gebhart/patrepeval huggingface dataset:
Effects of High-Volume Plasmapheresis on Ammonia, Urea, and Amino Acids in Patients With Acute Liver Failure (2001)

Arterial ammonia decreased during HVP in patients with ALF. The data suggest that this effect of HVP could be explained by increased hepatic urea synthesis and possibly by increased glutamine synthesis in muscle tissue.
State‐of‐the‐art technologies for rapid and high‐throughput sample preparation and analysis of <i>N</i>‐glycans from antibodies (2016)

Glycosylation is a PTM that occurs during production of many protein-based biologic drugs and can have a profound impact on their biological, clinical, and pharmacological properties. Quality by design, process optimization, and advance in manufacturing technology create a demand for robust, sensitive, and accurate profiling and quantification of antibody glycosylation. Potential drawbacks in antibody glycosylation profiling include the high hands-on time required for sample preparation and several hours for data acquisition and analysis. Rapid and high-throughput (HTP) N-glycan profiling and characterization along with automation for sample preparation and analysis are essential for extensive antibody glycosylation analysis due to the substantial improvement of turnaround time. The first part of this review article will focus on the recent progress in rapid and HTP sample preparation and analysis of antibody glycosylation. Subsequently, the article will cover a brief overview of various separation and mass spectrometric methods for the rapid and HTP analysis of N-glycans in antibodies. Finally, we will discuss the recent developments in process analytical technologies for the screening and quantification of N-glycans in antibodies.
CONTINUOUS BLOOD VOLUME MONITORING AND “DRY WEIGHT” ASSESSMENT (2007)

There are two distinct facets of adequate fluid balance control in haemodialysis patients--estimation of dry weight (DW) as the target and adequate ultrafiltration (UF) strategy, i.e. the way to reach the target in a possibly symptom-free way. The article reviews the continuous blood volume monitoring (CBVM) based procedures to deal with the former facet-DW determination. The existing approaches are divided in three groups--methods defining certain alert value of relative blood volume (RBV) reduction, methods working with RBV response to constant UF rate, and methods evaluating dynamics of RBV response to UF pulse or chain of UF pulses. While the first and the third approaches are relatively easy to automate, the second group of methods are suitable mainly for observational evaluations only. All the discussed methods, without exception, need large-scale verification, as they all were evaluated in the majority by their authors only and on small patient cohorts.
Intraneoplastic polymer-based delivery of cyclophosphamide for intratumoral bioconversion by a replicating oncolytic viral vector. (2001)

rRp450 is an oncolytic herpesvirus that expresses the CYP2B1 cDNA, responsible for bioconverting cyclophosphamide (CPA) into the active metabolites 4-hydroxyCPA/aldophosphamide (AP). However, formal proof of prodrug activation is lacking. We report that activation of CPA in cells infected with rRp450 generates a time-dependent increase of diffusible 4-hydroxyCPA/AP. For in vivo applications, a CPA-impregnated polymer was implanted into human tumor xenografts inoculated with rRp450. The area under the curve for 4-hydroxyCPA/AP was 806 microg/g of tumor tissue/h when CPA was administered via intraneoplastic polymer and 3 microg/g of tumor tissue/h when CPA was administered i.p. Therefore, (a) a lytic virus expressing a "suicide" gene can activate a prodrug; and (b) within rRp450-infected tumor, more prolonged and higher concentrations of activated metabolites are generated by intraneoplastic compared with systemic administration of prodrug.
Basis and therapeutical rationale of the urinary concentrating mechanism (2007)

