gebhart/patrepeval huggingface dataset:
Detection of cystic fibrosis alleles from single cells using molecular beacons and a novel method of asymmetric real-time PCR (2003)

We present a method for rapid and accurate identification of the normal and DeltaF508 alleles of the cystic fibrosis (CF) gene in single human cells that utilizes LATE (linear after the exponential)-PCR, a newly invented form of asymmetric PCR. Detection of the single-stranded amplicon is carried out in real time, using allele-specific molecular beacons. The LATE-PCR method permits controlled abrupt transition from exponential to linear amplification and thereby enhances the fluorescent signals and reduces variability between replicate samples relative to those obtained using typical real-time PCR. Of 239 single lymphoblasts generating amplification signals, 227 (95%) exhibited signals that met objective quantitative criteria required for diagnosis. Among these samples, 222 were genotyped correctly, for an assay accuracy of 98%. The small number of diagnostic errors was due to allele drop-out among heterozygous lymphoblasts, 4/119 (3.4%), and contamination among homozygous DeltaF508 lymphoblasts, 1/57 (1.8%). LATE-PCR offers a new strategy for preimplantation genetic diagnosis and other fields in which accurate quantitative detection of single copy genes is important.
Use of human surfactant low molecular weight apoproteins in the reconstitution of surfactant biologic activity. (1988)

Two low molecular weight (LMW) apoproteins were isolated from human pulmonary surfactant. SDS polyacrylamide gel analysis showed one protein (SP 18) to have an apparent molecular weight of 18,000 when unreduced and 9,000 D after reduction. The second protein (SP 9) migrated at approximately 9,000 D in the presence or absence of reducing agents. Both proteins contain a high number of hydrophobic amino acids. The NH2-terminal sequence of SP 18 was determined to be: NH2-phe-pro-ile-pro-leu-pro-tyr-. A cDNA clone isolated from a human adult lung cDNA library contained a long open reading frame encoding at an internal position the human SP 18 amino-terminal sequence. Mixtures of phospholipids (PL) and SP 9 and SP 18 were assessed for their capacity to reduce surface tensions on a pulsating bubble surfactometer. The addition of 1% apoprotein resulted in a reduction of surface tension after 15 s from 42.9 dyn/cm for PL alone to 16.7 and 6.3 dyn/cm for preparations containing SP 9 and SP 18, respectively. In vivo assessment of reconstituted surfactant activity was performed in fetal rabbits. Reconstituted surfactant consisting of PL + 0.5% SP 18 instilled intratracheally at delivery resulted in a marked increase in lung compliance, while the incorporation of 0.5% SP 9 yielded a moderate increase. These data show the ability to produce biologically active surfactant by the addition of isolated LMW apoproteins to defined PL.
Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. Comparison with IL-4 and modulation by IFN-gamma or IL-10. (1993)

Recently, we described the cloning and expression of a human cDNA which is the homologue to P600, a gene transcribed by mouse Th2 clones. Based on its activities on human monocytes and B cells this gene was designated IL-13. In the present study we investigated the effects of IL-13 alone or in combination with IL-4, IFN-gamma, or IL-10 on human monocytes. IL-13 induced significant changes in the phenotype of monocytes. Like IL-4, it enhanced the expression of CD11b, CD11c, CD18, CD29, CD49e (VLA-5), class II MHC, CD13, and CD23, whereas it decreased the expression of CD64, CD32, CD16, and CD14 in a dose-dependent manner. IL-13 induced up-regulation of class II MHC Ag and its down-regulatory effects on CD64, CD32, and CD16 expression were prevented by IL-10. IFN-gamma could also partially prevent the IL-13-induced down-regulation of CD64, but not that of CD32 and CD16. However, IL-13 strongly inhibited spontaneous and IL-10- or IFN-gamma-induced ADCC activity of human monocytes toward anti-D coated Rh+ erythrocytes, indicating that the cytotoxic activity of monocytes was inhibited. Furthermore, IL-13 inhibited production of IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, IL-12 p35, IL-12 p40, macrophage inflammatory protein-1 alpha, granulocyte/macrophage-CSF, granulocyte-CSF, IFN-alpha, and TNF alpha by monocytes activated with LPS. In contrast, IL-13 enhanced the production of IL-1 ra by these cells. Similar results on cytokine production were observed or have been obtained with IL-4. Thus IL-13 shares most of its activities on human monocytes with IL-4, but no additive or synergistic effects of IL-4 and IL-13 on human monocytes were observed, suggesting that these cytokines may share common receptor components. Taken together, these results indicate that IL-13 has anti-inflammatory and important immunoregulatory activities.
Segmental genomic replacement by Cre-mediated recombination: genotoxic stress activation of the p53 promoter in single-copy transformants (1997)

