gebhart/patrepeval huggingface dataset:
DbClustal: rapid and reliable global multiple alignments of protein sequences detected by database searches (2000)

DbClustal addresses the important problem of the automatic multiple alignment of the top scoring full-length sequences detected by a database homology search. By combining the advantages of both local and global alignment algorithms into a single system, DbClustal is able to provide accurate global alignments of highly divergent, complex sequence sets. Local alignment information is incorporated into a ClustalW global alignment in the form of a list of anchor points between pairs of sequences. The method is demonstrated using anchors supplied by the Blast post-processing program, Ballast. The rapidity and reliability of DbClustal have been demonstrated using the recently annotated Pyrococcus abyssi proteome where the number of alignments with totally misaligned sequences was reduced from 20% to <2%. A web site has been implemented proposing BlastP database searches with automatic alignment of the top hits by DbClustal.
High-Dose Therapy and Autologous Bone Marrow Transplantation after Failure of Conventional Chemotherapy in Adults with Intermediate-Grade or High-Grade Non-Hodgkin's Lymphoma (1987)

Adult patients with advanced non-Hodgkin's lymphoma in whom conventional chemotherapy has failed are seldom cured thereafter. We studied 100 such patients with intermediate-grade or high-grade non-Hodgkin's lymphoma who were subsequently treated with high-dose chemotherapy (61 patients) or high-dose chemotherapy plus total-body irradiation (39 patients), with bone marrow transplantation used for hematologic support. Thirty-four patients had disease that had been refractory to primary chemotherapy, and 66 patients had had a complete remission with primary chemotherapy but later relapsed. Before autologous bone marrow transplantation and high-dose chemotherapy, the 66 relapsed patients had also received conventional salvage chemotherapy; 22 had had no response or had had disease progression (a response termed "resistant relapse"), and 44 patients had responded partially or completely (a response termed "sensitive relapse"). After high-dose therapy and bone marrow transplantation, the actuarial three-year disease-free survival was zero in the refractory group, 14 percent in the resistant-relapse group, and 36 percent in the sensitive-relapse group. Patients who had had a complete remission in response to initial chemotherapy had a higher disease-free survival rate than those who had not (P less than 0.001), and patients with sensitive relapse had a higher disease-free survival rate than those with resistant relapse (P less than 0.003). These results should be considered in the planning or interpretation of trials of salvage chemotherapy in adults with non-Hodgkin's lymphoma.
Effect of stereospecificity of chemically synthesized lipid A‐subunit analogues GLA‐27 and GLA‐40 on the expression of immunopharmacological activities (1987)

Tumor necrosis factor (TNF)-inducing, mitogenic, polyclonal B cell activation (PBA), macrophage activation and antiviral activities of chemically synthesized lipid A-subunit analogues, GLA-27 and GLA-40, were investigated. The structure of GLA-27 comprises 4-O-phosphono-D-glucosamine carrying tetradecanoyl and 3-tetradecanoyloxytetradecanoyl [C14-O-(C14)] groups as the 3-O- and 2-N-acyl substituents, respectively. GLA-40 is a 1-deoxy compound of GLA-27. The activities of stereoisomers, (R) and (S) forms at the C3 position of the C14-O-(C14) group, of both compounds were also investigated. TNF-inducing activity of the (S) isomers of GLA-27 and GLA-40 was stronger than that of the (R) isomers while the (R) isomers exhibited stronger mitogenic and PBA activities than the (S) isomers. With respect to macrophage activation such as phagocytosis, acid phosphatase and N-acetyl-beta-D-glucosaminidase activity as cellular lysosomal enzymes and cytostasis, peritoneal macrophages obtained from mice administered i.p. with test samples showed significant activities. Among stereoisomers of GLA-27, the (R) isomer exhibited somewhat stronger phagocytic and lysosomal enzyme activities than those of the (S) isomer while there was no appreciable difference in the activities between the isomers of GLA-40. Significant cytostasis-inducing activity was observed in stereoisomers tested. All of the isomers showed remarkable antiviral activity against vaccinia virus.
Tumor necrosis factor receptor deficiency exacerbated Adriamycin-induced cardiomyocytes apoptosis: an insight into the Fas connection (2006)

