gebhart/patrepeval huggingface dataset:
Presenilin-1 Mutations Reduce Cytoskeletal Association, Deregulate Neurite Growth, and Potentiate Neuronal Dystrophy and Tau Phosphorylation (2001)

Mutations in presenilin genes are linked to early onset familial Alzheimer's disease (FAD). Previous work in non-neuronal cells indicates that presenilin-1 (PS1) associates with cytoskeletal elements and that it facilitates Notch1 signaling. Because Notch1 participates in the control of neurite growth, cultured hippocampal neurons were used to investigate the cytoskeletal association of PS1 and its potential role during neuronal development. We found that PS1 associates with microtubules (MT) and microfilaments (MF) and that its cytoskeletal association increases dramatically during neuronal development. PS1 was detected associated with MT in the central region of neuronal growth cones and with MF in MF-rich areas extending into filopodia and lamellipodia. In differentiated neurons, PS1 mutations reduced the interaction of PS1 with cytoskeletal elements, diminished the nuclear translocation of the Notch1 intracellular domain (NICD), and promoted a marked increase in total neurite length. In developing neurons, PS1 overexpression increased the nuclear translocation of NICD and inhibited neurite growth, whereas PS1 mutations M146V, I143T, and deletion of exon 9 (D9) did not facilitate NICD nuclear translocation and had no effect on neurite growth. In cultures that were treated with amyloid beta (Abeta), PS1 mutations significantly increased neuritic dystrophy and AD-like changes in tau such as hyperphosphorylation, release from MT, and increased tau protein levels. We conclude that PS1 participates in the regulation of neurite growth and stabilization in both developing and differentiated neurons. In the Alzheimer's brain PS1 mutations may promote neuritic dystrophy and tangle formation by interfering with Notch1 signaling and enhancing pathological changes in tau.
Disease-modifying therapeutic directions for Lewy-Body dementias (2015)

Dementia with Lewy bodies (DLB) is the second leading cause of dementia following Alzheimer's disease (AD) and accounts for up to 25% of all dementia. DLB is distinct from AD in that it involves extensive neuropsychiatric symptoms as well as motor symptoms, leads to enormous societal costs in terms of direct medical care and is associated with high financial and caregiver costs. Although, there are no disease-modifying therapies for DLB, we review several new therapeutic directions in treating DLB. We discuss progress in strategies to decrease the level of alpha-synuclein, to prevent the cell to cell transmission of misfolded alpha-synuclein, and the potential of brain stimulation in DLB.
Competition between two steinernematid nematode species for an insect host at different soil depths. (1996)

We studied interactions between 2 entomopathogenic nematode species, Steinernema carpocapsae, an ambusher forager, and Steinernema glaseri, a cruiser forager, when they were provided wax moth larvae as hosts at 0, 2, or 10 cm soil depth. Populations of infective juvenile nematodes in soil were monitored at 30-day intervals over 120 days using wax moth larvae as baits. After application of S. carpocapsae, S. glaseri, or the combination of both species, hosts were added at 30-day intervals. With hosts at 0 cm depth, each nematode species was negatively affected by the presence of the other species at the 30- and 60-day samples. At 90 and 120 days, S. carpocapsae numbers in the combined treatment were as high as in the single species treatment, whereas only few S. glaseri were recovered. With hosts at 2 or 10 cm depth, the presence of S. glaseri had a strong negative effect on S. carpocapsae, but S. glaseri was not affected by the presence of S. carpocapsae. In another experiment, S. carpocapsae dominated over S. glaseri in hosts located at 0 cm depth as measured by penetration efficiency into hosts and progeny production. In contrast, S. glaseri dominated at 2 cm depth. At 2 cm depth, S. carpocapsae penetrated into hosts too slowly to compete successfully with S. glaseri. Steinernema carpocapsae is superior to S. glaseri when competing for a host on the soil surface; however, below the surface S. glaseri is superior to S. carpocapsae.
Low-power high-speed level shifter design for block-level dynamic voltage scaling environment (2005)

