A probability-conserving cross-section biasing mechanism for variance reduction in Monte Carlo particle transport calculations

In Monte Carlo particle transport codes, it is often important to adjust reaction cross sections to reduce the variance of calculations of relatively rare events, in a technique known as non-analogous Monte Carlo. We present the theory and sample code for a Geant4 process which allows the cross section of a G4VDiscreteProcess to be scaled, while adjusting track weights so as to mitigate the effects of altered primary beam depletion induced by the cross section change. This makes it possible to increase the cross section of nuclear reactions by factors exceeding 10^4 (in appropriate cases), without distorting the results of energy deposition calculations or coincidence rates. The procedure is also valid for bias factors less than unity, which is useful, for example, in problems that involve computation of particle penetration deep into a target, such as occurs in atmospheric showers or in shielding

Mislocalization of Visual Stimuli: Independent Effects of Static and Dynamic Attention

Shifts of visual attention cause systematic distortions of the perceived locations of visual objects around the focus of attention. In the attention repulsion effect, the perceived location of a visual target is shifted away from an attention-attracting cue when the cue is presented before the target. Recently it has been found that, if the visual cue is presented after the target, the perceived location of the target shifts toward the location of the following cue. One unanswered question is whether a single mechanism underlies both attentional repulsion and attraction effects. We presented participants with two disks at diagonal locations as visual cues and two vertical lines as targets. Participants were asked to perform a forced-choice task to judge targets' positions. The present study examined whether the magnitude of the repulsion effect and the attraction effect would differ (Experiment 1), whether the two effects would interact (Experiment 2), and whether the location or the dynamic shift of attentional focus would determine the distortions effects (Experiment 3). The results showed that the effect size of the attraction effect was slightly larger than the repulsion effect and the preceding and following cues have independent influences on the perceived positions. The repulsion effect was caused by the location of attnetion and the attraction effect was due to the dynamic shift of attentional focus, suggesting that the underlying mechanisms for the retrospective attraction effect might be different from those for the repulsion effect

The expression and activity of β-catenin in the thalamus and its projections to the cerebral cortex in the mouse embryo

<p>Abstract</p> <p>Background</p> <p>The mammalian thalamus relays sensory information from the periphery to the cerebral cortex for cognitive processing via the thalamocortical tract. The thalamocortical tract forms during embryonic development controlled by mechanisms that are not fully understood. β-catenin is a nuclear and cytosolic protein that transduces signals from secreted signaling molecules to regulate both cell motility via the cytoskeleton and gene expression in the nucleus. In this study we tested whether β-catenin is likely to play a role in thalamocortical connectivity by examining its expression and activity in developing thalamic neurons and their axons.</p> <p>Results</p> <p>At embryonic day (E)15.5, the time when thalamocortical axonal projections are forming, we found that the thalamus is a site of particularly high β-catenin mRNA and protein expression. As well as being expressed at high levels in thalamic cell bodies, β-catenin protein is enriched in the axons and growth cones of thalamic axons and its growth cone concentration is sensitive to Netrin-1. Using mice carrying the β-catenin reporter <it>BAT-gal </it>we find high levels of reporter activity in the thalamus. Further, Netrin-1 induces <it>BAT-gal </it>reporter expression and upregulates levels of endogenous transcripts encoding β-actin and L1 proteins in cultured thalamic cells. We found that β-catenin mRNA is enriched in thalamic axons and its 3'UTR is phylogenetically conserved and is able to direct heterologous mRNAs along the thalamic axon, where they can be translated.</p> <p>Conclusion</p> <p>We provide evidence that β-catenin protein is likely to be an important player in thalamocortcial development. It is abundant both in the nucleus and in the growth cones of post-mitotic thalamic cells during the development of thalamocortical connectivity and β-catenin mRNA is targeted to thalamic axons and growth cones where it could potentially be translated. β-catenin is involved in transducing the Netrin-1 signal to thalamic cells suggesting a mechanism by which Netrin-1 guides thalamocortical development.</p

How Phytophthora cinnamomi became associated with the death of Eucalyptus marginata – the early investigations into jarrah dieback

