208 research outputs found

    Coverage, Continuity and Visual Cortical Architecture

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    The primary visual cortex of many mammals contains a continuous representation of visual space, with a roughly repetitive aperiodic map of orientation preferences superimposed. It was recently found that orientation preference maps (OPMs) obey statistical laws which are apparently invariant among species widely separated in eutherian evolution. Here, we examine whether one of the most prominent models for the optimization of cortical maps, the elastic net (EN) model, can reproduce this common design. The EN model generates representations which optimally trade of stimulus space coverage and map continuity. While this model has been used in numerous studies, no analytical results about the precise layout of the predicted OPMs have been obtained so far. We present a mathematical approach to analytically calculate the cortical representations predicted by the EN model for the joint mapping of stimulus position and orientation. We find that in all previously studied regimes, predicted OPM layouts are perfectly periodic. An unbiased search through the EN parameter space identifies a novel regime of aperiodic OPMs with pinwheel densities lower than found in experiments. In an extreme limit, aperiodic OPMs quantitatively resembling experimental observations emerge. Stabilization of these layouts results from strong nonlocal interactions rather than from a coverage-continuity-compromise. Our results demonstrate that optimization models for stimulus representations dominated by nonlocal suppressive interactions are in principle capable of correctly predicting the common OPM design. They question that visual cortical feature representations can be explained by a coverage-continuity-compromise.Comment: 100 pages, including an Appendix, 21 + 7 figure

    A systematic review of protocol studies on conceptual design cognition

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    This paper reports the first systematic review and synthesis of protocol studies on conceptual design cognition. 47 protocol studies from the domains of architectural design, engineering design, and product de-sign engineering were reviewed towards answering the following re-search question: What is our current understanding of the cognitive processes involved in conceptual design tasks carried out by individual designers? Studies were found to reflect three viewpoints on the cognitive nature of designing, namely: design as search; design as ex-ploration; and design activities. Synthesising the findings of individual studies yielded a classification of cognitive processes involved in con-ceptual design tasks, described in different terms across different viewpoints. Towards a common terminology, these processes are posi-tioned within the cognitive psychology literature, revealing seven basic types of process that appear to be fundamental to designing across all viewpoints: memory (working and long term); visual perception; men-tal imagery; attention; semantic association; cognitive control; and higher-order processes, e.g. analysis and reasoning. The development of common cognitive models of conceptual design, grounded in a sci-entifically rigorous understanding of design cognition, is identified as an avenue for future research

    Dimerisation induced formation of the active site and the identification of three metal sites in EAL-phosphodiesterases

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    The bacterial second messenger cyclic di-3′,5′-guanosine monophosphate (c-di-GMP) is a key regulator of bacterial motility and virulence. As high levels of c-di-GMP are associated with the biofilm lifestyle, c-di-GMP hydrolysing phosphodiesterases (PDEs) have been identified as key targets to aid development of novel strategies to treat chronic infection by exploiting biofilm dispersal. We have studied the EAL signature motif-containing phosphodiesterase domains from the Pseudomonas aeruginosa proteins PA3825 (PA3825EAL) and PA1727 (MucREAL). Different dimerisation interfaces allow us to identify interface independent principles of enzyme regulation. Unlike previously characterised two-metal binding EAL-phosphodiesterases, PA3825EAL in complex with pGpG provides a model for a third metal site. The third metal is positioned to stabilise the negative charge of the 5′-phosphate, and thus three metals could be required for catalysis in analogy to other nucleases. This newly uncovered variation in metal coordination may provide a further level of bacterial PDE regulation

    Knowing the enemy: ant behavior and control in a pediatric hospital of Buenos Aires

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    Ant control is difficult in systems even where a variety of control strategies and compounds are allowed; in sensitive places such as hospitals, where there are often restrictions on the methods and toxicants to be applied, the challenge is even greater. Here we report the methods and results of how we faced this challenge of controlling ants in a pediatric hospital using baits. Our strategy was based on identifying the species present and analyzing their behavior. On the one hand, we evaluated outdoors in the green areas of the hospital, the relative abundance of ant genera, their food preferences and the behavioral dominances. On the other hand, control treatments were performed using separately two boron compounds added to sucrose solution which was not highly concentrated to avoid constrains due to the viscosity. Most of the species in the food preference test accepted sugary food; only one species was recorded to visit it less than the protein foods. This result was consistent with the efficacy of control treatments by sugary baits within the rooms. For species that showed good acceptance of sugar solutions in the preference test outdoors, sugar bait control indoors was 100& effective. Conversely, for the only species that foraged significantly less on sugar food, the bait treatment was ineffective. This work reveals the importance of considering the behavior and feeding preferences of the species to be controlled by toxic baits.Fil: Josens, Roxana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Sola, Francisco Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Marchisio, Nahuel Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Di Renzo, María Agostina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental. Laboratorio del Grupo de Estudio de Insectos Sociales; ArgentinaFil: Giacometti, Alina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentin

    Somatostatin and dopamine receptors as targets for medical treatment of Cushing's Syndrome

