bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone deacetylase inhibitors valproate and trichostatin A are toxic to neuroblastoma cells and modulate cytochrome P450 1A1, 1B1 and 3A4 expression in these cells
Authors: Hřebačková Jana , Poljaková Jitka , Eckschlager Tomáš , Hraběta Jan , Procházka Pavel , Smutný Svatopluk , Stiborová Marie 
Published: September 2009

Histone deacetylase inhibitors valproate and trichostatin A are toxic to neuroblastoma cells and modulate cytochrome P450 1A1, 1B1 and 3A4 expression in these cellsHistone deacetylase inhibitors such as valproic acid (VPA) and trichostatin A (TSA) were shown to exert antitumor activity. Here, the toxicity of both drugs to human neuroblastoma cell lines was investigated using MTT test, and IC50 values for both compounds were determined. Another target of this work was to evaluate the effects of both drugs on expression of cytochrome P450 (CYP) 1A1, 1B1 and 3A4 enzymes, which are known to be expressed in neuroblastoma cells. A malignant subset of neuroblastoma cells, so-called N-type cells (UKF-NB-3 cells) and the more benign S-type neuroblastoma cells (UKF-NB-4 and SK-N-AS cell lines) were studied from both two points of view. VPA and TSA inhibited the growth of neuroblastoma cells in a dose-dependent manner. The IC50values ranging from 1.0 to 2.8 mM and from 69.8 to 129.4 nM were found for VPA and TSA, respectively. Of the neuroblastoma tested here, the N-type UKF-NB-3 cell line was the most sensitive to both drugs. The different effects of VPA and TSA were found on expression of CYP1A1, 1B1 and 3A4 enzymes in individual neuroblastoma cells tested in the study. Protein expression of all these CYP enzymes in the S-type SK-N-AS cell line was not influenced by either of studied drugs. On the contrary, in another S-type cell line, UKF-NB-4, VPA and TSA induced expression of CYP1A1, depressed levels of CYP1B1 and had no effect on expression levels of CYP3A4 enzyme. In the N-type UKF-NB-3 cell line, the expression of CYP1A1 was strongly induced, while that of CYP1B1 depressed by VPA and TSA. VPA also induced the expression of CYP3A4 in this neuroblastoma cell line.
FAN Stimulates TNFα-Induced Gene Expression, Leukocyte Recruitment, and Humoral Response
Authors: Montfort Anne , de Badts Bénédicte , Douin-Echinard Victorine , Martin Pascal G. P. , Iacovoni Jason , Nevoit Caroline , Therville Nicole , Garcia Virginie , Bertrand Marie-Antoinette , Bessières Marie-Hélène , Trombe Marie-Claude , Levade Thierry , Benoist Hervé , Ségui Bruno 
Published: September 2009

AbstractFactor associated with neutral sphingomyelinase activation (FAN) is an adaptor protein that constitutively binds to TNF-R1. Microarray analysis was performed in fibroblasts derived from wild-type or FAN knockout mouse embryos to evaluate the role of FAN in TNF-induced gene expression. Approximately 70% of TNF-induced genes exhibited lower expression levels in FAN-deficient than in wild-type fibroblasts. Of particular interest, TNF-induced expression of cytokines/chemokines, such as IL-6 and CXCL-2, was impaired in FAN-deficient cells. This was confirmed by real time RT-PCR and ELISA. Upon i.p. TNF or thioglycollate injection, neutrophil recruitment into the peritoneal cavity was reduced by more than 50% in FAN-deficient mice. Nevertheless, FAN-deficient animals did not exhibit an increased susceptibility to different microorganisms including bacteria and parasites, indicating that FAN is not essential for pathogen clearance. Specific Ab response to BSA was substantially impaired in FAN-deficient mice and this was associated with a reduced content of leukocytes in the spleen of BSA-challenged FAN-deficient mice as compared with their wild-type counterparts. Altogether, our results indicate the involvement of FAN in TNF-induced gene expression and leukocyte recruitment, contributing to the establishment of the specific immune response.
SH2 Domain-Containing Phosphatase-2 Protein-Tyrosine Phosphatase Promotes FcεRI-Induced Activation of Fyn and Erk Pathways Leading to TNFα Release from Bone Marrow-Derived Mast Cells
Authors: McPherson Victor A. , Sharma Namit , Everingham Stephanie , Smith Julie , Zhu Helen H. , Feng Gen-Sheng , Craig Andrew W. B. 
Published: September 2009

