gebhart/patrepeval huggingface dataset:
Calmodulin-dependent cyclic nucleotide phosphodiesterase in an experimental rat model of cardiac ischemiareperfusion (2002)

In the present study, we investigated the activity and expression of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) and the effects of calpains in rat heart after ischemia and reperfusion. Immunohistochemical studies indicated that CaMPDE in normal heart is localized in myocardial cells. Rat ischemic heart showed a decrease in CaMPDE activity in the presence of Ca2+ and calmodulin; however, in ischemic-reperfusion tissue a progressive increase in Ca2+ and calmodulin-independent cyclic nucleotide phosphodiesterase (CaM-independent PDE) activity was observed. Perfusion of hearts with cell-permeable calpain inhibitor suppressed the increase of Ca2+ and CaM-independent PDE activity. Protein expression of CaMPDE was uneffected by hypoxic injury to rat myocardium. The purified heart CaMPDE was proteolyzed by calpains into a 45 kDa immunoreactive fragment in vitro. Based on these results, we propose that hypoxic injury to rat myocardium results in the generation of CaM-independent PDE by calpain mediated proteolysis, allowing the maintenance of cAMP concentrations within the physiological range.
An optical oxygen sensor and reaction vessel for high‐pressure applications (1999)

We describe a simple hyperbaric chamber and optical oxygen probe (optrode), which is based on the dynamic fluorescent quenching of a ruthenium metal complex, that can be used to measure changes in oxygen concentration in either aqueous or gaseous media. Initial experiments illustrate the utility of this robust form of sensor. The optrode showed a typical response time of ≪10 s, a linear temperature response with greater fluorescent quenching at lower temperatures, and was unaffected by pressures as great as 34.4 mPa (340 atm). Yeast cultures measured at 27.8 mPa (275 atm) showed an up to ninefold decrease in respiration rate compared to cells at 1 atm. The oxygen optrode is a simple and rugged device that appears exceptionally well suited for experimentation under conditions in which polarographic electrodes or conventional chemical analysis is difficult, e.g., at high or variable pressures.
Endovascular treatment of renal artery aneurysms with conventional non‐detachable microcoils and Guglielmi detachable coils (1997)

Superselective endovascular treatment of RAAs with microcoils is a safe, efficient, and less invasive alternative to surgical treatment. The high flexibility and softness of the GDC and the controlled detachment enables a safer and more complete occlusion of RAA than current alternatives.
Long term results with 2'deoxycoformycin in hairy cell leukemia. (1994)

We have treated 159 patients with hairy cell leukemia (HCL) with 2'deoxycoformycin (DCF) in a phase II study that started in 1986. 151 patients had typical HCL and 8 HCL-variant. Ages ranged from 30 to 81 years. Most patients had previously received interferon-alpha, splenectomy or both and 23 had DCF as first line; all had active disease. In the first 40 patients DCF was given at 4 mg/m2 weekly for 4 weeks and every 2 weeks thereafter and in the remainder every 2 weeks until maximal response. Three patients died early on and were non-evaluable for response. The response rates in 148 patients with typical HCL were: CR 74.3%, PR 22.3% and NR 3.4%. None of the HCL-variants achieved CR; 4 had PR and 4 NR. The median number of DCF injections to CR was 9. Lymphopenia and neutropenia were seen in 52% and 34%, respectively, but 72% of patients started treatment with low leucocyte counts. 27% had infectious complications of which 6% were life threatening. The disease free interval of the first 105 remitters (CR + PR) was 84% at 4 years with no significant difference between CR (86%) and PR (77%). There have been 12 relapses at a median time of 22 months (range 6-60 months) since stopping DCF, of these, 5 had massive abdominal lymphadenopathy, a features seen also in 4 of the 5 primary non-responders. There were 13 deaths but 7 were unrelated to HCL. The 5-year survival from starting DCF in 110 patients with typical HCL was 88% and 97% if we exclude non-HCL deaths.(ABSTRACT TRUNCATED AT 250 WORDS)
Percolation, statistical topography, and transport in random media (1992)

