893 resultados para sickness absence
Resumo:
The decision of the U.S. Supreme Court in 1991 in Feist Publications, Inc. v. Rural Tel. Service Co. affirmed originality as a constitutional requirement for copyright. Originality has a specific sense and is constituted by a minimal degree of creativity and independent creation. The not original is the more developed concept within the decision. It includes the absence of a minimal degree of creativity as a major constituent. Different levels of absence of creativity also are distinguished, from the extreme absence of creativity to insufficient creativity. There is a gestalt effect of analogy between the delineation of the not original and the concept of computability. More specific correlations can be found within the extreme absence of creativity. "[S]o mechanical" in the decision can be correlated with an automatic mechanical procedure and clauses with a historical resonance with understandings of computability as what would naturally be regarded as computable. The routine within the extreme absence of creativity can be regarded as the product of a computational process. The concern of this article is with rigorously establishing an understanding of the extreme absence of creativity, primarily through the correlations with aspects of computability. The understanding established is consistent with the other elements of the not original. It also revealed as testable under real-world conditions. The possibilities for understanding insufficient creativity, a minimal degree of creativity, and originality, from the understanding developed of the extreme absence of creativity, are indicated.
Resumo:
Suppressors of cytokine signaling (SOCS) proteins are a family of proteins that are able to act in a classic negative feedback loop to regulate cytokine signal transduction. The regulation of the immune response by SOCS proteins may contribute to persistent infection or even a fatal outcome. In this study, we have investigated the induction of SOCS 1-3 after peripheral infection with West Nile virus (WNV) or tick-borne encephalitis virus (TBEV) in the murine model. We have shown that the cytokine response after infection of mice with WNV or TBEV induces an upregulation in the brain of mRNA transcripts for SOCS 1 and SOCS 3, but not SOCS 2. We hypothesize that SOCS proteins may play a role in limiting cytokine responses in the brain as a neuroprotective mechanism, which may actually enhance the ability of neuroinvasive viruses such as WNV and TBEV to spread and cause disease.
Resumo:
Mark Dornford-May’s widely-acclaimed adaptation of the medieval English Chester “mystery” plays, The Mysteries-Yiimimangaliso, reveal the extent to which theatrical translation, if it is to be intelligible to audiences, risks trading in cultural stereotypes belonging to both source and target cultures. As a South African production of a medieval English theatrical tradition which subsequently plays to an English audience, The Mysteries-Yiimimangaliso enacts a number of disorientating forms of cultural translation. Rather than facilitating the transmission of challenging literary and dramatic traditions, The Mysteries-Yiimimangaliso reveals the extent to which translation, as a politically correct - and thus politically anaemic - act, can become an end in itself in a globalised Anglophone theatrical culture.
Resumo:
The transformation of vaterite into calcite may be performed by heating in the presence and the absence of oxygen. Vaterite remains thermally stable until a calcination temperature of 450°C. It transforms progressively to calcite up to 500°C giving two exothermic peaks: 1) at 481°C due to the transformation of vaterite surface which is in contact with a small amount of calcite phase already formed with the time on the solid surface from the humidity atmosphere; 2) at 491°C due to the transformation of pure vaterite bulk. The calcite phase remains stable until 700°C. Above this temperature the formation of CaO is observed.
Resumo:
Intravenous (i.v.) administration of autoantigen effectively induces Ag-specific tolerance against experimental autoimmune encephalomyelitis (EAE). We and others have shown enhanced EAE severity in mice lacking IL-12 or its receptor, strongly suggesting an immunoregulatory effect of IL-12 signaling. To examine the role of IL-12 responsiveness in autoantigen-induced tolerance in EAE, we administered autoantigen i.v. in two distinct treatment regimes to wildtype and IL-12Rβ2(-/-) mice, immunized to develop EAE. Administration at the induction phase suppressed EAE in wildtype and IL-12Rβ2(-/-) mice however the effect was somewhat less potent in the absence of IL-12Rβ2. Expression of pro-inflammatory cytokines such as IFN-γ, IL-17 and IL-2, was inhibited in wild-type tolerized mice but less so in IL-12Rβ2(-/-) mice. I.v. antigen was also effective in suppressing disease in both genotypes when given during the clinical phase of disease with similar CNS inflammation, demyelination and peripheral inflammatory cytokine profiles observed in both genotypes. There was however a mild impact of a lack of IL-12 signaling on Treg induction during tolerance induction compared to WT mice in this treatment regime. These findings show that the enhanced severity of EAE that occurs in the absence of IL-12 signaling can be effectively overcome by i.v. autoantigen, indicating that this therapeutic effect is not primarily mediated by IL-12 and that i.v. tolerance could be a powerful approach in suppressing severe and aggressive MS.
Resumo:
During the past century, several epidemics of human African trypanosomiasis, a deadly disease caused by the protist Trypanosoma brucei, have afflicted sub-Saharan Africa. Over 10 000 new victims are reported each year, with hundreds of thousands more at risk. As current drug treatments are either highly toxic or ineffective, novel trypanocides are urgently needed. The T. brucei galactose synthesis pathway is one potential therapeutic target. Although galactose is essential for T. brucei survival, the parasite lacks the transporters required to intake galactose from the environment. UDP-galactose 4'-epimerase (TbGalE) is responsible for the epimerization of UDP-glucose to UDP-galactose and is therefore of great interest to medicinal chemists. Using molecular dynamics simulations, we investigate the atomistic motions of TbGalE in both the apo and holo states. The sampled conformations and protein dynamics depend not only on the presence of a UDP-sugar ligand, but also on the chirality of the UDP-sugar C4 atom. This dependence provides important insights into TbGalE function and may help guide future computer-aided drug discovery efforts targeting this protein.