gebhart/patrepeval huggingface dataset:
Inhibition of multidrug resistance by a new staurosporine derivative, NA-382, in vitro and in vivo. (1993)

The effects of a newly synthesized compound, N-ethoxycarbonyl-7-oxo-staurosporine (NA-382), on multidrug resistance in tumor cells were investigated. Protein kinase-inhibitory activity of NA-382 was lower but more selective to Ca2+/phospholipid-dependent protein kinase than that of staurosporine. NA-382 at noncytotoxic concentrations effectively reversed in vitro multidrug resistance of Adriamycin-resistant P388 (P388/ADR) cells, without influencing the drug sensitivity of sensitive P388 cells. NA-382 inhibited extrusion of vinblastine (VBL) and increased intracellular accumulation of VBL, more in P388/ADR cells than in sensitive P388 cells, with higher potency than staurosporine. This compound also reduced VBL resistance of other multidrug-resistant cell lines, AH66 and K562/ADR, by inhibiting VBL efflux and promoting VBL accumulation. NA-382 also dose dependently potentiated the effects of VBL and Adriamycin in P388/ADR-bearing mice. The toxicity of staurosporine was too high to use the combination with VBL in vitro and in vivo. NA-382 accumulated VBL in P388/ADR cells even after desensitization of Ca2+/phospholipid-dependent protein kinase by treatment with 12-O-tetradecanoylphorbol-13-acetate and 18 h, while being suppressed by 12-O-tetradecanoylphorbol-13-acetate added simultaneously or shortly before NA-382. Both staurosporine and NA-382 inhibited the photolabeling of [3H]azidopine on M(r) 140,000 P-glycoprotein in the plasma membrane from P388/ADR cells. These results indicate that this new staurosporine analogue, NA-382, reverses multidrug resistance by directly inhibiting the drug binding to P-glycoprotein, but not by Ca2+/phospholipid-dependent protein kinase inhibitory action.
Immunity to Cross‐Reactive Serotypes Induced by Pneumococcal Conjugate Vaccines in Infants (1999)

Infants were immunized with 1 of the 3 experimental pneumococcal conjugate vaccines that contain 6B and 19F but not 6A or 19A serotypes. Their sera were studied for the capacity to opsonize Streptococcus pneumoniae 6A, 6B, 19A, and 19F serotypes and the level of IgG antibody to the 4 serotypes. Significant increases were observed in the number of infants with detectable opsonophagocytic titers with 3 conjugate vaccines for 6B (vaccine) serotype but with only 2 vaccines for 6A (cross-reactive) serotype. Significant increases were observed with 2 conjugate vaccines for 19F serotype but with only 1 vaccine for 19A serotype. Thus, some conjugate vaccines may elicit cross-protection better than others. In addition, correlations between opsonophagocytic titers and IgG antibody levels by ELISA were high for 6B and 19F serotypes but low for 6A and 19A serotypes. Thus, ELISA may be an inadequate surrogate assay of vaccine response for cross-reactive serotypes.
Low-level c-myc amplification in human colonic carcinoma cell lines and tumors: a frequent, p53-independent mutation associated with improved outcome in a randomized multi-institutional trial. (1997)

Human colonic cancer is associated with multiple genetic deletions, mutations, and alterations in gene expression; in contrast, gene amplification has not been recognized as a prominent characteristic of human colonic tumors. Although the c-myc gene is overexpressed in approximately 70% of human colonic cancers, previous studies have not detected frequent gene amplification or rearrangement of c-myc in these tumors, although such amplification has been reported in chemically induced rodent colon cancer and quantitative analysis of gene copy number has shown the gene to be amplified at a low level in mucinous and poorly differentiated human colon carcinomas. Using rigorously controlled blot methodology, we have established that the c-myc gene, located at 8q21, exhibited amplification of 87% to 35-fold in 7 of 10 human colonic carcinoma cell lines. This was highly significant even at a low level of amplification in HT29 cells (P < 0.0001). Cytogenetic analysis by G-banding did not detect aneuploidy involving chromsome 8q, suggesting that the amplification for the c-myc gene on 8q was relatively specific, and this was consistent with a lack of amplification detected for the c-mos gene on 8q24, which was assayed similarly. The same methodology then revealed amplification of c-myc from 1.5-fold to 5-fold in 32% of tumors from 149 patients entered into a multi-institutional Phase III study of adjuvant therapy for colon cancer. c-myc status was not related to time to recurrence or death, but low levels of c-myc amplification identified a subset of patients who showed a statistically significant increase in disease-free survival, and a corresponding trend to longer overall survival, in response to adjuvant therapy with 5-fluorouracil plus levamisole. Presence of c-myc amplification was not related to incidence of p53 mutations.
Capillary Electrophoresis with Electrospray Ionization Mass Spectrometric Detection for Single-Cell Metabolomics (2009)

