gebhart/patrepeval huggingface dataset:
PDE4 inhibitors activate a mitochondrial apoptotic pathway in chronic lymphocytic leukemia cells that is regulated by protein phosphatase 2A (2003)

Chronic lymphocytic leukemia (CLL) cells, but not peripheral blood T cells, undergo apoptosis following treatment with inhibitors of type 4 cyclic nucleotide phosphodiesterase (PDE4), a process that correlates dose dependently with elevation of adenosine 3',5'-cyclic monophosphate (cAMP) in leukemic cells. We show that treatment of CLL cells with rolipram, a prototypic PDE4 inhibitor, and forskolin, an adenylate cyclase activator, induces mitochondrial depolarization, release of cytochrome c into the cytosol, caspase-9 and -3 activation, and cleavage of poly(adenosine diphosphate [ADP]-ribose)polymerase. Inhibitors of caspase-9, but not caspase-8, block rolipram/forskolin-induced CLL apoptosis. In a subset of CLL patients, B-cell lymphoma 2 (Bcl-2)-associated death promoter homolog (Bad), a proapoptotic Bcl-2 family member that when phosphorylated on specific serine residues is sequestered in the cytosol by 14-3-3, was dephosphorylated at Ser112 following rolipram/forskolin treatment of leukemic cells. Rolipram/forskolin treatment also induced Bad to accumulate in CLL heavy-membrane fractions, consistent with Bad translocation to mitochondria. To determine the mechanism for rolipram/forskolin-induced Bad dephosphorylation, we examined CLL phosphatase activity. Rolipram/forskolin treatment augmented protein phosphatase 2A (PP2A) activity, as well as levels of immunoreactive PP2A catalytic subunit. Treatment of CLL cells with a concentration of okadaic acid (5 nM) that selectively inhibits PP2A, reduced both rolipram/forskolin-induced mitochondrial cytochrome c release and mitochondrial depolarization. Okadaic acid restored Bad Ser112 phosphorylation and Bad association with 14-3-3 in rolipram/forskolin-treated CLL cells. These results suggest that PDE4 inhibitors may induce CLL apoptosis by activating PP2A-induced dephosphorylation of proapoptotic BH3-only Bcl-2 family members such as Bad.
Pharmacological targeting of long QT mutant sodium channels. (1997)

The congenital long QT syndrome (LQTS) is an inherited disorder characterized by a delay in cardiac cellular repolarization leading to cardiac arrhythmias and sudden death often in young people. One form of the disease (LQT3) involves mutations in the voltage-gated cardiac sodium channel. The potential for targeted suppression of the LQT defect was explored by heterologous expression of mutant channels in cultured human cells. Kinetic and steady state analysis revealed an enhanced apparent affinity for the predominantly charged, primary amine compound, mexiletine. The affinity of the mutant channels in the inactivated state was similar to the wild type (WT) channels (IC50 approximately 15-20 microM), but the late-opening channels were inhibited at significantly lower concentrations (IC50 = 2-3 microM) causing a preferential suppression of the late openings. The targeting of the defective behavior of the mutant channels has important implications for therapeutic intervention in this disease. The results provide insights for the selective suppression of the mutant phenotype by very low concentrations of drug and indicate that mexiletine equally suppresses the defect in all three known LQT3 mutants.
Isolation and sequence analysis of the fatty acid synthetase FAS2 gene from Penicillium patulum (1988)

The fatty acid synthetase complex of Penicillium patulum was isolated and shown to be structurally similar to other known fungal fatty acid synthetases. It is composed of two subunit, alpha and beta, each with a molecular mass of about 200 kDa. P. patulum genomic and cDNA libraries were constructed in lambda gt11 and EMBL3 vectors. From these libraries, the P. patulum FAS2 gene together with its flanking DNA was isolated. The cloned genomic DNA was sequenced over a length of 6357 base pairs. The coding sequence of fatty acid synthetase subunit alpha, being 5571 nucleotides long, was identified within this DNA segment. The FAS2 gene is a mosaic of three exons (514, 4949 and 108 base pairs) and two introns, each of 54 base pairs in length. Both introns were absent in the corresponding cDNA sequences. Like other fungal introns both contain an internal CTAAC sequence, located 10 base pairs upstream of their 3'-exon/intron boundaries. In addition, they have, at their ends, the GTCAAGT and TAG consensus sequences characteristic of all eucaryotic introns. Furthermore, two pairs of direct repeats, of as yet unknown significance, were found in the two P. patulum introns. The P. patulum FAS2 gene encodes a protein of 1857 amino acids and 204.5 kDa molecular mass. It is 90 nucleotides shorter than the corresponding S. cerevisiae gene. In both organisms, the FAS2 genes and their products exhibit a high degree of overall sequence similarity at both the DNA (63%) and protein (68%) levels. Therefore, the fatty acid synthetase alpha subunits of P. patulum and S. cerevisiae obviously contain the same catalytic domains in an identical sequential order.
Polyclonal Antibody Production Against Chito-Oligosaccharides (2001)