AbstractClustering of the high affinity IgE receptor (FcεRI) in mast cells leads to degranulation and production of numerous cytokines and lipid mediators that promote allergic inflammation. Initiation of FcεRI signaling involves rapid tyrosine phosphorylation of FcεRI and membrane-localized adaptor proteins that recruit additional SH2 domain-containing proteins that dynamically regulate downstream signaling. SH2 domain-containing phosphatase-2 (SHP2) is a protein-tyrosine phosphatase implicated in FcεRI signaling, but whose function is not well defined. In this study, using a mouse model allowing temporal shp2 inactivation in bone marrow-derived mast cells (BMMCs), we provide insights into SHP2 functions in the FcεRI pathway. Although no overt defects in FcεRI-induced tyrosine phosphorylation were observed in SHP2 knock-out (KO) BMMCs, several proteins including Lyn and Syk kinases displayed extended phosphorylation kinetics compared with wild-type BMMCs. SHP2 was dispensable for FcεRI-induced degranulation of BMMCs, but was required for maximal activation of Erk and Jnk mitogen-activated protein kinases. SHP2 KO BMMCs displayed several phenotypes associated with reduced Fyn activity, including elevated phosphorylation of the inhibitory pY531 site in Fyn, impaired signaling to Grb2-associated binder 2, Akt/PKB, and IκB kinase, and decreased TNF-α release compared with control cells. This is likely due to elevated Lyn activity in SHP2 KO BMMCs, and the ability of Lyn to antagonize Fyn activity. Overall, our study identifies SHP2 as a positive effector of FcεRI-induced activation of Fyn/Grb2-associated binder 2/Akt and Ras/Erk pathways leading to TNF-α release from mast cells.
Essential Roles for Dok2 and RasGAP in CD200 Receptor-Mediated Regulation of Human Myeloid Cells
Authors: Mihrshahi Robin , Barclay A. Neil , Brown Marion H. 
Published: September 2009

Abstract
The CD200 receptor (CD200R) acts as a negative regulator of myeloid cells by interacting with its widely expressed ligand CD200. Using mutants expressed in U937 cells, we show that inhibition is mediated by the PTB domain binding motif (NPLY) in the receptor’s cytoplasmic region. The adaptor protein downstream of tyrosine kinase 2 (Dok2) bound directly to the phosphorylated NPLY motif with a 10-fold higher affinity (KD of ∼1 μM at 37°C) than the closely related Dok1. Both of these proteins have been suggested to play a role in CD200R signaling in murine cells. Dok2 was phosphorylated in response to CD200R engagement and recruited RAS p21 protein activator 1 (RasGAP). Knockdown of Dok2 and RasGAP by RNA interference revealed that these proteins are required for CD200R signaling, while knockdown of Dok1 and the inositol 5-phosphatase SHIP did not affect CD200R-mediated inhibition. We conclude that CD200R inhibits the activation of human myeloid cells through direct recruitment of Dok2 and subsequent activation of RasGAP, which distinguishes this receptor from the majority of inhibitory receptors that utilize ITIMs and recruit phosphatases.
Vascular Endothelial Growth Factor Is a Key Mediator in the Development of T Cell Priming and Its Polarization to Type 1 and Type 17 T Helper Cells in the Airways
Authors: Kim You-Sun , Hong Sung-Wook , Choi Jun-Pyo , Shin Tae-Seop , Moon Hyung-Geun , Choi Eun-Jung , Jeon Seong Gyu , Oh Sun-Young , Gho Yong Song , Zhu Zhou , Kim Yoon-Keun 
Published: September 2009