A review of classical percolation theory is presented, with an emphasis on novel applications to statistical topography, turbulent diffusion, and heterogeneous media. Statistical topography involves the geometrical properties of the isosets (contour lines or surfaces) of a random potential $\ensuremath{\psi}(\mathrm{x})$. For rapidly decaying correlations of $\ensuremath{\psi}$, the isopotentials fall into the same universality class as the perimeters of percolation clusters. The topography of long-range correlated potentials involves many length scales and is associated either with the correlated percolation problem or with Mandelbrot's fractional Brownian reliefs. In all cases, the concept of fractal dimension is particularly fruitful in characterizing the geometry of random fields. The physical applications of statistical topography include diffusion in random velocity fields, heat and particle transport in turbulent plasmas, quantum Hall effect, magnetoresistance in inhomogeneous conductors with the classical Hall effect, and many others where random isopotentials are relevant. A geometrical approach to studying transport in random media, which captures essential qualitative features of the described phenomena, is advocated.
Effect of anti‐V3 antibodies on cell‐free and cell‐to‐cell human immunodeficiency virus transmission (1995)

The present study was undertaken to compare the effects of a type-specific (HIV-1 MN) anti-V3 antibody on in vitro human immunodeficiency virus (HIV) infection of peripheral blood mononuclear cells in systems of cell-free versus cell-to-cell transmission of virus. Anti-V3 antibody completely prevented HIV-1 infection when cell-free virus was the sole mechanism of infection. A significant reduction of the neutralizing activity of the anti-V3 antibody was observed when infectivity was dependent on both cell-free and cell-to-cell mechanisms of infection. Furthermore, when cell-to-cell transfer of virions was the primary mechanism of HIV-1 infection, inhibition of HIV-1 infection was not observed. Therefore, a potent neutralizing antibody with a single epitope specificity failed to effectively control dissemination of a persistent HIV-1 infection in a system characterized predominantly by cell-to-cell transfer of virus.
Monodisperse SiO<sub>2</sub> Nanospheres Prepared by Batch/Semibatch Process and Its Opals (2007)

Nearly monodispersed SiO2 nanospheres, with different size and size standard deviation smaller than 5%, have been prepared by using batch/semibatch process. The SiO2 colloids were used as building blocks to self-assemble into the colloidal crystals, which photonic band gaps are close to the theoretical values, and can be modified by changing the size SiO2 nanospheres. With the increase of the size of SiO2 spheres, the photonic band gap red shift.
Enantioselective, Ketoreductase-Based Entry into Pharmaceutical Building Blocks: Ethanol as Tunable Nicotinamide Reductant (2008)

The use of NADH- and NADPH-dependent ketoreductases to access enantioenriched pharmaceutical building blocks is reported. Seven structurally diverse synthons are obtained, including those for atomoxetine (KRED 132), talampanel (RS1-ADH and CPADH), Dolastatin (KRED 132), and fluoxetine (KRED 108/132). Ethanol may be used as stoichiometric reductant, regenerating both nicotinamide cofactors, particularly under four-electron redox conditions. Its favorable thermodynamic and economic profile, coupled with its advantageous dual cosolvent role, suggests a new application for biomass-derived ethanol.
Inhibition of Sialic Acid Loss Greatly Improves Survival of Refrigerated Platelets (2011)

