-peptide complexes elicit CD91-dependent cellular immunity. (2002)

Immunization of mice with in vitro reconstituted alpha2-macroglobulin-peptide complexes primes peptide-specific CTL responses. We show here using the H-Y antigenic system that naturally produced, immunogenic alpha2-macroglobulin-peptide complexes can be isolated from the sera of normal male mice. As an application of these ideas to cancer immunity, we show that the immunity evoked by alpha2-macroglobulin-peptide complexes reconstituted in vitro is effective in prophylaxis against tumors. Furthermore, complex peptide mixtures isolated from tumor lysates can be reconstituted non-covalently with alpha2-macroglobulin and such complexes elicit potent protective tumor immunity. This approach circumvents the need for prior knowledge of the identity of the immunogenic peptides. The heat shock protein/alpha2-macroglobulin receptor CD91 is shown to be involved in the ability of heat shock proteins or alpha2-macroglobulin to elicit an anti-tumor immune response.
Direct, genome-wide assessment of DNA mutations in single cells (2011)

DNA mutations are the inevitable consequences of errors that arise during replication and repair of DNA damage. Because of their random and infrequent occurrence, quantification and characterization of DNA mutations in the genome of somatic cells has been difficult. Random, low-abundance mutations are currently inaccessible by standard high-throughput sequencing approaches because they cannot be distinguished from sequencing errors. One way to circumvent this problem and simultaneously account for the mutational heterogeneity within tissues is whole genome sequencing of a representative number of single cells. Here, we show elevated mutation levels in single cells from Drosophila melanogaster S2 and mouse embryonic fibroblast populations after treatment with the powerful mutagen N-ethyl-N-nitrosourea. This method can be applied as a direct measure of exposure to mutagenic agents and for assessing genotypic heterogeneity within tissues or cell populations.
Role of fructose 2,6-bisphosphate in the control of glycolysis in mammalian tissues (1987)

bisphosphate; Fru-2,6-P2, fructose 2,6-bisphosphate; PFK-1, 6-phosphofructo-I-kinase; PFK-2, 6-phosphofructo-2-kinase; FBPase-1, fructose 1
A PRACTICAL METHOD FOR MEASURING THE RESILIENT MODULUS OF ASPHALT-TREATED MIXES (1972)

A NEW METHOD IS PRESENTED FOR DETERMINING THE RESILIENT MODULUS OF ASPHALT-TREATED MIXES. IT IS LOW IN COST AND IS MORE RAPID THAN THE CURRENTLY USED ROUTINE STABILITY TESTS. VALIDITY OF THE METHOD IS SUPPORTED BY ITS REASONABLE AGREEMENT WITH THE RESILIENT MODULUS VALUES DETERMINED BY DIRECT RESILIENT MODULUS TENSILE MEASUREMENTS ON A VARIETY OF POLYMERIC SAMPLES. EVEN WHEN A RELATIVELY WIDE RANGE OF VALUES IS ASSUMED FOR POISSON'S RATIO, THE DIAMETRAL METHOD GIVES RESILIENT MODULUS VALUES WITHIN 25 PERCENT OF THE VALUES FOUND BY DIRECT MEASUREMENT OF THE TENSILE OR COMPRESSIVE RESILIENT MODULUS ON ASPHALT CONCRETE MIXES. RESILIENT MODULUS VALUES DETERMINED FLEXURALLY AGREE ALMOST AS WELL. THE USEFULNESS OF THE METHOD IN DESIGNING ASPHALT-TREATED MIXES FOR OPTIMUM RESILIENT MODULUS IS SHOWN BY AN EXAMPLE OF A MIX DESIGN RELATING ASPHALT CONTENT TO THE RESILIENT MODULUS. /AUTHOR/
Base‐hydrolyzed starch‐polyacrylonitrile (S‐PAN) graft copolymer. S‐PAN‐1:1, PAN M.W. 794,000 (1969)

Abstract Starch‐polyacrylonitrile (S‐PAN) graft copolymer consisting of one part starch and one part polyacrylonitrile (M. W. 794,000) was hydrolyzed with aqueous KOH at 80 and 100°C to polyelectrolytes containing carboxyl and amide functionality but void of infrared‐detectable amounts of nitrile. Viscosities of potassium salts of the polyelectrolytes in water were pH dependent with peak viscosities at 8.5. These dispersions were characterized by unusually high viscosities, 15,000 to 26,500 cp at 1% concentration, and by the ability to retain significant viscosities, 300 to 950 cp, upon dilution to 0.03% concentrations. A 1% dispersion of hydrolyzed S‐PAN had a viscosity of 5,000 cp in the presence of 8% KCl; however, the depressing effect of added salts on viscosity of aqueous dispersions of hydrolyzed S‐PAN increases as the valence of the cation increases.
Hardware Support for Tamper-Resistant and Copy-Resistant Software (2000)

Although there have been many attempts to develop code transformations that yield tamper-resistant software, no reliable software-only methods are known. Motivated by numerous potential applications, we investigate a prototype hardware mechanism that supports software tamper-resistance with an atomic decrypt-and-execute operation. Our hardware architecture uses a novel combination of standard architectural units. As usual, security has its costs. In this design, the most difficult security tradeoffs involve testability and performance.
Syntrophin-dependent expression and localization of Aquaporin-4 water channel protein (2001)

The Aquaporin-4 (AQP4) water channel contributes to brain water homeostasis in perivascular astrocyte endfeet where it is concentrated. We postulated that AQP4 is tethered at this site by binding of the AQP4 C terminus to the PSD95-Discs large-ZO1 (PDZ) domain of syntrophin, a component of the dystrophin protein complex. Chemical cross-linking and coimmunoprecipitations from brain demonstrated AQP4 in association with the complex, including dystrophin, beta-dystroglycan, and syntrophin. AQP4 expression was studied in brain and skeletal muscle of mice lacking alpha-syntrophin (alpha-Syn(-/-)). The total level of AQP4 expression appears normal in brains of alpha-Syn(-/-) mice, but the polarized subcellular localization is reversed. High-resolution immunogold analyses revealed that AQP4 expression is markedly reduced in astrocyte endfeet membranes adjacent to blood vessels in cerebellum and cerebral cortex of alpha-Syn(-/-) mice, but is present at higher than normal levels in membranes facing neuropil. In contrast, AQP4 is virtually absent from skeletal muscle in alpha-Syn(-/-) mice. Deletion of the PDZ-binding consensus (Ser-Ser-Val) at the AQP4 C terminus similarly reduced expression in transfected cell lines, and pulse-chase labeling demonstrated an increased degradation rate. These results demonstrate that perivascular localization of AQP4 in brain requires alpha-Syn, and stability of AQP4 in the membrane is increased by the C-terminal PDZ-binding motif.