Abstract
Chronic inflammatory airway diseases including asthma are characterized by immune dysfunction to inhaled allergens. Our previous studies demonstrated that T cell priming to inhaled allergens requires LPS, which is ubiquitously present in household dust allergens. In this study, we evaluated the role of vascular endothelial growth factor (VEGF) in the development of T cell priming and its polarization to Th1 or Th17 cells when exposed to LPS-contaminated allergens. An asthma mouse model was induced by airway sensitization with LPS-contaminated allergens and then challenged with allergens alone. Therapeutic intervention was performed during allergen sensitization. The present study showed that lung inflammation induced by sensitization with LPS-contaminated allergens was decreased in mice with homozygous disruption of the IL-17 gene; in addition, allergen-specific Th17 immune response was abolished in IL-6 knockout mice. Meanwhile, in vivo production of VEGF was up-regulated by airway exposure of LPS. In addition, airway sensitization of allergen plus recombinant VEGF induced both type 1 and type 17 Th cell (Th1 and Th17) responses. Th1 and Th17 responses induced by airway sensitization with LPS-contaminated allergens were blocked by treatment with a pan-VEGF receptor (VEGFR; VEGFR-1 plus VEGFR-2) inhibitor during sensitization. These effects were accompanied by inhibition of the production of Th1 and Th17 polarizing cytokines, IL-12p70 and IL-6, respectively. These findings indicate that VEGF produced by LPS plays a key role in activation of naive T cells and subsequent polarization to Th1 and Th17 cells.
γδ T Cell Immune Manipulation during Chronic Phase of Simian HIV Infection Confers Immunological Benefits
Authors: Ali Zahida , Yan Lin , Plagman Nicholas , Reichenberg Armin , Hintz Martin , Jomaa Hassan , Villinger Francois , Chen Zheng W. 
Published: September 2009

Abstract
Vγ2Vδ2 T cells, a major human γδ T cell subset, recognize the phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) produced by mycobacteria and some opportunistic pathogens, and they contribute to innate/adaptive/homeostatic and anticancer immunity. As initial efforts to explore Vγ2Vδ2 T cell-based therapeutics against HIV/AIDS-associated bacterial/protozoal infections and neoplasms, we investigated whether a well-defined HMBPP/IL-2 therapeutic regimen could overcome HIV-mediated immune suppression to massively expand polyfunctional Vγ2Vδ2 T cells, and whether such activation/expansion could impact AIDS pathogenesis in simian HIV (SHIV)-infected Chinese rhesus macaques. While HMBPP/IL-2 coadministration during acute or chronic phase of SHIV infection induced massive activation/expansion of Vγ2Vδ2 T cells, the consequences of such activation/expansions were different between these two treatment settings. HMBPP/IL-2 cotreatment during acute SHIV infection did not prevent the increases in peak and set-point viral loads or the accelerated disease progression seen with IL-2 treatment alone. In contrast, HMBPP/IL-2 cotreatment during chronic infection did not exacerbate disease, and more importantly it could confer immunological benefits. Surprisingly, although viral antigenic loads were not increased upon HMBPP/IL-2 cotreatment during chronic SHIV infection, HMBPP activation of Vγ2Vδ2 T cells boosted HIV Env-specific Ab titers. Such increases in Abs were sustained for &gt;170 days and were immediately preceded by increased production of IFN-γ, TNF-α, IL-4, and IL-10 during peak expansion of Vγ2Vδ2 T cells displaying memory phenotypes, as well as the short-term increased effector function of Vγ2Vδ2 T cells and CD4+ and CD8+ αβ T cells producing antimicrobial cytokines. Thus, HMBPP/Vγ2Vδ2 T cell-based intervention may potentially be useful for combating neoplasms and HMBPP-producing opportunistic pathogens in chronically HIV-infected individuals.
Identifying and changing the normative beliefs about aggression which lead young Muslim adults to join extremist anti‐Semitic groups in Pakistan
Authors: Amjad Naumana , Wood Alex M. 
Published: September 2009

