gebhart/patrepeval huggingface dataset:
Responses of Pathogenic and Nonpathogenic Yeast Species to Steroids Reveal the Functioning and Evolution of Multidrug Resistance Transcriptional Networks (2007)

Steroids are known to induce pleiotropic drug resistance states in hemiascomycetes, with tremendous potential consequences for human fungal infections. Our analysis of gene expression in Saccharomyces cerevisiae and Candida albicans cells subjected to three different concentrations of progesterone revealed that their pleiotropic drug resistance (PDR) networks were strikingly sensitive to steroids. In S. cerevisiae, 20 of the Pdr1p/Pdr3p target genes, including PDR3 itself, were rapidly induced by progesterone, which mimics the effects of PDR1 gain-of-function alleles. This unique property allowed us to decipher the respective roles of Pdr1p and Pdr3p in PDR induction and to define functional modules among their target genes. Although the expression profiles of the major PDR transporters encoding genes ScPDR5 and CaCDR1 were similar, the S. cerevisiae global PDR response to progesterone was only partly conserved in C. albicans. In particular, the role of Tac1p, the main C. albicans PDR regulator, in the progesterone response was apparently restricted to five genes. These results suggest that the C. albicans and S. cerevisiae PDR networks, although sharing a conserved core regarding the regulation of membrane properties, have different structures and properties. Additionally, our data indicate that other as yet undiscovered regulators may second Tac1p in the C. albicans drug response.
Multilayer Active Shell Mirrors (2015)

This thesis presents a novel active mirror technology based on carbon fiber composites and replication manufacturing processes. Multiple additional layers are implemented into the structure in order to provide the reflective layer, actuation capabilities and electrode routing. The mirror is thin, lightweight, and has large actuation capabilities. These features, along with the associated manufacturing processes, represent a significant change in design compared to traditional optics. Structural redundancy in the form of added material or support structures is replaced by thin, unsupported lightweight substrates with large actuation capabilities. Several studies motivated by the desire to improve as-manufactured figure quality are performed. Firstly, imperfections in thin CFRP laminates and their effect on post-cure shape errors are studied. Numerical models are developed and compared to experimental measurements on flat laminates. Techniques to mitigate figure errors for thicker laminates are also identified. A method of properly integrating the reflective facesheet onto the front surface of the CFRP substrate is also presented. Finally, the effect of bonding multiple initially flat active plates to the backside of a curved CFRP substrate is studied. Figure deformations along with local surface defects are predicted and characterized experimentally. By understanding the mechanics behind these processes, significant improvements to the overall figure quality have been made. Studies related to the actuation response of the mirror are also performed. The active properties of two materials are characterized and compared. Optimal active layer thicknesses for thin surface-parallel schemes are determined. Finite element simulations are used to make predictions on shape correction capabilities, demonstrating high correctabiliity and stroke over low-order modes. The effect of actuator saturation is studied and shown to significantly degrade shape correction performance. The initial figure as well as actuation capabilities of a fully-integrated active mirror prototype are characterized experimentally using a Projected Hartmann test. A description of the test apparatus is presented along with two verification measurements. The apparatus is shown to accurately capture both high-amplitude low spatial-frequency figure errors as well as those at lower amplitudes but higher spatial frequencies. A closed-loop figure correction is performed, reducing figure errors by 94%.
GDF-15 Contributes to Proliferation and Immune Escape of Malignant Gliomas (2010)

Although previous studies focusing on ectopic overexpression of GDF-15 have proposed unclear or antitumorigenic effects of GDF-15 in glioma cells, we here show that GDF-15 at endogenous levels contributes to proliferation and immune escape of malignant gliomas in an immunocompetent host.
The use of exonuclease III for preparing single stranded DNA for use as a template in the chain terminator sequencing method (1979)

Exonuclease III, which degrades DNA 3' leads to 5' and is specific for duplex DNA, can be used to prepare single stranded DNA from linear duplexes. This is shown to be suitable as a template for use with the chain terminator DNA sequencing method of Sanger et al. [1]. Strategies are discussed for preparing single stranded DNA templates by this method and, in particular, its application to the sequence analysis of DNA cloned in plasmid vectors.
Targeting lung cancer through inhibition of checkpoint kinases (2015)