Chitin hexamer was conjugated to mono-BOC-diaminoethane, n -aminobutyric acid or glycine using reductive amination. Each hapten was conjugated to ovalbumin (OVA) or mouse serum albumin (MSA) for immunization and immunoassay, respectively. Serum from a mouse immunized with the diaminoethane conjugate, demonstrated competition with chitins in a modified indirect immunoassay.
Bone Marrow Purging for Autologous Bone Marrow Transplantation (1993)

High dose therapy with the resulting myeloablation rescued by infusion of autologous bone marrow (ABMT) has become a major treatment option for an increasing number of patients with hematologic and solid tumors. ABMT has several potential advantages over allogeneic transplantation. However, the major obstacle to the use of ABMT is that the infusion of occult tumor cells harbored within the harvested marrow would result in more rapid relapse of disease. To minimize the effects of the infusion of significant numbers of malignant cells, marrow for ABMT is obtained when the patient is either in complete remission or when there is no histologic evidence of bone marrow infiltration of disease. There is increasing evidence that minimal numbers of malignant cells can be detected within the remission marrow of these patients, particularly when assessed by sensitive clonogenic assays or polymerase chain reaction amplification. A variety of methods, pharmacologic and immunologic have been developed to "purge" malignant cells from the marrow. The aim of purging is to eliminate any contaminating malignant cells and leave intact the hematopoietic stem cells that are necessary for engraftment. Although the rationale for removing any contaminating cells from the autologous marrow appears compelling, the issue of purging remains highly controversial. Intense argument persists as to whether attempts to remove residual tumor cells from the harvested bone marrow have contributed to improving disease-free survival in these patients. To date there have been no clinical trials testing the efficacy of purging by comparison of infusion of purged versus unpurged autologous bone marrow. This is due primarily to the large number of patients that would be required for such studies.
Influence of High Mutation Rates on the Mechanisms and Dynamics of In Vitro and In Vivo Resistance Development to Single or Combined Antipseudomonal Agents (2007)

We studied the mechanisms and dynamics of the development of resistance to ceftazidime (CAZ) alone or combined with tobramycin (TOB) or ciprofloxacin (CIP) in vitro and in vivo (using a mouse model of lung infection with human antibiotic regimens). Pseudomonas aeruginosa strain PAO1 and its hypermutable derivative PAODeltamutS were used, and the results were compared with those previously obtained with CIP, TOB, and CIP plus TOB (CIP-TOB) under the same conditions. An important (200-fold) amplification of the number of resistant mutant cells was documented for PAODeltamutS-infected mice that were under CAZ treatment compared to the number for mice that received placebo, whereas the median number of resistant mutant cells was below the detection limits for mice infected by PAO1. These results were intermediate between the high amplification with CIP (50,000-fold) and the low amplification with TOB (10-fold). All CAZ-resistant single mutant cells selected in vitro or in vivo hyperproduced AmpC. On the other hand, the three combinations studied were found to be highly effective in the prevention of in vivo resistance development in mice infected with PAODeltamutS, although the highest therapeutic efficacy (in terms of mortality and total bacterial load reduction) compared to those of the individual regimens was obtained with CIP-TOB and the lowest was with CAZ-CIP. Nevertheless, mutant cells that were resistant to the three combinations tested were readily selected in vitro for PAODeltamutS (mutation rates from 1.2 x 10(-9) to 5.8 x 10(-11)) but not for PAO1, highlighting the potential risk for antimicrobial resistance development associated with the presence of hypermutable strains, even when combined therapy was used. All five independent CAZ-TOB-resistant PAODeltamutS double mutants studied presented the same resistance mechanism (AmpC hyperproduction plus an aminoglycoside resistance mechanism not related to MexXY), whereas four different combinations of resistance mechanisms were documented for the five CAZ-CIP-resistant double mutants.
Advances towards 4J lattice-matched including dilute nitride subcell for terrestrial and space applications (2016)