Genotoxic stress results in transcriptional activation of the p53 promoter. To gain more detailed information on genotoxic induction of the p53 promoter at a uniform genomic locus, we have developed an efficient strategy for replacing a defined genomic segment in mouse NIH 3T3 cells with exogenous transfected DNA using a 'double lox' targeting strategy mediated by Cre DNA recombinase. The strategy utilizes a pair of heterospecific lox sites engineered both into the genome and onto the targeting DNA. This allows direct replacement of genomic DNA by a Cre-catalyzed double crossover event. p53-CAT reporter constructs were site-specifically placed into the genomic target 20-fold more efficiently by double lox recombination than by Cre-mediated single crossover insertional recombination, and the absolute frequency of site-specific double lox targeting exceeded the frequency of transformation due to random illegitimate recombination of transfected DNA into the genome. Resulting targeted single-copy integrants of the p53-CAT reporter show strong genotoxic induction by mitomycin C, and a dynamic range of induction that exceeds that seen in transient transfection assays. The double lox strategy is generally applicable to Cre-mediated genomic targeting in any cell and should be of particular utility in the site-specific targeting of DNA into embryonic stem (ES) cells for the production of gene-modified mice.
Starvation-Associated Genome Restructuring Can Lead to Reproductive Isolation in Yeast (2013)

Knowledge of the mechanisms that lead to reproductive isolation is essential for understanding population structure and speciation. While several models have been advanced to explain post-mating reproductive isolation, experimental data supporting most are indirect. Laboratory investigations of this phenomenon are typically carried out under benign conditions, which result in low rates of genetic change unlikely to initiate reproductive isolation. Previously, we described an experimental system using the yeast Saccharomyces cerevisiae where starvation served as a proxy to any stress that decreases reproduction and/or survivorship. We showed that novel lineages with restructured genomes quickly emerged in starved populations, and that these survivors were more fit than their ancestors when re-starved. Here we show that certain yeast lineages that survive starvation have become reproductively isolated from their ancestor. We further demonstrate that reproductive isolation arises from genomic rearrangements, whose frequency in starving yeast is several orders of magnitude greater than an unstarved control. By contrast, the frequency of point mutations is less than 2-fold greater. In a particular case, we observe that a starved lineage becomes reproductively isolated as a direct result of the stress-related accumulation of a single chromosome. We recapitulate this result by demonstrating that introducing an extra copy of one or several chromosomes into naïve, i.e. unstarved, yeast significantly diminishes their fertility. This type of reproductive barrier, whether arising spontaneously or via genetic manipulation, can be removed by making a lineage euploid for the altered chromosomes. Our model provides direct genetic evidence that reproductive isolation can arise frequently in stressed populations via genome restructuring without the precondition of geographic isolation.
VLSI architecture for the discrete wavelet transform (1990)

The wavelet transform is a very effective signal analysis tool for many problems for which Fourier based methods have been inapplicable, expensive for real-time applications, or can only be applied with difficulty. The discrete wavelet transform can be implemented in VLSI more efficiently than the FFT. A single chip implementation is described.
Recent Advances in Synthetic Transformations Mediated by Cerium(IV) Ammonium Nitrate (2003)

Cerium(IV) ammonium nitrate (CAN) has recently emerged as a versatile reagent for oxidative electron transfer; the overwhelming number of reports serve as a testimony to the unparalleled utility of CAN in a variety of transformations of synthetic importance. Our recent work has uncovered novel carbon-carbon bond-forming reactions leading to the one-pot synthesis of dihydrofurans, tetrahydrofurans, and aminotetralins. In addition, we have developed a number of facile carbon-heteroatom bond-forming reactions by the CAN-mediated oxidative addition of soft anions to alkenes. A mechanistic rationale has been provided for the reactions explored. As might be expected of very powerful one-electron oxidants, the chemistry of cerium(IV) oxidation of organic molecules is dominated by radical and radical cation chemistry.
Activation of hypothalamic serotonin receptors reduced intake of dietary fat and protein but not carbohydrate (1999)