Inhibitors of checkpoint kinases ATR, Chk1, and Wee1 are currently being tested in preclinical and clinical trials. Here, we review the basic principles behind the use of such inhibitors as anticancer agents, and particularly discuss their potential for treatment of lung cancer. As lung cancer is one of the most deadly cancers, new treatment strategies are highly needed. We discuss how checkpoint kinase inhibition in principle can lead to selective killing of lung cancer cells while sparing the surrounding normal tissues. Several features of lung cancer may potentially be exploited for targeting through inhibition of checkpoint kinases, including mutated p53, low ERCC1 levels, amplified Myc, tumor hypoxia and presence of lung cancer stem cells. Synergistic effects have also been reported between inhibitors of ATR/Chk1/Wee1 and conventional lung cancer treatments, such as gemcitabine, cisplatin, or radiation. Altogether, inhibitors of ATR, Chk1, and Wee1 are emerging as new cancer treatment agents, likely to be useful in lung cancer treatment. However, as lung tumors are very diverse, the inhibitors are unlikely to be effective in all patients, and more work is needed to determine how such inhibitors can be utilized in the most optimal ways.
[Deep nonpenetrating sclerectomy and open angle glaucoma. Intermediate results from the first operated patients]. (1999)

NPDS is an interesting alternative to the classical trabeculectomy since the post operative complications are markedly reduced. However, the mid-term control in IOP appears to be slightly lower. The use of a collagen device does not lead to better control in IOP as compared to the use of a sponge of 5 FU.
A high association with cone dystrophy in Fundus albipunctatus caused by mutations of the RDH5 gene. (2000)

Fundus albipunctatus either with or without cone dystrophy is caused by mutations of the RDH5 gene. Cone dystrophy is frequently observed in elderly patients with fundus albipunctatus. The conclusion was reached that the mutations of the RDH5 gene caused a progressive cone dystrophy as well as night blindness.
Internalization of [DOTA°,125I‐Tyr3]Octreotide by Somatostatin Receptor–Positive Cells In Vitro and In Vivo: Implications for Somatostatin Receptor–Targeted Radio‐guided Surgery (1999)

We compared internalization of three radioiodinated octreotide (OCT) somatostatin (SS) analogs-[125I-Tyr3]OCT, [DTPA degrees, 125I-Tyr3]OCT, and [DOTA degrees,125I-Tyr3]OCT-by somatostatin receptor (SSR)-positive mouse AtT20 pituitary tumor cells and human insulinoma cells. The three SS analogs were internalized in a specific, time-dependent manner. Internalization was significantly inhibited by pertussis toxin (100 microg/l) by 38%, 43%, and 31%, and by an inhibitor of receptor-mediated endocytosis (phenyl arsine oxide; 10 microM) by 98%, 94%, and 92%, respectively. Binding affinities of the three radioligands were comparable (0.2, 0.2, and 0.3 nM, respectively). However, [DOTA degrees,125I-Tyr3]OCT was internalized in a five-fold higher amount in comparison with the two other radioligands. A comparably high uptake of [DOTA degrees, 125I-Tyr3]OCT was found in SSR-positive organs (pituitary, pancreas, and adrenals) in vivo in rats (a ten-fold, five-fold, and eight-fold higher uptake 4 hr post injection, respectively, compared with the two other radioligands). This resulted in very high target-background ratios for [DOTA degrees,125I-Tyr3]OCT 4 hr post injection amounting to 274, 566, and 623 in the pituitary, adrenals, and pancreas, respectively. Both in vivo and in vitro there was a rapid dissociation of radioactivity from the SSR-positive cells. Main conclusions are that: 1) coupling of chelating groups like DTPA or DOTA to the SS analog [Tyr3]OCT does not prevent the internalization of OCT after binding to SSRs; 2) [DOTA degrees, 125I-Tyr3]OCT is internalized in a significantly higher amount by AtT20 and human insulinoma cells and in vivo in rats in SSR-positive organs, in comparison with [DTPA degrees,125I-Tyr3]OCT and [125I-Tyr3]OCT; and 3) the very high target-background ratios in vivo make radioiodinated [DOTA degrees,Tyr3]OCT a very suitable ligand for SSR-targeted radioguided surgery of SSR-positive human neuroendocrine tumors.
Adhesion Receptors as Therapeutic Targets (1995)