Recent advances on the development of a 4J lattice-matched dilute nitride solar cell for terrestrial and space applications are described. Modeling of the solar cell is carried out using a drift-diffusion model and material parameters extracted from ad hoc electro-optical characterization resulting in an efficiency prediction of 47% for concentrations of 1000 suns AM1.5d G173 spectrum and 33% for 1× AM0. First experimental solar cell results of a dual-junction GaNAsSb/Ge solar cell and a triple-junction GaInP/Ga(In)As/GaNAsSb components of the full 4-Junction are shown.
Custom Zinc-Finger Nucleases for Use in Human Cells (2005)

Genome engineering through homologous recombination (HR) is a powerful instrument for studying biological pathways or creating treatment options for genetic disorders. In mammalian cells HR is rare but the creation of targeted DNA double-strand breaks stimulates HR significantly. Here, we present a method to generate, evaluate, and optimize rationally designed endonucleases that promote HR. The DNA-binding domains were synthesized by assembling predefined zinc-finger modules selected by phage display. Attachment of a transcriptional activation domain allowed assessment of DNA binding in reporter assays, while fusion with an endonuclease domain created custom nucleases that were tested for their ability to stimulate HR in episomal and chromosomal gene repair assays. We demonstrate that specificity, expression kinetics, and protein design are crucial parameters for efficient gene repair and that our two-step assay allows one to go quickly from design to testing to successful employment of the custom nucleases in human cells.
Weight reduction for primary prevention of stroke in adults with overweight or obesity (2006)

Obesity seems to be associated with an increased risk of stroke and it has been suggested that weight loss may lead to a reduction of stroke occurrence. However, this hypothesis is not based on strong scientific evidence resulting from randomised controlled clinical trials. This systematic review identified the urgent need for well-designed, adequately-powered, multi centre randomised controlled trials assessing the effects of weight reduction in persons with overweight or obesity on stroke occurrence.
Investigating the Structure of Human RNase H1 by Site-directed Mutagenesis (2001)

In this study we examine for the first time the roles of the various domains of human RNase H1 by site-directed mutagenesis. The carboxyl terminus of human RNase H1 is highly conserved with Escherichia coli RNase H1 and contains the amino acid residues of the putative catalytic site and basic substrate-binding domain of the E. coli RNase enzyme. The amino terminus of human RNase H1 contains a structure consistent with a double-strand RNA (dsRNA) binding motif that is separated from the conserved E. coli RNase H1 region by a 62-amino acid sequence. These studies showed that although the conserved amino acid residues of the putative catalytic site and basic substrate-binding domain are required for RNase H activity, deletion of either the catalytic site or the basic substrate-binding domain did not ablate binding to the heteroduplex substrate. Deletion of the region between the dsRNA-binding domain and the conserved E. coli RNase H1 domain resulted in a significant loss in the RNase H activity. Furthermore, the binding affinity of this deletion mutant for the heteroduplex substrate was 2-fold tighter than the wildtype enzyme suggesting that this central 62-amino acid region does not contribute to the binding affinity of the enzyme for the substrate. The dsRNA-binding domain was not required for RNase H activity, as the dsRNAdeletion mutants exhibited catalytic rates 2-fold faster than the rate observed for wild-type enzyme. Comparison of the dissociation constant of human RNase H1 and the dsRNA-deletion mutant for the heteroduplex substrate indicates that the deletion of this region resulted in a 5-fold loss in binding affinity. Finally, comparison of the cleavage patterns exhibited by the mutant proteins with the cleavage pattern for the wild-type enzyme indicates that the dsRNA-binding domain is responsible for the observed strong positional preference for cleavage exhibited by human RNase H1.
NAMBA: location-aware collaboration system for shopping and meeting (2002)

We have developed a location-aware collaboration system called NAMBA. The system exchanges position information and users' situation to one another using a PDA with built-in PHS and a GPS receiver in real time. NAMBA is a two-way communication system that sends position information and messages to one another. Users can see other users' position on the screen of a PDA easily using NAMBA. NAMBA has two specially devised functions, a meeting point sharing function and a self-assessment function of a position, for meeting mutually and for exchanging position information. We applied this system to an area of Osaka in Japan. From the result of the experiments, we found that position information and chat messages were important for communication with separated users. NAMBA was effective for meeting other users anywhere.
Fenofibrate induces HDL-associated PAF-AH but attenuates enzyme activity associated with apoB-containing lipoproteins (2003)