Two novel level shifters that are suitable for block-level dynamic voltage scaling environment (namely, V/sub DD/-hopping) are proposed. In order to achieve reduction in power consumption and delay, the first proposed level shifter which is called contention mitigated level shifter (CMLS) uses a contention-reduction technique. The simulation results with 65-nm CMOS model show 24% reduction in power and 50% decrease in delay with 4% area increase compared with the conventional level shifter. The second proposed level shifter which is called bypassing enabled level shifter (BELS) implements a bypass function and it is fabricated using 0.35/spl mu/m CMOS technology. The measurement results show that the power and delay of the proposed BELS are reduced by 50% and 65%, respectively with 60% area overhead over the conventional level shifter.
Nucleotide sequence of mouse prolactin and growth hormone mRNAs and expression of these mRNAs during pregnancy. (1985)

The mRNAs for mouse prolactin and growth hormone have been isolated from anterior pituitary glands and cloned as cDNAs. The nucleotide sequences of these mRNAs have been determined, and these sequences, along with the predicted amino acid sequences, are compared to those of other mammalian prolactin and growth hormone mRNAs. Levels of prolactin and growth hormone mRNAs during pregnancy have been monitored by hybridization to the cloned cDNA probes. We find the levels of these mRNAs to remain nearly constant during mid-to-late gestation.
Characteristics of a novel deep red/infrared fluorescent cell-permeant DNA probe, DRAQ5, in intact human cells analyzed by flow cytometry, confocal and multiphoton microscopy (2000)

The fluorescence excitation and emission characteristics of DRAQ5 in living and fixed cells permit the incorporation of the measurement of cellular DNA content into a variety of multiparameter cytometric analyses.
Macrophage synthesis of nitrite, nitrate, and N-nitrosamines: precursors and role of the respiratory burst. (1987)

The macrophage cell line RAW 264.7 when activated with Escherichia coli lipopolysaccharide and interferon-gamma synthesized nitrite (NO3-) and nitrate (NO3-). Medium change after the activation showed that L-arginine was the only amino acid essential for this synthesis. D-Arginine would not substitute for L-arginine. Other analogues that could replace L-arginine were L-homoarginine, L-arginine methyl ester, L-arginamide, and the peptide L-arginyl-L-aspartate. L-Argininic acid, L-agmatine, L-ornithine, urea, L-citrulline, and ammonia were among the nonprecursors, while L-canavanine inhibited this L-arginine-derived NO2-/NO3- synthesis. When morpholine was added to the culture medium of the activated RAW 264.7 macrophages, N-nitrosation took place, generating N-nitrosomorpholine. GC/MS experiments using L-[guanido-15N2]arginine established that the NO2-/NO3- and the nitrosyl group of N-nitrosomorpholine were derived exclusively from one or both of the terminal guanido nitrogens of arginine. Chromatographic analysis showed that the other product of the L-arginine synthesis of NO2-/NO3- was L-citrulline. The role of the respiratory burst in NO2-/NO3- synthesis was examined using the macrophage cell lines J774.16 and J774 C3C. Both cell lines synthesized similar amounts of NO2-/NO3-. However, J774 C3C cells do not produce superoxide and hence do not exhibit the respiratory burst. Additional experiments also ruled out the involvement of the respiratory burst in NO2-/NO3- synthesis.
Real-time Microwave Imaging of Differential Temperature for Thermal Therapy Monitoring (2014)

A microwave imaging system for real-time 3-D imaging of differential temperature has been developed for the monitoring and feedback of thermal therapy systems. Design parameters are constrained by features of a prototype-focused microwave thermal therapy system for the breast, operating at 915 MHz. Real-time imaging is accomplished with a precomputed linear inverse scattering solution combined with continuous vector network analyzer (VNA) measurements of a 36-antenna, HFSS-modeled, cylindrical cavity. Volumetric images of differential change of dielectric constant due to temperature are formed with a refresh rate as fast as 1 frame/s and 1 (°)C resolution. Procedures for data segmentation and postprocessed S-parameter error-correction are developed. Antenna pair VNA calibration is accelerated by using the cavity as the unknown thru standard. The device is tested on water targets and a simple breast phantom. Differentially heated targets are successfully imaged in cluttered environments. The rate of change of scattering contrast magnitude correlates 1:1 with target temperature.
London: Der Niedergang der Oper 1729–1737 (1992)