AbstractTwo studies investigated the role of beliefs about the acceptability of aggression (“normative beliefs”) against Jews in determining who would join an extremist group. In Study 1, students in a university in Pakistan (N=144) completed self‐report attitude measures, and were subsequently approached by a confederate who asked whether they wanted to join an extremist anti‐Semitic organization. Normative beliefs about aggression against Jews were very strong predictors of whether participants agreed to join. In Study 2, participants (N=92) were experimentally assigned to either a brief educational intervention, designed to improve inter‐group relations, or to a control group. They also filled in self‐report attitude measures pre and post intervention. Participants in the intervention group were much less likely to agree to join the extremist group, and this effect of the intervention on joining was mediated by changes in normative beliefs about aggression against Jews. The results have implications for theories of inter‐group aggression and interventions to prevent people from being recruited into extremist groups. Aggr. Behav. 35:514–519, 2009. © 2009 Wiley‐Liss, Inc.
An improved model for boron diffusion and activation in silicon
Authors: Kwok Charlotte T. M. , Braatz Richard D. , Paul Silke , Lerch Wilfried , Seebauer Edmund G. 
Published: September 2009

AbstractTechnologies such as solid‐phase epitaxial regrowth and millisecond annealing techniques have led to a wide range of maximum temperatures and heating rates for activating dopants and eliminating ion implantation damage for transistor junction formation. Developing suitable annealing strategies depends on mathematical models that incorporate accurate defect physics. The present work describes a model that includes a newly discovered representation of defect annihilation at surfaces and of near‐surface band bending, together with an improved representation of interstitial clustering. Key parameters are determined by maximum likelihood (ML) estimation and maximum a posteriori (MAP) estimation. The model yields a substantially improved ability to model the behavior of implanted boron over a wide range of annealing conditions. © 2009 American Institute of Chemical Engineers AIChE J, 2010
Influence of elevated pressure and particle lyophobicity on hydrodynamics and gas–liquid mass transfer in slurry bubble columns
Authors: Chilekar Vinit P. , van der Schaaf John , Kuster Ben F. M. , Tinge Johan T. , Schouten Jaap C. 
Published: September 2009

AbstractThis article reports on the influence of elevated pressure and catalyst particle lyophobicity at particle concentrations up to 3 vol % on the hydrodynamics and the gas‐to‐liquid mass transfer in a slurry bubble column. The study was done with demineralized water (aqueous phase) and Isopar‐M oil (organic phase) slurries in a 0.15 m internal diameter bubble column operated at pressures ranging from 0.1 to 1.3 MPa. The overall gas hold‐up, the flow regime transition point, the average large bubble diameter, and the centerline liquid velocity were measured along with the gas–liquid mass transfer coefficient. The gas hold‐up and the flow regime transition point are not influenced by the presence of lyophilic particles. Lyophobic particles shift the regime transition to a higher gas velocity and cause foam formation. Increasing operating pressure significantly increases the gas hold‐up and the regime transition velocity, irrespective of the particle lyophobicity. The gas–liquid mass transfer coefficient is proportional to the gas hold‐up for all investigated slurries and is not affected by the particle lyophobicity, the particle concentration, and the operating pressure. A correlation is presented to estimate the gas–liquid mass transfer coefficient as a function of the measured gas hold‐up:
$k_{\rm l}a_{\rm l}/\varepsilon_{\rm g} = 3.0 \sqrt{Du_{\rm b}/d_{\rm b}^3}\;{\rm s}^{-1}$. © 2009 American Institute of Chemical Engineers AIChE J, 2010
Rational design of shape selective separations and catalysis: Lattice relaxation and effective aperture size
Authors: Gounaris Chrysanthos E. , Wei James , Floudas Christodoulos A. , Ranjan Rajiv , Tsapatsis Michael 
Published: September 2009

