InGaAs/InP double heterostructures on InP/Si templates fabricated by wafer bonding and hydrogen-induced exfoliation

Hydrogen-induced exfoliation combined with wafer bonding has been used to transfer ~600-nm-thick films of (100) InP to Si substrates. Cross-section transmission electron microscopy (TEM) shows a transferred crystalline InP layer with no observable defects in the region near the bonded interface and an intimately bonded interface. InP and Si are covalently bonded as inferred by the fact that InP/Si pairs survived both TEM preparation and thermal cycles up to 620 °C necessary for metalorganic chemical vapor deposition growth. The InP transferred layers were used as epitaxial templates for the growth of InP/In0.53Ga0.47As/InP double heterostructures. Photoluminescence measurements of the In0.53Ga0.47As layer show that it is optically active and under tensile strain, due to differences in the thermal expansion between InP and Si. These are promising results in terms of a future integration of Si electronics with optical devices based on InP-lattice-matched materials

Investigation of the marine compound spongistatin 1 links the inhibition of PKCα translocation to nonmitotic effects of tubulin antagonism in angiogenesis

The aims of the study were to meet the demand of new tubulin antagonists with fewer side effects by characterizing the antiangiogenic properties of the experimental compound spongistatin 1, and to elucidate nonmitotic mechanisms by which tubulin antagonists inhibit angiogenesis. Although tubulin-inhibiting drugs and their antiangiogenic properties have been investigated for a long time, surprisingly little is known about their underlying mechanisms of action. Antiangiogenic effects of spongistatin 1 were investigated in endothelial cells in vitro, including functional cell-based assays, live-cell imaging, and a kinome array, and in the mouse cornea pocket assay in vivo. Spongistatin 1 inhibited angiogenesis at nanomolar concentrations (IC50: cytotoxicity>50 nM, proliferation 100 pM, migration 1.0 nM, tube formation 1.0 nM, chemotaxis 1.0 nM, aortic ring sprouting 500 pM, neovascularization in vivo 10 μg/kg). Further, a kinome array and validating data showed that spongistatin 1 inhibits the phosphorylation activity of protein kinase Cα (PKCα), an essential kinase in angiogenesis, and its translocation to the membrane. Thus, we conclude that PKCα might be an important target for the antiangiogenic effects of tubulin antagonism. In addition, the data from the kinase array suggest that different tubulin antagonists might have individual intracellular actions.—Rothmeier, A. S., Ischenko, I., Joore, J., Garczarczyk, D., Fu¨rst, R., Bruns, C. J., Vollmar, A. M., Zahler, S. Investigation of the marine compound spongistatin 1 links the inhibition of PKCα translocation to nonmitotic effects of tubulin antagonism in angiogenesis

A novel technique for selective NF-kappa B inhibition in Kupffer cells: contrary effects in fulminant hepatitis and ischaemia-reperfusion.

Background and aims: The transcription factor nuclear factor kappa B (NF-kB) has risen as a promising target for anti-inflammatory therapeutics. In the liver, however, NFkB inhibition mediates both damaging and protective effects. The outcome is deemed to depend on the liver cell type addressed. Recent gene knock-out studies focused on the role of NF-kB in hepatocytes, whereas the role of NF-kB in Kupffer cells has not yet been investigated in vivo. Here we present a novel approach, which may be suitable for clinical application, to selectively target NF-kB in Kupffer cells and analyse the effects in experimental models of liver injury. Methods: NF-kB inhibiting decoy oligodeoxynucleotides were loaded upon gelatin nanoparticles (D-NPs) and their in vivo distribution was determined by confocal microscopy. Liver damage, NF-kB activity, cytokine levels and apoptotic protein expression were evaluated after lipopolysaccharide (LPS), D-galactosamine (GalN)/LPS, or concanavalin A (ConA) challenge and partial warm ischaemia and subsequent reperfusion, respectively. Results: D-NPs were selectively taken up by Kupffer cells and inhibited NF-kB activation. Inhibition of NF-kB in Kupffer cells improved survival and reduced liver injury after GalN/LPS as well as after ConA challenge. While anti-apoptotic protein expression in liver tissue was not reduced, pro-apoptotic players such as cJun N-terminal kinase (JNK) were inhibited. In contrast, selective inhibition of NF-kB augmented reperfusion injury. Conclusions: NF-kB inhibiting decoy oligodeoxynucleotide- loaded gelatin nanoparticles is a novel tool to selectively inhibit NF-kB activation in Kupffer cells in vivo. Thus, liver injury can be reduced in experimental fulminant hepatitis, but increased at ischaemia–reperfusion

Endothelial preconditioning by transient oxidative stress reduces inflammatory responses of cultured endothelial cells to TNF-α

