gebhart/patrepeval huggingface dataset:
Recombinant human secretory phospholipase A2: Purification and characterization of the enzyme for active site studies (1992)

A secreted form of phospholipase A2 (PLA2) is thought to play an important role in inflammatory diseases. To characterize this enzyme the cDNA encoding a low molecular weight PLA2 was cloned from a human placental cDNA library. The cDNA encoding the human PLA2 was subcloned into an expression vector and subsequently transfected into Chinese hamster ovary (CHO) cells. A stable CHO cell clone, secreting ca 1 mg/L of recombinant PLA2 into the medium, was scaled up in culture to 180 L. The recombinant enzyme was purified from the cell supernatant to apparent homogeneity by a novel procedure combining adsorption to poly(vinylidene difluoride) membranes, ion exchange chromatography and size exclusion chromatography. The final recovery of PLA2 activity was 58%. A direct comparison between the purified recombinant human PLA2 and PLA2 purified from human synovial fluid, including molecular weight, antigenicity, ionic dependence, substrate specificity and sensitivity to known PLA2 inhibitors, indicated that the two enzymes exhibit identical biochemical properties. These results show that the recombinant PLA2 can be efficiently expressed and purified in sufficient quantities to characterize the enzyme active site, to aid in the rational development of PLA2 inhibitors as potential anti-inflammatory drugs, and to investigate further the role of PLA2 in inflammatory disease.
Investigating the long noncoding RNA SChLAP1 as a prognostic tissue and urine biomarker in prostate cancer. (2015)

7 Background: Improved prognostic biomarkers are needed for localized prostate cancer. We undertook an unbiased large-scale analysis of genes associated with metastatic progression and validated the prognostic ability of the top candidate gene. Methods: Prostate cancer samples from prostatectomy patients were analyzed for gene expression using a clinical-grade, high-density Affymetrix GeneChip platform, encompassing &gt;1 million genomic loci and assessed in a CLIA-certified laboratory. Nomination of prognostic candidate genes was performed on a discovery cohort (n=545) and validated on 3 independent cohorts (n=463). Multivariate analyses were performed for the primary endpoint of metastasis. The top prostate-specific gene was further evaluated in 208 additional tumor samples with a novel RNA in-situ hybridization (ISH) assay and in urine samples from 230 patients using PCR. Results: Of all known genes, the long noncoding RNA SChLAP1 ranked first for elevated expression in patients with metastatic progression by receiver-operator-curve analyses. Validation in three independent cohorts confirmed the prognostic value of SChLAP1. On multivariate modeling, SChLAP1 expression independently predicted metastasis within 10 years (odds ratio (OR) = 2.45, 95% confidence interval (CI) 1.70 – 3.53), death within 10 years (OR = 1.93, 95% CI 1.31 – 2.85), and biochemical recurrence within 5 years (OR = 1.76, 95% CI 1.28 – 2.41) with ORs comparable to Gleason score. Evaluation of SChLAP1 expression by RNA ISH confirmed a significant association with disease recurrence (OR = 1.99, 95% CI 1.06 – 3.73). Evaluation of urine SChLAP1 levels demonstrated increased expression in patients at higher risk for disease progression. Conclusions: We perform the largest high-throughput, unbiased study of prostate cancer prognostic biomarkers to date and discover SChLAP1 as a top gene predictive of metastatic progression. We validate SChLAP1 extensively with a clinical-grade assay. We show feasibility of a RNA ISH assay and a non-invasive urine test for SChLAP1. Our results, spanning 1,446 patients from 6 independent patient cohorts, suggest that SChLAP1 represents a very promising biomarker for aggressive clinical course.
A Novel Approach to Design Lesion-Specific Stents for Minimum Recoil (2016)

Stent geometries are obtained by topology optimization for minimized compliance under different stenosis levels and plaque material types. Three levels of stenosis by cross-sectional area, i.e., 30%, 40%, and 50% and three different plaque material properties, i.e., calcified, cellular, and hypocellular, were studied. The raw optimization results were converted to clear design concepts and their performance was evaluated by implanting them in their respective stenosed artery types using finite element analysis. The results were compared with a generic stent in similar arteries, which showed that the new designs showed less recoil. This work provides a concept that stents could be tailored to specific lesions in order to minimize recoil and maintain a patent lumen in stenotic arteries.
Medium voltage inverter to establish grid interface and provide ancillary support for a DC distributed wind farm (2013)

