Evaluation of the cutaneous microbiome in psoriasis

Psoriasis, a highly prevalent disease of humans of unknown cause, is a chronic inflammatory disorder primarily involving skin, with distinctive clinical characteristics. With the newly developed tools that facilitate microbiome research, it now is possible to assess whether the cutaneous microbiome plays a role in the pathogenesis of this disorder. Preliminary data from our studies suggest that the cutaneous microbiome in psoriasis is complex and possibly different from normal. To deal with this complexity, we propose to examine the cutaneous microbiome in relation to psoriasis with explorations at several taxonomic and informatic levels. Our overall objective is to examine how changes in the normal cutaneous microbiome contributes to the pathogenesis of psoriasis. Since causality is complex and often difficult to prove, our overall hypothesis is that there are alterations in the cutaneous microbiome in areas of skin affected by psoriasis in comparison with the range observed in clinically unaffected areas, or in healthy persons. We also hypothesize that the characteristics of the microbiome may affect clinical responses to the immunomodulatory agents used to treat psoriasis. An alternative hypothesis is that effective treatment of psoriasis with systemic immunomodulatory agents will not substantially affect the disordered microbial ecosystem. Such observations would provide evidence for the roles of the microbiota in this disorder. Since an important consideration in microbiome research is the optimal level (e.g. phylum, genus, species, strain, gene) at which to examine a scientific question, and we are not yet certain what are the optimal levels for psoriasis, this also will be examined. Our studies of psoriasis should allow development of both approaches and tools that will have general utility for microbiome research. To test our hypothesis, we propose the following specific aims: 1. To understand the cutaneous microbiome species composition overlaying psoriatic lesions; 2. To investigate differences in metagenome content for psoriatic lesions compared to normal skin; 3. To identify differences in the transcriptional profiles of the microbiome and the host between normal skin and psoriatic lesions using high-throughput sequencing; and 4. To estimate the effects of systemic immunomodulatory therapy for psoriasis on microbiome composition. In total, these studies should help us understand the role of the microbiome in psoriasis pathogenesis

From source to sink in central Gondwana: Exhumation of the Precambrian basement rocks of Tanzania and sediment accumulation in the adjacent Congo basin

Apatite fission track (AFT) and (U-Th)/He (AHe) thermochronometry data are reported and used to unravel the exhumation history of crystalline basement rocks from the elevated (>1000 m above sea level) but low-relief Tanzanian Craton. Coeval episodes of sedimentation documented within adjacent Paleozoic to Mesozoic basins of southern Tanzania and the Congo basin of the Democratic Republic of Congo indicate that most of the cooling in the basement rocks in Tanzania was linked to erosion. Basement samples were from an exploration borehole located within the craton and up to 2200 m below surface. Surface samples were also analyzed. AFT dates range between 317 ± 33 Ma and 188 ± 44 Ma. Alpha (Ft)-corrected AHe dates are between 433 ± 24 Ma and 154 ± 20 Ma. Modeling of the data reveals two important periods of cooling within the craton: one during the Carboniferous-Triassic (340–220 Ma) and a later, less well constrained episode, during the late Cretaceous. The later exhumation is well detected proximal to the East African Rift (70 Ma). Thermal histories combined with the estimated geothermal gradient of 9°C/km constrained by the AFT and AHe data from the craton and a mean surface temperature of 20°C indicate removal of up to 9 ± 2 km of overburden since the end of Paleozoic. The correlation of erosion of the craton and sedimentation and subsidence within the Congo basin in the Paleozoic may indicate regional flexural geodynamics of the lithosphere due to lithosphere buckling induced by far-field compressional tectonic processes and thereafter through deep mantle upwelling and epeirogeny tectonic processes

Surface pinning of fluctuating charge order: an "extraordinary" surface phase transition

We study the mean-field theory of charge-density wave (CDW) order in a layered system, including the effect of the long-range Coulomb interaction and of screening by uncondensed electrons. We particularly focus on the conditions necessary for an ``extraordinary'' transition, in which the surface orders at a higher temperature, and is more likely to be commensurate, than the bulk. We interpret recent experiments on NaCCOC as indicating the presence of commensurate CDW at the surface that is not present in the bulk. More generally, we show that poor screening of the Coulomb interaction tends to stabilize incommensurate order, possibly explaining why the CDW order in LSCO and NbSe2 remains incommensurate to T -> 0, despite the small magnitude of the incommensurability.Comment: 9 pages, no figures, 31 references; 1 new figure and minor editing of the tex

Structured evaluation of virtual environments for special-needs education

This paper describes the development of a structured approach to evaluate experiential and communication virtual learning environments (VLEs) designed specifically for use in the education of children with severe learning difficulties at the Shepherd special needs school in Nottingham, UK. Constructivist learning theory was used as a basis for the production of an evaluation framework, used to evaluate the design of three VLEs and how they were used by students with respect to this learning theory. From an observational field study of student-teacher pairs using the VLEs, 18 behaviour categories were identified as relevant to five of the seven constructivist principles defined by Jonassen (1994). Analysis of student-teacher behaviour was used to provide support for, or against, the constructivist principles. The results show that the three VLEs meet the constructivist principles in very different ways and recommendations for design modifications are put forward

Algebraic reduction of one-loop Feynman graph amplitudes

An algorithm for the reduction of one-loop n-point tensor integrals to basic integrals is proposed. We transform tensor integrals to scalar integrals with shifted dimension and reduce these by recurrence relations to integrals in generic dimension. Also the integration-by-parts method is used to reduce indices (powers of scalar propagators) of the scalar diagrams. The obtained recurrence relations for one-loop integrals are explicitly evaluated for 5- and 6-point functions. In the latter case the corresponding Gram determinant vanishes identically for d=4, which greatly simplifies the application of the recurrence relations.Comment: 18 pages, 1 figure, added references, expanded introduction, improved tex