Cardiomyopathy is a major dose-limiting factor for applications of Adriamycin, a potent chemotherapeutic agent. The present study tested the hypothesis that increased tumor necrosis factor (TNF)-alpha signaling via its receptors protects against Adriamycin-induced cardiac injury. We used mice in which both TNF receptor I and II have been selectively inactivated (DKO) with wild-type mice as controls. Morphometric studies of cardiac tissue following Adriamycin treatment revealed greater ultrastructural damage in cardiomyocyte mitochondria from DKO mice. Biochemical studies of cardiac tissues showed cytochrome c release and the increase in proapoptotic protein levels, suggesting that lack of TNF-alpha receptor I and II exacerbates Adriamycin-induced cardiac injury. The protective role of TNF receptor I and II was directly confirmed in isolated primary cardiomyocytes. Interestingly, following Adriamycin treatment, the levels of Fas decreased in the wild-type mice. In contrast, DKO mice had an increase in Fas levels and its downstream target, mitochondrial truncated Bid. These results suggested that TNF-alpha receptors play a critical role in cardioprotection by suppression of the mitochondrial-mediated associated cell death pathway.
Induction of Human Dendritic Cell Maturation Using Transfection with RNA Encoding a Dominant Positive Toll-Like Receptor 4 (2004)

Maturation of dendritic cells (DC) is critical for the induction of Ag-specific immunity. Ag-loaded DC matured with LPS, which mediates its effects by binding to Toll-like receptor 4 (TLR4), induce Ag-specific CTL in vitro and in vivo in animal models. However, clinical use of LPS is limited due to potential toxicity. Therefore, we sought to mimic the maturation-inducing effects of LPS on DC by stimulating TLR4-mediated signaling in the absence of exogenous LPS. We developed a constitutively active TLR4 (caTLR4) and demonstrated that transfection of human DC with RNA encoding caTLR4 led to IL-12 and TNF-alpha secretion. Transfection with caTLR4 RNA also induced a mature DC phenotype. Functionally, transfection of DC with caTLR4 RNA enhanced allostimulation of CD4(+) T cells. DC transfected with RNA encoding the MART (Melan-A/MART-1) melanoma Ag were then used to stimulate T cells in vitro. Cotransfection of these DC with caTLR4 RNA enhanced the generation of MART-specific CTL. This CTL activity was superior to that seen when DC maturation was induced using either LPS or a standard mixture of cytokines (TNF-alpha, IL-6, IL-1beta, and PGE(2)). We conclude that transfection of DC with RNA encoding a functional signaling protein, such as caTLR4, may provide a new tool for studying TLR signaling in DC and may be a promising approach for the induction of DC maturation for tumor immunotherapy.
Synthesis and Structure−Activity Relationships of 6,7-Benzomorphan Derivatives as Antagonists of the NMDA Receptor−Channel Complex (1997)

We have synthesized a series of stereoisomeric 6,7-benzomorphan derivatives with modified N-substituents and determined their ability to antagonize the N-methyl-D-aspartate (NMDA) receptor-channel complex in vitro and in vivo. The ability of the compounds to displace [3H]-MK-801 from the channel site of the NMDA receptor in rat brain synaptosomal membranes and to inhibit NMDA-induced lethality in mice was compared with their ability to bind to the mu opioid receptor. Examination of structure-activity relationships showed that the absolute stereochemistry is critically important for differentiating these two effects. (-)-1R,9 beta,2"S-enantiomers exhibited a higher affinity for the NMDA receptor-channel complex than for the mu opioid receptor. The aromatic hydroxy function was also found to influence the specificity of the compounds. Shift of the hydroxy group from the 2'-position to the 3'-position significantly increased the affinity for the NMDA receptor-channel complex and considerably reduced the affinity for the mu opioid receptor. From this series of 6,7-benzomorphan derivatives, the compound 15cr.HCl [(2R)-[2 alpha, 3(R*),6 alpha]-1,2,3,4,5,6-hexahydro-3-(2-methoxypropyl)-6,11,11-trimethyl -2,6-methano-3-benzazocin-9-ol hydrochloride] was chosen as the optimum candidate for further pharmacological investigations.
Topical Antibiotic, Antifungal, and Antiseptic Solutions Decrease Ciliary Activity in Nasal Respiratory Cells (2002)