More utility companies now require wind power plants to participate in grid support functions including frequency, voltage and inertia support. Typical wind turbine generator configurations cannot provide grid support. In this paper, a multi-level inverter based wind turbine power conversion system is investigated. The developed inverter interfaces between the DC bus of a wind turbine power conversion system supported by energy storage elements and the grid. Two control techniques are proposed for capacitor-based and battery-based storage systems to provide grid active and reactive power support. Details of control implementation for grid interface, frequency and voltage droop support are presented. Simulation and experimental results are discussed to verify the viability of the proposed system and control techniques.
Effect of Partial Deficiency of Threonine on Enzyme Activity and Fat Deposition in Liver. (1953)

The effect of a partial deficiency of threonine in the rat on the activities of several liver enzymes and on liver fat deposition has been determined. Liver fat deposition, in confirmation of earlier reports, was higher in animals receiving the threonine-deficient diet. The activities of the mitochondrial enzymes, succinic oxidase and choline oxidase, were higher in liver homogenates from threonine-deficient animals. Endogenous respiration and the activities of the cytoplasmic enzymes, xanthine oxidase and tyrosine oxidase, were lower in the livers of animals fed diets deficient in threonine.
An Efficient and Scalable Ritter Reaction for the Synthesis of tert-Butyl Amides (2009)

A scalable procedure for the conversion of nitriles to N-tert-butyl amides via the Ritter reaction was optimized employing tert-butyl acetate and acetic acid. The reaction has a broad scope for aromatic, alkyl, and alpha,beta-unsaturated nitriles.
Saturation profile measurement of atomic layer deposited film by X-ray microanalysis on lateral high-aspect-ratio structure (2021)

Atomic layer deposition (ALD) of aluminum oxide thin films were applied on lateral high-aspect-ratio silicon test structures. The leading front of the film thickness profile is of interest, since it is related to deposition kinetics and provides information for ALD process development. A deposited profile was characterized using energy-dispersive electron probe X-ray microanalysis (ED-EPMA) and the results were analyzed using Monte Carlo simulation. A new procedure for obtaining relative film thickness profile from X-ray microanalysis data is described. From the obtained relative thickness profile, penetration depth of film at 50% of initial thickness and corresponding slope of thickness profile were determined at the saturation front. Comparison of the developed procedure was performed against independent measurements using optical reflectometry. ED-EPMA characterization of saturation profiles on lateral high-aspect-ratio test structures, supported by Monte Carlo simulation, is expected to prove useful tool for ALD process development.
Osteoprotegerin Expression and Secretion Are Regulated by Calcium Influx through the L-Type Voltage-Sensitive Calcium Channel (2003)

Our previous studies showed that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] modulates the activity of the Ca(V1.2) alpha-subunit of the L-type voltage-sensitive calcium channel (VSCC) by two temporally distinct mechanisms. First, 1,25(OH)2D3 rapidly modulates local Ca2+ permeability in the plasma membrane of the proliferating osteoblast. Second, treatment with 1,25(OH)2D3 reduces biosynthesis of Ca(V1.2) such that transcript levels are half of original levels after 24 h. Osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) provide important regulatory mechanisms for controlling osteoclastogenesis and Ca2+ homeostasis. Because they often control Ca2+-activated secretion, we investigated the possibility that L-type VSCCs might regulate basal OPG and RANKL secretion in osteoblasts. We also studied 1,25(OH)2D3 effects on OPG and RANKL expression. To address this, we measured changes in expression and secretion of OPG and RANKL in MC3T3-E1 cells and calvarial organ cultures after treatment with 1,25(OH)2D3, VSCC inhibitors, and inhibitors of Ca2+-regulated signaling. RANKL production was increased in calvarial cultures by 1,25(OH)2D3 but was essentially undetectable in the medium of MC3T3-E1 cells. In contrast, OPG secretion in both systems was significantly reduced after 24 h treatment with 1,25(OH)2D3, by inhibitors of L-type VSCCs and calmodulin-sensitive protein kinases but not by inhibitors of protein kinase A, MAPKs, or other families of VSCCs. OPG secretion was abrogated by transfection with decoy cAMP response element binding sites. Our results suggest that OPG secretion is regulated through calmodulin-sensitive protein kinase signaling that depends on the activity of the L-type VSCC and is mediated through the cAMP response element-binding protein.
Circulating microRNAs as Biomarkers for Disease Staging in MS (S11.005) (2013)

