875 resultados para regulatory and signaling networks


Relevância:

100.00% 100.00%

Publicador:

Resumo:

The cAMP-dependent protein kinase (PKA) has been shown to play an important role in long-term potentiation (LTP) in the hippocampus, but little is known about the function of PKA in long-term depression (LTD). We have combined pharmacologic and genetic approaches to demonstrate that PKA activity is required for both homosynaptic LTD and depotentiation and that a specific neuronal isoform of type I regulatory subunit (RI beta) is essential. Mice carrying a null mutation in the gene encoding RI beta were established by use of gene targeting in embryonic stem cells. Hippocampal slices from mutant mice show a severe deficit in LTD and depotentiation at the Schaffer collateral-CA1 synapse. This defect is also evident at the lateral perforant path-dentate granule cell synapse in RI beta mutant mice. Despite a compensatory increase in the related RI alpha protein and a lack of detectable changes in total PKA activity, the hippocampal function in these mice is not rescued, suggesting a unique role for RI beta. Since the late phase of CA1 LTP also requires PKA but is normal in RI beta mutant mice, our data further suggest that different forms of synaptic plasticity are likely to employ different combinations of regulatory and catalytic subunits.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Nanomedicine is a new branch of medicine, based on the potentiality and intrinsic properties of nanomaterials. Indeed, the nanomaterials ( i.e. the materials with nano and under micron size) can be suitable to different applications in biomedicine. The nanostructures can be used by taking advantage of their properties (for example superparamagnetic nanoparticles) or functionalized to deliver the drug in a specific target, thanks the ability to cross biological barriers. The size and the shape of 1D-nanostructures (nanotubes and nanowires) have an important role on the cell fate: their morphology plays a key role on the interaction between nanostructure and the biological system. For this reason the 1D nanostructure are interesting for their ability to mime the biological system. An implantable material or device must therefore integrate with the surrounding extracellular matrix (ECM), a complex network of proteins with structural and signaling properties. Innovative techniques allow the generation of complex surface patterns that can resemble the structure of the ECM, such as 1D nanostructures. NWs based on cubic silicon carbide (3C-SiC), either bare (3C-SiC NWs) or surrounded by an amorphous shell (3C-SiC/SiO2 core/shell NWs), and silicon oxycarbide nanowires (SiOxCy NWs) can meet the chemical, mechanical and electrical requirements for tissue engineering and have a strong potential to pave the way for the development of a novel generation of implantable nano-devices. Silicon oxycarbide shows promising physical and chemical properties as elastic modulus, bending strength and hardness, chemical durability superior to conventional silicate glasses in aggressive environments and high temperature stability up to 1300 °C. Moreover, it can easily be engineered through functionalization and decoration with macro-molecules and nanoparticles. Silicon carbide has been extensively studied for applications in harsh conditions, as chemical environment, high electric field and high and low temperature, owing to its high hardness, high thermal conductivity, chemical inertness and high electron mobility. Also, its cubic polytype (3C) is highly biocompatible and hemocompatible, and some prototypes of biomedical applications and biomedical devices have been already realized starting from 3C-SiC thin films. Cubic SiC-based NWs can be used as a biomimetic biomaterial, providing a robust and novel biocompatible biological interface . We cultured in vitro A549 human lung adenocarcinoma epithelial cells and L929 murine fibroblast cells over core/shell SiC/SiO2, SiOxCy and bare 3C-SiC nanowire platforms, and analysed the cytotoxicity, by indirect and direct contact tests, the cell adhesion, and the cell proliferation. These studies showed that all the nanowires are biocompatible according to ISO 10993 standards. We evaluated the blood compatibility through the interaction of the nanowires with platelet rich plasma. The adhesion and activation of platelets on the nanowire bundles, assessed via SEM imaging and soluble P-selectin quantification, indicated that a higher platelet activation is induced by the core/shell structures compared to the bare ones. Further, platelet activation is higher with 3C-SiC/SiO2 NWs and SiOxCyNWs, which therefore appear suitable in view of possible tissue regeneration. On the contrary, bare 3C-SiC NWs show a lower platelet activation and are therefore promising in view of implantable bioelectronics devices, as cardiovascular implantable devices. The NWs properties are suitable to allow the design of a novel subretinal Micro Device (MD). This devices is based on Si NWs and PEDOT:PSS, though the well know principle of the hybrid ordered bulk heterojunction (OBHJ). The aim is to develop a device based on a well-established photovoltaic technology and to adapt this know-how to the prosthetic field. The hybrid OBHJ allows to form a radial p–n junction on a nanowire/organic structure. In addition, the nanowires increase the light absorption by means of light scattering effects: a nanowires based p-n junction increases the light absorption up to the 80%, as previously demonstrated, overcoming the Shockley-Queisser limit of 30 % of a bulk p-n junction. Another interesting employment of these NWs is to design of a SiC based epicardial-interacting patch based on teflon that include SiC nanowires. . Such contact patch can bridge the electric conduction across the cardiac infarct as nanowires can ‘sense’ the direction of the wavefront propagation on the survival cardiac tissue and transmit it to the downstream surivived regions without discontinuity. The SiC NWs are tested in terms of toxicology, biocompatibility and conductance among cardiomyocytes and myofibroblasts.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