AbstractGounaris et al. presented a computational method that can be used for the quick screening of zeolite structures and provide predictions regarding which of them have the potential to exhibit high selectivity among a set of molecules of interest. This article builds upon this earlier work and furthers our understanding of diffusion processes in zeolites and other microporous metal oxides. We first present an augmented formulation to account for the flexibility of the zeolitic portal and conduct an analysis to assess the effect of varying the parameters of the associated quadratic potential. We then introduce a methodology to map the energetic landscape, identify all locally optimal conformations, and probabilistically account for the multiplicity of conformers. Finally, we conduct sensitivity analysis on the effective size of the aperture, and show how the methodology can be fine–tuned through experimental observations. A comprehensive database of 290 molecules of industrial interest and a total of 123 different zeolite structures were used in this study. © 2009 American Institute of Chemical Engineers AIChE J, 2010
Synthesis of heat exchanger networks with nonisothermal phase changes
Authors: Hasan M. M. Faruque , Jayaraman Gopalakrishnan , Karimi I. A. , Alfadala H. E. 
Published: September 2009

AbstractMost literature on the synthesis of heat exchanger networks via mathematical programming methods has dealt with phase changes by assuming nearly isothermal conditions. Many multicomponent phase changes of practical interest (e.g., those in sub‐ambient processes) occur over ranges of temperatures and exhibit nonlinear temperature‐enthalpy relations (T‐H curve). In such cases, isothermal approximations may lead to inferior or unacceptable networks. In this article, we propose a mixed‐integer nonlinear programming formulation and a solution algorithm to incorporate nonisothermal phase changes in heat exchanger network synthesis. We approximate the nonlinear T‐H curves via empirical cubic correlations, and propose a procedure to ensure minimum temperature approach at all points in the exchangers. Our approach successfully solves two industry examples and shows promise for significant cost reductions when compared with existing processes. © 2009 American Institute of Chemical Engineers AIChE J, 2009
Beckmann rearrangement of cyclohexanone oxime to ε‐caprolactam in microreactors
Authors: Zuidhof K. T. , de Croon M. H. J. M. , Schouten J. C. 
Published: September 2009

AbstractSelectivities are presented of the Beckmann rearrangement of cyclohexanone oxime to ε‐caprolactam with oleum for various conditions in three microreactors, viz., Y‐junction, interdigital, and split and recombine mixers, followed by a 50‐cm long microchannel of 250 μm internal diameter. Cyclohexanone oxime is dissolved in cyclooctane, which is inert for oleum. The selectivity is measured in the temperature range of 80–132°C. The concentration range of caprolactam in the reaction mixture is 31–41 wt %, in oleum. The total volumetric flow rate is 0.4 ml/min, whereas the flow rate ratio of ε‐caprolactam/oleum over cyclohexanone oxime/cyclooctane ranges from 0.3 to 3. The selectivities measured with the three microreactors are: 70–99+%, 93–99+%, and 95–99+%, respectively. High ε‐caprolactam concentration (41 wt %), high temperature (110–132°C), and a ratio of free H2SO4 to SO3 of unity have a negative effect on the selectivity. © 2009 American Institute of Chemical Engineers AIChE J, 2010
Mathematical modeling of solid oxide fuel cells at high fuel utilization based on diffusion equivalent circuit model
Authors: Bao Cheng , Shi Yixiang , Li Chen , Cai Ningsheng , Su Qingquan 
Published: September 2009