Human plasma platelet-activating factor acetylhydrolase (PAF-AH) is an enzyme associated mainly with the apolipoprotein B (apoB)-containing lipoproteins and primarily with LDL. A small proportion of enzymatic activity is also associated with HDL. Plasma paraoxonase 1 (PON1) is an esterase exclusively associated with HDL. The effect of fenofibrate on PAF-AH and PON1 activities in patients with dyslipidemias of Types IIA, IIB, and IV were studied. Fenofibrate reduced plasma PAF-AH activity in all patient groups. In Type IIA patients, this reduction was mainly due to a fall in enzyme activity associated with the dense LDL subspecies, whereas in Type IIB and Type IV patients, it was due to the decrease in PAF-AH activity associated with both the VLDL+IDL and dense LDL subspecies. Drug therapy in Type IIB and Type IV patients significantly increased the HDL-associated PAF-AH activity due to the increase in enzyme activity associated with the HDL-3c subfraction. Fenofibrate did not affect serum PON1 activities toward paraoxon and phenylacetate in either patient group. The fenofibrate-induced elevation of HDL-associated PAF-AH activity in dyslipidemic patients of Type IIB and Type IV, as well as the reduction in enzyme activity associated with atherogenic apoB-containing lipoproteins in all patient groups, may represent a new and important antiatherogenic effect of this potent lipid-modulating agent.
Mechanically robust and electrically conductive carbon nanotube foams (2009)

We describe the fabrication of ultralow-density carbon nanotube (CNT) foams that simultaneously exhibit high electrical conductivities and robust mechanical properties. Our approach utilizes carbon nanoparticles as a binder to crosslink randomly oriented bundles of single-walled CNTs. The resulting CNT foams are the stiffest low-density nanoporous solids reported and exhibit elastic behavior up to strains as large as ∼80%. The use of the carbon binder also allows bulk electrical conductivity to be maintained at low densities.
Single-strand DNA molecule translocation through nanoelectrode gaps (2007)

Molecular dynamics simulations were performed to investigate the translocation of single-strand DNA through nanoscale electrode gaps under the action of a constant driving force. The application behind this theoretical study is a proposal to use nanoelectrodes as a screening gap as part of a rapid genomic sequencing device. Preliminary results from a series of simulations using various gap widths and driving forces suggest that the narrowest electrode gap that a single-strand DNA can pass is ∼1.5 nm. The minimum force required to initiate the translocation within nanoseconds is ∼0.3 nN. Simulations using DNA segments of various lengths indicate that the minimum initiation force is insensitive to the length of DNA. However, the average threading velocity of DNA varies appreciably from short to long DNA segments. We attribute such variation to the different nature of drag force experienced by the short and long DNA segments in the environment. It is found that DNA molecules deform significantly to fit in the shape of the nanogap during the translocation.
DNA analysis with multiplex microarray-enhanced PCR (2005)

We have developed a highly sensitive method for DNA analysis on 3D gel element microarrays, a technique we call multiplex microarray-enhanced PCR (MME-PCR). Two amplification strategies are carried out simultaneously in the reaction chamber: on or within gel elements, and in bulk solution over the gel element array. MME-PCR is initiated by multiple complex primers containing gene-specific, forward and reverse, sequences appended to the 3' end of a universal amplification primer. The complex primer pair is covalently tethered through its 5' end to the polyacryl- amide backbone. In the bulk solution above the gel element array, a single pair of unattached universal primers simultaneously directs pseudo-monoplex PCR of all targets according to normal solution-phase PCR. The presence of a single universal PCR primer pair in solution accelerates amplification within gel elements and eliminates the problem of primer interference that is common to conventional multiplex PCR. We show 10(6)-fold amplification of targeted DNA after 50 cycles with average amplification efficiency 1.34 per cycle, and demonstrate specific on-chip amplification of six genes in Bacillus subtilis. All six genes were detected at 4.5 pg of bacterial genomic DNA (equivalent to 10(3) genomes) in 60 independent amplification reactions performed simultaneously in single reaction chamber.
The sirens' songs of confirmatory sepsis trials (1998)