A method that enables metabolomic profiling of single cells and subcellular structures is described using capillary electrophoresis coupled to electrospray ionization time-of-flight mass spectrometry. A nebulizer-free coaxial sheath-flow interface completes the circuit and provides a stable electrospray, yielding a signal with a relative standard deviation of under 5% for the total ion electropherogram. Detection limits are in the low nanomolar range (i.e., <50 nM (<300 amol)) for a number of cell-to-cell signaling molecules, including acetylcholine (ACh), histamine, dopamine, and serotonin. The instrument also yields high-efficiency separations, e.g., approximately 600,000 for eluting ACh bands. The utility of this setup for single-cell metabolomic profiling is demonstrated with identified neurons from Aplysia californica--the R2 neuron and metacerebral cell (MCC). Single-cell electropherograms are reproducible, with a large number of metabolites detected; more than 100 compounds yield signals of over 10(4) counts from the injection of only 0.1% of the total content from a single MCC. Expected neurotransmitters are detected within the cells (ACh in R2 and serotonin in MCC), as are compounds that have molecular masses consistent with all of the naturally occurring amino acids (except cysteine). Tandem MS using a quadrupole time-of-flight tandem mass spectrometer distinguishes ACh from isobaric compounds in the R2 neuron and demonstrates the ability of this method to characterize and identify metabolites present within single cells.
Visualization of intermediate and transition-state structures in protein-tyrosine phosphatase catalysis. (1996)

Engineering site-specific amino acid substitutions into the protein-tyrosine phosphatase (PTPase) PTP1 and the dual-specific vaccinia H1-related phosphatase (VHR), has kinetically isolated the two chemical steps of the reaction and provided a rare opportunity for examining transition states and directly observing the phosphoenzyme intermediate. Changing serine to alanine in the active-site sequence motif HCXXGXXRS shifted the rate-limiting step from intermediate formation to intermediate hydrolysis. Using phosphorus 31P NMR, the covalent thiol-phosphate intermediate was directly observed during catalytic turnover. The importance of the conserved aspartic acid (D92 in VHR and D181 in PTP1) in both chemical steps was established. Kinetic analysis of D92N and D181N mutants indicated that aspartic acid acts as a general acid by protonating the leaving-group phenolic oxygen. Structure-reactivity experiments with native and aspartate mutant enzymes established that proton transfer is concomitant with P-O cleavage, such that no charge develops on the phenolic oxygen. Steady- and presteady-state kinetics, as well as NMR analysis of the double mutant D92N/S131A (VHR), suggested that the conserved aspartic acid functions as a general base during intermediate hydrolysis. As a general base, aspartate would activate a water molecule to facilitate nucleophilic attack. The amino acids involved in transition-state stabilization for cysteinylphosphate hydrolysis were confirmed by the x-ray structure of the Yersinia PTPase complexed with vanadate, a transition-state mimic that binds covalently to the active-site cysteine. Consistent with the NMR, x-ray, biochemical, and kinetic data, a unifying mechanism for catalysis is proposed.
Anomalous conical menisci under an ac field-departure from the dc Taylor cone (2006)

Observation of steady conical menisci with longitudinal growth is reported for electrospraying under high frequency alternating current (ac) electric fields. The authors report conical shapes that are analogous to the well-known direct-current (dc) cone-jet mode in the occurrence of conical menisci, but have some very distinctively ac features. The ac cones show a unique longitudinal growth that result in very high aspect ratio cones. The cone half angle for ethanol is approximately 9° for the ac case as compared to 47° for the dc case. These dissimilarities point to different mechanisms for dc and ac sprayings.
An Evaluation of Commercial Fluorescent Bead-Based Luminex Cytokine Assays (2008)