Der Zusammenbruch einer Operngesellschaft, der Bankrott eines Unternehmens, die Verfügung über das Vermögen, die Schließung von Theatertüren — oftmals klingen solche Vorgänge in ihrer Beschreibung durch den Historiker bewegender, als sie es für die am Drama tatsächlich Beteiligten je waren. Das Ende eines Regimes bedeutet (für den Historiker), daß er nun verlorene Fadenenden suchen muß, damit Altes und Neues aneinandergeknüpft werden kann. Für die Beteiligten war die ›Tragödie‹ ein momentanes Ärgernis und gleichzeitig ein Anlaß, die Karten neu zu verteilen. Der Earl of Shaftesbury brachte diese Tatsache ganz nüchtern zum Ausdruck: »Da die Mittel fur den Erhalt der Oper erschöpft waren, wurde sie eben aufgegeben — und die Sänger verließen England.« Doch die Übergabe der Königlichen Musikakademie bedeutete für niemanden den Ruin, und es gab (zumindest diesmal) keinen körperlichen Zusammenbruch. Jeder Sänger, Musiker, Maler und Mechaniker bekam sein Geld — Schuldscheine wurden nicht akzeptiert (bei Händel machte man später eine Ausnahme). Die unerfahrenen jungen Direktoren waren zufrieden damit, daß sie ihr Kapital mir langfristigerem Erfolg und auch befriedigender angelegt hatten als in ähnlichen Unternehmen wie Newmarket oder dem Redoute. Nun, da der erste Enthusiasmus für die eigene Oper verflogen war, war es ihnen ganz recht, daß sie das Unternehmen in professionelle Hände übergeben konnten.
Noninvasive Prenatal Diagnosis of Fetal Trisomy 21 by Allelic Ratio Analysis Using Targeted Massively Parallel Sequencing of Maternal Plasma DNA (2012)

Targeted massively parallel sequencing of single nucleotide polymorphism loci in maternal plasma DNA is a potential approach for trisomy 21 detection. However, the method appears to be less robust than approaches using non-polymorphism-based counting of sequence tags in plasma.
Study on Saponification Technology of Waste Edible Oil (2009)

With rapid economic development, resource shortage and environment pollution have increasingly became a bottleneck in the ongoing development of society. The concept of "cyclic economy" has been proposed to build a resource-saving and environment-friendly society. Under this concept, "waste" should be treated as "misplaced resources". Given more efficient utilization of waste can promote society development. The precursor of waste edible oil is natural oil with main component of glycerol ester. The saponification of glycerol ester could produce glycerol and detergent such as sodium, potassium soap, etc. Therefore, the saponification of waste edible oil could be used directly to produce soap and washing powder. Practically, there are problems like long period of reaction time of saponification, incomplete saponification or no saponification at all. This paper studied the method and mechanism of saponification of waste edible oil and the factors that influenced the saponification degree by analyzing infrared spectrum of the product. Our experiments showed that the saponification processing reached the optimal configuration with four-hour reaction at the temperature of 100degC, the mass ratio of sodium hydroxide solution to the waste edible oil was 1:2 and the concentration of sodium hydroxide was 30%. The research of this paper is far-reaching in saving resources and reducing environmental pollution.
Novel Photoreactions of 2-Aza-1,4-dienes in the Triplet Excited State and via Radical-Cation Intermediates. 2-Aza-di-π-methane Rearrangements Yielding Cyclopropylimines and N-Vinylaziridines (2003)

Triplet-sensitized irradiation of 2-aza-1,4-dienes affords N-cyclopropylimines via 2-aza-di-pi-methane (2-ADPM) rearrangement pathways. In the case of the pentaphenyl-substituted azadiene 1, irradiation leads to formation of cyclopropylimine 2 as well as N-vinylaziridine 3. The transformations represent the first examples of di-pi-methane rearrangement reactions that yield three-membered heterocyclic products. SET-sensitized irradiation of 2-aza-1,4-dienes, by using 9,10-dicyanoanthracene (DCA) as an electron-acceptor sensitizer and biphenyl as cosensitizer, brings about regioselective formation of N-vinylaziridines. Under these conditions, azadiene 1 also affords cyclopropylimine 37, resulting from an aryl-di-pi-methane rearrangement. This result demonstrates that di-pi-methane reactions can also take place via radical-cation intermediates. In some instances, imine and olefin centered cation-radical intermediates, generated by SET-sensitized irradiation, undergo alternative reactions to produce isoquinoline and benzoazepine products.
Identification of specific recognition molecules on murine mononuclear phagocytes and B lymphocytes for Vi capsular polysaccharide: modulation of MHC class II expression on stimulation with the polysaccharide (1997)