OBJECTIVE: To determine if circulating miRNAs could be identified in MS and whether they linked to disease stage and/or disability.
Factor VIII activation by factor VIIa analog (V158D/E296V/M298Q) in tissue factor-independent mechanisms (2011)

Factor (F)VIIa with tissue factor (TF) is a primary trigger of blood coagulation. The recombinant (r)FVIIa analog, NN1731 (V158D/E296V/ M298Q) containing a thrombin/FIXa-mimicking catalytic domain, is ~30-fold more effective on activated platelets without TF, but ~1.2-fold with TF, than rFVIIa for FX activation. We have recently demonstrated the FVIIa/TF-dependent FVIII activation in the early coagulation phase. We assessed the action of NN1731 on FVIII activation. NN1731/TF increased FVIII activity ~2.9-fold within 30 seconds, followed by rapid inactivation, and was slightly more active than rFVIIa/TF. NN1731-catalysed activation, however, was enhanced ~6-fold at 5 minutes (min), and its peak level persisted for ~30 min. NN1731/TF proteolysed FVIII at Arg⁷⁴⁰, Arg³⁷², and Arg³³⁶, similar to rFVIIa/TF, but cleavage by NN1731 alone was much slower at Arg³³⁶ than at Arg⁷⁴⁰ and Arg³⁷². The Km and Vmax for NN1731/TF-catalysed activation were ~1.8-fold lower and ~2.3-fold greater than rFVIIa/TF. The Km for NN1731 alone was ~1.3-fold lower than rFVIIa, whilst the Vmax was ~7.9-fold greater, indicating that the efficiency of FVIII activation by NN1731 and NN1731/TF was ~11- and ~4-fold greater, respectively, than equivalent reactions with rFVIIa. In SPR-based assays, NN1731 bound to FVIII and the heavy chain (Kd; 0.62 and 1.9 nM) with ~1.4- and ~3.1-fold higher affinity than rFVIIa, and the A2 domain contributed to this increase. Von Willebrand factor moderated NN1731-catalysed activation more significantly than NN1731/TF. In conclusion, NN1731 was a greater potential than rFVIIa in up-regulating FVIII activity, and the TF-independent FVIII activation might represent a potential extra mode of its enhanced haemostatic effect.
Si photonic crystal waveguide based delay lines (2012)

We report a four-channel on-chip true-time-delay (TTD) module based on a photonic crystal waveguide (PCW) array. By minimizing the coupling loss with a photonic crystal taper (PC taper), the delay lines with 1–3mm long PCWs can operate up to a group index ng~23 without significant loss. The large group velocity dispersion enables continuous and wavelength-tunable time delays. Measurements show a highly linear phase-frequency relation, highest time delay up to 216.7 ps, and large tuning ranges of 58.28 ps, 115.74 ps, and 194.16 ps for 1–3mm delay lines, respectively. The chip-scale TTD module can provide &plusmn;44.38&deg; steering for an X-band phased array antenna (PAA), but occupies only 0.18 mm<sup>2</sup> area.
Antibody-modified conduits for highly selective cytokine elimination from blood (2018)

