gebhart/patrepeval huggingface dataset:
Prostaglandin E Synthase, a Terminal Enzyme for Prostaglandin E<sup>2</sup> Biosynthesis (2005)

Biosynthesis of prostanoids is regulated by three sequential enzymatic steps, namely phospholipase A2 enzymes, cyclooxygenase (COX) enzymes, and various lineagespecific terminal prostanoid synthases. Prostaglandin E synthase (PGES), which isomerizes COX-derived PGH2 specifically to PGE2, occurs in multiple forms with distinct enzymatic properties, expressions, localizations and functions. Two of them are membrane-bound enzymes and have been designated as mPGES-1 and mPGES-2. mPGES-1 is a perinuclear protein that is markedly induced by proinflammatory stimuli, is down-regulated by antiinflammatory glucocorticoids, and is functionally coupled with COX-2 in marked preference to COX-1. Recent gene targeting studies of mPGES-1 have revealed that this enzyme represents a novel target for anti-inflammatory and anti-cancer drugs. mPGES-2 is synthesized as a Golgi membrane-associated protein, and the proteolytic removal of the N-terminal hydrophobic domain leads to the formation of a mature cytosolic enzyme. This enzyme is rather constitutively expressed in various cells and tissues and is functionally coupled with both COX-1 and COX-2. Cytosolic PGES (cPGES) is constitutively expressed in a wide variety of cells and is functionally linked to COX-1 to promote immediate PGE2 production. This review highlights the latest understanding of the expression, regulation and functions of these three PGES enzymes.
The Effect of Diet and Exercise on Intestinal Integrity and Microbial Diversity in Mice (2016)

These data suggest that exercise has a strong influence on gut integrity and host microbiome which points to the necessity for more mechanistic studies of the interactions between specific bacteria in the gut and its host.
Overcoming drug resistance in HIV‐1 chemotherapy: The binding thermodynamics of Amprenavir and TMC‐126 to wild‐type and drug‐resistant mutants of the HIV‐1 protease (2002)

Amprenavir is one of six protease inhibitors presently approved for clinical use in the therapeutic treatment of AIDS. Biochemical and clinical studies have shown that, unlike other inhibitors, Amprenavir is severely affected by the protease mutation I50V, located in the flap region of the enzyme. TMC-126 is a second-generation inhibitor, chemically related to Amprenavir, with a reported extremely low susceptibility to existing resistant mutations including I50V. In this paper, we have studied the thermodynamic and molecular origin of the response of these two inhibitors to the I50V mutation and the double active-site mutation V82F/I84V that affects all existing clinical inhibitors. Amprenavir binds to the wild-type HIV-1 protease with high affinity (5.0 x 10(9) M(-1) or 200 pM) in a process equally favored by enthalpic and entropic contributions. The mutations I50V and V82F/I84V lower the binding affinity of Amprenavir by a factor of 147 and 104, respectively. TMC-126, on the other hand, binds to the wild-type protease with extremely high binding affinity (2.6 x 10(11) M(-1) or 3.9 pM) in a process in which enthalpic contributions overpower entropic contributions by almost a factor of 4. The mutations I50V and V82F/I84V lower the binding affinity of TMC-126 by only a factor of 16 and 11, respectively, indicating that the binding affinity of TMC-126 to the drug-resistant mutants is still higher than the affinity of Amprenavir to the wild-type protease. Analysis of the data for TMC-126 and KNI-764, another second-generation inhibitor, indicates that their low susceptibility to mutations is caused by their ability to compensate for the loss of interactions with the mutated target by a more favorable entropy of binding.
Laser-induced migration and isotope separation of epi-thermal monomers and dimers in supercooled free jets (2005)

Explicit relations are developed to estimate the outflux of migrating isotopomers i QF 6 to the outskirts of a supersonic supercooled free jet whose core is irradiated by a co-axial laser beam and intercepted by a skimmer that separates core gas from peripheral gases. The QF 6 target gas is diluted in carrier gas G (G = He, N 2 , Ar, Xe, SF 6 , etc.) which determines the jet's supersonic characteristics and forms QF 6 :G dimers at low temperatures. Under isotope-selective laser excitation, excited i QF 6 * convert their vibrational energy V into kinetic energy T after forming transient i QF 6 *:G dimers that dissociate in sub-microseconds. Three migrating groups with different transport parameters are created in the jet: thermal monomers, faster-moving epithermal monomers, and slower-moving dimers. Jet-core-fleeing QF 6 is enriched in i QF 6 due to enhanced outwards migration of i QF 6 ! epithermals and reduced escape of j QF 6 :G dimers in the jet. Isotope enrichments in the rim gases are highest for heavier carrier gases such as G = Xe or G = SF 6 .
Detection of Voids in Prestressed Concrete Bridges using Thermal Imaging and Ground-Penetrating Radar (2008)