Abstract Abstract 1133 Platelets have the shortest shelf life of all major blood components and are the most difficult to store, a fact that complicates platelet transfusion practices. Platelet refrigeration could slow bacterial growth and possibly retard the loss of platelet function following storage. However, in contrast to other blood components, platelets do not tolerate refrigeration and are rapidly cleared from the circulation. We demonstrated that two distinct pathways recognizing GPIba remove refrigerated platelets in recipient's livers: 1) αMβ2 integrins (Mac-1) on hepatic resident macrophages (Kupffer cells) selectively recognize irreversibly clustered b-N-acetylglucosamine (β-GlcNAc)–terminated glycans on GPIbα, and 2) hepatic Asialoglycoprotein (Asg) receptors (Ashwell Morell receptors) recognize desialylated GPIba. We here investigated the mechanism of sialic acid loss during refrigeration. We show, that when refrigerated platelets are rewarmed, they secrete active sialidases, including the lysosomal sialidase Neu1 that remove sialic acid from platelet receptors, specifically from GPIbα. Platelets also express Neu3 on their surfaces, however Neu3 expression appears to be unaffected by platelet refrigeration. Importantly, the recovery and circulation of refrigerated platelets is greatly improved by storage in the presence of the competitive sialidase inhibitor N-Acetylneuraminic Acid, 2,3-Dehydro-2-deoxy-Sodium Salt (DANA). Desialylated von Willebrand receptor (vWfR) complex is also a target for metalloproteinases (MMPs), as GPIbα and GPV are cleaved from the surface of refrigerated platelets. Receptor shedding is inhibited by the metalloproteinase inhibitor GM6001 and does not occur in ADAM17ΔZn/ΔZn platelets expressing inactive ADAM17. Critically, desialylation in the absence of metalloproteinase-mediated receptor shedding is sufficient to induce the rapid clearance of platelets from circulation. Desialylation of platelet vWfR therefore triggers platelet clearance, and primes GPIbα and GPV for metalloproteinase-dependent cleavage. We conclude that desialylation of platelets is caused by increased surface sialidase activity following refrigeration and desialylation of glycoproteins, specifically of GPIbα, promotes receptor cleavage by MMPs. Disclosures: Liu: Velicomedical, Inc: Employment.
Antagonistic Regulation of Type I Collagen Gene Expression by Interferon-γ and Transforming Growth Factor-β (2001)

Among the extracellular signals that modulate the synthesis of collagen, transforming growth factor-beta (TGF-beta) and interferon-gamma (IFN-gamma) are preeminent. These two cytokines exert antagonistic effects on fibroblasts, and play important roles in the physiologic regulation of extracellular matrix turnover. We have shown previously that in normal skin fibroblasts, TGF-beta positively regulates alpha2(I) procollagen gene (COL1A2) promoter activity through the cellular Smad signal transduction pathway. In contrast, IFN-gamma activates Stat1alpha, down-regulates COL1A2 transcription, and abrogates its stimulation induced by TGF-beta. The level of integration of the two pathways mediating antagonistic collagen regulation is unknown. We now report that IFN-gamma abrogates TGF-beta-stimulated COL1A2 transcription in fibroblasts by inhibiting Smad activities. IFN-gamma appears to induce competition between activated Stat1alpha and Smad3 for interaction with limiting amounts of cellular p300/CBP. Overexpression of p300 restored COL1A2 stimulation by TGF-beta in the presence of IFN-gamma, and potentiated IFN-gamma-dependent positive transcriptional responses. In contrast to fibroblasts, in U4A cells lacking Jak1 and consequently unable to activate Stat1alpha-mediated responses, IFN-gamma failed to repress TGF-beta-induced transcription. These results indicate that as essential coactivators for both Smad3 and Stat1alpha, nuclear p300/CBP integrate signals that positively or negatively regulate COL1A2 transcription. The findings implicate a novel mechanism to account for antagonistic interaction of Smad and Jak-Stat pathways in regulation of target genes. In fibroblasts responding to cytokines with opposing effects on collagen transcription, the relative levels of cellular coactivators, and their interaction with regulated transcription factors, may govern the net effect.
U.S. Agriculture: Challenges for the Twenty-First Century (1997)

The U.S. agricultural sector faces both opportunities and challenges in the countdown to the next century. Opportunities include expanded farm export potential that stems from foreign population and income growth, as well as more liberal trade policies. Reflecting this, the annual growth in the value of U.S. farm exports in this decade is much improved over the uneven performance of the 1980s. In addition, advances in biotechnology are improving productivity, reducing costs and providing raw farm products more neatly tailored to the needs and desires of both processors and consumers.
An analysis of the dynamic behavior of JavaScript programs (2010)

The JavaScript programming language is widely used for web programming and, increasingly, for general purpose computing. As such, improving the correctness, security and performance of JavaScript applications has been the driving force for research in type systems, static analysis and compiler techniques for this language. Many of these techniques aim to reign in some of the most dynamic features of the language, yet little seems to be known about how programmers actually utilize the language or these features. In this paper we perform an empirical study of the dynamic behavior of a corpus of widely-used JavaScript programs, and analyze how and why the dynamic features are used. We report on the degree of dynamism that is exhibited by these JavaScript programs and compare that with assumptions commonly made in the literature and accepted industry benchmark suites.
Powering architectures for new needs in telecommunications (2002)

