gebhart/patrepeval huggingface dataset:
Modeling and Rescue of the Vascular Phenotype of Williams-Beuren Syndrome in Patient Induced Pluripotent Stem Cells (2012)

Elastin haploinsufficiency in Williams-Beuren syndrome (WBS) leads to increased vascular smooth muscle cell (SMC) proliferation and stenoses. Our objective was to generate a human induced pluripotent stem (hiPS) cell model for in vitro assessment of the WBS phenotype and to test the ability of candidate agents to rescue the phenotype. hiPS cells were reprogrammed from skin fibroblasts of a WBS patient with aortic and pulmonary stenosis and healthy control BJ fibroblasts using four-factor retrovirus reprogramming and were differentiated into SMCs. Differentiated SMCs were treated with synthetic elastin-binding protein ligand 2 (EBPL2) (20 μg/ml) or the antiproliferative drug rapamycin (100 nM) for 5 days. We generated four WBS induced pluripotent stem (iPS) cell lines that expressed pluripotency genes and differentiated into all three germ layers. Directed differentiation of BJ iPS cells yielded an 85%-92% pure SMC population that expressed differentiated SMC markers, were functionally contractile, and formed tube-like structures on three-dimensional gel assay. Unlike BJ iPS cells, WBS iPS cells generated immature SMCs that were highly proliferative, showed lower expression of differentiated SMC markers, reduced response to the vasoactive agonists, carbachol and endothelin-1, impaired vascular tube formation, and reduced calcium flux. EBPL2 partially rescued and rapamycin fully rescued the abnormal SMC phenotype by decreasing the smooth muscle proliferation rate and enhancing differentiation and tube formation. WBS iPS cell-derived SMCs demonstrate an immature proliferative phenotype with reduced functional and contractile properties, thereby recapitulating the human disease phenotype. The ability of rapamycin to rescue the phenotype provides an attractive therapeutic candidate for patients with WBS and vascular stenoses.
High Sensitivity Plasmonic Sensing of Hydrogen over a Broad Dynamic Range Using Catalytic Au-CeO2 Thin Film Nanocomposites (2018)

Next-generation gas-sensor technologies are needed for diverse applications including environmental surveillance, occupational safety, and industrial process control. However, the dynamic range using existing sensors is often too narrow to meet demands. In this work, plasmonic films of Au-CeO2 that detect hydrogen with 0.38% and 60% lower and upper detection limits in an oxygen-free atmosphere experiment are demonstrated. The observed 15 nm peak shift was 4 times stronger versus other plasmonic H2 sensors. The proposed sensing mechanism that involves H2 dissociation by Auδ+ nanoparticles was validated using XPS, kinetics, and Arrhenius studies. Our understanding of this remarkable sensing behavior in oxygen-free conditions opens new horizons for packaging, art conservation, industrial process control, and other applications where conventional oxygen-dependent sensors lack broad dynamic range.
Phytoremediation of Mercury and Organomercurials in Chloroplast Transgenic Plants: Enhanced Root Uptake, Translocation to Shoots, and Volatilization (2007)

Transgenic tobacco plants engineered with bacterial merA and merB genes via the chloroplast genome were investigated to study the uptake, translocation of different forms of mercury (Hg) from roots to shoots, and their volatilization. Untransformed plants, regardless of the form of Hg supplied, reached a saturation point at 200 microM of phenylmercuric acetate (PMA) or HgCl2, accumulating Hg concentrations up to 500 microg g(-1) with significant reduction in growth. In contrast, chloroplast transgenic lines continued to grow well with Hg concentrations in root tissues up to 2000 microg g(-1). Chloroplasttransgenic lines accumulated both the organic and inorganic Hg forms to levels surpassing the concentrations found in the soil. The organic-Hg form was absorbed and translocated more efficiently than the inorganic-Hg form in transgenic lines, whereas no such difference was observed in untransformed plants. Chloroplast-transgenic lines showed about 100-fold increase in the efficiency of Hg accumulation in shoots compared to untransformed plants. This is the first report of such high levels of Hg accumulation in green leaves or tissues. Transgenic plants attained a maximum rate of elemental-Hg volatilization in two days when supplied with PMA and in three days when supplied with inorganic-Hg, attaining complete volatilization within a week. The combined expression of merAB via the chloroplast genome enhanced conversion of Hg2+ into Hg,0 conferred tolerance by rapid volatilization and increased uptake of different forms of mercury, surpassing the concentrations found in the soil. These investigations provide novel insights for improvement of plant tolerance and detoxification of mercury.
A Charge-Sharing Locking Technique With a General Phase Noise Theory of Injection Locking (2021)

