gamma-delta T Cells Regulate the Early Inflammatory Response to Bordetella pertussis Infection in the Murine Respiratory Tract

The role of T cells in the regulation of pulmonary inflammation following Bordetella pertussis infection was investigated. Using a well-characterized murine aerosol challenge model, inflammatory events in mice with targeted disruption of the T-cell receptor -chain gene (TCR mice) were compared with those in wild-type animals. Early following challenge with B. pertussis, TCR mice exhibited greater pulmonary inflammation, as measured by intra-alveolar albumin leakage and lesion histomorphometry, yet had lower contemporaneous bacterial lung loads. The larger numbers of neutrophils and macrophages and the greater concentration of the neutrophil marker myeloperoxidase in bronchoalveolar lavage fluid from TCR mice at this time suggested that differences in lung injury were mediated through increased leukocyte trafficking into infected alveoli. Furthermore, flow cytometric analysis found the pattern of recruitment of natural killer (NK) and NK receptor T cells into airspaces differed between the two mouse types over the same time period. Taken together, these findings suggest a regulatory influence for T cells over the early pulmonary inflammatory response to bacterial infection. The absence of T cells also influenced the subsequent adaptive immune response to specific bacterial components, as evidenced by a shift from a Th1 to a Th2 type response against the B. pertussis virulence factor filamentous hemagglutinin in TCR mice. The findings are relevant to the study of conditions such as neonatal B. pertussis infection and acute respiratory distress syndrome where T cell dysfunction has been implicated in the inflammatory process

A PXY-Mediated Transcriptional Network Integrates Signaling Mechanisms to Control Vascular Development in Arabidopsis

Vascular meristems generate the majority of biomass in higher plants. They constitute a bifacial stem cell population from which xylem and phloem are specified on opposing sides by positional signals. The PHLOEM INTERCALATED WITH XYLEM (PXY) receptor kinase promotes vascular cell division and organisation. However, how these functions are specified and integrated is unknown. Here, a putative PXY-mediated transcriptional regulatory network comprised of 690 transcription factor-promoter interactions was mapped. Among these interactions was a feed-forward loop containing transcription factors WUSCHEL HOMEOBOX RELATED 14 (WOX14) and TARGET OF MONOPTEROS 6 (TMO6), which each regulate the expression of a third transcription factor, LATERAL ORGAN BOUNDARIES DOMAIN 4 (LBD4). PXY signalling in turn regulates the WOX14, TMO6, LBD4 loop to control vascular proliferation. Genetic interaction between LBD4 and PXY suggests that LBD4 marks the phloem-procambium boundary, thus defining the shape of the vascular bundle. These data collectively support a novel mechanism that influences recruitment of cells into the phloem lineage, and defines the role of PXY signalling in this context to the arrangement of vascular tissue

Heating rate and electrode charging measurements in a scalable, microfabricated, surface-electrode ion trap

We characterise the performance of a surface-electrode ion "chip" trap fabricated using established semiconductor integrated circuit and micro-electro-mechanical-system (MEMS) microfabrication processes which are in principle scalable to much larger ion trap arrays, as proposed for implementing ion trap quantum information processing. We measure rf ion micromotion parallel and perpendicular to the plane of the trap electrodes, and find that on-package capacitors reduce this to <~ 10 nm in amplitude. We also measure ion trapping lifetime, charging effects due to laser light incident on the trap electrodes, and the heating rate for a single trapped ion. The performance of this trap is found to be comparable with others of the same size scale.Comment: 6 pages, 10 figure

Type-based allocation analysis for co-recursion in lazy functional languages

This paper presents a novel type-and-effect analysis for pre-dicting upper-bounds on memory allocation costs for co-recursive def-initions in a simple lazily-evaluated functional language. We show thesoundness of this system against an instrumented variant of Launch-bury’s semantics for lazy evaluation which serves as a formal cost model.Our soundness proof requires an intermediate semantics employing indi-rections. Our proof of correspondence between these semantics that weprovide is thus a crucial part of this work.The analysis has been implemented as an automatic inference system.We demonstrate its effectiveness using several example programs thatpreviously could not be automatically analysed.Postprin

Systematic review of economic evaluations and cost analyses of guideline implementation strategies