This paper sets out the state of power supplies for France Telecom telecommunications systems. It attempts to predict future changes in requirements and the consequences this will have on the powering architecture. The first part of this paper deals with equipment installed in central offices and suggests a complete rethink of powering principles. The second part sets out the problems relating to powering of optical fibre access networks of the FITL type.
Both early and delayed anti-CD40L antibody treatment induces a stable plaque phenotype (2000)

In the present study, we investigated the role of the CD40L-CD40 pathway in a model of progressive atherosclerosis. ApoE-/- mice were treated with an anti-CD40L antibody or a control antibody for 12 wk. Antibody treatment started early (age 5 wk) or was delayed until after the establishment of atherosclerosis (age 17 wk). In both the early and delayed treatment groups, anti-CD40L antibody did not decrease plaque area or inhibit lesion initiation or age-related increase in lesion area. The morphology of initial lesions was not affected, except for a decrease in T-lymphocyte content. Effects of anti-CD40L antibody treatment on the morphology of advanced lesions were pronounced. In both the early and delayed treatment groups, T-lymphocyte content was significantly decreased. Furthermore, a pronounced increase in collagen content, vascular smooth muscle cell/myofibroblast content, and fibrous cap thickness was observed. In the delayed treatment group, a decrease in lipid core and macrophage content occurred. Interestingly, advanced lesions of anti-CD40L antibody-treated mice exhibited an increased transforming growth factor beta1 immunoreactivity, especially in macrophages. In conclusion, both early and delayed treatment with an anti-CD40L antibody do not affect atherosclerotic lesion initiation but do result in the development of a lipid-poor collagen-rich stable plaque phenotype. Furthermore, delayed treatment with anti-CD40L antibody can transform the lesion profile from a lipid-rich to a lipid-poor collagen-rich phenotype. Postulated mechanisms of this effect on plaque phenotype are the down-regulation of proinflammatory pathways and up-regulation of collagen-promoting factors like transforming growth factor beta.
Abiraterone in the treatment of metastatic castration-resistant prostate cancer (2014)

Androgen deprivation therapy remains the single most effective treatment for the initial therapy of advanced prostate cancer, but is uniformly marked by progression to castration-resistant prostate cancer (CRPC). Residual tumor androgens and androgen axis activation are now recognized to play a prominent role in mediating CRPC progression. Despite suppression of circulating testosterone to castrate levels, castration does not eliminate androgens from the prostate tumor microenvironment and residual androgen levels are well within the range capable of activating the androgen receptor (AR) and AR-mediated gene expression. Accordingly, therapeutic strategies that more effectively target production of intratumoral androgens are necessary. The introduction of abiraterone, a potent suppressor of cytochrome P450 17 α-hydroxysteroid dehydrogenase-mediated androgen production, has heralded a new era in the hormonal treatment of men with metastatic CRPC. Herein, the androgen and AR-mediated mechanisms that contribute to CRPC progression and establish cytochrome P450 17 α-hydroxysteroid dehydrogenase as a critical therapeutic target are briefly reviewed. The mechanism of action and pharmacokinetics of abiraterone are reviewed and its recently described activity against AR and 3-β-hydroxysteroid dehydrogenase is discussed. The Phase I and II data initially demonstrating the efficacy of abiraterone and Phase III data supporting its approval for patients with metastatic CRPC are reviewed. The safety and tolerability of abiraterone, including the incidence and management of side effects and potential drug interactions, are discussed. The current place of abiraterone in CRPC therapy is reviewed and early evidence regarding cross-resistance of abiraterone with taxane therapy, mechanisms of resistance to abiraterone, and observations of an abiraterone withdrawal response are presented. Future directions in the use of abiraterone, including optimal dosing strategies, the role of abiraterone in earlier disease settings, including castration sensitive, biochemically recurrent, or localized disease, and the rationale for combinatorial treatment strategies of abiraterone with enzalutamide and other targeted agents are also discussed.
Towards dial-a-molecule by integrating continuous flow, analytics and self-optimisation (2016)