This study was designed to investigate whether topical solutions, as they are used in the treatment of selected cases of rhinosinusitis, influence nasal mucociliary clearance. The objective of this study was to evaluate the effects of the following topical solutions on the ciliary beat frequency (CBF) of nasal respiratory cells: ofloxacin as an antibiotic; Betadine and hydrogen peroxide (H2O2) as antiseptic; and amphotericin B, itraconazole, and clotrimazole as antifungal solutions. Differences are described between effects of each of these substances and we clarify whether ciliotoxic effects are dose dependent and if they can be reduced or eliminated by diluting the concentration of the applied solution. In a prospective study, nasal respiratory cells were harvested from healthy individuals and CBF was measured while cells were perfused with cell culture medium and the respective topical solution, using a Dvorak/Stotler exposure chamber. Controls were perfused with cell culture medium only. Video interference contrast microscopy was used to monitor CBF. A decrease of CBF occurred after application of all topical solutions used in this study. Except for clotrimazole, all solutions showed significantly stronger effects at high concentrations compared with diluted solutions. Our results indicate that topical application of antifungal, antibiotic, and antiseptic solutions may cause a marked impairment of mucociliary clearance. The strong dose dependence of these ciliotoxic effects indicates the need for a careful selection of the adequate concentration when using topical treatment in the nose.
IDF: A graphical data flow programming language for image processing and computer vision (2002)

Data-flow languages and visual programming environments are reviewed. The iconic data flow (IDF) system, a visual programming environment initially oriented toward the development of image processing and computer vision algorithms, is described. It is intended to exploit the intuitive nature of flow charts and the human capability for comprehending pictures, while providing a fully featured, easy to use programming language, including a full set of data types and control flow operators. Experimental performance results on the size of the programs that can be described and how fast they run are reported. Areas for future work are indicated.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Genetic Polymorphisms of Flavin Monooxygenase 3 in Sulindac-Induced Regression of Colorectal Adenomas in Familial Adenomatous Polyposis (2005)

Sulindac is a nonsteroidal antiinflammatory drug with a chemopreventive effect in patients with familial adenomatous polyposis (FAP). In vivo, the active form of sulindac is sulindac sulfide, which is inactivated by the hepatic microsomal enzyme, flavin monooxygenase 3 (FMO3). In humans, numerous polymorphisms exist in FMO3, which alter enzymatic activity and subsequent substrate metabolism. We recently showed that certain polymorphic forms of FMO3 with reduced activity were associated with a more favorable response to sulindac in preventing the formation of adenomas in patients with FAP without polyps at baseline. Here, we determined whether these FMO3 polymorphisms correlated with the ability of sulindac to regress polyposis in patients with FAP who had polyps prior to treatment. Nineteen patients were treated with 150 mg sulindac twice a day for 6 months. The size and number of polyps in each patient was assessed at baseline (prior to the administration of sulindac), and at 3 and 6 months. Genotyping was done on seven established FMO3 polymorphisms with functional significance-M66I, E158K, P153L, V257M, E305X, E308G, and R492W. Statistical analyses were done with Wilcoxon rank sum test. Of the loci examined, only E158K and E308G showed polymorphic changes. Six patients exhibited polymorphisms in both E158K and E308G loci and were designated as genotype combination 1. The remaining patients were designated as genotype combination 2. Over the course of treatment, patients with genotype combination 1 had a greater reduction in both the size and number of polyps than those with genotype combination 2. These results suggest that combined polymorphic changes in the E158K and E308G alleles may protect against polyposis in patients with FAP treated with sulindac.
All-optical packet switching for metropolitan area networks: opportunities and challenges (2001)

The fast evolution of networks has been continuously driven by new advances in enabling technologies, as well as the growth of Internet traffic. All-optical packet switching provides high throughput, rich routing functionalities, and excellent flexibility. These characteristics make it an excellent candidate for next-generation metropolitan area networks, which will be much more dynamic and demanding than today's networks. In this article we not only discuss some of the architectural challenges involved in the design of all-optical packet switched networks, but also present the reader a high-level picture of how such future networks could be integrated with other network segments, to provide users end-to-end connectivity with performance and simplicity.
Fcγ receptor type IIIA is associated with rheumatoid arthritis in two distinct ethnic groups (2000)