The name jarrah dieback was used in the 1940s to describe a serious economic problem in the jarrah forest in the south west of Western Australia. This was the sudden death of groups of jarrah (Eucalyptus marginata) trees that occurred on previously logged sites that had a tendency to become waterlogged in winter. Although the cause was not determined at the time, from symptoms recorded in early investigations the most likely explanation is that the trees died as the result of waterlogging damage. In the 1960s it was shown that many of these sites were infested by the introduced oomycete Phytophthora cinnamomi and tree deaths, together with the deaths of many mid- and under-storey plants, were attributed to this pathogen. A chronology of the research, based on contemporary unpublished documents, shows that in 1968 the conclusion that P. cinnamomi caused jarrah deaths was not supported by the available evidence, because the work did not satisfy the first and fourth of Koch’s postulates. The evidence that P. cinnamomi killed many mid- and under-storey plants was much stronger. There are two problems that have been confused: the death of groups of jarrah trees (jarrah dieback) that is caused by waterlogging and the death of many mid- and under-storey plants (Phytophthora dieback) caused by P. cinnamomi infection

Influence of HLA-DRB1 and HLA-DQB1 Alleles on IgG Antibody Response to the P. vivax MSP-1, MSP-3α and MSP-9 in Individuals from Brazilian Endemic Area

Background: the antibody response generated during malaria infections is of particular interest, since the production of specific IgG antibodies is required for acquisition of clinical immunity. However, variations in antibody responses could result from genetic polymorphism of the HLA class II genes. Given the increasing focus on the development of subunit vaccines, studies of the influence of class II alleles on the immune response in ethnically diverse populations is important, prior to the implementation of vaccine trials.Methods and Findings: in this study, we evaluated the influence of HLA-DRB1* and -DQB1* allelic groups on the naturally acquired humoral response from Brazilian Amazon individuals (n = 276) against P. vivax Merozoite Surface Protein-1 (MSP-1), MSP-3 alpha and MSP-9 recombinant proteins. Our results provide information concerning these three P. vivax antigens, relevant for their role as immunogenic surface proteins and vaccine candidates. Firstly, the studied population was heterogeneous presenting 13 HLA-DRB1* and 5 DQB1* allelic groups with a higher frequency of HLA-DRB1*04 and HLA-DQB1*03. the proteins studied were broadly immunogenic in a naturally exposed population with high frequency of IgG antibodies against PvMSP1-19 (86.7%), PvMSP-3 (77%) and PvMSP-9 (76%). Moreover, HLA-DRB1*04 and HLA-DQB1*03 alleles were associated with a higher frequency of IgG immune responses against five out of nine antigens tested, while HLA-DRB1* 01 was associated with a high frequency of non-responders to repetitive regions of PvMSP-9, and the DRB1*16 allelic group with the low frequency of responders to PvMSP3 full length recombinant protein.Conclusions: HLA-DRB1*04 alleles were associated with high frequency of antibody responses to five out of nine recombinant proteins tested in Rondonia State, Brazil. These features could increase the success rate of future clinical trials based on these vaccine candidates.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Yerkes National Primate Research Center BaseNational Center for Research Resources of the National Institutes of HealthNIHCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Inst Oswaldo Cruz, Lab Immunoparasitol, BR-20001 Rio de Janeiro, BrazilOswaldo Cruz Fdn Fiocruz, Ctr Technol Dev Hlth CDTS, Rio de Janeiro, BrazilInst Oswaldo Cruz, Lab Simulideos & Oncocercose, BR-20001 Rio de Janeiro, BrazilEmory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USAUniv Estado Rio de Janeiro, Histocompatibil & Cryopreservat Lab, Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol CTCMol, Escola Paulista Med, São Paulo, BrazilEmory Univ, Sch Med, Div Infect Dis, Atlanta, GA USACDC Natl Ctr Infect Dis, Div Parasit Dis, Atlanta, GA USAUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol CTCMol, Escola Paulista Med, São Paulo, BrazilFAPESP: 2009/15132-4Yerkes National Primate Research Center Base: RR00165NIH: RO1 AI0555994Web of Scienc

Creative aspiration and the betrayal of promise? The experience of new creative workers