Brief episodes of ischemia can render an organ resistant to subsequent severe ischemia. This ‘ischemic preconditioning’ is ascribed to various mechanisms, including oxidative stress. We investigated whether preconditioning exists on an endothelial level. Human umbilical vein endothelial cells (HUVECs) were transiently confronted with oxidative stress (1 mM H2O2, 5 min). Adhesion molecules ICAM-1 and E-selectin and release of cytokines IL-6 and IL-8 to subsequent stimulation with TNF-α (2.5 ng/ml, 4 h) were measured (flow cytometry and immunoassay), as were nuclear translocation of the transcription factor NFkB (Western blotting, confocal microscopy) and redox status of HUVECs (quantification of glutathione by HPLC). TNF-α elevated IL-6 in the cell supernatant from 8.8 ± 1 to 41 ± 3 pg/ml and IL-8 from 0.5 ± 0.03 to 3 ± 0.2 ng/ml. ICAM-1 was increased threefold and E-selectin rose eightfold. Oxidative stress (decrease of glutathione by 50%) reduced post-TNF-α levels of IL-6 to 14 ± 3 and IL-8 to 1 ± 0.2; the rise of ICAM-1 was completely blocked and E-selectin was only doubled. The anti-inflammatory effects of preconditioning via oxidative stress were paralleled by reduction of the translocation of NFkB on stimulation with TNF-α, and antagonized by the intracellular radical scavenger N-acetylcysteine. ‘Anti-inflammatory preconditioning’ of endothelial cells by oxidative stress may account for the inhibitory effects of preconditioning on leukocyte adhesion in vivo

Trade and financial liberalization in the context of external shocks and inconsistent domestic policies

Includes bibliograph

Efectos macroeconómicos de cambios en las barreras al comercio y al movimiento de capitales: un modelo de simulación

Incluye BibliografíaEl estudio está centrado en las características de la trayectoria del ajuste, en el corto y mediano plazo, de algunas de las principales variables macroeconómicas como consecuencia de la apertura de la economía al libre flujo de bienes y capitales financieros. Describe la estructura básica del modelo, los distintos ejercicios de simulación, y en anexo, incluye el modelo de simulación

Liberalización financiera y comercial en el contexto de impactos externos y políticas internas inconsistentes

Incluye BibliografíaMediante experimentos de simulación usando el modelo de equilibrio general, analiza los efectos de corto y mediano plazo que algunos tipos de crisis externas y una política fiscal expansiva pueden tener sobre algunas variables macroeconómicas claves, mientras la economía se abre al comercio y a las finanzas internacionales

Community-Based User Experience: Evaluating the Usability of Health Insurance Information With Immigrant Patients

User experience (UX), a common practice in corporate settings, is new for many nonprofit organizations. This case study details a community-based research project between nonprofit staff at a community health center and UX professionals to improve the design and usability of a document designed to help immigrant patients sign up for health insurance. UX professionals may need to adapt and be flexible with their efforts, but can offer valuable skills to community partners. Research questions: (1) What are the information needs and barriers faced by immigrant populations signing up for health insurance? (2) How does a usability study, adapted to meet the needs of immigrant populations, inform the design of a supplemental guidebook about health insurance? (3) What are the challenges and opportunities when engaging in community-based UX research projects? Situating the case: Other community-based research projects in technical communication and UX point to the need for a clear conceptualization of participation, a strong partnership with nonprofits, and the need to develop meaningful and actionable insights. Furthermore, when conducting studies with immigrant populations, the role of the translator on the research team is crucial. Methodology: As a community-based research project focused on the collaborative generation of practical knowledge, we conducted a usability study with 12 participants in two language groups, Chinese and Vietnamese, to evaluate the design and usability of a guidebook designed to provide guidance about enrolling in a health insurance plan. Data were analyzed to identify usability concerns and used to inform a second iteration of the guidebook. About the case: Immigrant populations struggle to sign up for health insurance for a variety of reasons, including limited English and health insurance literacy. As a result, a nonprofit community health center developed a guidebook to support immigrant populations. Version 1 of this guidebook was evaluat- d in a usability study, with results showing that users struggled to correctly choose a plan, determine their eligibility, and interpret abstract examples. As a result, Version 2 was designed to support the in-person experience, reduce visual complexity, and support patients\u27 key questions. Conclusions: Community-based UX collaborations can amplify the expertise of UX and nonprofit professionals. However, UX methods may need to be adapted in community-based projects to better incorporate local knowledge and needs

Persistent inhibition of pore-based cell migration by sub-toxic doses of miuraenamide, an actin filament stabilizer

Opposed to tubulin-binding agents, actin-binding small molecules have not yet become part of clinical tumor treatment, most likely due to the fear of general cytotoxicity. Addressing this problem, we investigated the long-term efficacy of sub-toxic doses of miuraenamide, an actin filament stabilizing natural compound, on tumor cell (SKOV3) migration. No cytotoxic effects or persistent morphological changes occurred at a concentration of miuraenamide of 20 nM. After 72 h treatment with this concentration, nuclear stiffness was increased, causing reduced migration through pores in a Boyden chamber, while cell migration and chemotaxis per se were unaltered. A concomitant time-resolved proteomic approach showed down regulation of a protein cluster after 56 h treatment. This cluster correlated best with the Wnt signaling pathway. A further analysis of the actin associated MRTF/SRF signaling showed a surprising reduction of SRF-regulated proteins. In contrast to acute effects of actin-binding compounds on actin at high concentrations, long-term low-dose treatment elicits much more subtle but still functionally relevant changes beyond simple destruction of the cytoskeleton. These range from biophysical parameters to regulation of protein expression, and may help to better understand the complex biology of actin, as well as to initiate alternative regimes for the testing of actin-targeting drugs