The urine-concentrating mechanism performs one of the most essential functions in water and electrolyte metabolism and serves primarily to maintain extracellular osmolality within a very narrow range. The history of anti-diuresis dates back more than 100 years and includes the discovery of antidiuretic hormone (AVP), the renal AVP receptor, and most recently the water channel (aquaporin) proteins. Today, the mechanisms of antidiuresis are understood on a highly detailed molecular level including both short term and long-term regulation of AQP2 function. Furthermore, the background behind many acquired and inherited disturbances of water balance has now been revealed and has enabled a precise differential diagnosis. These include different forms of diabetes insipidus, nocturnal enuresis and nocturia in the elderly. Diabetes insipidus represents a dramatic but rare disturbance of water balance caused by deficient AVP secretion (neurogenic), reduced renal sensitivity to AVP (nephrogenic), an abnormally high fluid intake (primary polydipsia), or in rare cases by placental enzymatic degradation of AVP (gestational). Nocturnal enuresis and nocturia in the elderly represents much more common disturbances and share common pathogenic features including an abnormally high nocturnal urine production. This seems at least in part to be caused by abnormally low levels of plasma AVP during night. The increased understanding of such water balance disturbances have changed dramatically prior treatment practice by introducing antidiuresis as a treatment modality. The ongoing progress in our understanding of antidiuresis may provide the basis for the development of new antidiuretic compounds.
Atom-Selective Bond Breaking in a Chemisorbed Homonuclear Molecule Induced by Core Excitation:<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msub><mml:mrow><mml:mi>N</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow></mml:msub></mml:mrow><mml:mi>/</mml:mi><mml:mi>Ru</mml:mi><mml:mo>(</mml:mo><mml:mn>001</mml:mn><mml:mo>)</mml:mo></mml:math> (2000)

We observe photochemical selectivity for N 1s to pi(*) excitations of chemisorbed N2. By narrow bandwidth synchrotron radiation we selectively excite one of the two atoms of the molecule. Photon stimulated desorption of neutral N atoms predominates for excitations of the N atom close to the surface, whereas excitation of the outer atom ejects predominantly N02 and small amounts of N+, demonstrating the predominant breaking of the inner or outer bond, respectively, of the N2 adsorbate. Analysis on the basis of previously obtained decay electron spectra after atom-selective excitation can explain the mechanism of localized bond breaking.
High‐Performance Ceramic Membranes with a Separation Layer of Metal Oxide Nanofibers (2007)

Layers of randomly oriented fibers arranged in a hierarchical structure as the separation layer in ceramic membranes (see figure) are shown to greatly improve the separation efficiency compared to conventionally fabricated ceramic membranes, and remove the problems of cracks, pinholes, and serious sintering. The membranes have many potential applications, for example, removing viruses and waterborne pathogens.
Proteomic Technologies for the Discovery of Type 1 Diabetes Biomarkers (2010)

In this review, we discuss several important issues concerning the discovery of protein biomarkers for complex human diseases, with a focus on type 1 diabetes. Serum or plasma is the first choice of specimen due to its richness in biological information and relatively easy availability. It is a challenging task to comprehensively characterize the serum/plasma proteome because of the large dynamic range of protein concentration. Therefore, sample pretreatment is required in order to explore the low- to medium-abundance proteins contained in serum/ plasma. In this regard, enrichment of low-abundance proteins using random hexapeptide library beads has distinct advantages over the traditional immune-depletion methods, including higher efficiency, higher binding capacity, and lower cost. In-depth mining of serum/plasma proteome using different separation techniques have also been evaluated and are discussed in this review. Overall, the shotgun proteomics—multidimensional separation of digested peptides followed by mass spectrometry analysis—is highly Efficient and therefore has become a preferred method for protein biomarker discovery.
Genetic evidence for ubiquitin-specific proteases<i>USP24</i>and<i>USP40</i>as candidate genes for late-onset Parkinson disease (2006)

Linkage studies have defined susceptibility regions for late-onset Parkinson disease (PD) on chromosomes 1 and 2, but specific genetic variants have not been definitively identified. Here we report the results of a case-control study to identify disease-associated single nucleotide polymorphisms (SNPs) in these loci. In the initial phase of our study, we genotyped two putative functional SNPs in ubiquitin-specific protease 24 (USP24), a biological candidate gene within the chromosome 1 linkage region, and scanned the chromosome 2 linkage peak with 43 SNPs in a sample set of 224 PD cases and 186 matched controls. Both USP24 SNPs were significantly associated with disease risk (p = 0.0037 for rs1165222:T > C, p.Thr195ILe, and p = 0.037 for rs13312:C > G, a SNP in the 3'-untranslated region), and one marker, rs1048603:C > T, p.Arg1123Cys, in USP40 was significant from the chromosome 2 scan (p = 0.038). Further genotyping of the region surrounding these initial markers led us to identify 19 additional SNPs with strong disease association. In the second phase, we genotyped the 22 significant markers in an additional 110 cases and 162 controls, which together with part of the initial sample set (201 cases and 149 controls) constitute an expanded sample set of 311 age- and gender-matched case-control pairs. Twenty-one markers were significant in the expanded sample set (most significant allelic p-value: 0.0006 for rs287235:C > G on chromosome 1, and 0.005 for rs838552:T > C on chromosome 2), and six SNPs in USP24 remained significant after conservatively adjusting for testing 27 markers (pBonferroni = 0.017-0.049). It is unlikely that population stratification contributed to this finding, as population stratification was undetectable in our sample set using 78 null markers. Our data suggest that genetic variants in USP24 and USP40 affect the risk for late-onset PD, which is consistent with the predicted role of the ubiquitination pathway in PD etiology.
Characterization of the sequences of the human cytomegalovirus enhancer that mediate differential regulation by natural and synthetic retinoids (1996)

