Pastagens em sistemas silvipastoris.

bitstream/item/78735/1/am.pd

Shp-2 Is Dispensable for Establishing T Cell Exhaustion and for PD-1 Signaling In Vivo.

In chronic infection and cancer, T cells acquire a dysfunctional state characterized by the expression of inhibitory receptors. In vitro studies implicated the phosphatase Shp-2 downstream of these receptors, including PD-1. However, whether Shp-2 is responsible in vivo for such dysfunctional responses remains elusive. To address this, we generated T cell-specific Shp-2-deficient mice. These mice did not show differences in controlling chronic viral infections. In this context, Shp-2-deleted CD8 <sup>+</sup> T lymphocytes expanded moderately better but were less polyfunctional than control cells. Mice with Shp-2-deficient T cells also showed no significant improvement in controlling immunogenic tumors and responded similarly to controls to α-PD-1 treatment. We therefore showed that Shp-2 is dispensable in T cells for globally establishing exhaustion and for PD-1 signaling in vivo. These results reveal the existence of redundant mechanisms downstream of inhibitory receptors and represent the foundation for defining these relevant molecular events

NLRC5 shields T lymphocytes from NK-cell-mediated elimination under inflammatory conditions.

NLRC5 is a transcriptional regulator of MHC class I (MHCI), which maintains high MHCI expression particularly in T cells. Recent evidence highlights an important NK-T-cell crosstalk, raising the question on whether NLRC5 specifically modulates this interaction. Here we show that NK cells from Nlrc5-deficient mice exhibit moderate alterations in inhibitory receptor expression and responsiveness. Interestingly, NLRC5 expression in T cells is required to protect them from NK-cell-mediated elimination upon inflammation. Using T-cell-specific Nlrc5-deficient mice, we show that NK cells surprisingly break tolerance even towards 'self' Nlrc5-deficient T cells under inflammatory conditions. Furthermore, during chronic LCMV infection, the total CD8(+) T-cell population is severely decreased in these mice, a phenotype reverted by NK-cell depletion. These findings strongly suggest that endogenous T cells with low MHCI expression become NK-cell targets, having thus important implications for T-cell responses in naturally or therapeutically induced inflammatory conditions

"Clone Wars": Episode II - The Next Generation: The Copyright Implications relating to 3D Printing and Computer-Aided Design (CAD) Files

The future market potential of 3D printing will rest on the dissemination of Computer Aided Design (CAD) files. Without clear instructions from a CAD file, a 3D printer will not function. In fact, “a 3D printer without an attached computer and a good design file is as useless as an iPod without music”. The importance of CAD-based design files, therefore, cannot be underestimated. Drawing on UK and EU copyright laws and their application to 3D printing and CAD files, this paper will, first, question whether CAD files can be protected by copyright law before considering the copyright implications thrown up by the modification of CAD files as a result of scanning and the use of online tools. Highlighting some of the challenges for rights holders and users existent in the present law the paper advocates new business models over a premature call for stringent intellectual property laws before concluding with some recommendations for the future