Systemic treatment with dexfenfluramine (dF), fluoxetine, or serotonin (5-hydroxytryptamine, 5-HT) recently was shown to suppress fat and occasionally protein but not carbohydrate intake in rats when a macronutrient selection paradigm was employed. These reports contrast with the prevailing literature, which for the past decade has described a role for serotonin neurotransmission in the modification of dietary carbohydrate consumption. To test the hypothesis that the suppression of fat selection and/or consumption by systemic serotonin agonists involves stimulation of central 5-HT receptors, a series of experiments was performed in nondeprived rats. In experiment 1, third cerebroventricular (3V) infusion of the nonselective 5-HT antagonist metergoline prevented the reduction in fat but not carbohydrate feeding caused by systemic dF. Furthermore, 3V metergoline alone increased fat intake. In experiments 2 and 3, 3V infusion of 5-HT(1B/2C) receptor agonists D-norfenfluramine (DNF) or quipazine inhibited fat intake exclusively. Next, the infusion of DNF or 5-HT into the region of the paraventricular nucleus (PVN) reduced both fat and protein intake (experiments 4 and 5). Finally, in experiment 6, when rats were grouped by baseline diet preference, 5-HT infused into the PVN led to a dose-related decrease in fat intake in both carbohydrate- and fat-preferring rats. In contrast, there were no dose effects of 5-HT on carbohydrate or protein intake in either preference group. However, in fat-preferring rats, the highest dose of 5-HT reduced intake of all three macronutrient diets. These results demonstrate a selective effect of exogenous serotonergic drugs in the hypothalamus to reduce fat rather than carbohydrate intake and suggest that higher baseline fat intake enhances responsivity to serotonergic drugs.
Specific Modulation of Na+Channels in Hippocampal Neurons by Protein Kinase Cϵ (2005)

Acetylcholine binding to muscarinic acetylcholine receptors activates G-proteins, phospholipase C, and protein kinase C (PKC), which phosphorylates brain Na+ channels and reduces peak Na+ current in hippocampal neurons. Because multiple PKC isozymes with different regulatory properties are expressed in hippocampal neurons, we investigated which ones are responsible for mediating this effect. The diacylglycerol analog oleoylacetylglycerol (OAG) reduced the amplitude of Na+ current in dissociated mouse hippocampal neurons by 28.5 +/- 5.3% (p < 0.01). The reduction of peak Na+ current was similar with Ca2+-free internal solution and in 92 nm internal Ca2+, suggesting that calcium-dependent, conventional PKC isozymes were unlikely to mediate this response. Gö6976, which inhibits conventional PKC isozymes, reduced the effect of PKC activators only slightly, whereas rottlerin, which inhibits PKCdelta preferentially at 5 microm, had no effect. Ro-31-8425 (20 nm), which inhibits conventional PKC isozymes, did not reduce the response to OAG. However, higher concentrations of Ro-31-8425 (100 nm or 1 microm) that inhibit novel PKC isozymes effectively blocked OAG inhibition of Na+ current. Inclusion of a selective PKCepsilon-anchoring inhibitor peptide (PKCepsilon-I) in the recording pipette prevented the reduction of peak Na+ current by OAG, whereas an anchoring inhibitor peptide specific for PKCbeta and an inactive scrambled PKCepsilon-I peptide had no effect. In addition, OAG had no effect on Na+ current in hippocampal neurons from PKCepsilon null mice. Overall, our data from four experimental approaches indicate that anchored PKCepsilon is the isozyme responsible for PKC-mediated reduction of peak Na+ currents in mouse hippocampal neurons.
Design of an internal quad-band antenna for mobile phones (2004)

