883 resultados para regulatory objects
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addplot adds twoway plot objects to an existing twoway graph. This is useful if you want to add additional objects such as titles or extra data points to a twoway graph after it has been created. Most of what addplot can do, can also be done by rerunning the original graph command including additional options or plot statements. addplot, however, might be useful if you have to modify a graph for which you cannot rerun the original command, for example, because you only have the graph file but not the data that were used to create the graph. Furthermore, addplot can do certain things that would be difficult to achieve in a single graph command (e.g. customizing individual subgraphs within a by-graph). addplot also provides a substitute for some of the functionality of the graph editor.
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The liberalization process of the Swiss telecommunications sector follows a logic of ‘autonomous adaptation’ to the regulations of the European Union (EU). Switzerland, which is not a Member State of the EU, voluntarily adapts to the European policy without being for- mally required to do so (Sciarini et al., 2004). This process went hand in hand with the partial privatization of the legal statute and assets of the former monopolist and with the re-regulation of the liberalized telecommunications sector.
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Recent research suggests that great apes are less vulnerable to cohesion violations than human infants are. In contrast to human infants, apes successfully track nonsolid substances or split solid objects through occlusion (Cacchione & Call, 2010a; Cacchione, Hrubesch, & Call, 2012, 2013). The present study aims to investigate whether the lower vulnerability of great apes to cohesion violations also manifests when they are tracking collections. While even very young human infants appreciate the continuous existence of solid bound objects, they fail to show similar intuitions when tracking collections of objects (Chiang & Wynn, 2000). In a manual search task inspired by recent infant research, we tested whether humans’ closest relatives, the great apes, showed a similar contrast in their reasoning about single solid objects and objects within collections. The results suggest that, in contrast to human infants, great apes appreciate the continuous existence of objects within collections and successfully track them through occlusion. This confirms the view that great apes are generally less vulnerable to cohesion violations than human infants.
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Previous research has demonstrated that adults are successful at visually tracking rigidly moving items, but experience great difficulties when tracking substance-like ‘‘pouring’’ items. Using a comparative approach, we investigated whether the presence/absence of the grammatical count–mass distinction influences adults and children’s ability to attentively track objects versus substances. More specifically, we aimed to explore whether the higher success at tracking rigid over substance-like items appears universally or whether speakers of classifier languages (like Japanese, not marking the object–substance distinction) are advantaged at tracking substances as compared to speakers of non-classifier languages (like Swiss German, marking the object–substance distinction). Our results supported the idea that language has no effect on low-level cognitive processes such as the attentive visual processing of objects and substances. We concluded arguing that the tendency to prioritize objects is universal and independent of specific characteristics of the language spoken.
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Spinal Muscular Atrophy (SMA) is caused by deletions or mutations in the Survival Motor Neuron 1 (SMN1) gene. The second gene copy, SMN2, produces some, but not enough, functional SMN protein. SMN is essential to assemble small nuclear ribonucleoproteins (snRNPs) that form the spliceosome. However, it is not clear whether SMA is caused by defects in this function that could lead to splicing changes in all tissues, or by the impairment of an additional, less well characterized, but motoneuron-specific SMN function. We addressed the first possibility by exon junction microarray analysis of motoneurons (MNs) isolated by laser capture microdissection from a severe SMA mouse model. This revealed changes in multiple U2-dependent splicing events. Moreover, splicing appeared to be more strongly affected in MNs than in other cells. By testing mutiple genes in a model of progressive SMN depletion in NB2a neuroblastoma cells, we obtained evidence that U2-dependent splicing changes occur earlier than U12-dependent ones. As several of these changes affect genes coding for splicing regulators, this may acerbate the splicing response induced by low SMN levels and induce secondary waves of splicing alterations.
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The color red has been considered to indicate threat in achievement contexts. Recent studies have used brief confrontations with red — either as the color or as the word red — to prime for implicit threat, and have found a related impairment of cognitive performance. In another line of research, it has been shown that initial self-regulatory efforts cause diminished investment of self-regulatory resources afterwards, leading to a relative shift from a controlled to an automatic mode of information processing. We assume that activation of implicit threat via the color or the word red impairs cognitive performance more strongly during automatic compared to controlled processing of information. To test this hypothesis, we manipulated undergraduates’ (n = 78) momentary processing mode (automatic vs. controlled) by an initial task that required either high or low self-regulatory effort. Afterwards, participants were briefly confronted with red or gray stimuli and were then asked to complete a standardized intelligence measure. As expected, confrontation with red, as opposed to gray, impaired intellectual performance when participants were in an automatic processing mode. In contrast, no color effect emerged when participants were in a relatively controlled processing mode. In a second study, we replicated this finding in a sample of secondary school students (n = 130), using the black-printed word red or gray to experimentally manipulate implicit threat. Among others, the present findings may help to explain occasional difficulties in replicating findings of priming research.