The recent introduction of fluorescent bead-based technology, allowing the measurement of multiples analytes in a single 25-50 microl sample has revolutionized the study of cytokine responses. However, such multiplex approaches may compromise the ability of these assays to accurately measure actual cytokine levels. This study evaluates the performance of three commercially available multiplex cytokine fluorescent bead-based immunoassays (Bio-Rad's Cytokine 17-plex kit; LINCO Inc's 29-plex kit; and RnD System's Fluorokine-Multi Analyte Profiling (MAP) base kit A and B). The LINCO Inc kit was found to be the most sensitive assay for measuring concentrations of multiple recombinant cytokines in samples that had been spiked with serial dilutions of the standard provided by the manufacturer, followed respectively by the RnD Fluorokine-(MAP) and Bio-Rad 17-plex kits. A positive correlation was found in the levels of IFN-gamma measured in antigen stimulated whole blood culture supernatants by the LINCO Inc 29-plex, RnD Fluorokine-(MAP) and RnD system IFN-gamma Quantikine ELISA kits across a panel of controls and stimulated samples. Researchers should take the limitation of such multiplexed assays into account when planning experiments and the most appropriate use for these tests may currently be as screening tools for the selection of promising markers for analysis by more sensitive techniques.
Upregulation of ERG Genes in Candida Species by Azoles and Other Sterol Biosynthesis Inhibitors (2000)

Infections due to Candida albicans are usually treated with azole antifungals such as fluconazole, but treatment failure is not uncommon especially in immunocompromised individuals. Relatedly, in vitro studies demonstrate that azoles are nonfungicidal, with continued growth at strain-dependent rates even at high azole concentrations. We hypothesized that upregulation of ERG11, which encodes the azole target enzyme lanosterol demethylase, contributes to this azole tolerance in Candida species. RNA analysis revealed that ERG11 expression in C. albicans is maximal during logarithmic-phase growth and decreases as the cells approach stationary phase. Incubation with fluconazole, however, resulted in a two- to fivefold increase in ERG11 RNA levels within 2 to 3 h, and this increase was followed by resumption of culture growth. ERG11 upregulation also occurred following treatment with other azoles (itraconazole, ketoconazole, clotrimazole, and miconazole) and was not dependent on the specific medium or pH. Within 1 h of drug removal ERG11 upregulation was reversed. Azole-dependent upregulation was not limited to ERG11: five of five ERG genes tested whose products function upstream and downstream of lanosterol demethylase in the sterol biosynthetic pathway were also upregulated. Similarly, ERG11 upregulation occurred following treatment of C. albicans cultures with terbinafine and fenpropimorph, which target other enzymes in the pathway. These data suggest a common mechanism for global ERG upregulation, e.g., in response to ergosterol depletion. Finally, azole-dependent ERG11 upregulation was demonstrated in three additional Candida species (C. tropicalis, C. glabrata, and C. krusei), indicating a conserved response to sterol biosynthesis inhibitors in opportunistic yeasts.
Octree-Related Data Structures and Algorithms (1984)

The octree is not always a desirable data structure. Here, together with their formal definitions and related algorithms, are two data structures more suitable for graphics operations.
Speech enhancement using a soft-decision noise suppression filter (1980)

One way of enhancing speech in an additive acoustic noise environment is to perform a spectral decomposition of a frame of noisy speech and to attenuate a particular spectral line depending on how much the measured speech plus noise power exceeds an estimate of the background noise. Using a two-state model for the speech event (speech absent or speech present) and using the maximum likelihood estimator of the magnitude of the speech spectrum results in a new class of suppression curves which permits a tradeoff of noise suppression against speech distortion. The algorithm has been implemented in real time in the time domain, exploiting the structure of the channel vocoder. Extensive testing has shown that the noise can be made imperceptible by proper choice of the suppression factor.
Calcineurin-independent regulation of plasma membrane Ca2+ ATPase-4 in the vascular smooth muscle cell cycle (2003)