This article presents a millimeter-wave (mmW) frequency synthesizer based on a new charge-sharing locking (CSL) technique. A charge-preset capacitor is introduced for charge sharing with a resonant <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">LC</i> -tank for phase correction, while the resulting charge residue on the sharing capacitor is processed by a digital frequency-tracking loop (FTL) against the process, voltage, and temperature (PVT) variations. Furthermore, a general phase noise (PN) theory of CSL, with injection locking (IL) being a special case, is proposed based on a unified multirate <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${z}$ </tex-math></inline-formula> -domain model, supporting any frequency division ratio <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${N}$ </tex-math></inline-formula> and CSL (or IL) strength <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\beta $ </tex-math></inline-formula> . The new theory sheds light not only on all IL-like PN phenomena (chiefly, its “loop” bandwidth being up to half of the reference frequency, and the oscillator PN increasing 3 dB beyond the “loop” cutoff frequency) but also on how to choose the CSL bandwidth via the sharing capacitor in order to optimize the rms jitter performance. The prototype in 28-nm CMOS achieves 77-fs rms jitter in 21.75—26.25 GHz while consuming 16.5 mW for mmW quadrature frequency generation.
Learning Local Patterns of Time Series for Anomaly Detection (2023)

The problem of anomaly detection in time series has recently received much attention, but in most practical applications, labels for normal and anomalous data are not available. Furthermore, reasons for anomalous results must often be determined. In this paper, we propose a new anomaly detection method based on the expectation–maximization algorithm, which learns the probabilistic behavior of local patterns inherent in time series in an unsupervised manner. The proposed method is simple yet enables anomaly detection with accuracy comparable with that of the conventional method. In addition, the representation of local patterns based on probabilistic models provides new insight that can be used to determine reasons for anomaly detection decisions.
Field Trial of a Novel Self-Reciprocating Hydraulic Pump for Deliquification (2016)

Abstract A novel hydraulically-powered, Self-Reciprocating Valve Pump (SRVP) was piloted in a Western Colorado gas well for deliquification operations. The objective was to pump fluids from a deep gas well and later retrieve and redeploy the SRVP without a workover rig. This paper will describe the SRVP technology, areas of applicability, and pilot program, including the completion design, deployment/retrieval workovers, performance, teardowns, learnings, and future plans. Gas production wells tend to load up with produced or condensed liquids that create an impediment to flow and reduce or stop gas production. Pumps are typically used when the reservoir pressure is too low for less intrusive artificial lift methods or when significant amounts of fluid must be removed. Pumps can suffer from reliability issues and considerable installation/deployment costs because a workover rig is typically required for intervention. Unfavorable producing conditions and tortuous wellbore trajectories further tend to decrease run lives. These issues can make economical hydrocarbon production impossible. The SRVP was developed to overcome these challenges. The SRVP is installed downhole inside a concentric tubing string and is powered by injecting a high pressure fluid. The injected (power) fluid causes the SRVP to reciprocate, driving a piston pump to produce formation liquids and power fluid back to surface up the concentric string by production tubing annulus. Removal of the produced fluids decreases backpressure on the formation, enabling gas production up the casing. Because there is no mechanical linkage to surface for pump operation, the SRVP can be deployed in highly-deviated and/or small-diameter wells that standard artificial lift methods would struggle with. Additionally, the SRVP is designed to be pumped into and out of the well following initial installation, greatly reducing deployment costs. Three industry-first SRVPs were installed consecutively in a concentric flush-joint tubing string and were powered with a compact surface pumping unit. The SRVP proved the ability to lift 20 to 40 BFPD net fluids up the concentric string by production tubing annulus from more than 12,000 ft vertical depth while gas was produced up the casing. The SRVP was retrieved and redeployed several times either hydraulically and/or with slickline. System design, operation, and performance were continuously improved through the duration of the pilot program. Run life steadily increased to 50+ days with the third installation.
Spontaneous Immortalization of Clinically Normal Colon-Derived Fibroblasts from a Familial Adenomatous Polyposis Patient (2004)