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BACKGROUND/AIMS Several countries are working to adapt clinical trial regulations to align the approval process to the level of risk for trial participants. The optimal framework to categorize clinical trials according to risk remains unclear, however. Switzerland is the first European country to adopt a risk-based categorization procedure in January 2014. We assessed how accurately and consistently clinical trials are categorized using two different approaches: an approach using criteria set forth in the new law (concept) or an intuitive approach (ad hoc). METHODS This was a randomized controlled trial with a method-comparison study nested in each arm. We used clinical trial protocols from eight Swiss ethics committees approved between 2010 and 2011. Protocols were randomly assigned to be categorized in one of three risk categories using the concept or the ad hoc approach. Each protocol was independently categorized by the trial's sponsor, a group of experts and the approving ethics committee. The primary outcome was the difference in categorization agreement between the expert group and sponsors across arms. Linear weighted kappa was used to quantify agreements, with the difference between kappas being the primary effect measure. RESULTS We included 142 of 231 protocols in the final analysis (concept = 78; ad hoc = 64). Raw agreement between the expert group and sponsors was 0.74 in the concept and 0.78 in the ad hoc arm. Chance-corrected agreement was higher in the ad hoc (kappa: 0.34 (95% confidence interval = 0.10-0.58)) than in the concept arm (0.27 (0.06-0.50)), but the difference was not significant (p = 0.67). LIMITATIONS The main limitation was the large number of protocols excluded from the analysis mostly because they did not fit with the clinical trial definition of the new law. CONCLUSION A structured risk categorization approach was not better than an ad hoc approach. Laws introducing risk-based approaches should provide guidelines, examples and templates to ensure correct application.
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Regulatory T cells (T(reg)) have been shown to restrict vaccine-induced T cell responses in different experimental models. In these studies CD4(+)CD25(+) T(reg) were depleted using monoclonal antibodies against CD25, which might also interfere with CD25 on non-regulatory T cell populations and would have no effect on Foxp3(+)CD25(-) T(reg). To obtain more insights in the specific function of T(reg) during vaccination we used mice that are transgenic for a bacterial artificial chromosome expressing a diphtheria toxin (DT) receptor-eGFP fusion protein under the control of the foxp3 gene locus (depletion of regulatory T cell mice; DEREG). As an experimental vaccine-carrier recombinant Bordetella adenylate cyclase toxoid fused with a MHC-class I-restricted epitope of the circumsporozoite protein (ACT-CSP) of Plasmodium berghei (Pb) was used. ACT-CSP was shown by us previously to introduce the CD8+ epitope of Pb-CSP into the MHC class I presentation pathway of professional antigen-presenting cells (APC). Using this system we demonstrate here that the number of CSP-specific T cells increases when T(reg) are depleted during prime but also during boost immunization. Importantly, despite this increase of T effector cells no difference in the number of antigen-specific memory cells was observed.
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Immunomodulation is a common feature of chronic helminth infections and mainly attributed to the secretion of bioactive molecules, which target and modify host immune cells. In this study, we show that the helminth immunomodulator AvCystatin, a cysteine protease inhibitor, induces a novel regulatory macrophage (Mreg; AvCystatin-Mreg), which is sufficient to mitigate major parameters of allergic airway inflammation and colitis in mice. A single adoptive transfer of AvCystatin-Mreg before allergen challenge suppressed allergen-specific IgE levels, the influx of eosinophils into the airways, local and systemic Th2 cytokine levels, and mucus production in lung bronchioles of mice, whereas increasing local and systemic IL-10 production by CD4(+) T cells. Moreover, a single administration of AvCystatin-Mreg during experimentally induced colitis strikingly reduced intestinal pathology. Phenotyping of AvCystatin-Mreg revealed increased expression of a distinct group of genes including LIGHT, sphingosine kinase 1, CCL1, arginase-1, and costimulatory molecules, CD16/32, ICAM-1, as well as PD-L1 and PD-L2. In cocultures with dendritic cells and CD4(+) T cells, AvCystatin-Mreg strongly induced the production of IL-10 in a cell-contact-independent manner. Collectively, our data identify a specific suppressive macrophage population induced by a single parasite immunomodulator, which protects against mucosal inflammation.