Reduced frontal activation with increasing 2nd language proficiency

The factors influencing the degree of separation or overlap in the neuronal networks responsible for the processing of first and second language are still subject to investigation. This longitudinal study investigates how increasing second language proficiency influences activation differences during lexico-semantic processing of first and second language. Native English speaking exchange students learning German were examined with functional magnetic resonance imaging while reading words in three different languages at two points in time: at the beginning of their stay (day 1) and 5 months later (day 2), when second language proficiency had significantly increased. On day 1, second language words evoked more frontal activation than words from the mother tongue. These differences were diminished on day 2. We therefore conclude that with increasing second language proficiency, lexico-semantic processing of second language words needs less frontal control. Our results demonstrate that lexico-semantic processing of first and second language converges onto similar networks as second language proficiency increases.

Residual stress distribution in ferritic to austenitic steel joints made by laser welding,

In this study, autogenous laser welding was used to join thin plates of low carbon ferritic and austenitic stainless steel. Due to the differences in the thermo-physical properties of base metals, this kind of weld exhibits a complex microstructure, which frequently leads to an overall loss of joint quality. Four welded samples were prepared by using different sets of processing parameters, with the aim of minimizing the induced residual stress field. The dissimilar austenitic-ferritic joints obtained under all welding conditions were uniform and free of defects. Variations in beam position did not influence the weld geometiy, which is a typical keyhole welding. Microstructural characterization and residual strain scanning (by neutron diffraction) were used to assess the features of the joints. By varying laser beam power density and by displacing the laser beam towards the carbon steel side, an optimum combination of processing parameters was found.

Increased mononuclear cell activation and apoptosis early after human liver transplantation is associated with a reduced frequency of acute rejection

Experimental models of orthotopic liver transplantation (OLT) have shown that the very early events post-OLT are critical in distinguishing immunogenic and tolerogenic reactions. In rodents, increased leukocyte apoptosis and cytokine expression have been demonstrated in tolerogenic strain combinations. Information from human OLT recipients is less abundant. The aim of this study was to determine the amount of early leukocyte activation and apoptosis following human OLT, and to correlate this with subsequent rejection status. Peripheral blood mononuclear cells (PBMC) were isolated from 76 patients undergoing OLT - on the day prior, 5 hrs after reperfusion (day 0), and 18-24 hrs post-OLT (day 1). The mean level of apoptotic PBMCs on post OLT day 1 was higher than healthy recipients (0.9% +/- 0.2 vs. 0.2% +/- 0.1, p = 0.013). Apoptosis was greater in nonrejecting (NR) (1.1% +/- 0.3) compared with acutely-rejecting (R) (0.3% +/- 0.1, p = 0.021) patients. On day 1, PBMC from NR patients had increased expression of IFN-gamma (p = 0.006), IL-10 (p = 0.016), and CD40 ligand (p = 0.02) compared with R. Donor cell chimerism on day 1 did not differ between the groups indicating that this was unlikely to account for increased PBMC apoptosis in the NR group. Interestingly, the level of chimerism on day 0 was significantly higher in NR (3.8% +/- 0.6) compared with R (1.2% +/- 0.4, p = 0.004) patients and there was a close correlation between chimerism on day 0 and cytokine expression on day 1. These results imply that similar mechanisms are occurring in the human liver to promote graft acceptance as in the experimental models of liver transplantation and suggest that strategies that promote liver transplant acceptance in rodents might be applicable to humans.

Influence of cutting parameters and tool wear on martensitic stainless steel surface integrity after a face milling process

Surface finish is one of the most relevant aspects of machining operations, since it is one of the principle methods to assess quality. Also, surface finish influences mechanical properties such as fatigue behavior, wear, corrosion, etc. The feed, the cutting speed, the cutting tool material, the workpiece material and the cutting tool wear are some of the most important factors that affects the surface roughness of the machined surface. Due to the importance of the martensitic 416 stainless steel in the petroleum industry, especially in valve parts and pump shafts, this material was selected to study the influence of the feed per tooth and cutting speed on tool wear and surface integrity. Also the influence of tool wear on surface roughness is analyzed. Results showed that high values of roughness are obtained when using low cutting speed and feed per tooth and by using these conditions tool wear decreases prolonging tool life. Copyright © 2009 by ASME.

