621 research outputs found
Burton Mill Pond vision and work programme
This Report, commissioned by West Sussex County Council, provides environmental and
ecological evidence to determine the current conservation value and status of Burton Mill
Pond (BMP), and builds the evidence into a vision for the site. Site management is
discussed within the context of achieving this vision, and a work programme presented,
from which WSCC can develop and detailed management schedule
Axisymmetric pulse recycling and motion in bulk semiconductors
The Kroemer model for the Gunn effect in a circular geometry (Corbino disks)
has been numerically solved. The results have been interpreted by means of
asymptotic calculations. Above a certain onset dc voltage bias, axisymmetric
pulses of the electric field are periodically shed by an inner circular
cathode. These pulses decay as they move towards the outer anode, which they
may not reach. As a pulse advances, the external current increases continuously
until a new pulse is generated. Then the current abruptly decreases, in
agreement with existing experimental results. Depending on the bias, more
complex patterns with multiple pulse shedding are possible.Comment: 8 pages, 15 figure
Free boundary problems describing two-dimensional pulse recycling and motion in semiconductors
An asymptotic analysis of the Gunn effect in two-dimensional samples of bulk
n-GaAs with circular contacts is presented. A moving pulse far from contacts is
approximated by a moving free boundary separating regions where the electric
potential solves a Laplace equation with subsidiary boundary conditions. The
dynamical condition for the motion of the free boundary is a Hamilton-Jacobi
equation. We obtain the exact solution of the free boundary problem (FBP) in
simple one-dimensional and axisymmetric geometries. The solution of the FBP is
obtained numerically in the general case and compared with the numerical
solution of the full system of equations. The agreement is excellent so that
the FBP can be adopted as the basis for an asymptotic study of the
multi-dimensional Gunn effect.Comment: 19 pages, 9 figures, Revtex. To appear in Phys. Rev.
Skateboarding in the Anthropocene: Grey spaces of polluted leisure
This is the final version. Available from Routledge via the DOI in this record.âŻThis paper explores a symbolic environmental schema of skateboarding
through the concept of âgrey spacesâ. We provide evidence of how skateboarding demonstrates a greyness â political and environmental ambiguities, contradictions, liminality, nuances and paradoxes â to outdoor
urban leisure in the Anthropocene. We build on a chromatic turn in leisure
studies which attends to blue and green spaces; however, we shift focus
from the therapeutic discussion of nature that tends to underscore that
turn to a contested realm of urban grey spaces. A concept of âgreynessâ is
adopted to connote not simply the urban but also the ambivalence of
polluted leisure and the ambiguous position of skateboarding working as
pollutant, and a form of alternative sustainability, while acting with complicity in neoliberal processes that contribute to escalating consumption
and the proliferation of concrete spaces of play. In framing skateboarding
in both the material and symbolic space of greyness, we seek to stimulate
discussion about the greyness of leisure in the Anthropocene beyond
skateboarding
Small Intestine Early Innate Immunity Response during Intestinal Colonization by Escherichia coli Depends on Its Extra-Intestinal Virulence Status
International audienceUropathogenic Escherichia coli (UPEC) strains live as commensals in the digestive tract of the host, but they can also initiate urinary tract infections. The aim of this work was to determine how a host detects the presence of a new UPEC strain in the digestive tract. Mice were orally challenged with UPEC strains 536 and CFT073, non-pathogenic strain K12 MG1655, and ÎPAI-536, an isogenic mutant of strain 536 lacking all 7 pathogenicity islands whose virulence is drastically attenuated. Intestinal colonization was measured, and cytokine expression was determined in various organs recovered from mice after oral challenge. UPEC strain 536 efficiently colonized the mouse digestive tract, and prior Enterobacteriaceae colonization was found to impact strain 536 colonization efficiency. An innate immune response, detected as the production of TNFα, IL-6 and IL-10 cytokines, was activated in the ileum 48 hours after oral challenge with strain 536, and returned to baseline within 8 days, without a drop in fecal pathogen load. Although inflammation was detected in the ileum, histology was normal at the time of cytokine peak. Comparison of cytokine secretion 48h after oral gavage with E. coli strain 536, CFT073, MG1655 or ÎPAI-536 showed that inflammation was more pronounced with UPECs than with non-pathogenic or attenuated strains. Pathogenicity islands also seemed to be involved in host detection, as IL-6 intestinal secretion was increased after administration of E. coli strain 536, but not after administration of ÎPAI-536. In conclusion, UPEC colonization of the mouse digestive tract activates acute phase inflammatory cytokine secretion but does not trigger any pathological changes, illustrating the opportunistic nature of UPECs. This digestive tract colonization model will be useful for studying the factors controlling the switch from commensalism to pathogenicity
Altering Host Resistance to Infections through Microbial Transplantation