Normal human diploid cells do not spontaneously immortalize in culture, but instead enter replicative senescence after a finite number of population doublings. Ablation of key checkpoint arrest or cancersuppressor genes, through dominantly inherited germline mutation (p53+/-, Li-Fraumeni) or viral oncogene expression (SV40 large T, HPV16/18, E6/E7) can lead to escape from senescence, additional doublings, entrance into crisis phase, where immortal clones emerge at low frequency. In the vast majority of cases, telomerase is reactivated and telomeres are stabilized. Here we describe the spontaneous immortalization of clinically normal fibroblasts derived from colonic stroma of a familial adenomatous polyposis (FAP) patient. The preimmortal (C26C) and the spontaneously immortalized derivative (C26Ci) cells are heterozygous for a characterized germline mutation in exon 15 of the adenomatous polyposis coli gene. Immortalization was accompanied by spontaneous reactivation of endogenous telomerase and establishment of telomeres at presenescent lengths. Normal checkpoint behavior is retained and a diploid karyotype is maintained. These cells provide a valuable new addition to the limited number of spontaneously immortalized human cell types, particularly fibroblast cells, will be useful in experimentally determining the functional pathways in neoplastic development and in the identification of potential molecular targets for cancer chemoprevention.
Zeolite Microneedles for Controlled Transdermal Drug Delivery (2013)

Skin provides a protective barrier against harmful chemicals and pathogens, but also hinders transdermal delivery of therapeutic drugs, particularly large molecules of low lipophilicity. Skin poration methods including iontophoresis, phonophoresis, chemical, laser and RF ablation and microneedles have been used to improve transdermal drug delivery with minimal pain and skin trauma. The key feature of this work is the use of porous zeolite microneedles for regulating the transport and delivery of drug molecules (i.e., diclofenac and insulin). Pure silica zeolites with composition similar to glass were used because of their inert properties and good biocompatibility. The zeolite was formed into needle lumen and its drug permeability was adjusted by controlling the intra- and inter-crystalline pores to deliver from 20 to 100 kDa. The zeolite microneedles are sharp and strong, and can easily penetrate the stratum corneum, without damage. Unlike polymer materials, the greater mechanical strength of zeolite makes it less susceptible to deformation and damage from osmosis and fluid flow. The biocompatibility of the zeolite microneedles was tested in animal models with no observable skin irritation or redness. Both in vitro and in vivo studies of insulin delivery by the zeolite microneedles were carried out. A diabetic rat was used for the in vivo study wherein the blood glucose and insulin levels were monitored during the duration of the studies.
Os romances juvenis de Alvaro Magalhaes (2015)

With his works translated in countries such as Spain, France and Brazil, Álvaro Magalhães is not only one of the great writers of Portuguese and Lusophone juvenile fiction, but also one of the most prominent names in European and world literature. Through the various thematic and narrative resources that he employs in the creation of a unique language, among the multiple and unusual senses of serious and humorous, among the elements of various domains of knowledge and universal culture that he invokes and contrasts, this author has a unique place in universe of novels aimed primarily at young readers.
Segments from red blood cell units should not be used for quality testing (2013)

The quality of samples from tubing segments is not representative of the quality of the corresponding RBC unit. Segments are not suitable surrogates with which to assess RBC quality.
Forced Unfolding of Single-Chain Polymeric Nanoparticles (2015)

Atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) is applied to single-chain polymeric nanoparticles (SCPNs) to acquire information about the internal folding structure of SCPNs and inherent kinetic parameters of supramolecular self-assembling motifs embedded into the SCPNs. The SCPNs used here are polyacrylate-based polymers carrying 2-ureido-4-[1H]-pyrimidinone (UPy) or benzene-1,3,5-tricarboxamide (BTA) pendants that induce an intramolecular chain collapse into nanoparticles consisting of one polymer chain only via internal supramolecular cross-linking. The SCPN is stretched by an AFM cantilever to unfold mechanically, which allows measuring of force-extension profiles of the SCPNs. Consecutive peaks observed in the force profiles are attributed to rupture events of self-assembled UPy/BTA units in the SCPNs. The force profiles have been analyzed statistically for a series of polymers with different UPy/BTA incorporation densities. The results provide insights into the internal conformation of SCPNs, where the folding structure can be changed with the incorporation density of UPy/BTA. In addition, dynamic loading rate analysis allows the determination of kinetic parameters of BTA self-assembly, which has not been accessible by any other method. This study offers a rational tool for understanding the folding structure, kinetics, and pathway of two series of SCPNs.
In vivo NCL targeting affects breast cancer aggressiveness through miRNA regulation (2013)

Numerous studies have described the altered expression and the causal role of microRNAs (miRNAs) in human cancer. However, to date, efforts to modulate miRNA levels for therapeutic purposes have been challenging to implement. Here we find that nucleolin (NCL), a major nucleolar protein, posttranscriptionally regulates the expression of a specific subset of miRNAs, including miR-21, miR-221, miR-222, and miR-103, that are causally involved in breast cancer initiation, progression, and drug resistance. We also show that NCL is commonly overexpressed in human breast tumors and that its expression correlates with that of NCL-dependent miRNAs. Finally, inhibition of NCL using guanosine-rich aptamers reduces the levels of NCL-dependent miRNAs and their target genes, thus reducing breast cancer cell aggressiveness both in vitro and in vivo. These findings illuminate a path to novel therapeutic approaches based on NCL-targeting aptamers for the modulation of miRNA expression in the treatment of breast cancer.
Optimization of Second-Generation Antisense Drugs: Going Beyond Generation 2.0 (2007)

This chapter will summarize recent progress in the optimization of oligonucleotide design to increase antisense potency in animals by maximizing RNase H activity for oligonucleotides that contain chemical modifications that do not support RNase H activity, but yet offer other benefits for antisense drug technology. Readers are directed to other chapters in this volume to review recent progress in the medicinal chemistry of oligonucleotides that act through siRNA pathways.
Electroweak production of two jets in association with a Z boson in proton–proton collisions at $$\sqrt{s}= $$ s = 13 $$\,\text {TeV}$$ TeV (2018)

A measurement of the electroweak (EW) production of two jets in association with a Z boson in protonproton collisions at s = 13 TeV is presented, based on data recorded in 2016 by the CMS experiment at the LHC corresponding to an integrated luminosity of 35.9 fb -1 . The measurement is performed in the jj final state with including electrons and muons, and the jets j corresponding to the quarks produced in the hard interaction. The measured cross section in a kinematic region defined by invariant masses m > 50 GeV, m jj > 120 GeV, and transverse momenta p Tj > 25 GeV is EW ( jj) = 534 20 (stat) 57 (syst) fb, in agreement with leading-order standard model predictions. The final state is also used to perform a search for anomalous trilinear gauge couplings. No evidence is found and limits on anomalous trilinear gauge couplings associated with dimension-six operators are given in the framework of an effective field theory. The corresponding 95% confidence level intervals are -2.6 < c W W W / 2 < 2.6 TeV -2 and -8.4 < c W / 2 < 10.1 TeV -2 . The additional jet activity of events in a signal-enriched region is also studied, and the measurements are in agreement with predictions.
Detrimental Influence of Alveolar Macrophages on Protective Humoral Immunity during Francisella tularensis SchuS4 Pulmonary Infection (2018)