Objectives To appraise the quality of economic studies undertaken as part of evaluations of guideline implementation strategies; determine their resources use; and recommend methods to improve future studies. Methods Systematic review of economic studies undertaken alongside robust study designs of clinical guideline implementation strategies published (1966-1998). Studies assessed against the BMJ economic evaluations guidelines for each stage of the guideline process (guideline development, implementation and treatment). Results 235 studies were identified, 63 reported some information on cost. Only 3 studies provided evidence that their guideline was effective and efficient. 38 reported the treatment costs only, 12 implementation and treatment costs, 11 implementation costs alone, and two guideline development, implementation and treatment costs. No study gave reasonably complete information on costs. Conclusions Very few satisfactory economic evaluations of guideline implementation strategies have been performed. Current evaluations have numerous methodological defects and rarely consider all relevant costs and benefits. Future evaluations should focus on evaluating the implementation of evidence based guidelines. Keywords: Cost-effectiveness analysis, physician (or health care professional) behaviour, practice guidelines, quality improvement, systematic review.Peer reviewedAuthor versio

Restructuring of colloidal aggregates in shear flow: Coupling interparticle contact models with Stokesian dynamics

A method to couple interparticle contact models with Stokesian dynamics (SD) is introduced to simulate colloidal aggregates under flow conditions. The contact model mimics both the elastic and plastic behavior of the cohesive connections between particles within clusters. Owing to this, clusters can maintain their structures under low stress while restructuring or even breakage may occur under sufficiently high stress conditions. SD is an efficient method to deal with the long-ranged and many-body nature of hydrodynamic interactions for low Reynolds number flows. By using such a coupled model, the restructuring of colloidal aggregates under stepwise increasing shear flows was studied. Irreversible compaction occurs due to the increase of hydrodynamic stress on clusters. Results show that the greater part of the fractal clusters are compacted to rod-shaped packed structures, while the others show isotropic compaction.Comment: A simulation movie be found at http://www-levich.engr.ccny.cuny.edu/~seto/sites/colloidal_aggregates_shearflow.htm

Charged AdS Black Holes and Catastrophic Holography

We compute the properties of a class of charged black holes in anti-de Sitter space-time, in diverse dimensions. These black holes are solutions of consistent Einstein-Maxwell truncations of gauged supergravities, which are shown to arise from the inclusion of rotation in the transverse space. We uncover rich thermodynamic phase structures for these systems, which display classic critical phenomena, including structures isomorphic to the van der Waals-Maxwell liquid-gas system. In that case, the phases are controlled by the universal `cusp' and `swallowtail' shapes familiar from catastrophe theory. All of the thermodynamics is consistent with field theory interpretations via holography, where the dual field theories can sometimes be found on the world volumes of coincident rotating branes.Comment: 19 pages, revtex, psfig, 6 multicomponent figures, typos, references and a few remarks have been repaired, and adde

Physics Opportunities with the 12 GeV Upgrade at Jefferson Lab

This white paper summarizes the scientific opportunities for utilization of the upgraded 12 GeV Continuous Electron Beam Accelerator Facility (CEBAF) and associated experimental equipment at Jefferson Lab. It is based on the 52 proposals recommended for approval by the Jefferson Lab Program Advisory Committee.The upgraded facility will enable a new experimental program with substantial discovery potential to address important topics in nuclear, hadronic, and electroweak physics.Comment: 64 page

Genome-wide functional analysis reveals key roles for kinesins in the mammalian and mosquito stages of the malaria parasite life cycle

Kinesins are microtubule (MT)-based motors important in cell division, motility, polarity, and intracellular transport in many eukaryotes. However, they are poorly studied in the divergent eukaryotic pathogens Plasmodium spp., the causative agents of malaria, which manifest atypical aspects of cell division and plasticity of morphology throughout the life cycle in both mammalian and mosquito hosts. Here, we describe a genome-wide screen of Plasmodium kinesins, revealing diverse subcellular locations and functions in spindle assembly, axoneme formation, and cell morphology. Surprisingly, only kinesin-13 is essential for growth in the mammalian host while the other 8 kinesins are required during the proliferative and invasive stages of parasite transmission through the mosquito vector. In-depth analyses of kinesin-13 and kinesin-20 revealed functions in MT dynamics during apical cell polarity formation, spindle assembly, and axoneme biogenesis. These findings help us to understand the importance of MT motors and may be exploited to discover new therapeutic interventions against malaria