Host resistance to bacterial infections is thought to be dictated by host genetic factors. Infections by the natural murine enteric pathogen Citrobacter rodentium (used as a model of human enteropathogenic and enterohaemorrhagic E. coli infections) vary between mice strains, from mild self-resolving colonization in NIH Swiss mice to lethality in C3H/HeJ mice. However, no clear genetic component had been shown to be responsible for the differences observed with C. rodentium infections. Because the intestinal microbiota is important in regulating resistance to infection, and microbial composition is dependent on host genotype, it was tested whether variations in microbial composition between mouse strains contributed to differences in âhostâ susceptibility by transferring the microbiota of resistant mice to lethally susceptible mice prior to infection. Successful transfer of the microbiota from resistant to susceptible mice resulted in delayed pathogen colonization and mortality. Delayed mortality was associated with increased IL-22 mediated innate defense including antimicrobial peptides Reg3Îł and Reg3ÎČ, and immunono-neutralization of IL-22 abrogated the beneficial effect of microbiota transfer. Conversely, depletion of the native microbiota in resistant mice by antibiotics and transfer of the susceptible mouse microbiota resulted in reduced innate defenses and greater pathology upon infection. This work demonstrates the importance of the microbiota and how it regulates mucosal immunity, providing an important factor in susceptibility to enteric infection. Transfer of resistance through microbial transplantation (bacteriotherapy) provides additional mechanisms to alter âhostâ resistance, and a novel means to alter enteric infection and to study host-pathogen interactions
Genetic risk for aortic aneurysm in adolescent idiopathic scoliosis
BACKGROUND: Scoliosis is a feature of several genetic disorders that are also associated with aortic aneurysm, including Marfan syndrome, Loeys-Dietz syndrome, and type-IV Ehlers-Danlos syndrome. Life-threatening complications of aortic aneurysm can be decreased through early diagnosis. Genetic screening for mutations in populations at risk, such as patients with adolescent idiopathic scoliosis, may improve recognition of these disorders. METHODS: The coding regions of five clinically actionable genes associated with scoliosis (COL3A1, FBN1, TGFBR1, TGFBR2, and SMAD3) and aortic aneurysm were sequenced in 343 adolescent idiopathic scoliosis cases. Gene variants that had minor allele frequencies of <0.0001 or were present in human disease mutation databases were identified. Variants were classified as pathogenic, likely pathogenic, or variants of unknown significance. RESULTS: Pathogenic or likely pathogenic mutations were identified in 0.9% (three) of 343 adolescent idiopathic scoliosis cases. Two patients had pathogenic SMAD3 nonsense mutations consistent with type-III Loeys-Dietz syndrome and one patient had a pathogenic FBN1 mutation with subsequent confirmation of Marfan syndrome. Variants of unknown significance in COL3A1 and FBN1 were identified in 5.0% (seventeen) of 343 adolescent idiopathic scoliosis cases. Six FBN1 variants were previously reported in patients with Marfan syndrome, yet were considered variants of unknown significance based on the level of evidence. Variants of unknown significance occurred most frequently in FBN1 and were associated with greater curve severity, systemic features of Marfan syndrome, and joint hypermobility. CONCLUSIONS: Clinically actionable pathogenic mutations in genes associated with adolescent idiopathic scoliosis and aortic aneurysm are rare in patients with adolescent idiopathic scoliosis who are not suspected of having these disorders, although variants of unknown significance are relatively common. CLINICAL RELEVANCE: Routine genetic screening of all patients with adolescent idiopathic scoliosis for mutations in clinically actionable aortic aneurysm disease genes is not recommended on the basis of the high frequency of variants of unknown significance. Clinical evaluation and family history should heighten indications for genetic referral and testing
Transcriptome profiling of the small intestinal epithelium in germfree versus conventional piglets
<p>Abstract</p> <p>Background</p> <p>To gain insight into host-microbe interactions in a piglet model, a functional genomics approach was used to address the working hypothesis that transcriptionally regulated genes associated with promoting epithelial barrier function are activated as a defensive response to the intestinal microbiota. Cesarean-derived germfree (GF) newborn piglets were colonized with adult swine feces, and villus and crypt epithelial cell transcriptomes from colonized and GF neonatal piglets were compared using laser-capture microdissection and high-density porcine oligonucleotide microarray technology.</p> <p>Results</p> <p>Consistent with our hypothesis, resident microbiota induced the expression of genes contributing to intestinal epithelial cell turnover, mucus biosynthesis, and priming of the immune system. Furthermore, differential expression of genes associated with antigen presentation (pan SLA class I, <it>B2M</it>, <it>TAP1 </it>and <it>TAPBP</it>) demonstrated that microbiota induced immune responses using a distinct regulatory mechanism common for these genes. Specifically, gene network analysis revealed that microbial colonization activated both type I (IFNAR) and type II (IFNGR) interferon receptor mediated signaling cascades leading to enhanced expression of signal transducer and activator of transcription 1 (STAT1), STAT2 and IFN regulatory factor 7 (IRF7) transcription factors and the induction of IFN-inducible genes as a reflection of intestinal epithelial inflammation. In addition, activated RNA expression of NF-kappa-B inhibitor alpha (<it>NFÎșBIA</it>; a.k.a I-kappa-B-alpha, IKBα) and toll interacting protein (<it>TOLLIP</it>), both inhibitors of inflammation, along with downregulated expression of the immunoregulatory transcription factor GATA binding protein-1 (<it>GATA1</it>) is consistent with the maintenance of intestinal homeostasis.</p> <p>Conclusion</p> <p>This study supports the concept that the intestinal epithelium has evolved to maintain a physiological state of inflammation with respect to continuous microbial exposure, which serves to sustain a tight intestinal barrier while preventing overt inflammatory responses that would compromise barrier function.</p
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