This letter presents the design of a compact Planar Inverted-F Antenna (PIFA) suitable for cellular telephone applications. The quarter-wavelength antenna combines the use of a slot, shorted parasitic patches and capacitive loads to achieve multiband operation. The commercial electromagnetic software IE3D is used to design and optimize the structure. The resulting antenna can operate from 880 to 960 MHz and 1710 to 2170 MHz covering GSM, DCS, PCS, and UMTS standards with a VSWR better than 2.5. Good agreement is found between simulated and measured results.
Development of the indirect-drive approach to inertial confinement fusion and the target physics basis for ignition and gain (1995)

Inertial confinement fusion (ICF) is an approach to fusion that relies on the inertia of the fuel mass to provide confinement. To achieve conditions under which inertial confinement is sufficient for efficient thermonuclear burn, a capsule (generally a spherical shell) containing thermonuclear fuel is compressed in an implosion process to conditions of high density and temperature. ICF capsules rely on either electron conduction (direct drive) or x rays (indirect drive) for energy transport to drive an implosion. In direct drive, the laser beams (or charged particle beams) are aimed directly at a target. The laser energy is transferred to electrons by means of inverse bremsstrahlung or a variety of plasma collective processes. In indirect drive, the driver energy (from laser beams or ion beams) is first absorbed in a high-Z enclosure (a hohlraum), which surrounds the capsule. The material heated by the driver emits x rays, which drive the capsule implosion. For optimally designed targets, 70%–80% of the driver energy can be converted to x rays. The optimal hohlraum geometry depends on the driver. Because of relaxed requirements on laser beam uniformity, and reduced sensitivity to hydrodynamic instabilities, the U.S. ICF Program has concentrated most of its effort since 1976 on the x-ray or indirect-drive approach to ICF. As a result of years of experiments and modeling, we are building an increasingly strong case for achieving ignition by indirect drive on the proposed National Ignition Facility (NIF). The ignition target requirements for hohlraum energetics, radiation symmetry, hydrodynamic instabilities and mix, laser plasma interaction, pulse shaping, and ignition requirements are all consistent with experiments. The NIF laser design, at 1.8 MJ and 500 TW, has the margin to cover uncertainties in the baseline ignition targets. In addition, data from the NIF will provide a solid database for ion-beam-driven hohlraums being considered for future energy applications. In this paper we analyze the requirements for indirect drive ICF and review the theoretical and experimental basis for these requirements. Although significant parts of the discussion apply to both direct and indirect drive, the principal focus is on indirect drive.
Use of Acute Headache and Migraine Medications in Patients with Episodic Migraine in the STRIVE Phase 3 Trial of Erenumab for Migraine Prevention (P4.118) (2018)

Toanalyze (A) change in acute headache medication days/month (AHM, includingacute migraine-specific medications (AMSM) as well as paracetamol, NSAIDS etc.)in the overall population as 97.7% used AHM during baseline; (B) change in AMSM days/month in the subgroup who used AMSM during baseline.
Preparation of Free-Standing Nanowire Arrays on Conductive Substrates (2004)

By combining supercritical drying technique with AAO template-assisted electrodeposition, noncollapsed, vertically aligned, and free-standing nanowire arrays on a conductive Au film have been fabricated. We also demonstrate that these free-standing nanowire arrays can be feasibly used for fabricating nanowire-based electrically driven devices.
Dehydroepiandrosterone and 16α-Br-epiandrosterone inhibit 12-O-tetradecanoylphorbol-13-acetate stimulation of superoxide radical production by human polymorphonuclear leukocytes (1985)

Both dehydroepiandrosterone (DHEA) and the synthetic steroid 16 alpha-Br-epiandrosterone (Br-Epi), a more potent inhibitor of glucose-6-phosphate dehydrogenase (G6PDH) than DHEA, inhibit the 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulation of superoxide anion (O2-) formation by human neutrophils. DHEA has previously been shown to inhibit the development of spontaneous breast cancer and chemically induced tumors of the lung and colon as well as TPA promoted skin tumors in the mouse. The inhibition of TPA stimulated O2- formation by DHEA may contribute to the cancer preventive activity of this steroid.
Mutation of melanosome protein RAB38 in chocolate mice (2002)