The promise of ‘doing what you love’ continues to attract new aspirants to creative work, yet most creative industries are so characterised by low investment, shifting foci and ongoing technological innovation that all promises must be unreliable. Some would-be creative workers negotiate their own pathways from the outset, ‘following their dream’ as they attempt to convert personal enthusiasms and amateur activities into income-earning careers. Others look to the proliferation of available training and education options, including higher education courses, as possible pathways into creative work. This chapter reviews recent research from the USA, Australia and the UK on the effectiveness – or otherwise – of higher education as preparation for a creative career. The chapter discusses the obstacles that many creative workers, including graduates, encounter on their creative pathways, for instance, as a result of informal work practices and self-employment. The chapter also looks at sources of advantage and disadvantage, such as those associated with particular geographic locations or personal identities. The chapter concludes by introducing the subsequent chapters in the collection. These critically explore the experience of new creative workers in a wide range of national contexts including Australia, Belgium, China, Ireland, Italy, Finland, the Netherlands, Russia and the United Kingdom

Distinct Regulatory Functions of Calpain 1 and 2 during Neural Stem Cell Self-Renewal and Differentiation

Calpains are calcium regulated cysteine proteases that have been described in a wide range of cellular processes, including apoptosis, migration and cell cycle regulation. In addition, calpains have been implicated in differentiation, but their impact on neural differentiation requires further investigation. Here, we addressed the role of calpain 1 and calpain 2 in neural stem cell (NSC) self-renewal and differentiation. We found that calpain inhibition using either the chemical inhibitor calpeptin or the endogenous calpain inhibitor calpastatin favored differentiation of NSCs. This effect was associated with significant changes in cell cycle-related proteins and may be regulated by calcium. Interestingly, calpain 1 and calpain 2 were found to play distinct roles in NSC fate decision. Calpain 1 expression levels were higher in self-renewing NSC and decreased with differentiation, while calpain 2 increased throughout differentiation. In addition, calpain 1 silencing resulted in increased levels of both neuronal and glial markers, β-III Tubulin and glial fibrillary acidic protein (GFAP). Calpain 2 silencing elicited decreased levels of GFAP. These results support a role for calpain 1 in repressing differentiation, thus maintaining a proliferative NSC pool, and suggest that calpain 2 is involved in glial differentiation

A Novel Tetrameric PilZ Domain Structure from Xanthomonads

PilZ domain is one of the key receptors for the newly discovered secondary messenger molecule cyclic di-GMP (c-di-GMP). To date, several monomeric PilZ domain proteins have been identified. Some exhibit strong c-di-GMP binding activity, while others have barely detectable c-di-GMP binding activity and require an accessory protein such as FimX to indirectly respond to the c-di-GMP signal. We now report a novel tetrameric PilZ domain structure of XCC6012 from the plant pathogen Xanthomonas campestris pv. campestris (Xcc). It is one of the four PilZ domain proteins essential for Xcc pathogenicity. Although the monomer adopts a structure similar to those of the PilZ domains with very weak c-di-GMP binding activity, it is nevertheless interrupted in the middle by two extra long helices. Four XCC6012 proteins are thus self-assembled into a tetramer via the extra heptad repeat α3 helices to form a parallel four-stranded coiled-coil, which is further enclosed by two sets of inclined α2 and α4 helices. We further generated a series of XCC6012 variants and measured the unfolding temperatures and oligomeric states in order to investigate the nature of this novel tetramer. Discovery of this new PilZ domain architecture increases the complexity of c-di-GMP-mediated regulation

Venture capital-backed firms, unavoidable value-destroying trade sales, and fair value protections

This paper investigates the implications of the fair value protections contemplated by the standard corporate contract (i.e., the standard contract form for which corporate law provides) for the entrepreneur–venture capitalist relationship, focusing, in particular, on unavoidable value-destroying trade sales. First, it demonstrates that the typical entrepreneur–venture capitalist contract does institutionalize the venture capitalist’s liquidity needs, allowing, under some circumstances, for counterintuitive instances of contractually-compliant value destruction. Unavoidable value-destroying trade sales are the most tangible example. Next, it argues that fair value protections can prevent the entrepreneur and venture capitalist from allocating the value that these transactions generate as they would want. Then, it shows that the reality of venture capital-backed firms calls for a process of adaptation of the standard corporate contract that has one major step in the deactivation or re-shaping of fair value protections. Finally, it argues that a standard corporate contract aiming to promote social welfare through venture capital should feature flexible fair value protections.info:eu-repo/semantics/publishedVersio