gebhart/patrepeval huggingface dataset:
Mesothelin Is Shed from Tumor Cells (2006)

To the Editors: We read with great interest the article by Hellstrom et al. (1) about characterization of soluble mesothelin proteins (SMP) in cancer patients. The authors found that the SMP in ascites from a patient with ovarian carcinoma contained the sequence of extracellular domain of a membrane-bound mesothelin (2, 3) rather than a soluble form speculated previously by Scholler et al. (4). Their results indicate that membrane-bound mesothelin could be shed from the tumor cells to generate SMP detected in patient sera by ELISA. We agree with their conclusion that membrane-bound mesothelin is the predominant protein present in the serum and here provides direct evidence showing that such shedding does in fact take place.Our experiments are summarized in Fig. 1. Using an SS1P affinity column, we purified SMP from culture supernatants of a well-documented A431/K5 cell line (3) expressing only membrane-bound mesothelin. SS1P is an immunotoxin with an Fv specific for mesothelin. About 100 ng/mL SMP was found in the culture supernatant. The molecular weight of purified SMP was ∼40 kDa (Fig. 1A), consistent with the SMP described in Hellstrom et al. (1). The full-length mesothelin precursor proteins were not detected in culture supernatant. After deglycosylation with PNGase, the molecular weight of SMP was ∼34 kDa. The SMP bands were cut out from a Coomassie-stained gel, protein in the gel was digested with trypsin, and the tryptic peptides were analyzed using liquid chromatography ion trap mass spectrometry (Fig. 1B). The sequence of NH2 terminal (EVEK) was determined by automated Edman degradation, and peptides corresponding to multiple internal regions of mesothelin were determined using the mass spectrometry/mass spectrometry mode on the ion trap mass spectrometer. Our results confirmed that the SMP was the extracellular domain of membrane-bound mesothelin shed from cells.Mesothelin is a glycosyl-phosphatidylinositol–anchored protein. Release of such proteins from the cell surface into the serum and other body fluids can be mediated by phospholipase or proteases (5). To determine whether the shedding of mesothelin is dependent on phosphatidylinositol-specific phospholipase C, we did anti-cross-reacting determinant assay (Prozyme, San Leandro, CA) by Western blot. The SMP was not recognized by anti-cross-reacting determinant (Anti-CRD) antibodies (Fig. 1C).In conclusion, our data show that the extracellular domain of membrane-bound mesothelin can be shed from tumor cells. The shedding may not require phosphatidylinositol-specific phospholipase C phospholipolysis. The precise mechanisms need further investigation.
Squalamine as an Example of a New Potent Antimicrobial Agents Class: A Critical Review (2010)

An important strategy to circumvent the problem of antimicrobial resistance is to search for new compounds with antimicrobial activity. In this context, aminosterols, which include squalamine-like compounds and ceragenins, have gained interest due to their wide spectrum of antibacterial and antifungal properties. In light of recently reported data, we decided to analyze the mechanism of action of these compounds as well as their antimicrobial properties. Aminosterols are active against both bacterial reference strains and multidrug-resistant antibiotics as they disrupt the integrity of the bacterial membrane. Thus, these compounds could be useful in the development of new topical decontaminants or disinfecting agents.
Control techniques for power factor correction converters (1994)

Abstract. The aspects regarding control strategies for Power Factor Correction (PFC) converters are investigated. The major control techniques to absorb sinusoidal input currents in boost PFC&amp;apos;s are reviewed and analyzed. Their extension to other converter topologies is discussed and some experimental results for a PFC based on the Sepic topology are reported, which allow comparison of converter performance with different control techniques. Lastly, some considerations regarding dynamic operation are given, together with information about control IC&amp;apos;s specifically developed for PFC applications.
Particle Size Distribution (1987)

This paper is a brief review of original basic engineering research in morphological analysis applied to particle characterization which has been conducted during the last 20 years at the University of Iowa, Center for Particulate Material Processing Sciences. The topics discussed include definitions, theory, instrumental and experimental aspects of size, shape and texture measurements of particulate material.
Transmembrane Insertion of the<i>Toxoplasma gondii</i>GRA5 Protein Occurs after Soluble Secretion into the Host Cell (1999)