Thermal imaging and ground-penetrating radar was conducted on concrete specimens with simulated air voids. For the thermal imaging inspections, six concrete specimens were constructed during the month of June 2007 to simulate the walls of post-tensioned box girder bridges. The objective was to detect simulated air voids within grouted post-tensioning ducts, thus locating areas where the post-tensioning steel strands are vulnerable to corrosion. The most important deduction taken from these inspections was that PT-ducts and simulated voids were more detectable in the 20 cm (8 in.) thick specimens than in the 30 cm (12 in.) thick specimens. While inspections of the 20 cm (8 in.) thick specimens revealed the majority of their simulated voids, only one thicker specimen inspection (12c) indicated the presence of simulated voids (four voids in two ducts). Also, PT-ducts were much clearer and visible in the thermal images of the thinner specimens. Ground-penetrating radar (GPR) inspection was conducted on fourteen concrete specimens between August and October 2007. Based on the GPR surveys conducted in this study, it is apparent that the detection of post-tensioning strands and simulated voids within grouted ducts embedded in concrete is possible with a 1.5 GHz GPR system. The layout of the top layer of steel reinforcement in each concrete specimen was evident in the GPR images, but the bottom layer of reinforcement was not clearly detected since it was effectively “hidden” beneath the top layer of rebar. Although none of the post-tensioning strands and simulated air voids within the grouted steel ducts was detectable, simulated voids within plastic ducts were generally detectable in GPR images. The high dielectric constant of the steel ducts did not allow the microwaves to transmit through the surface of the duct and reach the simulated voids. However, the general location of the duct, its orientation and its depth in the concrete were accurately determined using GPR. Thus it can be inferred that the void orientation is critical for detection in GPR images.
Prolonged schedule of temozolomide (Temodal) plus liposomal doxorubicin (Caelyx) in advanced solid cancers (2004)

Temozolomide (Temodal) is an oral imidazotetrazine. Increased temozolomide exposure and subsequent depletion of O-alkylguanine alkyltransferase may improve the activity of temozolomide. The rationale for investigating temozolomide plus Caelyx is based on their antitumor activity, their formulation and no significant overlapping toxicities. We conducted a study of a prolonged schedule of temozolomide (orally on days 1-7 and 15-21) plus Caelyx (day 1) every 28 days. Twenty-one patients (melanoma n=10, sarcoma n=7 and other n=4) were assigned to four dose levels (DL; temozolomide+Caelyx, mg/m): DL1: 100+30 (n=3 patients), DL2: 100+40 (n=6 patients), DL3: 125+40 (n=6 patients) and DL4: 150+40 (n=6 patients). Dose-limiting toxicities were noted after 2 or more cycles in one patient at DL3 (stomatitis) and one patient at DL4 (grade 4 ANC >/=7 days). Treatment delays and/or dose reductions (due to hematological toxicity) were necessary in five of six patients receiving DL4 compared with one of six patients at DL3, and one patient at DL1 and 2. Thus, the recommended dose was temozolomide 125 mg/m (daily for 7 days every other week) plus Caelyx 40 mg/m (day 1 every 4 weeks). Other toxicities were mild. Antitumor activity was observed in eight patients, including one complete response (melanoma), three partial responses (one melanoma, two sarcomas) and four patients with stable disease (three melanomas, one Ewing), with a duration lasting from 14 to 135+weeks. Two melanoma patients showed tumor stabilization in non-irradiated cerebral lesions. This schedule of temozolomide allowed higher dose intensity (1750 mg/m in 4 weeks) compared to the standard 5-day regimen (1000 mg/m in the same amount of time).
Synthesis of Eu<sup>3+</sup>-Doped Core and Core/Shell Nanoparticles and Direct Spectroscopic Identification of Dopant Sites at the Surface and in the Interior of the Particles (2004)