Evidence exists to suggest that human cytomegalovirus (hCMV) may opportunistically use retinoic acid (RA) to advance its own replication, in which transcriptional activation of the viral major immediate-early promoter is a crucial control point. We demonstrate that the enhancer of the viral promoter contains three RA-response-elements that cooperate in mediating RA activation. These elements are direct repeats of two sequence motifs separated by 2 bp (DR2 site, REa) and 5 bp (DR5 sites, REb and c). DNA-binding experiments revealed that each of these elements bind RA receptor (RAR)-retinoid X receptor (RXR) heterodimers more efficiently than either homodimer. Apparent equilibrium dissociation constants of RAR-RXR heterodimers for sites REa, REb, and REc were estimated to be 5 nm, 10 nm, and 20 nm, respectively. The level of contribution of each of these elements to RA inducibility correlated with the strength of binding by RAR-RXR heterodimers to each site. These experiments demonstrate that RAR and RXR are necessary for RA responsiveness of the viral promoter. Using synthetic RA analogs, which selectively activate RARs and RXRs, the RAR partner within the heterodimeric complex appeared to be sufficient while the RXR partner was insufficient to independently activate transcription. However, joint activation of RARs and RXRs indicated that RXRs (in the presence of a transcriptionally active RAR) could contribute to transactivation. This restricted co-dependent ligand activation of RXR varied depending on the particular response element and the cell context. These studies further indicate that signaling of retinoid receptors (in particular RAR) by RA plays an important role in modulating hCMV infection.
Current Steering in Magnetic Circuits (1957)

Magnetic switches are described in which the current from an energizing source is guided or steered through one out of many possible parallel branches, the conducting branch being selected by the presetting of appropriate magnetic elements. Only a few tubes are required for energization, and the outputs, obtained with reasonable efficiency, are substantially independent of exact circuit parameters. Current steering is achieved either by core-diode combinations or by transfluxors. Decoding switches, of both types, for the selection of one out-of-many outputs according to an input code are described in detail. A current of precise amplitude of the order of amperes is switched to a selected path in microseconds. Steered decoders are ideal for addressing core memories. A commutator switch for delivering sequentially a given current to a number of loads is described. Current steering makes possible simple magnetic counters and universal code converters. Experimental results of laboratory models of decoders and commutators are given. The principle of current steering broadens greatly the usefulness of magnetic switches by providing economy of associated electronic drivers and accuracy of switched currents.
Channel P waves II<i>g</i> in the Earth's crust (1956)

The prominence on seismograms of channel S waves ( Lg ) suggests the existence of the corresponding longitudinal wave (II g ). Examination of seismograms from North American stations for the Kern County earthquake of 1952 revealed the existence of this phase. It is characterized by small amplitude and erratic occurrence. The weakness of II g in contrast to the great strength of Lg is interpreted in terms of propagation in a crustal channel bounded on top by the Earth's surface.
Structural characterization of amorphous electrodeposited cobalt-phosphorus alloys (1979)