Vi bacterial polysaccharide is a homopolymer of alpha 1-4 N-acetyl polygalacturonic acid with variable O-acetylation at position C-3 and forms a capsule around many bacteria. It has been referred to as the virulence factor of Salmonella typhi and is also a candidate vaccine against typhoid fever. The present study reports the interaction of this polysaccharide with murine mononuclear phagocytes and lymphocytes, and with human monocytes. Vi showed a dose-dependent binding to the murine monocyte cell lines WEHI-274.1 and J774. This binding was abrogated if the polysaccharide was deacetylated, suggesting involvement of acetyl groups in this interaction. Vi also bound to the murine B-cell lymphoma line A20, to peritoneal exudate cells and to a lesser degree to spleen cells and thymocytes from BALB/c mice. The polysaccharide also interacted with the human histiocytic lymphoma line U937 but not with the human monocyte cell line THP-1. Stimulation with Vi led to up-regulation of surface major histocompatibility complex (MHC) class II expression on A20 cells. Immunoprecipitation of Vi-bound molecules from cell surface biotinylated A20 and WEHI-274.1 revealed two bands with MW of about 32,000 and 36,000. The study demonstrates that Vi capsular polysaccharide can interact with mononuclear phagocytes and lymphocytes through specific cell surface molecules and modulate MHC class II expression.
Molecular basis for the polymorphic forms of human serum paraoxonase/arylesterase: glutamine or arginine at position 191, for the respective A or B allozymes. (1993)

The paraoxonase/arylesterase gene is located close to the cystic fibrosis gene on chromosome 7. Human serum contains two paraoxonase/arylesterase allozymes, A and B, which differ in their substrate specificities and kinetic properties. Purified A, AB, and B esterases were digested with trypsin, and the resultant peptides were compared by high-performance liquid chromatography. The elution profiles were very similar for all three samples, except for (1) one peptide (i.e., peptide A) seen only in the A and AB profiles and (2) another peptide (i.e., peptide B) seen only in the B and AB profiles. Sequencing revealed that peptide A had glutamine at amino acid position 191, whereas peptide B was generated by cleavage on the carboxy side of position 191, presumably because there was a basic (trypsin-specific) amino acid at that position. Working independently, our laboratory and one other laboratory have sequenced the coding region for paraoxonase from human liver cDNA libraries and have identified two polymorphic sites: Arg/Gln at position 191 and Leu/Met at position 54. Using PCR amplification and direct sequencing of nucleotides in both polymorphic regions with genomic DNA, we have estimated the allelic frequencies and have determined their concordance with the serum paraoxonase allozyme phenotypes in 27 unrelated adults and in 16 members of a three-generation pedigree. Among unrelated individuals, the Met/Leu polymorphism at position 54 did not correlate with the serum esterase phenotype. In contrast, the particular amino acid at position 191 correlated perfectly with serum phenotypes: A-type individuals had Gln at position 191, and B-type individuals had Arg at position 191; AB-type serum was found only with the heterozygous (Arg/Gln) combination. Pedigree analysis showed both polymorphisms to be inherited in the expected Mendelian manner and confirmed that only the 191 polymorphism showed concordance with the serum paraoxonase/arylesterase phenotypes.
Fast and robust deconvolution of tumor infiltrating lymphocyte from expression profiles using least trimmed squares (2019)

Gene-expression deconvolution is used to quantify different types of cells in a mixed population. It provides a highly promising solution to rapidly characterize the tumor-infiltrating immune landscape and identify cold cancers. However, a major challenge is that gene-expression data are frequently contaminated by many outliers that decrease the estimation accuracy. Thus, it is imperative to develop a robust deconvolution method that automatically decontaminates data by reliably detecting and removing outliers. We developed a new machine learning tool, Fast And Robust DEconvolution of Expression Profiles (FARDEEP), to enumerate immune cell subsets from whole tumor tissue samples. To reduce noise in the tumor gene expression datasets, FARDEEP utilizes an adaptive least trimmed square to automatically detect and remove outliers before estimating the cell compositions. We show that FARDEEP is less susceptible to outliers and returns a better estimation of coefficients than the existing methods with both numerical simulations and real datasets. FARDEEP provides an estimate related to the absolute quantity of each immune cell subset in addition to relative percentages. Hence, FARDEEP represents a novel robust algorithm to complement the existing toolkit for the characterization of tissue-infiltrating immune cell landscape. The source code for FARDEEP is implemented in R and available for download at https://github.com/YuningHao/FARDEEP.git.
Quantitative determination of nifedipine in human plasma by selected ion monitoring (1978)