A variety of redispersible Eu(3+)-doped LaPO(4) nanoparticles have been prepared in a high-boiling coordinating solvent mixture, and the Eu(3+) lattice sites of these materials have been investigated by luminescence line-narrowing measurements. In this spectroscopic method, Eu(3+) ions occupying different lattice sites are selectively excited with a tunable narrow-bandwidth laser system and distinguished by their luminescence spectra ("site-selective spectroscopy"). Depending on the concentration of the dopant, up to three different lattice sites could be identified in the interior of the LaPO(4) nanoparticles. These sites correspond to those known from bulk LaPO(4). In addition, a variety of surface sites is observed, which could be converted completely into bulk sites by overgrowing the nanoparticles with a shell of pure LaPO(4). The surface sites are identical to those obtained by reacting Eu(3+) with the surface of pure LaPO(4) nanoparticles. The spectroscopic properties of Eu(3+)-doped LaPO(4) nanoparticles differ from those of pure EuPO(4) nanoparticles, which were also investigated. Remarkably, the core/shell synthesis investigated in this paper allows one to prepare doped nanoparticles that contain no other dopant sites than those known from the corresponding bulk material.
Human centrosomal epitope is shared specifically with human lactate dehydrogenase‐B isozyme (1992)

A rabbit serum (0013) used to identify pericentriolar proteins from isolated centrosomes (Gosti‐Testu, F., Marty, M.C., Berges, J., Maunoury, R. and Bornens, M. (1986) EMBO J. 5, 2545–2550) was shown also to react through the same epitope with several non‐centrosomal proteins including a major 36 kDa cytosolic antigen. This protein was identified to be human lactate dehydrogenase and the co‐distribution of 0013 epitope on the centrosomal protein and on lactate dehydrogenase (LDH) was shown to be specific for human cells (Gosti, F., Marty, M.C., Courvalin, J.C., Maunoury, R. and Bornens, M. (1987) Proc. Natl. Acad. Sci. USA 84, 1000–1004). Human hepatic cells constitute, so far, the only exception to this co‐distribution rule. By using this cell type which expresses only the LDH‐A4 isozyme, we demonstrate that 0013 epitope is specific for the human LDH‐B subunit, making serum 0013 the strongest anti‐LDH‐B available so far. The evolutionary and physiological significance of this situation is discussed.
CD24 overexpression in cancer development and progression: A meta-analysis (2009)

CD24 has emerged as a new oncogene and metastasis promoter. However, there is a controversy as to whether CD24 expression is a prognostic factor for poor outcomes in many human cancers. To shed light on this controversy, we performed a meta-analysis of the relationship between CD24 expression and prognostic parameters in different carcinomas. Studies published in the period 1990-2009 were reviewed for the meta-analysis and selected according to defined criteria. The effect sizes of prognostic parameters and overall survival were calculated by an odds ratio (OR) or an adjusted hazard ratio (HR). Twenty-eight studies reported CD24 expression for 2,925 cases. The frequency of CD24 expression by immunohistochemistry was 68% in all the carcinomas of the breast, female genital tract, gastrointestinal tract, biliary tract and pancreas, urinary system, prostate and skin. Overall, CD24 was more frequently overexpressed in their carcinomas than their benign lesions (OR=4.21; 95% CI, 1.826-9.731; P=0.001) and was significantly associated with lymph node metastasis (OR=2.41; CI, 1.013-5.720; P=0.047), advanced clinical stages (OR=1.59; 95% CI, 1.244-2.032; P<0.001) and shortened overall survival (HR=2.13; 95% CI, 1.656-2.730; P<0.001). CD24 expression was highly associated with lymph node metastases in breast cancer (OR=3.55; 95% CI, 1.664-7.554; P=0.001), advanced clinical stages (OR=2.22; 95% CI, 1.442-3.418; P<0.001) and lymphovascular invasions (OR=2.78; 95% CI, 1.522-5.068; P=0.001) in urothelial carcinomas and with higher grades in endometrial adenocarcinomas (OR=3.88; 95% CI, 1.548-9.715; P=0.004). CD24 was more frequently and strongly expressed in breast (OR=35.80; 95% CI, 8.907-143.921; P<0.001) and ovarian carcinomas (OR=35.92; CI, 7.156-180.311; P<0.001), than in their benign counterparts. In conclusion, the meta-analysis strongly supports the idea that CD24 is an important marker of malignancy and poor prognosis in various cancers. In particular, CD24 may promote cancer development and progression in the breast, ovary and urinary bladder.
Toward an efficient parallel in time method for partial differential equations (2012)