AbstractMass transfer and electrochemical phenomena in the membrane electrode assembly (MEA) are the core components for modeling of solid‐oxide fuel cell (SOFC). The general MEA model is simply governed with the Stefan‐Maxwell equation for multicomponent gas diffusion, Ohm's law for the charge transfer and the current‐overpotential equation for the polarization calculation. However, it has obvious discrepancy at high‐fuel utilization or high‐current density. An advanced MEA model is introduced based on the diffusion equivalent circuit model. The main purpose is to correct the real‐gas concentrations at the triple‐phase boundary by assuming that the resistance of surface diffusion is in series with that of the gaseous bulk diffusion. Thus, it can obtain good prediction of cell performance in a wide range by avoiding the decrement of effective gas diffusivity via unreasonable increment of the electrode tortuosity in the general MEA model. The mathematical model has been validated in the cases of H2H2O, COCO2 and H2CO fuel system. © 2009 American Institute of Chemical Engineers AIChE J, 2010
Integration of on‐the‐fly kinetic reduction with multidimensional CFD
Authors: He Kaiyuan , Ierapetritou Marianthi G. , Androulakis Ioannis P. 
Published: September 2009

AbstractA reduction approach for coupling complex kinetics with engine computational fluid dynamics (CFD) code has been developed. An on‐the‐fly reduction scheme was used to reduce the reaction mechanism dynamically during the reactive flow calculation in order to couple comprehensive chemistry with flow simulations in each computational cell. KIVA‐3V code is used as the CFD framework and CHEMKIN is employed to formulate chemistry, hydrodynamics and transport. Mechanism reduction was achieved by applying element flux analysis on‐the‐fly in the context of the multidimensional CFD calculation. The results show that incorporating the on‐the‐fly reduction approach in CFD code enables the simulation of ignition and combustion process accurately compared with detailed simulations. Both species and time‐dependant information can be provided by the current model with significantly reduced CPU time. © 2009 American Institute of Chemical Engineers AIChE J, 2010
Living together: behavior and welfare in single and mixed species groups of capuchin (Cebus apella) and squirrel monkeys (Saimiri sciureus)
Authors: Leonardi Rebecca , Buchanan‐Smith Hannah M. , Dufour Valérie , MacDonald Charlotte , Whiten Andrew 
Published: September 2009

AbstractThere are potential advantages of housing primates in mixed species exhibits for both the visiting public and the primates themselves. If the primates naturally associate in the wild, it may be more educational and enjoyable for the public to view. Increases in social complexity and stimulation may be enriching for the primates. However, mixed species exhibits might also create welfare problems such as stress from interspecific aggression. We present data on the behavior of single and mixed species groups of capuchin monkeys (Cebus apella) and squirrel monkeys (Saimiri sciureus) housed at the Living Links to Human Evolution Research Centre in the Royal Zoological Society of Scotland's Edinburgh Zoo. These species associate in the wild, gaining foraging benefits and decreased predation. ButCebusare also predators themselves with potential risks for the smallerSaimiri. To study their living together we took scan samples at ≥15 min intervals on single (n=109) and mixed species groups (n=152), and all occurrences of intraspecific aggression and interspecific interactions were recorded. We found no evidence of chronic stress andSaimiriactively chose to associate withCebus. On 79% of scans, the two species simultaneously occupied the same part of their enclosure. No vertical displacement was observed. Interspecific interactions were common (>2.5/hr), and equally divided among mildly aggressive, neutral, and affiliative interactions such as play. Only one aggressive interaction involved physical contact and was non‐injurious. Aggressive interactions were mostly (65%) displacements and vocal exchanges, initiated almost equally byCebusandSaimiri. Modifications to the enclosure were successful in reducing these mildly aggressive interactions with affiliative interactions increasing in frequency and diversity. Our data suggest that in carefully designed, large enclosures, naturally associating monkeys are able to live harmoniously and are enriched by each other. Am. J. Primatol. 72:33–47, 2010. © 2009 Wiley‐Liss, Inc.