Legion Of Victory : Military March

https://digitalcommons.library.umaine.edu/mmb-ps/1977/thumbnail.jp

Productivity in the Financial Services Sector

On 11-12 November 2008, SUERF and Banque Centrale du Luxembourg organized a conference on Productivity in the Financial Services Sector on the occasion of the tenth anniversary of the Banque Centrale du Luxembourg. The conference addressed three main themes: first, stylized facts on banks' productivity developments and the measurement of productivity; second, sources of productivity in banking; and third, the possible repercussions and consequences of the financial crisis on financial institutions' future productivity development. These three topics are taken up from various angles in the papers contained in the present volume, which represent a selection of the papers presented at the conference. Coming back to the three themes mentioned at the outset, the conference yielded some interesting results and raised many issues for further research. As regards theme 1, the papers presented overall suggest that financial integration in Europe has brought some, albeit according to some studies limited, convergence of bank efficiency among countries but on average productivity improvement has been weak. Various interesting attempts to capture banks' output were presented, but the various performance and efficiency measures yield different results. Linked to the difficulty of measuring the value of financial institutions' services, it remains far from clear what the "fair value" of a bank should be. This problem may also in part explain the very sharp ups and downs of bank stocks recently. Concerning theme 2, sources of productivity in financial services, several potentially important factors were mentioned: investments in ICT, investments in human resources, the quality of managers and remuneration policy, process effectiveness, mergers and acquisitions and economies of scale, privatizations, risk diversification versus regional and/or product specialisation, and risk-taking. Yet, no unambiguous picture emerged on which of these factors are most important. Regarding theme 3, the financial crisis may have far-reaching implications on our view of financial innovation and efficiency, on the way how to measure productivity appropriately as well as on the future development of financial institutions' productivity. First, the question arises whether the quest for productivity and profitability may under certain circumstances compromise the quality of banks' services (such as, e.g. the care invested into credit assessments and risk monitoring) and as a consequence put the stability of banks and the financial system at risk. As the recent crisis and its underlying causes suggest, there may at times be trade-offs between innovation and financial stability. If financial supervision and risk management do not keep up with financial innovation, the social value of such innovation may not be positive at all times. Financial innovation may also have blurred signals on banks? financial and risk positions, and thus have misled bank shareholders, clients and supervisors in their assessment of banks? business models and conduct of business. Second, the crisis might also affect banks? future performance: Increased government interference and stricter surveillance and capital adequacy rules might curb banks? profitability and efficiency, as measured by traditional performance indicators. However, the conventional measures of performance as presented and discussed at the conference - however varied and multifaceted they may be in trying to measure efficieny (i.e. the avoidance of unnecessary costs in the production process) and competition (the avoidance of inappropriately high profits) - basically seem to have a short-term focus. A longer-term perspective would also consider e.g. the financial institutions? solvency and the safety of deposits, as well as their stability and continued performance in periods of severe stress. Such extensions to the concept of ?performance? should certainly be explored more deeply in the light of the current crisis. In particular, bank efficiency should be considered by supervisors with a view to its influence on risk behaviour. The current debate on regulatory reform in response to the crisis also addresses the need for closer international coordination among supervisory regimes. Tighter regulatory coordination may, on the one hand, close regulatory loopholes, thus curbing banks? profit opportunities, at least in the short run. On the other hand, international harmonization of regulatory rules may generate considerable cost savings for internationally active financial institutions. By contributing to financial market integration it could also stiffen competition and in this way improve efficiency. A related issue is how the crisis will affect the size of banks in the future. Will consolidation in the sector ultimately result in fewer and bigger banks? Or will governments? and regulators? bad experience with institutions which are ?too big to fail? create pressure towards more and smaller institutions? The outcome of this may in turn have possible implications for competition and thus, ultimately, on future innovation, efficiency and productivity developments. Finally, in the coming months and years the issue of exit strategies from state intervention will have to be solved. In particular, how long should partial or full nationalisations of troubled banks last? Historical experiences vary, ranging from rather rapid re-privatisations in some cases to continued strong government influence decades. How can banks? increased reliance on government assistance be abolished and market-based incentives for productivity-enhancing strategies be restored, given the massive moral hazard created by the ? unavoidable ? government bail outs of banks? In conclusion, the conference demonstrated that various disciplines ? business administration, management, organisation and economics ? as well as different professional perspectives ? those of academia, practitioners and of policy makers ? need to be combined to do full justice to the complexity of the subject at hand. SUERF?s triple constituency and multiple-discipline approach again proved particularly suitable to approaching such a far-reaching topic