The structure of amorphous electrodeposited Co-P alloy foils has been examined by x-ray scattering techniques. Samples with phosphorus contents from 18 to 26 at.% have been examined with large-angle x-ray scattering. Atomic arrangements in these alloys are described in terms of radial distribution functions. Effects of alloy composition on randomness of short-range order, atomic-pair distances, and strength of long-range order have been observed. Evidence of large-scale (10–104-Å) composition fluctuations has been obtained from small-angle x-ray scattering on amorphous Co77.5P22.5 samples. The composition fluctuation regions are anisotropically shaped (rodlike) with their largest extent (≳2000 Å) perpendicular to the foil plane and their smallest extent (∼60 Å) in the foil plane.
The nucleus, a site for signal termination by sequestration and inactivation of p42/p44 MAP kinases (2001)

We previously reported that nuclear translocation is essential for p42/p44 MAPKs (ERKs) mitogenic signaling. Here we show that, during long-term stimulation, p42/p44 MAPKs become inactive while they accumulate in the nucleus. This inactivation was monitored by phospho-specific immunostaining and dephosphorylation of a nuclear p42/p44 MAPKs substrate, HIF-1 alpha. The phosphatases responsible for p42/p44 MAPKs nuclear inactivation are neo-synthesized, show tyrosine or dual specificity, and interact with p42/p44 MAPKs via a specific docking site. Likely candidates are MKP1/2 phosphatases. In addition, p42/p44 MAPKs permanently shuttle between the cytoplasm and the nucleus in quiescent as well as in serum stimulated cells. Hence, the nucleus is a critical site for mitogenic signal termination by: (1) nuclear sequestration of p42/p44 MAPKs away from MEK, their cytoplasmic activator; and (2) dephosphorylation by specific nuclear phosphatases.
Immunodominance in Virus-Induced CD8 <sup>+</sup> T-Cell Responses Is Dramatically Modified by DNA Immunization and Is Regulated by Gamma Interferon (2002)

The phenomenon whereby the host immune system responds to only a few of the many possible epitopes in a foreign protein is termed immunodominance. Immunodominance occurs not only during microbial infection but also following vaccination, and clarification of the underlying mechanism may permit the rational design of vaccines which can circumvent immunodominance, thereby inducing responses to all epitopes, dominant and subdominant. Here, we show that immunodominance affects DNA vaccines and that the effects can be avoided by the simple expedient of epitope separation. DNA vaccines encoding isolated dominant and subdominant epitopes induce equivalent responses, confirming a previous demonstration that coexpression of dominant and subdominant epitopes on the same antigen-presenting cell (APC) is central to immunodominance. We conclude that multiepitope DNA vaccines should comprise a cocktail of plasmids, each with its own epitope, to allow maximal epitope dispersal among APCs. In addition, we demonstrate that subdominant responses are actively suppressed by dominant CD8(+) T-cell responses and that gamma interferon (IFN-gamma) is required for this suppression. Furthermore, priming of CD8(+) T cells to a single dominant epitope results in strong suppression of responses to other normally dominant epitopes in immunocompetent mice, in effect rendering these epitopes subdominant; however, responses to these epitopes are increased 6- to 20-fold in mice lacking IFN-gamma. We suggest that, in agreement with our previous observations, IFN-gamma secretion by CD8(+) T cells is highly localized, and we propose that its immunosuppressive effect is focused on the APC with which the dominant CD8(+) T cell is in contact.
Mechanisms of Transmural Heparin Transport in the Rat Abdominal Aorta After Local Vascular Delivery (1995)

Abstract Local vascular drug delivery systems provide elevated concentrations in target arterial tissues, while minimizing systemic side effects. Drug can now be released to isolated arterial segments from the endovascular or perivascular aspects of the blood vessel, yet the forces that determine drug distribution and deposition for these different modes of delivery have not been rigorously investigated. This study examines mechanisms of transmural transport of a model vasoactive drug, heparin, and compares estimates of the distribution after administration from either aspect of the artery. We showed that (1) heparin traversed the arterial wall rapidly; (2) diffusion far outweighed convection in the control of transmural heparin transport in the normal artery, but after endothelial injury, convective forces rose to one quarter the magnitude of diffusive forces; (3) the endothelium posed a minimal diffusive barrier to heparin; and (4) the diffusive barrier imposed by the adventitia depended on its thickness. These findings strongly suggest that vasoregulatory compounds can be administered to target tissue by either perivascular or endovascular means with equal efficacy, because the forces governing transport of heparin from either aspect of the blood vessel wall are not significantly different. Furthermore, the differences in arterial transport properties between heparin and other macromolecules suggest that distribution and the optimal aspect of delivery will depend just as much on the physicochemical properties of the drug as the state of the blood vessel wall.
Refractive-index based tomosynthesis using dark-field imaging optics (2013)