Opsonizing antibody is a critical component of the host protective immune response against many respiratory pathogens. However, the role of antibodies in protection against pulmonary infection with highly virulent <i>Francisella tularensis</i> strain SchuS4 is unclear, and the mechanism that allows <i>F. tularensis</i> to evade antibody-mediated bacterial clearance is not fully understood. We have now found that depletion of alveolar macrophages reveals an otherwise cryptic protective effect of opsonizing antibody. While antibody opsonization alone failed to confer any survival benefit against SchuS4 lung infection, significant protection was observed when mice were depleted of alveolar macrophages prior to infection. Blood immune signature analyses and bacterial burden measurements indicated that the treatment regimen blocked establishment of productive, systemic infection. In addition, protection was found to be dependent upon neutrophils. The results show for the first time a protective effect of opsonizing antibodies against highly virulent <i>F. tularensis</i> SchuS4 pulmonary infection through depletion of alveolar macrophages, the primary bacterial reservoir, and prevention of systemic dissemination. These findings have important implications for the potential use of therapeutic antibodies against intracellular pathogens that may escape clearance by residing within mucosal macrophages.
P2.6.4 Characterization of New Structural Ion Sensor using Electrochemical Impedance Method (2012)

We developed a new structural ion sensor for measuring sodium ions without using a reference electrode. The ion sensor, which is all solid state, has a structure of double electrodes inside the sodium ion sensitive membrane. The ion sensitivity of the sensor was 45 mV/decade in the range of 10 -1 to 10 -4 mol/l. To investigate the response mechanism of the potential between two electrodes, the impedance characteristic was measured using the electrochemical impedance method. The impedance of the ion sensitive membrane changed by changing the sodium ion concentration in solution. These results suggest a correlation between the membrane potential and the membrane impedance. In conclusion, ions in the ion sensitive membrane result in the potential gradient of the ion sensitive membrane.
Effects of μ‐specific antibodies on B cell growth and maturation (1984)

Over a wide range of concentrations affinity-purified rabbit anti-mouse mu chain antibodies, or their F(ab')2 fragments, inhibit the appearance of immunoglobulin-secreting cells (plaque-forming cells; PFC) in lipopolysaccharide-stimulated murine spleen cell cultures without affecting proliferation. Both IgM and IgG PFC are inhibited although the number of blasts bearing surface IgG remains unaltered. The IgM and IgG PFC response could be reconstituted to normal levels in cell cultures suppressed by mu-specific antibodies by the addition of supernatants from in vitro propagated helper T cell clones, or from EL4 lymphoma cells induced with phorbol ester. Interleukin 1-containing P388 supernatant, or recombinant DNA-derived murine interferon-gamma, did not reconstitute the PFC response in cell cultures suppressed by mu-specific antibodies, indicating that other factors are responsible for these effects. When spleen cell cultures, pre-activated with either lipopolysaccharide or monoclonal mouse mu-specific antibodies coupled to Sepharose, were exposed to EL4 supernatants in the presence of soluble mu-specific antibodies, maturation to secretion was inhibited while proliferation was not. The implications of these findings on assay systems for B cell growth and maturation factors are discussed.
A Novel Technique for Pulsed Operation of Magnetrons without Modulation of Cathode Voltage (2019)

Modern pulsed superconducting accelerators of megawatt beams require efficient RF sources controllable in phase and power. For each Superconducting RF (SRF) cavity is desirable a separate RF source with power up to hundreds of kW with pulse duration in the millisecond range. The efficiency of the traditional RF sources (klystrons, IOTs, solid-state amplifiers) is lower than that of the magnetrons, while the cost of a unit of RF power is much higher. Therefore the magnetron-based RF sources would significantly reduce the capital and operation costs in comparison with the traditional RF sources. A recently developed an innovative technique makes possible the pulsed generation of magnetrons powered below the self-excitation threshold voltage. This technique does not require pulse modulators to form RF pulses. The magnetron operation in this regime is stable, low noise, controllable in phase and power, and provides higher efficiency than other types of RF power sources. It allows operation in pulsed modes with large duty factor. The developed technique and its experimental verification are considered and discussed.
Natural Resources and Social Conflicts in the Sahel: Proceedings of the 5th Sahel Workshop, 4-6 January 1993 (2016)

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