Calcineurin mediates repression of plasma membrane Ca2+-ATPase-4 (PMCA4) expression in neurons, whereas c-Myb is known to repress PMCA1 expression in vascular smooth muscle cells (VSMC). Here, we describe a novel mouse VSMC line (MOVAS) in which 45Ca efflux rates decreased 50%, fura 2-AM-based intracellular Ca2+ concentrations ([Ca2+]i) increased twofold, and real-time RT-PCR and Western blot revealed a approximately 40% decrease in PMCA4 expression levels from G0 to G1/S in the cell cycle, where PMCA4 constituted approximately 20% of total PMCA protein. Although calcineurin activity increased fivefold as MOVAS progressed from G0 to G1/S, inhibition of this increase with either BAPTA or retroviral transduction with peptide inhibitors of calcineurin (CAIN), or its downstream target nuclear factor of activated T cells (NFAT) (VIVIT), had no effect on the repression of PMCA4 mRNA expression at G1/S. By contrast, Ca2+-independent activity of the calmodulin-dependent protein kinase-II (CaMK-II) increased eightfold as MOVAS progressed from G0 to G1/S, and treatment with an inhibitor of CaMK-II (KN-93) or transduction of a c-Myb-neutralizing antibody significantly alleviated the G1/S-associated repression of PMCA4. These data show that G1/S-specific PMCA4 repression in proliferating VSMC is brought about by c-Myb and CaMK-II and that calcineurin may regulate cell cycle-associated [Ca2+]i through alternate targets.
Caspase Pathways, Neuronal Apoptosis, and CNS Injury (2000)

Caspases are a family of mammalian proteases related to the ced-3 gene of Caenorhabditis elegans. They mediate many of the morphological and biochemical features of apoptosis, including structural dismantling of cell bodies and nuclei, fragmentation of genomic DNA, destruction of regulatory proteins, and propagation of other pro-apoptotic molecules. Based on their substrate specificities and DNA sequence homologies, the 14 currently identified caspases may be divided into three groups: apoptotic initiators, apoptotic executioners, and inflammatory mediators. Caspases are activated through two principal pathways, known as the "extrinsic pathway," which is initiated by cell surface death receptor ligation, and the intrinsic pathway, which arises from mitochondria. Endogenous inhibitors, such as the inhibitors of apoptosis (IAP) family, modulate caspase activity at various points within these pathways. Upon activation, caspases appear to play an important role in sequelae of traumatic brain injury, spinal cord injury, and cerebral ischemia. In addition, they may also play a role in mediating cell death in chronic neurodegenerative conditions such as Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. This article reviews the current literature on the role of caspases in acute and chronic CNS injury, and provides evidence for the potential therapeutic use of caspase inhibitors in the setting of these conditions.
Optical Time Domain Reflectometer with a Laser Diode Operating as Light Emitter/Photodetector (1985)

A new optical time domain reflectometer is proposed that uses a semiconductor laser diode (LD) as a pulse emitter and a photodetector. By employing LDs with center wavelengths of 1.31 and 1.56 µm, fault location lengths longer than 10 km were attained in both wavelengths for a graded-index multimode fiber.
Peroxisome Proliferator‐activated Receptor γ Induces Growth Arrest and Differentiation Markers of Human Colon Cancer Cells (1999)

Peroxisome proliferator-activated receptor gamma (PPAR gamma), one of the nuclear receptors expressed in adipose tissue, plays an important role in adipocyte differentiation. In this study, we investigated the expression of PPAR gamma and its role in cellular growth and differentiation in six colon cancer cell lines: HT-29, CaCo-2, SW-480, DLD-1, LoVo, and T-84. All six expressed PPAR gamma mRNA and protein, shown respectively on northern and western blot analyses. Luciferase assay in HT-29 cells, which strongly express PPAR gamma, showed that troglitazone, a selective ligand for PPAR gamma, transactivated the transcription of a peroxisome proliferator response element (PPRE)-driven promoter. Furthermore, troglitazone caused a marked decrease in [3H]thymidine incorporation and G1 cell-cycle arrest determined by flow cytometry. Finally, troglitazone induced expression of mRNAs for villin and intestinal alkaline phosphatase, markers for enterocyte differentiation. In conclusion, human colon cancer cells express PPAR gamma, the ligands of which inhibit cell growth and induce differentiation markers.
Global quantitative phosphoprotein analysis using Multiplexed Proteomics technology (2003)