Tomosynthesis (TS) is a pseudo-3-dimensional image reconstruction method to recover depth-resolved information using restricted number of projections. In this research, refraction index based TS imaging using dark-field imaging (DFI) optics is proposed and biomedical soft tissues were imaged in low dose exposure. By a single exposure of an object, two projected images are obtained from a Laue-case analyzer of DFI. Calculating the both images refraction component is deduced, while two exposures are needed in DEI (diffraction enhanced imaging). Thus the measurement time and the radiation dose in DFI are half of DEI. In addition, the proposed reconstruction algorithm, derived from the quantitative relationship in measurement process, allows high contrast tomographic imaging in spite of one order smaller number of projections for CT (computed tomography). To demonstrate the proposed imaging protocol efficacy, an ex-vivo excised tissue of human lung were imaged using a system constructed at the vertical wiggler beamline at PF-BL14C at KEK. TS image is successfully delineated high quality soft tissue structures comparable to CT.
Protein-tyrosine Phosphatase 1B Expression Is Induced by Inflammation in Vivo (2008)

Protein-tyrosine phosphatase 1B (PTP1B) is a major negative regulator of insulin and leptin sensitivity. PTP1B overexpression in adipose tissue and skeletal muscle of humans and rodents may contribute to insulin resistance and obesity. The mechanisms mediating PTP1B overexpression in obese and diabetic states have been unclear. We find that adipose tissue inflammation and the pro-inflammatory cytokine tumor necrosis factor alpha (TNFalpha) regulate PTP1B expression in vivo. High fat feeding of mice increased PTP1B expression 1.5- to 7-fold in adipose tissue, liver, skeletal muscle, and arcuate nucleus of hypothalamus. PTP1B overexpression in high fat-fed mice coincided with increased adipose tissue expression of the macrophage marker CD68 and TNFalpha, which is implicated in causing obesity-induced insulin resistance. TNFalpha increased PTP1B mRNA and protein levels by 2- to 5-fold in a dose- and time-dependent manner in adipocyte and hepatocyte cell lines. TNFalpha administration in mice increased PTP1B mRNA 1.4- to 4-fold in adipose tissue, liver, skeletal muscle, and hypothalamic arcuate nucleus and PTP1B protein 2-fold in liver. Actinomycin D treatment blocked, and high dose salicylate treatment inhibited by 80%, TNFalpha-induced PTP1B expression in adipocyte cell lines, suggesting TNFalpha may induce PTP1B transcription via nuclear factor kappaB (NFkappaB) activation. Chromatin immunoprecipitation from adipocyte cell lines and liver of mice demonstrated TNFalpha-induced recruitment of NFkappaB subunit p65 to the PTP1B promoter in vitro and in vivo. In mice with diet-induced obesity, TNFalpha deficiency also partly blocked PTP1B overexpression in adipose tissue. Our data suggest that PTP1B overexpression in multiple tissues in obesity is regulated by inflammation and that PTP1B may be a target of anti-inflammatory therapies.
Development of real-time fluorescent reverse transcription loop-mediated isothermal amplification assay with quenching primer for influenza virus and respiratory syncytial virus (2019)

Influenza virus and respiratory syncytial virus cause acute upper and lower respiratory tract infections, especially in children and the elderly. Early treatment for these infections is thought to be important, so simple and sensitive detection methods are needed for use at clinical sites. Therefore, in this study, real-time reverse transcription loop-mediated isothermal amplification assays with quenching primer for influenza virus and respiratory syncytial virus were developed. Evaluation of a total of 113 clinical specimens compared to real-time RT-PCR assays showed that the novel assays could distinguish between the types and subtypes of influenza virus and respiratory syncytial virus and had 100% diagnostic specificity. The diagnostic sensitivity of each assay exceeded 85.0% and the assays showed sufficient clinical accuracy. Furthermore, positive results could be obtained in around 15 min using the novel assays in cases with high concentrations of virus. The developed assays should be useful for identifying influenza virus and respiratory syncytial virus cases not only in experimental laboratories but also in hospital and quarantine laboratories.