Mutations of genes needed for melanocyte function can result in oculocutaneous albinism. Examination of similarities in human gene expression patterns by using microarray analysis reveals that RAB38, a small GTP binding protein, demonstrates a similar expression profile to melanocytic genes. Comparative genomic analysis localizes human RAB38 to the mouse chocolate (cht) locus. A G146T mutation occurs in the conserved GTP binding domain of RAB38 in cht mice. Rab38(cht)/Rab38(cht) mice exhibit a brown coat similar in color to mice with a mutation in tyrosinase-related protein 1 (Tyrp1), a mouse model for oculocutaneous albinism. The targeting of TYRP1 protein to the melanosome is impaired in Rab38(cht)/Rab38(cht) melanocytes. These observations, and the fact that green fluorescent protein-tagged RAB38 colocalizes with end-stage melanosomes in wild-type melanocytes, suggest that RAB38 plays a role in the sorting of TYRP1. This study demonstrates the utility of expression profile analysis to identify mammalian disease genes.
Iterative control of dynamics-coupling-caused errors in piezoscanners during high-speed AFM operation (2005)

This paper addresses the compensation of the dynamics-coupling effect in piezoscanners used for positioning in atomic force microscopes (AFMs). Piezoscanners are used to position the AFM probe, relative to the sample, both parallel to the sample surface (x and y axes) and perpendicular to the sample surface (z axis). In this paper, we show that dynamics-coupling from the scan axes (x and y axes) to the perpendicular z axis can generate significant positioning errors during high-speed AFM operation, i.e., when the sample is scanned at high speed. We use an inversion-based iterative control approach to compensate for this dynamics-coupling effect. Convergence of the iterative approach is investigated and experimental results show that the dynamics-coupling-caused error can be reduced, close to the noise level, using the proposed approach. Thus, the main contribution of this paper is the development of an approach to substantially reduce the dynamics-coupling-caused error and thereby, to enable high-speed AFM operation.
Organism Identification using a Genome Sequence-Independent Universal Microarray Probe Set (2004)

There has been increasing interest and efforts devoted to developing biosensor technologies for identifying pathogens, particularly in the biothreat area. In this study, a universal set of short 12- and 13-mer oligonucleotide probes was derived independently of a priori genomic sequence information and used to generate unique species-dependent genomic hybridization signatures. The probe set sequences were algorithmically generated to be maximally distant in sequence space and not dependent on the sequence of any particular genome. The probe set is universally applicable because it is unbiased and independent of hybridization predictions based upon simplified assumptions regarding probe-target duplex formation from linear sequence analysis. Tests were conducted on microarrays containing 14,283 unique probes synthesized using an in situ light-directed synthesis methodology. The genomic DNA hybridization intensity patterns reproducibly differentiated various organisms (Bacillus subtilis, Yersinia pestis, Streptococcus pneumonia, Bacillus anthracis, and Homo sapiens), including the correct identification of a blinded "unknown" sample. Applications of this method include not only pathological and forensic genome identification in medicine and basic science, but also potentially a novel method for the discovery of unknown targets and associations inherent in dynamic nucleic acid populations such as represented by differential gene expression.
Features of TAP‐independent MHC class I ligands revealed by quantitative mass spectrometry (2008)

TAP is responsible for transferring cytosolic peptides into the ER, where they can be loaded onto MHC molecules. Deletion of TAP results in a drastic reduction of MHC class I surface expression and alters the presented peptide pattern. This key molecule in antigen processing is tackled by several viruses and lost in some tumors, rendering the altered cells less vulnerable to T cell-based immune surveillance. Using the TAP-deficient cell line LCL721.174 and its TAP-expressing progenitor cell line LCL721.45, we identified and quantified more than 160 HLA ligands, 50 of which were presented TAP-independently. Peptides which were predominantly presented on the TAP-deficient LCL721.174 cell line had a decreased MHC binding affinity according to their SYFPEITHI and BIMAS score. About half of the identified TAP-independently presented peptides were not derived from signal sequences and may partly be generated by the proteasome. Furthermore, we have excluded the possibility that differences in HLA ligand presentation between LCL721.45 and LCL721.174 were due to varying expression of the source proteins or due to changes in the antigen loading complex. Features of peptides presented independently of TAP as well as proteasomal contribution to their generation provide an insight into basic immunological mechanisms.