Cell adhesion receptors and their ligands as therapeutic targets - an overview, M.A. Horton laminin isoforms and their integrin receptors, G.O. Delwel and A. Sonnenberg the intracellular adhesion molecules (ICAMs), C. Gahmberg et al selectins and their ligands, S. Watson functional domains of cell adhesion molecules, A.P. Mould and M.J. Humphries signal transduction by integrins and other adhesion receptors, R.J. Juliano regulation of integrin mediated adhesion, R.C. Bates and G. Burns Adhesive platelet glycoproteins and platelet function, N. Keiffer leukocyte-endothelium interactions, C. Godin adhesion receptors in epithelial tumours, M. Pignatelli and J. Wilding anti-adhesive extracellular matrix proteins, J. Lawler integrins as therapeutic targets in bone disease, M.A. Horton and G. rodan identification and development of integrin/ligand antagonists for the treatment of human disease, T. Gadek and B.K. Blackburn adhesion molecules and cytokines in experimental inflammatory disease, P.A. Ward preclinical development of c7E3 Fab - a mouse/human chimeric monoclonal antibody fragment that inhibits platelet function by blockade of GPIIb/IIIa receptors with observations on the immunogenicity of c7E3 Fab in humans, R.E. Jordan et al clinical trials of adhesion receptor antagonists in renal transplantation, B. le Mauff and M. Hourmant.
A Novel Recombinant Vaccinia Virus Expressing the Human Norepinephrine Transporter Retains Oncolytic Potential and Facilitates Deep-Tissue Imaging (2009)

Noninvasive and repetitive monitoring of a virus in target tissues and/or specific organs of the body is highly desirable for the development of safe and efficient cancer virotherapeutics. We have previously shown that the oncolytic vaccinia virus GLV-1h68 can target and eradicate human tumors in mice and that its therapeutic effects can be monitored by using optical imaging. Here, we report on the development of a derivative of GLV-1h68, a novel recombinant vaccinia virus (VACV) GLV-1h99, which was constructed to carry the human norepinephrine transporter gene (hNET) under the VACV synthetic early promoter placed at the F14.5L locus for deep-tissue imaging. The hNET protein was expressed at high levels on the membranes of cells infected with this virus. Expression of the hNET protein did not negatively affect virus replication, cytolytic activity in cell culture, or in vivo virotherpeutic efficacy. GLV-1h99-mediated expression of the hNET protein in infected cells resulted in specific uptake of the radiotracer [131I]-meta-iodobenzylguanidine (MIBG). In mice, GLV-1h99-infected tumors were readily imaged by [124I]-MIBG positron emission tomography. To our knowledge, GLV-1h99 is the first oncolytic virus expressing the hNET protein that can efficiently eliminate tumors and simultaneously allow deep-tissue imaging of infected tumors.
<title>Alternating phase-shift generation for complex circuit designs</title> (1996)

One of the main challenges for the industrialization of the alternating phase shift mask technique is the geometrical design of the phase shifters. The problem is complex and software development is required to achieve automation. This data preparation is necessary in order to apply the most powerful optical enhancement technique, the alternating PSM, to the gate lithography of logic designs. After the implementation of an algorithm, very promising on small flat geometrical designs of a few hundred transistors, it has been decided to test this software on complete circuits. This paper deals with the issues associated with alternating pattern generation on complex circuits. In particular, the use of layout hierarchy is essential to obtain an acceptable amount of manual intervention and computer processing time. There are two kinds of limitations to this global approach. First, the overlapping or the proximity of cells in the hierarchy may not be compatible with a cell-by-cell generation of phase shifters. Secondly, some local design configurations may be difficult to phase shift. The question is: `is the number of occurrences of such cases manageable?' This presentation is illustrated by our experience on a multiplier design of about 15000 transistors, created using a standard cell library in 0.25 micron technology. This work shows that the theoretically difficult cases of layout hierarchy or geometrical design are not critical in practice. In particular, the design method based on standard cell libraries creates a hierarchy which is very favorable to our approach. This article presents a method for the alternating pattern generation on complex circuits which is based on two main points: first, on a software able to generate alternating phase shifters on small flat cells, and secondly, on the advantage of using layout hierarchy.
Sets of short tandem repeat polymorphisms for efficient linkage screening of the human genome (1995)

