Defining Rules for Kinematic Shapes with Variable Spatial Relations

Designing mechanisms can be a challenging problem, because the underlying kinematics involved are typically not intuitively incorporated into common techniques for design representation. Kinematic shapes and kinematic grammars build on the shape grammar and making grammar formalisms to enable a visually intuitive approach to model and explore mechanisms. With reference to the lower kinematic pairs this paper introduces kinematic shapes. These are connected shapes with parts which have variable spatial relations that account for the relative motion of the parts. The paper considers how such shapes can be defined, the role of elements shared by connected parts, and the motions that result. It also considers how kinematic shape rules can be employed to generate and explore the motion of mechanisms

Genotypic Diversity Is Associated with Clinical Outcome and Phenotype in Cryptococcal Meningitis across Southern Africa.

Cryptococcal meningitis is a major cause of mortality throughout the developing world, yet little is known about the genetic markers underlying Cryptococcal virulence and patient outcome. We studied a cohort of 230 Cryptococcus neoformans (Cn) isolates from HIV-positive South African clinical trial patients with detailed clinical follow-up using multi-locus sequence typing and in vitro phenotypic virulence assays, correlating these data with clinical and fungal markers of disease in the patient. South African Cn displayed high levels of genetic diversity and locus variability compared to globally distributed types, and we identified 50 sequence types grouped within the main molecular types VNI, VNII and VNB, with 72% of isolates typed into one of seven 'high frequency' sequence types. Spatial analysis of patients' cryptococcal genotype was not shown to be clustered geographically, which might argue against recent local acquisition and in favour of reactivation of latent infection. Through comparison of MLST genotyping data with clinical parameters, we found a relationship between genetic lineage and clinical outcome, with patients infected with the VNB lineage having significantly worse survival (n=8, HR 3.35, CI 1.51-7.20, p=0.003), and this was maintained even after adjustment for known prognostic indicators and treatment regimen. Comparison of fungal genotype with in vitro phenotype (phagocytosis, laccase activity and CSF survival) performed on a subset of 89 isolates revealed evidence of lineage-associated virulence phenotype, with the VNII lineage displaying increased laccase activity (p=0.001) and ex vivo CSF survival (p=0.0001). These findings show that Cryptococcus neoformans is a phenotypically heterogeneous pathogen, and that lineage plays an important role in cryptococcal virulence during human infection. Furthermore, a detailed understanding of the genetic diversity in Southern Africa will support further investigation into how genetic diversity is structured across African environments, allowing assessment of the risks different ecotypes pose to infection

Host Cell Factors in HIV Replication: Meta-Analysis of Genome-Wide Studies

We have analyzed host cell genes linked to HIV replication that were identified in nine genome-wide studies, including three independent siRNA screens. Overlaps among the siRNA screens were very modest (<7% for any pairwise combination), and similarly, only modest overlaps were seen in pairwise comparisons with other types of genome-wide studies. Combining all genes from the genome-wide studies together with genes reported in the literature to affect HIV yields 2,410 protein-coding genes, or fully 9.5% of all human genes (though of course some of these are false positive calls). Here we report an “encyclopedia” of all overlaps between studies (available at http://www.hostpathogen.org), which yielded a more extensively corroborated set of host factors assisting HIV replication. We used these genes to calculate refined networks that specify cellular subsystems recruited by HIV to assist in replication, and present additional analysis specifying host cell genes that are attractive as potential therapeutic targets

E-Democracy and the European Public Sphere

The chapter starts with an outline of outstanding recent contributions to the discussion of the EU democratic deficit and the so-called “no demos” problem and the debate about European citizenship and European identity—mainly in the light of insights from the EU crisis. This is followed by reflections on the recent discussion on the state of the mass media-based European public sphere. Finally, the author discusses the state of research on the Internet’s capacity to support the emergence of a (renewed) public sphere, with a focus on options for political actors to use the Internet for communication and campaigning, on the related establishment of segmented issue-related publics as well as on social media and its two-faced character as an enabler as well as a distorting factor of the public sphere. The author is sceptic about the capacities of Internet-based political communication to develop into a supranational (European) public sphere. It rather establishes a network of a multitude of discursive processes aimed at opinion formation at various levels and on various issues. The potential of online communication to increase the responsiveness of political institutions so far is set into practice insufficiently. Online media are increasingly used in a vertical and scarcely in a horizontal or interactive manner of communication

Genetic variability and ontogeny predict microbiome structure in a disease-challenged montane amphibian

Amphibian populations worldwide are at risk of extinction from infectious diseases, including chytridiomycosis caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd). Amphibian cutaneous microbiomes interact with Bd and can confer protective benefits to the host. The composition of the microbiome itself is influenced by many environment- and host-related factors. However, little is known about the interacting effects of host population structure, genetic variation and developmental stage on microbiome composition and Bd prevalence across multiple sites. Here we explore these questions in Amietia hymenopus, a disease-affected frog in southern Africa. We use microsatellite genotyping and 16S amplicon sequencing to show that the microbiome associated with tadpole mouthparts is structured spatially, and is influenced by host genotype and developmental stage. We observed strong genetic structure in host populations based on rivers and geographic distances, but this did not correspond to spatial patterns in microbiome composition. These results indicate that demographic and host genetic factors affect microbiome composition within sites, but different factors are responsible for host population structure and microbiome structure at the between-site level. Our results help to elucidate complex within- and among- population drivers of microbiome structure in amphibian populations. That there is a genetic basis to microbiome composition in amphibians could help to inform amphibian conservation efforts against infectious diseases