We have demonstrated that the FcgammaRIIIA-158V/F polymorphism is a susceptibility and/or severity marker for RA in 2 distinct ethnic groups. This finding may ultimately provide additional insights into the pathogenesis of RA and other autoantibody/immune complex-driven autoimmune diseases.
Grafting sulfobetaine monomer onto silicone surface to improve haemocompatibility (2003)

Abstract Silicone rubber has been used as a biomaterial for more than two decades and displays good mechanical and optical properties, but its chemical nature, poor antithrombogenicity, as well as its hydrophobicity, prevents its use in many demanding biomedical applications. In order to provide modified silicone with enhanced haemocompatibility, surface modification techniques were used. Ozonization was used to introduce active peroxide groups onto the silicone film surface and, subsequently, graft polymerization of N , N ′‐dimethyl‐ N ‐methacryloyloxyethyl‐ N ‐(3‐sulfopropyl) ammonium (DMMSA), a zwitterionic sulfobetaine structure, onto the ozone activated silicone surface was conducted. Surface analysis was accomplished by means of attenuated total reflectance‐Fourier‐transform infrared (ATR‐FTIR), and X‐ray photoelectron spectra (XPS), and scanning electron microscopy (SEM) and contact angle measurement. ATR‐FTIR and XPS investigation confirmed the graft polymerization. The grafted film possessed a relatively hydrophilic surface as indicated by contact angle measurement. The blood compatibility of the grafted films was evaluated by platelet adhesion in platelet‐rich plasma (PRP) and protein adsorption in bovine fibrinogen using silicone film as the reference. No platelet adhesion was observed for the grafted films incubated in PRP for 120 min. The protein adsorption was reduced on the grafted films after incubated in bovine fibrinogen for 120 min. These results confirmed that the improved blood compatibility was obtained by grafting this new zwitterronic sulfobetaine structure onto silicone film. Copyright © 2003 Society of Chemical Industry
Effects on fluid and Na+ flux of varying luminal hydraulic resistance in rat colon in vivo. (1994)

1. A new method of measuring fluid and ionic movements and the dehydrating power of the colon in vivo is described. A range of agarose gel cylinders, with calibrated hydraulic conductivities (Lp), were inserted into the lumen of the descending colon of anaesthetized rats. Fluxes of fluid, Na+ and K+ out of the gels were measured over a period of 60-110 min. 2. Fluid absorption by the colon from 2.5% agarose gels was not slower than from solution without gel. Fluid absorption was inhibited by 66% when the agarose concentration was raised to 10%. In contrast 2.5% agarose gels caused a 73% (P < 0.001) reduction in water flow from rat ileum. 3. Increasing gel concentration to 10% or above caused the absorbate from the gels to become hypertonic (P < 0.001). 4. The measured suction pressure applied by the colonic hypertonic absorbate to the gels increased from 44 +/- 2.3 cmH2O (n = 23) with 2.5% agarose gels to 6713 +/- 960 cmH2O (n = 13) with 15% (P < 0.001). 5. Deoxycholate (2 mM) produced a decrease in fluid and Na+ absorption and reduced the suction pressure and power exerted by the colon.
Determination of Secondary Structure Populations in Disordered States of Proteins Using Nuclear Magnetic Resonance Chemical Shifts (2012)

One of the major open challenges in structural biology is to achieve effective descriptions of disordered states of proteins. This problem is difficult because these states are conformationally highly heterogeneous and cannot be represented as single structures, and therefore it is necessary to characterize their conformational properties in terms of probability distributions. Here we show that it is possible to obtain highly quantitative information about particularly important types of probability distributions, the populations of secondary structure elements (α-helix, β-strand, random coil, and polyproline II), by using the information provided by backbone chemical shifts. The application of this approach to mammalian prions indicates that for these proteins a key role in molecular recognition is played by disordered regions characterized by highly conserved polyproline II populations. We also determine the secondary structure populations of a range of other disordered proteins that are medically relevant, including p53, α-synuclein, and the Aβ peptide, as well as an oligomeric form of αB-crystallin. Because chemical shifts are the nuclear magnetic resonance parameters that can be measured under the widest variety of conditions, our approach can be used to obtain detailed information about secondary structure populations for a vast range of different protein states.
Low expression level but potent antigen presenting function of CD1d on monocyte lineage cells (2000)