Cytokines play an important role in dysregulated immune responses to infection, pancreatitis, ischemia/reperfusion injury, burns, hemorrhage, cardiopulmonary bypass, trauma, and many other diseases. Moreover, the imbalance between inflammatory and antiinflammatory cytokines can have deleterious effects. Here, we demonstrated highly selective blood-filtering devices - antibody-modified conduits (AMCs) - that selectively eliminate multiple specific deleterious cytokines in vitro. AMCs functionalized with antibodies against human vascular endothelial growth factor A or tumor necrosis factor α (TNF-α) selectively eliminated the target cytokines from human blood in vitro and maintained them in reduced states even in the face of ongoing infusion at supraphysiologic rates. We characterized the variables that determine AMC performance, using anti-human TNF-α AMCs to eliminate recombinant human TNF-α. Finally, we demonstrated selective cytokine elimination in vivo by filtering interleukin 1 β from rats with lipopolysaccharide-induced hypercytokinemia.
Tyrosine kinase-defective insulin receptors undergo insulin-induced microaggregation but do not concentrate in coated pits. (1991)

Biologically active colloid-gold complexes were used to compare ligand-induced microaggregation, redistribution, and internalization of insulin receptors on Rat 1 fibroblasts expressing wild type (HIRc) or tyrosine kinase-defective (HIR A/K1018) human insulin receptors. Insulin-like growth factor I (IGF I) and alpha 2-macroglobulin receptors also were compared. On both cell types, all four unoccupied receptor types occurred predominantly as single receptors. Ligand binding caused receptor microaggregation. Microaggregation of wild type or kinase-defective insulin receptors or IGF I receptors was not different. alpha 2-Macroglobulin receptors formed larger microaggregates. Compared to wild type insulin or IGF I receptors, accumulation of kinase-defective insulin receptor microaggregates in endocytic structures was decreased, and the size of microaggregates in coated pits was significantly smaller. As a result, receptor-mediated internalization of gold-insulin by HIR A/K1018 cells was less than 6% of the cell-associated particles compared to approximately 60% of the particles in HIRc cells. On HIR A/K1018 cells, alpha 2-macroglobulin and IGF I were internalized via coated pits demonstrating that those structures were functional. These results suggest that: 1) ATP binding, receptor autophosphorylation, and activation of receptor kinase activity are not required for receptor microaggregation; 2) receptor microaggregation per se is not sufficient to cause ligand-induced receptor-mediated internalization or the biological effects of insulin; and 3) autophosphorylation of the beta-subunit or activation of the receptor kinase activity is required for the insulin-induced concentration of occupied receptors in coated pits.
Mass spectrometry-based clinical proteomics (2003)

In recent years, mass spectrometry (MS) has been recognized as a 'Gold Standard' tool for the identification and analysis of individual proteins in expression proteomics studies. Moreover, MS has proven useful for the analysis of nucleic acids for single nucleotide polymorphism (SNP) genotyping purposes. With the increased usage of MS as a standard tool for life science applications and the advancement of MS instrumentation, sample preparation and bioinformatics, MS technology has entered novel screening and discovery application areas that are beyond the traditional protein identification and characterization applications. The areas of clinical diagnostics and predictive medicine are just two prime examples of these fields. Predictive markers or biomarkers for early diagnosis of diseases are of growing importance for the human healthcare community. The goal of using MS in clinical proteomics is to generate protein profiles (mass to charge [m/z] ratio versus signal intensity) from readily available body fluids like serum, saliva and urine to detect changes in protein levels that reflect changes in the disease states. Whereas the results originating from individual protein markers may be intriguing, data resulting from the analysis of complex, multiple biomarker patterns may be unequivocal. These biomarker patterns are hidden in complex mass spectra and are not always obvious to the human eye. Sophisticated bioinformatics algorithms have to be applied to determine these unique biomarker patterns. Here, we review the latest developments concerning the use of MS for the discovery of biomarker patterns and for the identification of individual biomarkers in the field of clinical proteomics applications.
Ultrasound quantification of molecular marker concentration in large blood vessels (2014)