A new method for the parallelization of numerical methods for partial differential equations (PDEs) in the temporal direction is presented. The method is iterative with each iteration consisting of deferred correction sweeps performed alternately on fine and coarse space-time discretizations. The coarse grid problems are formulated using a space-time analog of the full approximation scheme popular in multigrid methods for nonlinear equations. The current approach is intended to provide an additional avenue for parallelization for PDE simulations that are already saturated in the spatial dimensions. Numerical results and timings on PDEs in one, two, and three space dimensions demonstrate the potential for the approach to provide efficient parallelization in the temporal direction.
Scalability issues for high performance digital libraries on the World Wide Web (2002)

We investigate scalability issues involved in developing high performance digital library systems. Our observations and solutions are based on our experience with the Alexandria Digital Library (ADL) testbed under development at UCSB. The current ADL system provides online browsing and processing of digitized maps and other geospatially mapped data via the World Wide Web (WWW). A primary activity of the ADL system involves computation and disk I/O for accessing compressed multi resolution images with hierarchical data structures, as well as other duties such as supporting database queries and on the fly HTML page generation. Providing multi resolution image browsing services can reduce network traffic but impose some additional cost at the server. We discuss the necessity of having a multiprocessor DL server to match potentially huge demands in simultaneous access requests from the Internet. We have developed a distributed scheduling system for processing DL requests, which actively monitors the usages of CPU, I/O channels and the interconnection network to effectively distribute work across processing units to exploit task and I/O parallelism. We present an experimental study on the performance of our scheme in addressing the scalability issues arising in ADL wavelet processing and file retrieval. Our results indicate that the system delivers good performance on these types of tasks.
Cross-Sectional Study of Lipids and Liver Enzymes Related to a Serum Biomarker of Exposure (ammonium perfluorooctanoate or APFO) as Part of a General Health Survey in a Cohort of Occupationally Exposed Workers (2007)

Our findings indicate a modest positive association of PFOA on some lipid parameters and a need for follow-up studies.
Prediction of the limits of detection of hazardous vapors by passive infrared with the use of MODTRAN (1996)

Passive infrared remote detection of hazardous gases, vapors, and aerosols is based on the difference, Δ T, between the air temperature of the threat vapor cloud and the effective radiative temperature of the background. In this paper I address the problem of detection with a low-angle-sky background. I used Modtran to predict Δ T and atmospheric transmittance for standard atmospheric models. The detection limits, at 2-cm(-1) resolution, are discussed for sulfur hexafluoride, Sarin, trichloroethylene, methyl isocyanate, mustard gas, methyl chloride, and sulfur dioxide for selected cases with the U.S. Standard, the Subarctic Winter, and the Tropical models. I used a particularly interesting case of Sarin detection with the Subarctic Winter atmospheric model to illustrate the power of Modtran to predict subtle changes in Δ T with angle of elevation (AOE).
Quasi-Fixed Costs and Their Impact (1958)

In analyzing the behavior of firms, economists have long distinguished between the in,f1nence of fixed and variable costs. There have gradually appeared in the budgets of many companies certain cost items like promotion and advertising which are allocated for a given period, but which are essentially independent of actual production for the same period in the manner of fixed costs. In this article, the growth in the importance of such budgeted items is outlined and their meaning analyzed in terms of pricing under monopolistic competition.
Antitumor effectiveness of electrochemotherapy with cis-diamminedichloroplatinum(II) in mice. (1995)

One of the ways to increase drug delivery into cells and tissues is by a local application of short, intense electric pulses, i.e., electropermeabilization. This approach is used in electrochemotherapy to potentiate antitumor effectiveness of chemotherapeutic drugs. To determine whether electropermeabilization can potentiate antitumor effectiveness of cis-diamminedichloroplatinum(II) (CDDP), electrochemotherapy with CDDP was tested in vitro and in vivo on s.c. SA-1, EAT, and melanoma B16 tumors in mice. Electric pulses were applied to the tumors by percutaneously placed electrodes after i.v. injection of CDDP. Severalfold potentiation of CDDP antitumor effectiveness with electric pulses was obtained, inducing partial or complete responses in tumor growth. Electrochemotherapy was CDDP dose dependent, as well as dependent upon the amplitude of electric pulses. Also important was the sequencing and the interval of CDDP administration, relative to application of electric pulses. Specifically, a good antitumor effect without side effects was obtained with eight electric pulses (electric pulse amplitude, 1040 V; repetition frequency, 1 Hz; pulse width, 100 microseconds; electrode distance, 8 mm; 1300 V/cm) applied 3 min after i.v. injection of 4 mg/kg CDDP. With a higher CDDP dose (8 mg/kg), some long-term complete responses were obtained (14%) on melanoma B16 tumors. Thus, electrochemotherapy with CDDP offers an approach to making chemotherapy with CDDP more effective.
Formation of Carbon–Halogen Bonds ( <scp>Cl</scp> , <scp>Br</scp> , <scp>I</scp> ) (2009)