CD1d is a key antigen-presenting molecule involved in the selection and activation of a highly conserved T cell subset known as NK T cells. In this study, we analyzed the expression, regulation and function of human CD1d by various antigen-presenting cells (APC) of myeloid origin, including circulating monocytes, monocyte-derived dendritic cells and macrophages. CD1d was expressed as a mature glycoprotein by these cells, and unlike the other members of the human CD1 family its expression was constitutive and was not strongly up-regulated by GM-CSF and IL-4 or a range of other cytokines. Despite their remarkably low surface expression of CD1d, all myeloid lineage cells tested were extremely potent APC for responses of NK T cell clones to the synthetic glycolipid antigen, alpha-galactosyl ceramide. Prominent localization of CD1d to the endocytic system of monocyte lineage cells was observed, and functional studies suggested that this was important for achieving efficient antigen loading onto CD1d. Overall, these results support the view that monocyte lineage cells are important stimulators of CD1d-restricted immune responses, while also underscoring the unique regulation of CD1d expression by these cells.
Development of a highly sensitive RT-PCR luminometric hybridization assay for human telomerase reverse-transcriptase beta-plus transcript. (2004)

The developed hybridization assay is highly sensitive and specific for the detection of hTERT beta-plus transcript in clinical samples.
Miniaturization of BAW devices and the impact of wafer level packaging technology (2013)

As wireless mobile applications continue to drive shrinkage of the individual components, consequently a corresponding decrease in required footprint and component thickness needs to go along with it. Over the last years, the size of power amplifier duplexer (PAD) front-end modules as well as standalone duplexers has steadily decreased. A significant portion of this shrinkage has been contributed by a decrease in BAW die size. This decrease is driven by various technology improvements. In this paper we will first discuss the introduction of on-chip capacitors. These capacitors not only allow for a reduction of the required external component count, but also for an increased degree of design freedom. Second, we will discuss how the shrinkage of reflector metal dimensions leads as a direct result to an significant reduction in die sizes. Although core technology improvements can allow for radical BAW die shrinkage, the packaging technology that comes along with the BAW die needs to contribute its share to maintain this trend. Last, a novel approach for wafer-level packaging BAW die will be presented.
T-DNA Insertion Mutagenesis in Arabidopsis : Prospects and Perspectives (1992)

Approximately 13 000 independent transformants of Arabidopsis have been generated utilising the Agrobacterium-mediated seed infection/transformation procedure. The average number of functional independent T-DNA insertion events per transformed line is 1.5, thus constituting a population with 19 500 independent inserts. These transformed lines have been screened under two environmental regimes for visible alterations in phenotype. In one screen the lines were grown under greenhouse conditions and examined at weekly intervals. In the second, seeds from each line were plated under axenic conditions in vertically oriented square petri plates and examined 4 and 9 days after germination. The mutants observed were placed into 7 distinct phenotypic classes: seedling-lethal, size variant, reduced-fertility, pigment defect, embryo-defective, dramatic morphological, and physiological. The mutational spectrum of the first 8000 transformed lines has been reported earlier. The mutational spectrum for a further 5000 transformed lines is reported here and, with several notable exceptions, is similar to that observed previously.
Biochemical and molecular characterization of the NAD+-dependent isocitrate dehydrogenase from the chemolithotroph Acidithiobacillus thiooxidans (2002)

An isocitrate dehydrogenase (ICDH) with an unique coenzyme specificity from Acidithiobacillus thiooxidans was purified and characterized, and its gene was cloned. The native enzyme was homodimeric with a subunit of Mr 45 000 and showed a 78-fold preference for NAD+ over NADP+. The cloned ICDH gene (icd) was expressed in an icd-deficient strain of Escherichia coli EB106; the activity was found in the cell extract. The gene encodes a 429-amino acid polypeptide and is located between open reading frames encoding a putative aconitase gene (upstream of icd) and a putative succinyl-CoA synthase β-subunit gene (downstream of icd). A. thiooxidans ICDH showed high sequence similarity to bacterial NADP+-dependent ICDH rather than eukaryotic NAD+-dependent ICDH, but the NAD+-preference of the enzyme was suggested due to residues conserved in the coenzyme binding site of the NAD+-dependent decarboxylating dehydrogenase.