Reduced lipoapoptosis, hedgehog pathway activation and fibrosis in caspase-2 deficient mice with non-alcoholic steatohepatitis

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Toll-like Receptor 4 Activation Promotes Cardiac Arrhythmias By Decreasing The Transient Outward Potassium Current (ito) Through An Irf3-dependent And Myd88-independent Pathway.

Cardiac arrhythmias are one of the main causes of death worldwide. Several studies have shown that inflammation plays a key role in different cardiac diseases and Toll-like receptors (TLRs) seem to be involved in cardiac complications. In the present study, we investigated whether the activation of TLR4 induces cardiac electrical remodeling and arrhythmias, and the signaling pathway involved in these effects. Membrane potential was recorded in Wistar rat ventricle. Ca(2+) transients, as well as the L-type Ca(2+) current (ICaL) and the transient outward K(+) current (Ito), were recorded in isolated myocytes after 24 h exposure to the TLR4 agonist, lipopolysaccharide (LPS, 1 μg/ml). TLR4 stimulation in vitro promoted a cardiac electrical remodeling that leads to action potential prolongation associated with arrhythmic events, such as delayed afterdepolarization and triggered activity. After 24 h LPS incubation, Ito amplitude, as well as Kv4.3 and KChIP2 mRNA levels were reduced. The Ito decrease by LPS was prevented by inhibition of interferon regulatory factor 3 (IRF3), but not by inhibition of interleukin-1 receptor-associated kinase 4 (IRAK4) or nuclear factor kappa B (NF-κB). Extrasystolic activity was present in 25% of the cells, but apart from that, Ca(2+) transients and ICaL were not affected by LPS; however, Na(+)/Ca(2+) exchanger (NCX) activity was apparently increased. We conclude that TLR4 activation decreased Ito, which increased AP duration via a MyD88-independent, IRF3-dependent pathway. The longer action potential, associated with enhanced Ca(2+) efflux via NCX, could explain the presence of arrhythmias in the LPS group.

Activation Of The Low Molecular Weight Protein Tyrosine Phosphatase In Keratinocytes Exposed To Hyperosmotic Stress.

Herein, we provide new contribution to the mechanisms involved in keratinocytes response to hyperosmotic shock showing, for the first time, the participation of Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP) activity in this event. We reported that sorbitol-induced osmotic stress mediates alterations in the phosphorylation of pivotal cytoskeletal proteins, particularly Src and cofilin. Furthermore, an increase in the expression of the phosphorylated form of LMWPTP, which was followed by an augment in its catalytic activity, was observed. Of particular importance, these responses occurred in an intracellular milieu characterized by elevated levels of reduced glutathione (GSH) and increased expression of the antioxidant enzymes glutathione peroxidase and glutathione reductase. Altogether, our results suggest that hyperosmostic stress provides a favorable cellular environment to the activation of LMWPTP, which is associated with increased expression of antioxidant enzymes, high levels of GSH and inhibition of Src kinase. Finally, the real contribution of LMWPTP in the hyperosmotic stress response of keratinocytes was demonstrated through analysis of the effects of ACP1 gene knockdown in stressed and non-stressed cells. LMWPTP knockdown attenuates the effects of sorbitol induced-stress in HaCaT cells, mainly in the status of Src kinase, Rac and STAT5 phosphorylation and activity. These results describe for the first time the participation of LMWPTP in the dynamics of cytoskeleton rearrangement during exposure of human keratinocytes to hyperosmotic shock, which may contribute to cell death.