The intracellular parasite Toxoplasma gondii resides within a specialized compartment, the parasitophorous vacuole (PV), that resists fusion with host cell endocytic and lysosomal compartments. The PV is extensively modified by secretion of parasite proteins, including the dense granule protein GRA5 that is specifically targeted to the delimiting membrane of the PV (PVM). We show here that GRA5 is present both in a soluble form and in hydrophobic aggregates. GRA5 is secreted as a soluble form into the PV after which it becomes stably associated with the PVM. Topological studies demonstrated that GRA5 was inserted into the PVM as a transmembrane protein with its N-terminal domain extending into the cytoplasm and its C terminus in the vacuole lumen. Deletion of 8 of the 18 hydrophobic amino acids of the single predicted transmembrane domain resulted in the failure of GRA5 to associate with the PVM; yet it remained correctly packaged in the dense granules and was secreted as a soluble protein into the PV. Collectively, these studies demonstrate that the secretory pathway in Toxoplasma is unusual in two regards; it allows soluble export of proteins containing typical transmembrane domains and provides a mechanism for their insertion into a host cell membrane after secretion from the parasite.
Structural insights into the processivity of endopolygalacturonase I from <i>Aspergillus niger</i> (2003)

Endopolygalacturonase I is a processive enzyme, while the 60% sequence identical endopolygalacturonase II is not. The 1.70 A resolution crystal structure of endopolygalacturonase I reveals a narrowed substrate binding cleft. In addition, Arg96, a residue in this cleft previously shown to be critical for processivity, interacts with the substrate mimics glycerol and sulfate in several well-defined conformations in the six molecules in the asymmetric unit. From this we conclude that both Arg96 and the narrowed substrate binding cleft contribute to retaining the substrate while it moves through the active site after a cleavage event has occurred.
Weakly-supervised relation classification for information extraction (2004)

This paper approaches the relation classification problem in information extraction framework with bootstrapping on top of Support Vector Machines. A new bootstrapping algorithm is proposed and empirically evaluated on the ACE corpus. We show that the supervised SVM classifier using various lexical and syntactic features can achieve promising classification accuracy. More importantly, the proposed <i>BootProject</i> algorithm based on random feature projection can significantly reduce the need for labeled training data with only limited sacrifice of performance.
Coronary Heart Disease (1970)

Right atrial pacing was performed in 41 subjects with coronary heart disease. Twenty developed angina pectoris during pacing, while 21 did not. The extent of coronary artery disease, as judged by selective cinearteriography, was similar in the two groups. Both had significant increases in heart rate and pressure-time per minute, but there was no significant difference in either of these parameters between groups. Among the hemodynamic parameters measured, the only statistically significant change was in the cardiac index which fell slightly but significantly in the angina group. There were no differences in myocardial oxygen extraction either within each group or between groups. In the angina group, however, 14 of 20 subjects exhibited abnormal myocardial lactate metabolism during pacing. The mean change was highly significant ( P &lt; 0.01). In the nonangina group, eight of 21 subjects had abnormal lactate metabolism during pacing and the mean change was significant ( P &lt; 0.05). There was no correlation between abnormal lactate metabolism and electrocardiographic evidence of myocardial ischemia in either group. Sublingual nitroglycerin, given to five subjects with angina while pacing was continued, resulted in prompt relief of symptoms, but abnormal lactate metabolism and ST-segment depression were unaffected after 10 min. By contrast, when anginal symptoms were relieved in five subjects by cessation of pacing, symptomatic improvement was accompanied by marked improvement in lactate metabolism after 10 min. Although angina pectoris appears to be related statistically to subnormal left ventricular function and abnormal lactate metabolism, there is significant individual variation.
Construction of low-density parity-check codes from Kirkman triple systems (2002)