The aging workforce is becoming the majority of the working population in the United States. Although the literature on the aging workforce is sizable, little exists on how public agencies use the older workers. This capstone project examines the challenges and opportunities related to the employment of older workers as seen through a case study of the Federal Emergency Management Agency (FEMA). Knowledge gained from a synthesis of the literature review with survey data collected and analyzed will enable HR professionals to better understand the demographic, economic, regulatory, and intellectual influences of the aging workforce. The results from the survey of FEMA employees suggest a basis to plan and implement successful hiring and retention policies related to the aging workforce.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Although cultural industries can benefit from social networks in many ways, few Spanish studies examine the extent to which firms within this economic sector actually use such networks. This study's objective is to investigate the role of online social networks in Spanish cultural firms. The study begins with a literature review on cultural industries and social networks. Then the study proceeds to a Delphi analysis that draws upon experts' opinions. Results reveal a predominance of utilitarian uses over expressive ones, as well as an overriding use of proactive motivations rather than reactive ones within the context of cultural firms' use of social networks. The study confirms the profitability of these networks and the transfer of influence or power from providers to the consumers of cultural goods and services.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Although Portugal does not have a significant radical right presence in its party system, in the last decades the country did witness the development of a neo-Nazi skinhead movement that expresses its white nationalist nature and goals through the musical genres of Rock Against Communism (RAC) and the related Oi!. Utilizing various historical sources and theoretical analysis, this study contextualizes the development of nationalist music in Portugal, both before and especially during the democratic period (1974-2015). It focuses on its protagonists, domestic and international networks, as well as on the few attempts to establish a common cause with radical right-wing political parties at the turn of the century and in present times.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Given the size of the financial markets on both sides of the Atlantic and the symmetry in the follow-up of the G-20 standards, Karel Lannoo argues in this Policy Brief that the Transatlantic Trade and Investment Partnership (TTIP) provides a good opportunity to put in place a more institutionalised framework. He finds that both blocs have reacted in similar ways to the financial crisis in strengthening their regulatory and supervisory frameworks and incorporating the G-20 recommendations into federal law. He also notes that consumer protection has been reinforced, certainly in the US, with the creation of the Consumer Financial Protection Bureau. And on the EU side, the Single Supervisory Mechanism (SSM) will radically change banking supervision. In his view, inclusion of financial services could also be an opportunity to strengthen prudential rules and consumer protection provisions on both sides. Rather than leading to a reduction of consumer protection, as had been feared in the post-crisis environment, it could lead to an examination, exchange and recognition of best practices in regulation and enforcement. Finally, he concludes that inclusion of financial services would make it part of the permanent regulatory dialogue that will be established as a result of a successful TTIP.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

This book is the result of one year of solid work among a multinational research team assembled from seven states (Poland, Czechia, Hungary, Slovakia, Ukraine, Belarus and Moldova). It aims at a detailed analysis of migration patterns and migration forecasts from Ukraine, Belarus and Moldova to the EU/V4. In particular, the nexus between EU visa policy and migration dynamics as well as the impact of economic, political and institutional factors on migration from Eastern Europe have been investigated. The importance of migration policy must be stressed here. Together with demand for the foreign labour force (labour market needs, level of wages, existing work opportunities) and migration networks (including ethnic links), migration policy has a powerful influence on the scale, directions and characteristics of human flows.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Strategic Knowledge: While entrepreneurship may occur as a natural result of personal drive, it occurs most often, most robustly and is most sustainable in an environment designed to encourage it. Potential entrepreneurs become active entrepreneurs when the conditions are most supportive of their commercial opportunities and their business thus helping channel the two key qualities they exhibit as individuals obsessed maniacs and clairvoyant oracles (Carayannis, GWU Lectures, 2000-2005) and (Carayannis et at, 2003a) towards the generation of sustainable wealth. So far, entrepreneurial scholars who turn into intellectual venture capitalists by founding knowledge-driven companies remain one of the least explored specie in the territory of entrepreneurship. GloCal: The increasing engagement of firms within global knowledge and production networks and their ability to source knowledge globally as well as locally (GloCally), for the development of innovation capacities will shape the future of UK's knowledge resources and its role in the global economy. Practices such as off-shoring R&D activities are widely adopted, creating challenging, and not very well understood, issues related to cross-country and inter-firm knowledge and technology flows. We seek to address the internationalisation and networking of research and innovation activities, including the roles and strategies of enterprises, universities, research centres, governments in a cross-country and inter-sectoral way, to assess the impact and the implications for sustaining and enhancing the competitiveness of UK firms and other British knowledge producers and users.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