A highly sensitive and specific method for the determination of nifedipine in plasma is described. Nifedipine was oxidized to its pyridine analogue with nitrous acid and determined by selected ion monitoring. Deuterium labeled nifedipine was used as an internal standard. Plasma levels as low as 5 ng ml-1 were measured. The usefulness of the method was demonstrated by obtaining plasma concentration curves for humans after an oral dose of 10 mg.
Model-based design of stimulus trains for selective microstimulation of targeted neuronal populations (2005)

Selective activation of targeted neuronal populations is required for central nervous system (CNS) neuroprosthetic device efficacy. However in many regions of the CNS, cells and fibers of passages are intermingled. The goal of this project was to design stimulus trains that would enhance selectivity between microstimulation of cells and fibers of passage. Detailed computer-based models were developed that accurately reproduced the dynamic firing properties of mammalian neurons. The neuron models were coupled to a three-dimensional finite element model of the spinal cord that solved for the potentials generated in the tissue medium by an extracellular electrode. The results demonstrate that alterations in the stimulus frequency, based on differences in the post-action-potential recovery cycles of cells and axons, enabled differential activation of cells or fibers of passage. The results also show that asymmetrical charge-balanced biphasic stimulus waveforms, designed to exploit the non-linear conductance properties of the neural elements, can be used in combination with the appropriate stimulus frequency to further enhance selectivity. These outcomes provide useful tools for selective stimulation of the CNS, as well as basis for understanding frequency-dependent outputs during CNS stimulation.
Interleukin-8 Messenger Ribonucleic Acid Expression Correlates with Tumor Progression, Tumor Angiogenesis, Patient Survival, and Timing of Relapse in Non–Small-Cell Lung Cancer (2000)

Tumor-associated angiogenesis is important for tumor growth and metastasis. Interleukin (IL)-8 was recently reported to be an important angiogenic factor both in vitro and in vivo. In this study we evaluated, for the first time, IL-8 messenger RNA (mRNA) expression in non-small-cell lung cancer (NSCLC), using real-time quantitative reverse-transcription-polymerase chain reaction, and correlated IL-8 mRNA expression in tumor and nontumor lung samples from 58 patients with NSCLC (29 with squamous cell carcinoma and 29 with adenocarcinoma, of whom 20 had Stage I, 10 had Stage II, and 28 had Stage III disease) with these patients' clinicopathologic characteristics, angiogenesis, and outcome. IL-8 protein expression and tumor microvessel count (MC) were assessed immunohistochemically. IL-8 mRNA expression was significantly greater in tumor tissue; high expression was highly associated with tumor in advanced stages (p = 0.03), distant lymph node metastasis (p = 0.02), high tumor MC (> 123) (p = 0.00003), short survival (< 26 mo) (p < 0.00001), and early relapse (< 16 mo) (p < 0.00001). Tumor MC correlated strongly with IL-8 mRNA expression (r = 0.56, p < 0.001). Multivariate analysis showed IL-8 mRNA expression and intratumor MC to be the most important predictors of patient survival and relapse. Thus, in NSCLC, IL-8 mRNA expression is strongly associated with tumor progression, tumor angiogenesis, survival, and time to relapse, suggesting its use as a prognostic indicator.
The Phosphoinositide-3 Kinase Survival Signaling Mechanism in Sepsis (2010)

Phosphoinositide-3 kinases (PI3Ks) are critical regulatory proteins in the immunologic defense system against sepsis. The PI3K mechanism helps modulate cellular survival, innate and adaptive immunities, inflammation, nuclear factor-κB transcription, and may, in turn, play a protective role in sepsis. Animal studies confirm its role in the prevention of organ dysfunction and improvement of survival outcomes. Further advances in the understanding of this key immunomodulatory pathway may provide valuable insights into the manipulation of cellular function for therapeutic treatment of sepsis and other inflammatory diseases.