Gallager introduced low-density parity-check (LDPC) codes in 1962, presenting a construction method to randomly allocate bits in the parity-check matrix subject to certain structural constraints. Since then improvements have been made to Gallager's construction method and some analytic constructions for LDPC codes have been presented. However analytically constructed LDPC codes comprise only a very small subset of possible codes and as a result LDPC codes are still, for the most part, constructed randomly. This paper extends the class of LDPC codes that can be systematically generated by presenting a construction method for regular LDPC codes based on combinatorial designs known as Kirkman triple systems. That is, we construct (3, /spl rho/)-regular codes whose Tanner (1981) graph is free of 4-cycles for any integer /spl rho/.
Local correction of non-periodic motion in computed tomography (2009)

This paper presents a new iterative motion correction technique composed of motion estimation in projection space, motion segmentation in image space, and motion compensation within an analytical filtered-backprojection (FBP) image reconstruction algorithm. The motion is estimated by elastic registration of acquired projections on reference projections. Reference projections are sampled from the image, reconstructed in a previous iteration step. To apply the motion compensation locally, the image regions significantly affected by motion are segmented. First the perceived motion is identified in projection space by computing the absolute difference between acquired line integrals and reference line integrals. Then, differences are reconstructed in image space, and the image is regularized with a pipeline of standard image processing operators. The result of this procedure is a normalized motion map, associating each image element with a measure of the local motion detected there. The estimated displacement vectors in projection space and the reconstructed motion map in image space are then used by an adaptive motion-compensated FBP algorithm to reconstruct a sharper image. Results are shown qualitatively and quantitatively for reconstructions from realistic projections, simulated from clinical patient data. Since the method does not assume any periodicity of the motion model, it can correct reconstruction artifacts due to unstructured patient motion, such as breath-hold failure, abdominal contractions, and nervous movements.
Requirement of BMP-2-induced Phosphatidylinositol 3-Kinase and Akt Serine/Threonine Kinase in Osteoblast Differentiation and Smad-dependent BMP-2 Gene Transcription (2002)

The mechanism by which bone morphogenetic protein-2 (BMP-2) induces osteoblast differentiation is not precisely known. We investigated the involvement of the phosphatidylinositol (PI) 3-kinase/Akt signal transduction pathway in modulation of this process. BMP-2 stimulated PI 3-kinase activity in osteogenic cells. Inhibition of PI 3-kinase activity with the specific inhibitor Ly-294002 prevented BMP-2-induced alkaline phosphatase, an early marker of osteoblast differentiation. Expression of dominant-negative PI 3-kinase also abolished osteoblastic induction of alkaline phosphatase in response to BMP-2, confirming the involvement of this lipid kinase in this process. BMP-2 stimulated Akt serine/threonine kinase activity in a PI 3-kinase-dependent manner in osteoblast precursor cells. Inhibition of Akt activity by a dominant-negative mutant of Akt blocked BMP-2-induced osteoblastic alkaline phosphatase activity. BMP-2 stimulates its own expression during osteoblast differentiation. Expression of dominant-negative PI 3-kinase or dominant-negative Akt inhibited BMP-2-induced BMP-2 transcription. Because all the known biological activities of BMP-2 are mediated by transcription via BMP-specific Smad proteins, we investigated the involvement of PI 3-kinase in Smad-dependent BMP-2 transcription. Smad5 stimulated BMP-2 transcription independent of addition of the ligand. Dominant-negative PI 3-kinase or dominant-negative Akt inhibited Smad5-dependent transcription of BMP-2. Furthermore dominant-negative Akt inhibited translocation of BMP-specific Smads into nucleus. Together these data provide the first evidence that activation of BMP receptor serine/threonine kinase stimulates the PI 3 kinase/Akt pathway and define a role for this signal transduction pathway in BMP-specific Smad function during osteoblast differentiation.
A Complete Integrated Model for Design and Real-Time Analysis of Hydraulic Fracturing Operations (1986)