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    Somatostatin (SS) and dopamine (DA) receptors are widely expressed in neuroendocrine tumours that cause Cushing's Syndrome (CS). Increasing knowledge of specific subtype expression within these tumours and the ability to target these receptor subtypes with high-affinity compounds, has driven the search for new SS- or DA-based medical therapies for the various forms of CS. In Cushing's disease, corticotroph adenomas mainly express dopamine receptor subtype 2 (D2) and somatostatin receptor subtype 5 (sst5), whereas sst2is expressed at lower levels. Activation of these receptors can inhibit ACTH-release in primary cultured corticotroph adenomas and compounds that target either sst5(pasireotide, or SOM230) or D2(cabergoline) have shown significant efficacy in subsets of patients in recent clinical studies. Combination therapy, either by administration of both types of compounds separately or by treatment with novel somatostatin-dopamine chimeric molecules (e.g. BIM-23A760), appears to be a promising approach in this respect. In selected cases of Ectopic ACTH-producing Syndrome (EAS), the sst2-preferring compound octreotide is able to reduce cortisol levels effectively. A recent study showed that D2receptors are also significantly expressed in the majority of EAS and that cabergoline may decrease cortisol levels in subsets of these patients. In both normal adrenal tissue as well as in adrenal adenomas and carcinomas that cause CS, sst and DA receptor expression has been demonstrated. Although selected cases of adrenal CS may benefit from sst or DA-targeted treatment, its total contribution to the treatment of these patients is likely to be low as surgery is effective in most cases

    Young and vulnerable: Spatial-temporal trends and risk factors for infant mortality in rural South Africa (Agincourt), 1992-2007

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    <p>Abstract</p> <p>Background</p> <p>Infant mortality is an important indicator of population health in a country. It is associated with several health determinants, such as maternal health, access to high-quality health care, socioeconomic conditions, and public health policy and practices.</p> <p>Methods</p> <p>A spatial-temporal analysis was performed to assess changes in infant mortality patterns between 1992-2007 and to identify factors associated with infant mortality risk in the Agincourt sub-district, rural northeast South Africa. Period, sex, refugee status, maternal and fertility-related factors, household mortality experience, distance to nearest primary health care facility, and socio-economic status were examined as possible risk factors. All-cause and cause-specific mortality maps were developed to identify high risk areas within the study site. The analysis was carried out by fitting Bayesian hierarchical geostatistical negative binomial autoregressive models using Markov chain Monte Carlo simulation. Simulation-based Bayesian kriging was used to produce maps of all-cause and cause-specific mortality risk.</p> <p>Results</p> <p>Infant mortality increased significantly over the study period, largely due to the impact of the HIV epidemic. There was a high burden of neonatal mortality (especially perinatal) with several hot spots observed in close proximity to health facilities. Significant risk factors for all-cause infant mortality were mother's death in first year (most commonly due to HIV), death of previous sibling and increasing number of household deaths. Being born to a Mozambican mother posed a significant risk for infectious and parasitic deaths, particularly acute diarrhoea and malnutrition.</p> <p>Conclusions</p> <p>This study demonstrates the use of Bayesian geostatistical models in assessing risk factors and producing smooth maps of infant mortality risk in a health and socio-demographic surveillance system. Results showed marked geographical differences in mortality risk across a relatively small area. Prevention of vertical transmission of HIV and survival of mothers during the infants' first year in high prevalence villages needs to be urgently addressed, including expanded antenatal testing, prevention of mother-to-child transmission, and improved access to antiretroviral therapy. There is also need to assess and improve the capacity of district hospitals for emergency obstetric and newborn care. Persisting risk factors, including inadequate provision of clean water and sanitation, are yet to be fully addressed.</p

    Managing software engineers and their knowledge

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    This chapter begins by reviewing the history of software engineering as a profession, especially the so-called software crisis and responses to it, to help focus on what it is that software engineers do. This leads into a discussion of the areas in software engineering that are problematic as a basis for considering knowledge management issues. Some of the previous work on knowledge management in software engineering is then examined, much of it not actually going under a knowledge management title, but rather “learning” or “expertise”. The chapter goes on to consider the potential for knowledge management in software engineering and the different types of knowledge management solutions and strategies that might be adopted, and it touches on the crucial importance of cultural issues. It concludes with a list of challenges that knowledge management in software engineering needs to address

    Expression of methylation-related genes is associated with overall survival in patients with non-small cell lung cancer

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    The abnormality of DNA methylation is involved in tumour progression, and thus has a modulating effect on clinical outcome of cancer patients. In this study, we measured the mRNA expression levels of three methylation-regulating genes (DNMT1, DNMT3b, and MBD2) in 148 tumour samples from patients with non-small cell lung cancer (NSCLC) using quantitative real-time polymerase chain reaction and then determined their prognostic values. Our data showed that the high level of DNMT1 expression was significantly associated with an increased risk of death in all NSCLC patients (hazard ratio (HR), 1.74; 95% confidence interval (95% CI), 1.04–2.90). However, the high level of DNMT3b expression was significantly associated with poor prognosis only in young patients (<65 years). The high level of MBD2 expression had a significantly reduced risk for death only in male patients and in squamous cell lung carcinoma (SQLC) patients. All three combination groups with DNMT1 and DNMT3b, DNMT1 and MBD2 or DNMT3b and MBD2 revealed significant combined effects in male patients and SQLC patients. Our results suggest that DNMT1, DNMT3b, and MBD2 may play important roles in modulating NSCLC patient survival and thus be useful for identifying NSCLC patients who would benefit most from aggressive therapy
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