Abstract Introduction Halogenation in Presence of Solid Supports or Catalysts Halogen Exchange and Transhalogenation Reactions Oxyhalogenations Cohalogenation and Mixed Halogenation Halogen–Halogen Reagents Carbon–Halogen Reagents Nitrogen–Halogen and Phosphorus–Halogen Reagents Oxygen–Halogen Reagents Sulfur–Halogen Reagents Silicon–Halogen Reagents Halogenation with Metal Halides and Halodemetallation Halogenation in Special Environments Carbon–Halogen Bond Formation by Extrusion of CO , CO 2 or SO 2 Ring Opening of Oxiranes
Novel therapies for the treatment of inflammatory airway disease (2003)

Asthma and chronic obstructive pulmonary disease (COPD) are diseases of the airways with an underlying inflammatory component. The prevalence and healthcare burden of asthma and COPD is still rising and is predicted to continue to rise in the current century. The β-agonists and corticosteroids form the basis of the treatments available to alleviate the symptoms of asthma, whereas the treatments available for COPD have been shown to have a limited effect on slowing the progression of the disease. Asthma and COPD are both in need of novel, safe treatments to tackle the underlying inflammation that characterises their pathology. The inflammatory processes inherent in asthma and COPD provide the opportunity for innovative drug research. This review will outline the new approaches and targets being investigated, which may provide opportunities for novel therapeutic interventions in these debilitating diseases.
On the Mechanism of the γ → β Frequency Shift in Neuronal Oscillations Induced in Rat Hippocampal Slices by Tetanic Stimulation (1999)

Tetanic stimulation of the CA1 region of rat hippocampal slices can induce gamma frequency population oscillations (30-100 Hz) after a latency of 50-150 msec that are synchronized to within 1-2 msec when simultaneous stimuli are delivered to two sites 2 mm or more apart. When tetanic stimuli, twice-threshold for eliciting gamma oscillations, are used, new phenomena occur. (1) After a period of gamma, there is a switch to beta frequencies (10-25 Hz); (2) during the switch, pyramidal cell spike afterhyperpolarizations (AHPs) increase and rhythmic EPSPs occur in pyramidal cells; and (3) after an episode of single-site, twice-threshold-induced gamma/beta oscillations, simultaneous two-site threshold stimuli induce gamma oscillations that are locally synchronized, but no longer are capable of long-range synchrony. We studied the cellular mechanisms of the gamma/beta switch with electrophysiological techniques and computer simulations. Our model predicts that the observed increases in both pyramidal cell AHPs and in pyramidal/pyramidal cell EPSPs are necessary and sufficient for the beta switch to occur. Firing patterns generated by the model, both for pyramidal cells and for interneurons, resemble experimental records. A one-site twice-threshold stimulus might lead to an inability of the two sites to synchronize at gamma frequencies, after subsequent two-site stimulation, via this mechanism. If depression is induced at synapses coupling pyramidal cells at one site to interneurons at the other site, then two-site stimulation cannot produce interneuron doublets; hence, as shown previously, the two sites will be unable to synchronize. This mechanism works in simulations, and we provide experimental evidence that synaptic depression and loss of doublets occur after a sufficiently strong local tetanus to one site. We suggest that long-range excitatory connections onto interneurons determine whether different pyramidal cell "assemblies" can synchronize at gamma frequencies, whereas excitatory connections onto pyramidal cells determine whether such assemblies can synchronize at beta frequencies.
Characterization of polyacrylamide based monolithic columns (2004)

Supermacroporous monolithic polyacrylamide (pAAm)-based columns have been prepared by radical cryo-copolymerization (copolymerization in the moderately frozen system) of acrylamide with functional co-monomer, allyl glycidyl ether (AGE), and cross-linker N,N'-methylene-bis-acrylamide (MBAAm) directly in glass columns (ID 10 mm). The monolithic columns have uniform supermacroporous sponge-like structure with interconnected supermacropores of pore size 5-100 microm. The monoliths can be dried and stored in the dry state. High mechanical stability of the monoliths allowed sterilization by autoclaving. Column-to-column reproducibility of pAAm-monoliths was demonstrated on 5 monolithic columns from different batches prepared under the same cryostructuration conditions.