Natanson, Charles MD; Esposito, Claire J. MD; Banks, Steven M. PhD Author Information
Identification of opioid receptor-like (ORL1) peptide-stimulated [35S]GTPγS binding in rat brain (1996)

Recent reports have identified an endogenous peptide ligand for the opioid receptor-like (ORL1) receptor. In the present study, ORL1 peptide-stimulated [35>]GTP gamma S binding was assessed in rat cortical membranes and brain sections to localize ORL1 receptor-activated G-proteins. In membrane assays, with 20 microM GDP, ORL1 peptide stimulated [35S]GTP gamma S binding by approximately two-fold with an ED50 value of 20 nM. ORL1 peptide-stimulated [35S]GTP gamma S binding was unaffected by opioid or other G-protein-coupled receptor antagonists. In brain sections, ORL1 peptide-stimulated [35S]GTP gamma S binding was identified in regions including cortex, amygdala, hypothalamus, thalamus and brain stem. The anatomical distribution of ORL1 peptide-stimulated [35S]GTP gamma S binding suggests its involvement in cognition, emotion and homeostasis.
Intercalative G-Tetraplex Stabilization of Telomeric DNA by a Cationic Porphyrin1 (1999)

DNA tetraplex (“quadruplex”) structures formed from guanine tetrads and significant to the regulation of telomerase activity have recently been shown to be stabilized by interaction with a cationic porphyrin [Anantha, N. V.; Azam, M.; Sheardy, R. D. Biochemistry 1998, 37, 2709−2714. Wheelhouse, R. T.; Sun, D.; Han, H.; Han, F. X.; Hurley, L. H. J. Am. Chem. Soc. 1998, 120, 3261−3262]. Porphyrin binding to DNA sequences from the Oxytricha and human telomeres and a thrombin-binding aptamer is here examined by isothermal titration calorimetry (ITC) and spectrophotometry under conditions that favor self-assembly to their respective intermolecular or intramolecular tetraplex structures. Analysis of the ITC and optical data reveals (i) saturating porphyrin/tetraplex binding stoichiometries of 1:1, 2:1, and 3:1 for d(G2T2G2TGTG2T2G2), d(AG3[T2AG3]3), and [d(T4G4)]4, respectively, involving near-equivalent sites, (ii) weak binding of only (0.3−2) × 105 M-1 per site, and (iii) no evidence for stepwise complexation in solutions containing K+ ions. This stoichiometry is maintained in Na+ solutions, if the tetraplex is stable, but nondegenerate sites are implicated for the 2:1 and 3:1 complexes where the first porphyrin binds with 20−40-fold greater affinity than any subsequent ligand(s). Importantly, the stoichiometries correspond to the number of intervals between successive G-tetrad planes in each tetraplex. The results indicate binding by threading intercalation at each closely similar GpG site, possibly without invoking neighbor exclusion for adjacent sites, rather than through either external electrostatic processes or end-pasted stacking modes. This mechanism is supported by dynamic molecular modeling simulations with two DNA tetraplexes which show that stable intercalated complexes can be realized. A plausible model is developed that accounts for the occupation of adjacent sites, where unfavorable interligand contacts are avoided by phased asymmetric positioning of the porphyrin molecules within each G-tetrad intercalation pocket.
Surface Cleaning and Carbonaceous Film Removal Using High Pressure, High Temperature Water, and Water/  CO 2 Mixtures (1998)

Silicon surface cleaning was investigated using water and water/ mixtures at elevated temperature (100 to 170°C) and elevated pressure [10.3 bar (150 psi) to 137.9 bar (2000 psi)]. Several "model" carbon‐containing materials were invoked to determine the ability of the fluids to remove different forms of carbonaceous layers. Polymethylmethacrylate, amorphous carbon, photoresist (KTI 820), and laboratory contamination were studied using X‐ray photoelectron spectroscopy (XPS) to evaluate removal. A model was developed to assist quantitative XPS data interpretation by mathematical simulation of sample surfaces. Results demonstrated that water removed hydrocarbon contamination and polymeric films, but could not remove amorphous carbon layers; water/ mixtures removed all of these materials. Surface cleanliness levels achievable by treating RCA‐cleaned silicon and thermally grown silicon dioxide samples with water and water/ were determined via XPS analysis. Native oxide levels and metal contamination resulting from the cleaning cycles were also evaluated.