High Iodine Concentration Attenuates RET/PTC3 Oncogene Activation in Thyroid Follicular Cells

Background: Papillary thyroid carcinoma (PTC) is frequently associated with a RET gene rearrangement that generates a RET/PTC oncogene. RET/PTC is a fusion of the tyrosine kinase domain of RET to the 50 portion of a different gene. This fusion results in a constitutively active MAPK pathway, which plays a key role in PTC development. The RET/PTC3 fusion is primarily associated with radiation-related PTC. Epidemiological studies show a lower incidence of PTC in radiation-exposed regions that are associated with an iodine-rich diet. Since the influence of excess iodine on the development of thyroid cancer is still unclear, the aim of this study is to evaluate the effect of high iodine concentrations on RET/PTC3-activated thyroid cells. Methods: PTC3-5 cells, a rat thyroid cell lineage harboring doxycycline-inducible RET/PTC3, were treated with 10(-3) M NaI. Cell growth was analyzed by cell counting and the MTT assay. The expression and phosphorylation state of MAPK pathway-related (Braf, Erk, pErk, and pRet) and thyroid-specific (natrium-iodide symporter [Nis] and thyroid-stimulating hormone receptor [Tshr]) proteins were analyzed by Western blotting. Thyroid-specific gene expression was further analyzed by quantitative reverse transcription (RT)-polymerase chain reaction. Results: A significant inhibition of proliferation was observed, along with no significant variation in cell death rate, in the iodine-treated cells. Further, iodine treatment attenuated the loss of Nis and Tshr gene and protein expression induced by RET/PTC3 oncogene induction. Finally, iodine treatment reduced Ret and Erk phosphorylation, without altering Braf and Erk expression. Conclusion: Our results indicate an antioncogenic role for excess iodine during thyroid oncogenic activation. These findings contribute to a better understanding of the effect of iodine on thyroid follicular cells, particularly how it may play a protective role during RET/PTC3 oncogene activation.

Activation of endogenous p53 by combined p19Arf gene transfer and nutlin-3 drug treatment modalities in the murine cell lines B16 and C6

Background: Reactivation of p53 by either gene transfer or pharmacologic approaches may compensate for loss of p19Arf or excess mdm2 expression, common events in melanoma and glioma. In our previous work, we constructed the pCLPG retroviral vector where transgene expression is controlled by p53 through a p53-responsive promoter. The use of this vector to introduce p19Arf into tumor cells that harbor p53wt should yield viral expression of p19Arf which, in turn, would activate the endogenous p53 and result in enhanced vector expression and tumor suppression. Since nutlin-3 can activate p53 by blocking its interaction with mdm2, we explored the possibility that the combination of p19Arf gene transfer and nutlin-3 drug treatment may provide an additive benefit in stimulating p53 function. Methods: B16 (mouse melanoma) and C6 (rat glioma) cell lines, which harbor p53wt, were transduced with pCLPGp19 and these were additionally treated with nutlin-3 or the DNA damaging agent, doxorubicin. Viral expression was confirmed by Western, Northern and immunofluorescence assays. p53 function was assessed by reporter gene activity provided by a p53-responsive construct. Alterations in proliferation and viability were measured by colony formation, growth curve, cell cycle and MTT assays. In an animal model, B16 cells were treated with the pCLPGp19 virus and/or drugs before subcutaneous injection in C57BL/6 mice, observation of tumor progression and histopathologic analyses. Results: Here we show that the functional activation of endogenous p53wt in B16 was particularly challenging, but accomplished when combined gene transfer and drug treatments were applied, resulting in increased transactivation by p53, marked cell cycle alteration and reduced viability in culture. In an animal model, B16 cells treated with both p19Arf and nutlin-3 yielded increased necrosis and decreased BrdU marking. In comparison, C6 cells were quite susceptible to either treatment, yet p53 was further activated by the combination of p19Arf and nutlin-3. Conclusions: To the best of our knowledge, this is the first study to apply both p19Arf and nutlin-3 for the stimulation of p53 activity. These results support the notion that a p53 responsive vector may prove to be an interesting gene transfer tool, especially when combined with p53- activating agents, for the treatment of tumors that retain wild-type p53.