The employment of continuous-flow platforms for synthetic chemistry is becoming increasingly popular in research and industrial environments. Integrating analytics in-line enables obtaining a large amount of information in real-time about the reaction progress, catalytic activity and stability, etc. Furthermore, it is possible to influence the reaction progress and selectivity via manual or automated feedback optimisation, thus constituting a dial-a-molecule approach employing digital synthesis. This contribution gives an overview of the most significant contributions in the field to date.
Myeloid Cells Obtained from the Blood but Not from the Tumor Can Suppress T-cell Proliferation in Patients with Melanoma (2012)

Our findings provide a first characterization of the nature and suppressive function of the melanoma myeloid infiltrate and indicate that the suppressive function of MDSC in patients with melanoma seems far less than that based on murine tumor models.
Expression of an omega-conotoxin-sensitive calcium channel in Xenopus oocytes injected with mRNA from Torpedo electric lobe. (1987)

Xenopus laevis oocytes were injected with poly(A)+ RNA isolated from the electric lobe of Torpedo californica. Six to nine days after mRNA injection of the oocytes a cadmium-sensitive inward current could be detected in oocytes bathed in a calcium- and chloride-free solution containing 40 mM barium. This inward current could be distinguished from the native barium current of control oocytes by its high sensitivity to blockade by cadmium ions and its inhibition by omega-conotoxin, a peptide neurotoxin from Conus geographicus. Neither the current of control cells nor that of injected cells was detectably affected by nisoldipine (1 microM) or nitrendipine (1 microM). However, the barium current of control oocytes showed appreciably more inactivation (in the barium solution used for recording) than the omega-conotoxin-sensitive current that develops in mRNA-injected oocytes. Culturing of mRNA-injected oocytes in medium containing actinomycin D failed to prevent the appearance of the omega-conotoxin-sensitive current. These results support the conclusion that mRNA from Torpedo electric lobe is translated to produce an additional calcium channel in Xenopus oocytes. The features of this channel suggest that it may be the same type of calcium channel that controls transmitter release at nerve endings in Torpedo electroplax.
Synthesis and Binding Affinity of 2-Phenylimidazo[1,2-a]pyridine Derivatives for both Central and Peripheral Benzodiazepine Receptors. A New Series of High-Affinity and Selective Ligands for the Peripheral Type (1997)

A number of 6-substituted or 6,8-disubstituted alkyl 2-phenylimidazo[1,2-alpha]pyridine-3-carboxylates 5a-h, -acetates 5i-s, 6a-g, and -propionates 5t, 6h and of N,N-dialkyl-2-phenylimidazo[1,2-alpha]pyridine-3-carboxamides 7a-d,-acetamides 7e-t or -propionamide 7u were prepared following new synthetic methods, and their affinities for both the central (CBR) and the peripheral (PBR) benzodiazepine receptors evaluated. The compounds of the ester series displayed low affinity for both receptor types. Conversely, most of N,N-dialkyl(2-phenylimidazo[1,2-alpha]pyridin-3-yl)acetamides 7e-t proved to possess high affinity and selectivity for CBR or PBR depending on the nature of substituents at C(6)- and/or C(8) on the heterocyclic ring system. In particular, the 6-substituted compounds 7f-n displayed ratios of IC50 values (IC50(CBR)/IC50(PBR)) ranging from 0.32 (7m) to 232 (7k), while the 6,8-disubstituted compounds 7o-t were more than 1000-fold more selective for PBR versus CBR. Compounds 7f,m were examined in several different benzodiazepine receptor subtypes. Expression of specific GABAA, receptor subunit assemblies in Xenopus oocytes was utilized to evaluate functionally both the efficacy and potency of the positive modulation of GABA-evoked Cl- currents by 7f and 7m in comparison with Zolpidem. The rank order of potencies of these drugs was 7f (EC50 = 3.2 x 10(-8) M) > Zolpidem (EC50 = 3.6 x 10(-8) M) > 7m (EC50 = 2.2 x 10(-7) M). The actions of these compounds were also tested on alpha 2 beta 2 gamma 2s, receptors. However, the EC50 of these compounds was increased, compared to alpha 1 beta 2 gamma 2s receptors, by 30-, 4-, and 5-fold for 7m, 7f, and Zolpidem, respectively. Finally, these compounds were almost completely devoid of activity at receptors containing the alpha 5 subunit.