For the purpose of initial screening of the human genome in linkage mapping, two overlapping sets of high quality short tandem repeat polymorphisms (STRPs) which span the autosomes have been assembled. The higher density set contains a total of 363 markers with an average heterozygosity of 79% and an average sex-equal genetic distance between markers of 10.5 cM. The lower density set, which is a subset of the other, contains 156 markers with an average heterozygosity of 80% and an average spacing of 26.5 cM. Tri- and tetranucleotide STRPs comprised 47 and 63%, respectively, of the markers within the higher and lower density sets. Markers within the screening sets were selected to have maximum quality, where quality was defined as a blend of high informativeness, strong amplification under standard PCR conditions, low amplification background, and ease in scoring. The screening sets along with combinations of STRPs which can be amplified and electrophoresed simultaneously are available electronically through anonymous ftp.
Synchronization of multimedia data for a multimedia news-on-demand application (1996)

We present a complete software control architecture for synchronizing multiple data streams generated from distributed media-storing database servers without the use of a global clock. Independent network connections are set up to remote workstations for multimedia presentations. Based on the document scenario and traffic predictions, stream delivery scheduling is performed in a centralized manner. Certain compensation mechanisms at the receiver are also necessary due to the presence of random network delays. A stream synchronization protocol (SSP) allows for synchronization recovery, ensuring a high quality multimedia display at the receiver. SSP uses synchronization quality of service parameters to guarantee the simultaneous delivery of the different types of data streams. In the proposed architecture, a priority-based synchronization control mechanism for MPEG-2 coded data streams is also provided. A performance modeling of the SSP is presented using the DSPN models. Relevant results such as the effect of the SSP, the number of synchronization errors, etc., are obtained.
Azacitidine for Front-Line Therapy of Patients with AML: Reproducible Efficacy Established by Direct Comparison of International Phase 3 Trial Data with Registry Data from the Austrian Azacitidine Registry of the AGMT Study Group (2017)

We recently published a clinically-meaningful improvement in median overall survival (OS) for patients with acute myeloid leukaemia (AML), >30% bone marrow (BM) blasts and white blood cell (WBC) count ≤15 G/L, treated with front-line azacitidine versus conventional care regimens within a phase 3 clinical trial (AZA-AML-001; NCT01074047; registered: February 2010). As results obtained in clinical trials are facing increased pressure to be confirmed by real-world data, we aimed to test whether data obtained in the AZA-AML-001 trial accurately represent observations made in routine clinical practice by analysing additional AML patients treated with azacitidine front-line within the Austrian Azacitidine Registry (AAR; NCT01595295; registered: May 2012) and directly comparing patient-level data of both cohorts. We assessed the efficacy of front-line azacitidine in a total of 407 patients with newly-diagnosed AML. Firstly, we compared data from AML patients with WBC ≤ 15 G/L and >30% BM blasts included within the AZA-AML-001 trial treated with azacitidine ("AML-001" cohort; <i>n</i> = 214) with AAR patients meeting the same inclusion criteria ("AAR (001-like)" cohort; <i>n</i> = 95). The current analysis thus represents a new sub-analysis of the AML-001 trial, which is directly compared with a new sub-analysis of the AAR. Baseline characteristics, azacitidine application, response rates and OS were comparable between all patient cohorts within the trial or registry setting. Median OS was 9.9 versus 10.8 months (<i>p</i> = 0.616) for "AML-001" versus "AAR (001-like)" cohorts, respectively. Secondly, we pooled data from both cohorts (<i>n</i> = 309) and assessed the outcome. Median OS of the pooled cohorts was 10.3 (95% confidence interval: 8.7, 12.6) months, and the one-year survival rate was 45.8%. Thirdly, we compared data from AAR patients meeting AZA-AML-001 trial inclusion criteria (<i>n</i> = 95) versus all AAR patients with World Health Organization (WHO)-defined AML ("AAR (WHO-AML)" cohort; <i>n</i> = 193). Within the registry population, median OS for AAR patients meeting trial inclusion criteria versus all WHO-AML patients was 10.8 versus 11.8 months (<i>p</i> = 0.599), respectively. We thus tested and confirmed the efficacy of azacitidine as a front-line agent in patients with AML, >30% BM blasts and WBC ≤ 15 G/L in a routine clinical practice setting. We further show that the efficacy of azacitidine does not appear to be limited to AML patients who meet stringent clinical trial inclusion criteria, but instead appears efficacious as front-line treatment in all patients with WHO-AML.
Synthesis and Characterization of Rhodium Complexes Containing 2,4,6-Tris(2-pyridyl)-1,3,5-triazine and Its Metal-Promoted Hydrolytic Products: Potential Uses of the New Complexes in Electrocatalytic Reduction of Carbon Dioxide (1998)