Leukotriene B(4) amplifies NF-kappa B activation in mouse macrophages by reducing SOCS1 inhibition of MyD88 expression

Activation of NF-kappa B and 5-lipoxygenase-mediated (5-LO-mediated) biosynthesis of the lipid mediator leukotriene B(4) (LTB(4)) are pivotal components of host defense and inflammatory responses. However, the role of LTB(4) in mediating innate immune responses elicited by specific TLR ligands and cytokines is unknown. Here we have shown that responses dependent on MyD88 (an adaptor protein that mediates signaling through all of the known TLRs, except TLR3, as well as IL-1 beta and IL-18) are reduced in mice lacking either 5-LO or the LTB(4) receptor BTL1, and that macrophages from these mice are impaired in MyD88-dependent activation of NF-kappa B. This macrophage defect was associated with lower basal and inducible expression of MyD88 and reflected impaired activation of STAT1 and overexpression of the STAT1 inhibitor SOCS1. Expression of MyD88 and responsiveness to the TLR4 ligand LPS were decreased by Stat1 siRNA silencing in WT macrophages and restored by Socs1 siRNA in 5-LO-deficient macrophages. These results uncover a pivotal role in macrophages for the GPCR BLT1 in regulating activation of NF-kappa B through Stat1-dependent expression of MyD88.

A simple method for non-linear analysis of steel fiber reinforced concrete

This paper proposes a physical non-linear formulation to deal with steel fiber reinforced concrete by the finite element method. The proposed formulation allows the consideration of short or long fibers placed arbitrarily inside a continuum domain (matrix). The most important feature of the formulation is that no additional degree of freedom is introduced in the pre-existent finite element numerical system to consider any distribution or quantity of fiber inclusions. In other words, the size of the system of equations used to solve a non-reinforced medium is the same as the one used to solve the reinforced counterpart. Another important characteristic of the formulation is the reduced work required by the user to introduce reinforcements, avoiding ""rebar"" elements, node by node geometrical definitions or even complex mesh generation. Bounded connection between long fibers and continuum is considered, for short fibers a simplified approach is proposed to consider splitting. Non-associative plasticity is adopted for the continuum and one dimensional plasticity is adopted to model fibers. Examples are presented in order to show the capabilities of the formulation.

Microstructure and mechanical properties of laser-welded joints of TWIP and TRIP steels

With the aim of investigating a laser-welded dissimilar joint of TWIP and TRIP steel sheets, the microstructure was characterized by means of OM, SEM, and EBSD to differentiate the fusion zone, heat-affected zone, and the base material. OIM was used to differentiate between ferritic, bainitic, and martensitic structures. Compositions were measured by means of optical emission spectrometry and EDX to evaluate the effect of manganese segregation. Microhardness measurements and tensile tests were performed to evaluate the mechanical properties of the joint. Residual stresses and XRD phase quantification were used to characterize the weld. Grain coarsening and martensitic areas were found in the fusion zone, and they had significant effects on the mechanical properties of the weld. The heat-affected zone of the TRIP steel and the corresponding base material showed considerable differences in the microstructure and properties. (C) 2009 Elsevier B.V. All rights reserved.

Study on Iron Formation During the Carbothermic Reduction of Iron Ore in Carbon Composite Pellets in the Temperature Range 1423 K-1623 K

The aim of this work is to study the reaction rate and the morphology of the intermediary reaction products during reduction of iron ore, when iron ore and carbonaceous material are agglomerated together as a carbon composite iron ore pellet. The reaction was performed at high temperatures, and in order to avoid heat transfer constraints small size samples were used. The carbonaceous materials employed were coke breeze and pure graphite. Portland cement was employed as a binder, and the pellets diameter was 5.2 mm. The experimental technique involved the measurement of the pellets weight loss, as well as interruption of the reaction at different stages in order to submit the partially reduced pellet to scanning electron microscopy. It has been observed that above 1523 K there is the formation of liquid slag inside the pellets, which partially dissolves iron oxides. The apparent activation energies obtained were 255 kJ/mol for coke breeze containing pellets, and 230 kJ/mol for those pellets containing graphite. It was possible to avoid heat transfer control of the reaction rate up to 1523 K by employing small composite pellets.