Intellectual Property, Open Science and Research Biobanks

In biomedical research and translational medicine, the ancient war between exclusivity (private control over information) and access to information is proposing again on a new battlefield: research biobanks. The latter are becoming increasingly important (one of the ten ideas changing the world, according to Time magazine) since they allow to collect, store and distribute in a secure and professional way a critical mass of human biological samples for research purposes. Tissues and related data are fundamental for the development of the biomedical research and the emerging field of translational medicine: they represent the “raw material” for every kind of biomedical study. For this reason, it is crucial to understand the boundaries of Intellectual Property (IP) in this prickly context. In fact, both data sharing and collaborative research have become an imperative in contemporary open science, whose development depends inextricably on: the opportunities to access and use data, the possibility of sharing practices between communities, the cross-checking of information and results and, chiefly, interactions with experts in different fields of knowledge. Data sharing allows both to spread the costs of analytical results that researchers cannot achieve working individually and, if properly managed, to avoid the duplication of research. These advantages are crucial: access to a common pool of pre-competitive data and the possibility to endorse follow-on research projects are fundamental for the progress of biomedicine. This is why the "open movement" is also spreading in the biobank's field. After an overview of the complex interactions among the different stakeholders involved in the process of information and data production, as well as of the main obstacles to the promotion of data sharing (i.e., the appropriability of biological samples and information, the privacy of participants, the lack of interoperability), we will firstly clarify some blurring in language, in particular concerning concepts often mixed up, such as “open source” and “open access”. The aim is to understand whether and to what extent we can apply these concepts to the biomedical field. Afterwards, adopting a comparative perspective, we will analyze the main features of the open models – in particular, the Open Research Data model – which have been proposed in literature for the promotion of data sharing in the field of research biobanks. After such an analysis, we will suggest some recommendations in order to rebalance the clash between exclusivity - the paradigm characterizing the evolution of intellectual property over the last three centuries - and the actual needs for access to knowledge. We argue that the key factor in this balance may come from the right interaction between IP, social norms and contracts. In particular, we need to combine the incentives and the reward mechanisms characterizing scientific communities with data sharing imperative

Legal Issues about Metadata: Data Privacy vs Information Security

International audienceFor the purposes of our work we use the concept of metadata to implement enterprise digital right management mechanisms in an intelligent document environment. Such metadata allow us to firstly define contextual security rules and secondly to ensure the information traceability. However, its use may have legal implications, especially with regard to metadata that can be stored (see personal data, privacy), how it should be stored (see probative value in case of litigation, digital forensics) or computer processing in which it may be involved. Another topical issue is the storage and the processing of data using a service provider: the cloud. We must ensure, however, that this solution does not lead to a loss of information controllability for the company. This article aims to position our work with respect to these legal issues

The Nlrp3 inflammasome regulates acute graft-versus-host disease

The success of allogeneic hematopoietic cell transplantation is limited by acute graft-versus-host disease (GvHD), a severe complication accompanied by high mortality rates. Yet, the molecular mechanisms initiating this disease remain poorly defined. In this study, we show that, after conditioning therapy, intestinal commensal bacteria and the damage-associated molecular pattern uric acid contribute to Nlrp3 inflammasome-mediated IL-1β production and that gastrointestinal decontamination and uric acid depletion reduced GvHD severity. Early blockade of IL-1β or genetic deficiency of the IL-1 receptor in dendritic cells (DCs) and T cells improved survival. The Nlrp3 inflammasome components Nlrp3 and Asc, which are required for pro-IL-1β cleavage, were critical for the full manifestation of GvHD. In transplanted mice, IL-1β originated from multiple intestinal cell compartments and exerted its effects on DCs and T cells, the latter being preferentially skewed toward Th17. Compatible with these mouse data, increased levels of active caspase-1 and IL-1β were found in circulating leukocytes and intestinal GvHD lesions of patients. Thus, the identification of a crucial role for the Nlrp3 inflammasome sheds new light on the pathogenesis of GvHD and opens a potential new avenue for the targeted therapy of this severe complication