Ultrasound-based molecular imaging has been used in pre-clinical studies of cancer and cardiovascular diseases. Current techniques involve the detection of molecularly bound microbubbles through some combination of nonlinear microbubble detection and lengthy waiting periods or low-pass interframe filtering techniques. Non-specific adhesion is typically measured using additional control microbubble injections. In addition to having prolonged protocols, current limitations include the inability to quantify molecular marker concentration in human tissue environments where attenuation and imaging path lengths are highly variable. Consequently, we developed a new modulated Acoustic Radiation Force-based imaging sequence, which can detect targeted adhesion without the requirement of separate control measurements. Results indicate that the metric extracted from the sequence (residual-to-saturation ratio, R <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">resid</inf> ) was independent of acoustic pressures and attenuation levels (p > 0.5, n = 10). R <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">resid</inf> exhibited a linear relationship with measured molecular marker concentration (R <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> > 0.94). Consequently, the feasibility was demonstrated in vitro for quantification of molecular marker concentration in large vessel environments. Additionally, the feasibility of using the modulated ARF-based sequence to separate specific adhesion of adherent microbubbles was also demonstrated in a mouse model of inflammation in vivo.
Metabolisches Tumorvolumen als Prädiktor für das Therapieansprechen bei Patienten im fortgeschrittenen Stadium des Hodgkin-Lymphoms (2019)

18F-2-Fluoro-2-deoxy-D-glucose (18F-FDG)-Positronen-Emissions-Tomografie (PET)/Computertomografie (CT) ermöglicht die einfache Bestimmung des metabolischen Tumorvolumens (MTV) als möglichen Risikofaktor im Rahmen des initialen Stagings bei Patienten mit Hodgkin-Lymphom. Das Ziel dieser Arbeit war es die prädiktive und prognostische Aussagekraft unterschiedlich erhobener MTV mithilfe des Patientenkollektivs der HD18 Studie der Deutschen Hodgkin Studiengruppe (GHSG) zu untersuchen.
Impact of Estimation Uncertainty in PMU-Based Resynchronization of Continental Europe Synchronous Areas (2023)

Power system stability is a task that every system operator (SO) is required to achieve daily to ensure an uninterruptible power supply. Especially at the transmission level, for each SO it is of utmost importance to ensure proper exchange of information with other SOs, mainly in case of contingencies. However, in the last years, two major events led to the splitting of Continental Europe into two synchronous areas. These events were caused by anomalous conditions which involved in one case the fault of a transmission line and in the other a fire outage in proximity to high-voltage lines. This work analyzes these two events from the measurement point of view. In particular, we discuss the possible impact of estimation uncertainty on control decisions based on measurements of instantaneous frequency. For this purpose, we simulate five different configurations of phasor measurement units (PMUs), as characterized by different signal models, processing routines, and estimation accuracy in the presence of off-nominal or dynamic conditions. The objective is to establish the accuracy of the frequency estimates in transient conditions, more specifically during the resynchronization of the Continental Europe area. Based on this knowledge, it is possible to set more suitable conditions for resynchronization operations: the idea is to consider not only the frequency deviation between the two areas but also to take into account the respective measurement uncertainty. As confirmed by the analysis of the two real-world scenarios, such an approach would allow for minimizing the probability of adverse or even dangerous conditions such as dampened oscillations and inter-modulations.
Development of advanced, continuous mild gasification process for the production of co-products (1991)

The current objective of the University of North Dakota Energy and Environmental Research Center (EERC) mild gasification project is to optimize reaction char and marketable liquids production on a 100-lb/hr scale using Wyodak subbituminous and Indiana No. 3 bituminous coals. Tests performed using the EERC 100-lb/hr process development unit (PDU) include a refractory-cure (Test P001), a test using petroleum coke (Test P002), and tests using Wyodak and Indiana coals. The reactor system used for the 11 PDU tests conducted to date consists of a spouted, fluid-bed carbonizer equipped with an on-line condensation train that yields three boiling point fractions of coal liquids ranging in volatility from about (77{degrees}--750{degrees}F) (25{degrees}--400{degrees}C). The September--December 1990 quarterly report described reaction conditions and the bulk of the analytical results for Tests P010 and P011. This report describes further P010 and P011 analytical work, including the generation of simulated distillation curves for liquid samples on the basis of sulfur content, using gas chromatography coupled with atomic emission detection (GC/AED) analysis. 13 figs., 3 tabs.