The reaction of 2,4,6-tris(2-pyridyl)-1,3,5-triazine (tptz) with RhCl3·3H2O has been studied under different experimental conditions. This reaction in ethanol resulted in the formation of [Rh(tptz)Cl3]·2H2O (1), whereas the bis-chelate complex [Rh(tptz)2][ClO4]3·2H2O (2) was obtained in a two-step reaction in acetone; the chlorides from RhCl3 were removed in the first step using AgClO4, and the ligand tptz was added in the second step. Complexes 1 and 2, when refluxed in ethanol−water (1:1), resulted in metal-promoted hydrolysis of tptz to bis(2-pyridylcarbonyl)amide anion (bpca) and 2-picolinamide (pa), yielding the complexes [Rh(bpca)(pa)Cl][PF6]·H2O (3) and [Rh(bpca)2][ClO4] (6), respectively. A mixed-ligand complex, [Rh(bpca)(tpy)][PF6]2·CH3CN (4), was obtained by the reaction of either 1 with tpy or [Rh(tpy)Cl3] (5) with tptz in ethanol−water medium. The crystal structures of complexes 1 and 4 have been determined. Crystal data: complex 1, monoclinic, P21/c, a = 11.642(2) Å, b = 7.302(2) Å, c = 24.332(3) Å, β = 96.420(10)°, Z = 4, R = 0.040, and wR2 = 0.117; complex 4, triclinic, P1̄, a = 9.581(1) Å, b = 12.933(2) Å, c = 14.493(2) Å, α = 82.480(10)°, β = 71.810(10)°, γ = 75.100(10)°, Z = 2, R = 0.030, and wR2 = 0.082. The two water molecules of complex 1 make short contacts with the carbon atoms adjacent to the metal-bound nitrogen atom of the triazine ring; this observation provides some insight about the "intermediate" of the hydrolysis. X-ray and NMR data suggest that the electron-withdrawing effect of the metal ion is the major responsible factor for the hydrolysis of tptz. The cyclic voltammograms of the complexes exhibit a metal-based 2e reduction (Rh(III) → Rh(I)) at the potential range −0.42 to −0.98 V vs SCE, followed by ligand-based redox couple(s). These novel complexes show effective catalytic properties for the electrocatalytic reduction of carbon dioxide in the potential range −1.26 to −1.44 V.
Fuzzy concepts in expert systems (1988)

The authors present a comprehensive expert-system building tool, called System Z-II, that can deal with exact, fuzzy (or inexact), and combined reasoning, allowing fuzzy and normal terms to be freely mixed in the rules and facts of an expert system. This fully implemented tool has been used to build several expert systems in the fields of student curriculum advisement, medical diagnosis, psychoanalysis, and risk analysis. System Z-II is a rule-based system that uses fuzzy logic and fuzzy numbers for its inexact reasoning. It uses two basic inexact concepts, fuzziness and uncertainty, which are distinct from each other in the system.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Fingolimod Immune Effects Beyond Its Sequestration Ability (2019)

Fingolimod is the first orally administered drug approved for the treatment of relapsing-remitting multiple sclerosis (MS). This drug, modulating sphingosine receptors, regulates the trafficking of lymphocytes between primary and secondary lymphoid organs, trapping naïve T cells and central memory T cells in secondary lymphoid organs, without affecting effector memory T cells and therefore without compromising immunosurveillance. Additionally, fingolimod inhibits expression of Th1 and Th17 cytokines and enhances regulatory T-cell differentiation. It also acts on the B arm of immunity through an increased ratio of naïve to memory B cells, higher percentage of plasma cells, and highly increased proportion of transitional B cells as well as additional regulatory subsets. Fingolimod treatment enhances the capacity of regulatory B cells to transmigrate across brain endothelial cells. In fact, patients treated with fingolimod have increased regulatory B-cell frequency in the cerebrospinal fluid. These findings suggest a novel role for fingolimod in MS, by both direct effects and indirect partitioning effects on lymphocytes.