Abstract A new comprehensive model of hydraulic fracturing is presented which has been developed for the Gas Research Institute (GRI) mobile fracture monitoring and analysis facility. The main purpose of the model is to simulate the hydraulic fracturing process in real-time, that is on-site during the fracturing operation, but the model can also be used for pre-fracture design and post-fracture analysis. Sensor data obtained during the course of the job — such as wellhead pressure, flow rates, frac-fluid viscosity, and proppant staging — can be received directly by the model as input, superceding the pre-frac job design schedule, and making possible more accurate model estimates of current fracturing conditions and predictions of final fracture geometry, as the job proceeds. The overall model has four major components describing: — flow of fluids and slurry in tubular goods — creation and propagation of the hydraulic fracture — transport of proppant, deposition, and fracture closure — heat and fluid exchange between fracture and reservoir. This fully-integrated, numerically robust model of the hydraulic fracturing process takes directly into account as much of the essential physics as possible, given the computational limitations of the real-time application. Additional information, pertaining to very complex reservoir characteristics, can be indirectly supplied to the model through data-based results obtained prior to the job from other more comprehensive (e.g., 3D, cross-sectional) fracture simulations. Having thereby embedded more elaborate fracture analysis into a simple lumped model, accurate predictions are achieved at execution speeds faster than real-time, allowing on-the-job analysis and even real-time history matching for unknown reservoir parameters. Sample results are presented from model simulations of a fracture treatment performed in the Travis Peak formation of East Texas. Actual sensor data from the job was used as input and model predictions are compared with field measurements.
Consciousness and body image: lessons from phantom limbs, Capgras syndrome and pain asymbolia (1998)

Words such as 'consciousness' and 'self' actually encompass a number of distinct phenomena that are loosely lumped together. The study of neurological syndromes allows us to explore the neural mechanisms that might underlie different aspects of self, such as body image and emotional responses to sensory stimuli, and perhaps even laughter and humour. Mapping the 'functional logic' of the many different attributes of human nature on to specific neural circuits in the brain offers the best hope of understanding how the activity of neurons gives rise to conscious experience. We consider three neurological syndromes (phantom limbs, Capgras delusion and pain asymbolia) to illustrate this idea.
Membrane resealing in cultured rat septal neurons after neurite transection: evidence for enhancement by Ca(2+)-triggered protease activity and cytoskeletal disassembly (1991)

Neurites of cultured septal neurons were transected with a laser under sterile conditions, and the subsequent membrane resealing was assayed using a dye exclusion method. In agreement with findings in other preparations, Ca2+ enhanced resealing: in normal culture medium the percentage of lesioned neurons that resealed within 20-30 min after transection increased with increasing bath [Ca2+] over the range 10(-7) to 2 x 10(-3) M; about 75% of cells resealed in 2 mM Ca2+. Mn2+ and Sr2+ also enhanced resealing, but Mg2+ inhibited it. The percentage of resealing neurons was sensitive to agents known to alter the stability of cytoskeletal components. Agents that tend to disassemble microtubules and/or neurofilaments (e.g., colchicine, low-ionic-strength media) strongly promoted resealing, whereas treatments that tend to stabilize microtubules (taxol, Mg2+) inhibited resealing. Addition of exogenous proteases (papain, trypsin, or dispase) enhanced resealing, whereas inhibitors of cysteine proteases (including a specific inhibitor of calpain, a Ca-activated neutral protease) strongly inhibited resealing. Calmodulin inhibitors inhibited resealing, consistent with reports that calmodulin facilitates calpain-mediated proteolysis of fodrin, a component of the cortical cytoskeleton. Based on these results, we hypothesize that one of the major mechanisms involved in resealing is activation of endogenous proteases by Ca2+ entry into the injured neurite. The resulting changes in the cellular cytoskeleton might promote fusion and resealing of the cut ends of the plasma membrane by enhancing membrane mobility and/or by removing structures that normally prevent membrane-membrane contact.
Population Pharmacokinetic Analysis and Simulation of the Time‐Concentration Profile of Etanercept in Pediatric Patients With Juvenile Rheumatoid Arthritis (2005)