Systematic parallel analysis of the phosphorylation status of networks of interacting proteins involved in the regulatory circuitry of cells and tissues is certain to drive research in the post-genomics era for many years to come. Reversible protein phosphorylation plays a critical regulatory role in a multitude of cellular processes, including alterations in signal transduction pathways related to oncogene and tumor suppressor gene products in cancer. While fluorescence detection methods are likely to offer the best solution to global protein quantitation in proteomics, to date, there has been no satisfactory method for the specific and reversible fluorescent detection of gel-separated phosphoproteins from complex samples. The newly developed Pro-Q Diamond phosphoprotein dye technology is suitable for the fluorescent detection of phosphoserine-, phosphothreonine-, and phosphotyrosine-containing proteins directly in sodium dodecyl sulfate (SDS)-polyacrylamide gels and two-dimensional (2-D) gels. Additionally, the technology is appropriate for the determination of protein kinase and phosphatase substrate preference. Other macromolecules, such as DNA, RNA, and sulfated glycans, fail to be detected with Pro-Q Diamond dye. The staining procedure is rapid, simple to perform, readily reversible and fully compatible with modern microchemical analysis procedures, such as matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry. Pro-Q Diamond dye technology can detect as little as 1-2 ng of beta-casein, a pentaphosphorylated protein, and 8 ng of pepsin, a monophosphorylated protein. Fluorescence signal intensity correlates with the number of phosphorylated residues on the protein. Through combination of Pro-Q Diamond phosphoprotein stain with SYPRO(R) Ruby protein gel stain, Multiplexed Proteomics technology permits quantitative, dichromatic fluorescence detection of proteins in 2-D gels. This evolving discovery platform allows the parallel determination of protein expression level changes and altered post-translational modification patterns within a single 2-D gel experiment. The linear responses of the fluorescence dyes utilized, allow rigorous quantitation of changes over an unprecedented 500-1000-fold concentration range.
Application of Two-Dimensional Gas Chromatography with Electron Capture Chemical Ionization Mass Spectrometry to the Detection of 11-nor- 9-Tetrahydrocannabinol-9-carboxylic Acid (THC-COOH) in Hair (2006)

The proposed federal regulations for the detection in hair of 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), a metabolite of marijuana, require a confirmatory detection level of 0.05 pg/mg. At present, the only way to achieve this on a routine basis has been with the use gas chromatography with tandem mass spectrometry (GC-MS-MS) technology. Tandem MS is an expensive approach and dissuades laboratories from attempting to enter the hair-testing market. A procedure for the determination of THC-COOH in hair using two-dimensional gas chromatography (GC x GC) coupled to mass spectrometry (GC-GC-MS) is described for the first time. The method makes use of several small improvements in the extraction, GC, and MS procedures to allow the required sensitivity to be achieved. The results of this approach demonstrate detection of THC-COOH in hair at a concentration level of 0.05 pg/mg with both a target quantitation ion and a unique confirming qualifier ion, using a single-quadrupole mass selective detector. These two ions and the enhanced separation of the GC-GC provide a high degree of confidence in the determinations. The method has been successfully applied to the detection of THC-COOH in hair specimens from known marijuana users, and it reaches the levels currently proposed in the Federal Register.
Lung Cancer (2008)

The Molecular Origins of Cancer series continues with this review of molecular and genetic mechanisms of lung cancer. The authors review genetic susceptibility to lung cancer and four genes of importance in the evolution of the disease: EGFR, KRAS, the PI3K–Akt–mTOR complex, and TITF1. They also discuss gene profiling and protein profiling, with emphasis on the clinical value of these methods.
<title>One-level gray-tone lithography: mask data preparation and pattern transfer</title> (1996)

This paper reports on a methodology for fabrication of arbitrarily shaped structures using technologies common to standard IC manufacturing processes. Particular emphasis is put on the design and use of halftone transmission masks for the lithography step required in the fabrication process of mechanical, optical or electronics components. The algorithms to transfer an initial height profile into a design representation in the common data format GDSII are discussed. This set of data could be used directly by a commercial mask shop. The great data amount of a reticle layout has been reduced significantly by a first order data compaction. The possibly nonlinear influences of the different process steps on the transfer function have been regarded. The specific parameters for the mask making and the resist process are determined. Several components like shaped gratings or lenses have been realized in resist up to 10 micrometers thick. In the field of transferring the pattern into a substrate material like silicon or glass, a dry etching process was evaluated.