The increasing engagement of firms within global knowledge and production networks and their ability to source knowledge globally as well as locally (GloCally), for the development of innovation capacities will shape the future of UK's knowledge resources and its role in the global economy. Practices such as off-shoring R&D activities are widely adopted, creating challenging, and not very well understood, issues related to cross-country and inter-firm knowledge and technology flows. We seek to address the internationalisation and networking of research and innovation activities, including the roles and strategies of enterprises, universities, research centres, governments in a cross-country and inter-sectoral way, to assess the impact and the implications for sustaining and enhancing the competitiveness of UK firms and other British knowledge producers and users.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

The research team reviewed numerous several multi- sectoral entities and identified nine GGNs that became the subject of our case studies. The research team conducted semi-structured interviews with executives and staff from each of these GNNs and prepared a profile, including a description of the unique evolution of the organization, goals and objectives, organizational structure and governance arrangements for each GGN. The following list provides an overview of the nine GGNs profiled: 1. Every Woman Every Child is an unprecedented global effort that mobilizes and amplifies action by governments, multilaterals, the private sector, research centers, academia and civil society to address life-threatening health challenges facing women and children globally. 2. HERproject catalyzes global partnerships and local Networks to improve female workers’ general and reproductive health in eight emerging economies. 3. R4 Rural Resilience Initiative is a cutting-edge, strategic, large-scale partnership between the public and private sectors to innovate and develop better tools to help the world’s most vulnerable people build resilient livelihoods. 4. Extractive Industry Transparency Initiative is a coalition of governments, companies, civil society groups, investors and international organizations that aims to improve transparency and accountability in the extractives sector. 5. Global Network for Neglected Tropical Diseases works with international partners at the highest level of government, business and society to break down the logistical and financial barriers to delivering existing treatments for the seven most common neglected tropical diseases. 6. Global Alliance for Improved Nutrition is an alliance that supports public-private partnerships to increase access to the missing nutrients in diets necessary for people, communities and economies to be stronger and healthier. 7. Inter-Agency Network For Education in Emergencies is a global Network of individuals and representatives from NGOs, United Nations and donor agencies, governments, academic institutions, schools and affected populations working to ensure all persons have the right to a quality and safe education in emergencies and post- crisis recovery. 8. mHealth Alliance works with diverse partners to advance mobile-based or mobile-enhanced solutions that deliver health through research, advocacy, support for the development of interoperable solutions and sustainable deployment models. 9. The Rainforest Alliance is a global non-profit that focuses on environmental conservation and sustainable development and works through collaborative partnerships with various stakeholders.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Globalization is both an integrative and deconstructive process. Globalization integrates states and non-state actors into transnational and global networks (Keohane & Nye, 2000, p. 105). These networks are based on multiple channels of interdependence that include trade, politics, security, environment, and socio-cultural ties (pp. 106-107). Due to advances in telecommunications technology, the expansion of globalization “shrinks” the distance between peoples (p. 105). On the other hand, globalization can also break up the existing political and social order (Mathews, 1997, p. 50). Globalization disperses power and information flows, thus enabling local and transnational identity movements to challenge states (pp. 51-52). This can be exemplified by separatist movements that seek to break away from central authorities.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Vertebrate limbs develop in a temporal proximodistal sequence, with proximal regions specified and generated earlier than distal ones. Whereas considerable information is available on the mechanisms promoting limb growth, those involved in determining the proximodistal identity of limb parts remain largely unknown. We show here that retinoic acid (RA) is an upstream activator of the proximal determinant genes Meis1 and Meis2. RA promotes proximalization of limb cells and endogenous RA signaling is required to maintain the proximal Meis domain in the limb. RA synthesis and signaling range, which initially span the entire lateral plate mesoderm, become restricted to proximal limb domains by the apical ectodermal ridge (AER) activity following limb initiation. We identify fibroblast growth factor (FGF) as the main molecule responsible for this AER activity and propose a model integrating the role of FGF in limb cell proliferation, with a specific function in promoting distalization through inhibition of RA production and signaling.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Jan. 1979.