This study was performed to estimate the population pharmacokinetic (PK) parameters of etanercept in pediatric juvenile rheumatoid arthritis (JRA) patients and to compare the steady-state time-concentration profiles between etanercept 0.8-mg/kg once-weekly and 0.4-mg/kg twice-weekly subcutaneous (SC) regimens by clinical trial simulation. To this end, mixed-effect analysis (NONMEM, Version 5.1) was performed using the etanercept PK database consisting of 69 JRA patients (4-17 years). Based on the population PK parameters obtained herein, a Monte Carlo clinical trial simulation experiment was conducted to compare the PK profiles in 200 virtual JRA patients who randomly received either etanercept 0.4 mg/kg SC twice weekly or 0.8 mg/kg once weekly for 12 weeks. The following population PK model could adequately describe etanercept PK profiles for twice-weekly SC dosing of 0.4 mg/kg: CL/F (L/h)=0.0576 (female) or 0.0772 (male) x (body surface area in m2/1.071)1.41, V/F(L)=7.88 x (body weight in kg/30.8). The means +/- standard deviations of simulated trough concentrations for 0.8-mg/kg once-weekly and 0.4-mg/kg twice-weekly dosing regimens were 1.58 +/- 1.07 mg/L and 1.92 +/- 1.09 mg/L, respectively. Peaks during 0.8-mg/kg once-weekly dosing (2.92 +/- 1.41 mg/L) were only 11% higher than during 0.4 mg/kg twice-weekly dosing (2.62 +/- 1.23 mg/L). In conclusion, the clinical trial simulation confirmed that 0.8-mg/kg once-weekly and 0.4-mg/kg twice-weekly SC regimens of etanercept are expected to yield overlapping steady-state time-concentration profiles, leading to equivalent clinical outcomes. This has been the basis of the recent Food and Drug Administration approval of the 0.8-mg/kg once-weekly regimen in pediatric patients with JRA.
Copolymerization of CO<sub>2</sub> and Epoxides Catalyzed by Metal Salen Complexes (2004)

The design of efficient metal catalysts for the selective coupling of epoxides and carbon dioxide to afford completely alternating copolymers has made significant gains over the past decade. Hence, it is becoming increasingly clear that this "greener" route to polycarbonates has the potential to supplement or supplant current processes for the production of these important thermoplastics, which involve the condensation polymerization of diols and phosgene or organic carbonates. On the basis of the experiences in our laboratory, this Account summarizes our efforts at optimizing (salen)CrIIIX catalysts for the selective formation of polycarbonates from alicyclic and aliphatic epoxides with CO2. An iterative catalyst design process is employed in which the salen ligand, initiator, cocatalyst, and reaction conditions are systematically varied, with the reaction rates and product selectivity being monitored by in situ infrared spectroscopy.
Performance of modularity maximization in practical contexts (2010)

Although widely used in practice, the behavior and accuracy of the popular module identification technique called modularity maximization is not well understood in practical contexts. Here, we present a broad characterization of its performance in such situations. First, we revisit and clarify the resolution limit phenomenon for modularity maximization. Second, we show that the modularity function Q exhibits extreme degeneracies: it typically admits an exponential number of distinct high-scoring solutions and typically lacks a clear global maximum. Third, we derive the limiting behavior of the maximum modularity Qmax for one model of infinitely modular networks, showing that it depends strongly both on the size of the network and on the number of modules it contains. Finally, using three real-world metabolic networks as examples, we show that the degenerate solutions can fundamentally disagree on many, but not all, partition properties such as the composition of the largest modules and the distribution of module sizes. These results imply that the output of any modularity maximization procedure should be interpreted cautiously in scientific contexts. They also explain why many heuristics are often successful at finding high-scoring partitions in practice and why different heuristics can disagree on the modular structure of the same network. We conclude by discussing avenues for mitigating some of these behaviors, such as combining information from many degenerate solutions or using generative models.