SHH signalling in acute pulmonary cell injury and chronic fibrosis

This thesis addresses the hypothesis that the sonic hedgehog (Shh) signalling pathway is up regulated in response to cellular injury and that this signal acts as a potential pro-fibrogenic signal in pulmonary inflammation. In vitro studies utilised human (A549) and mouse (CMT) type II like epithelial cell lines in an analysis of epithelial response to injury. An immediate up regulation and release of soluble Shh in response to hydrogen peroxide exposure was identified in mouse epithelium, utilising both RT-PCR and a novel Shh ELISA developed here. Subsequent up-regulation and release of GM-CSF was shown to be Shh independent. Human epithelial cells demonstrated a similar release of Shh, suggesting a common pathway in both species. In contrast GM-CSF was not up regulated in human cells, but IL-8 up regulation did occur. The relevance of these studies to in vivo signalling was ascertained through use of the FITC instillation mouse model of inflammatory fibrosis.Previous work by our group has illustrated epithelial up-regulation of Shh in areas of inflammatory fibrotic disease in the FITC model, and in biopsies from patients with idiopathic pulmonary fibrosis. Transoral intratracheal delivery of FITC on two occasions six weeks apart reproduced previous histological findings made in the lab using a surgical intratracheal FITC instillation. However, use of improved immunohistochemical (IHC) techniques would suggest that, unlike human disease, Shh expression in the FITC mouse model is not solely restricted to epithelium in areas of inflammation or fibrosis. To determine the Shh responder cell populations in human disease and determine the validity of the IHC findings in the FITC model, a laser micro-dissection technique was developed. Viable mRNA for sequences including the Shh receptor patched (Ptc), and downstream signalling component smoothened (Smo) have been recovered from archival formalin fixed human biopsy material, sufficient for RT-PCR and agarose gel electrophoresis visualisation. mRNA analysis of material derived from fibrotic areas of a single standard section of archival human lung biopsy has now been performed.Observations correlating levels of FITC specific lgG1 antibody and disease severity in FITC treated animals suggest an immuno-modulatory role for T lymphocyte dependent, Th2 type antibodies in disease progression. In support of this iBALT has also been identified in diseased lung and T-lymphocyte depletion results in disease amelioration.Taken together these findings suggest that Shh is an indicator of acute cellular injury, but that the principal component of FITC induced fibrotic disease progression is immune mediated and that this does not depend on Shh up regulation

An increased CD25-positive intestinal regulatory T-lymphocyte population is dependent on Cox-2 activity in the Apc Min/+ model

Summary Only mismatch repair (MMR)-deficient colorectal cancer (CRC) appears to respond well to programmed death (PD)-1 inhibition at the present time. Emerging evidence suggests a role for micro-environmental factors such as CD25+ cells modulating response to PD-1 inhibition. In the ApcMin/+ model of familial adenomatous polyposis (MMR-proficient CRC), increased Cyclooxygenase-2 (Cox-2) expression by cells which include alternatively activated mononuclear phagocytes promotes intestinal tumorigenesis by mechanisms which may include immune suppression. To gain insight into this, we compared regulatory T cell (Treg) populations between ApcMin/+ and wild-type mice prior to and after the phase of increased intestinal Cox-2-dependent prostaglandin E2 (PGE2) production. There was no difference in systemic Treg function or numbers between ApcMin/+ and wild-type mice. However, increased numbers of small intestinal CD25+ Tregs were observed with increased Cox-2 activity in the absence of any difference in the expression of Tgf-β or Tslp between ApcMin/+ and wild-type mice. Cox-2 inhibitor therapy (Celecoxib) reversed the increase in ApcMin/+ intestinal CD25+ Treg numbers, without decreasing numbers of CD25+ systemic Tregs. Forkhead box protein 3 (FoxP3+) and Cox-2+ cells were co-localized to the interstitium of adenomas of Apcmin/+ mice. These results suggest selective dependence of an ‘activated Treg’ phenotype on paracrine Cox-2 activity in ApcMin/+ small intestine. For therapeutic potential, further studies are required to evaluate the relevance of these findings to human cancer as well as the functional significance of CD25+ intestinal Tregs in cancer.</jats:p

Thermal decomposition of vinyl- and allylsilane platinum(II) complexes and platinum(II)catalysed synthesis of (E),(E)-1,4-diphenyl-1,3-butadiene

Thermal stabilities of Pt(II) complexes: K[PtCl3(CH2=CHSiMe3)], K[PtCl3(CH2=CHCH2SiMe3)], K[(acac)PtCl(CH2=CHSiMe3)] and [PtCl(CH2=CHCH2SiMe3)]2, were examined. All complexes were found to be stable at room temperature but they decomposed without melting above about 90 oC. The allylsilane complex decomposed above about 125 oC. All complexes liberated chlorotrimethylsilane on decomposition, showing the facile cleavage of the C-Si bond by nucleophilic attack on the silicon by the chloride ion. (E),(E)-1,4-diphenyl-1,3-butadiene was stereoselectively synthesised in good yield from (E)-β-styrylsilane in the presence of Zeise’s salt. KEY WORDS: Thermal analysis, Vinyl- and allylsilane platinum(II) π-complexes, Platinum(II) catalysed synthesis, (E),(E)-1,4-diphenyl-1,3-butadiene  Bull. Chem. Soc. Ethiop. 2008, 22(3), 445-448

Mechanical design engineering. NASA/university advanced design program: Lunar Bulk Material Transport Vehicle

The design of a Lunar Bulk Material Transport Vehicle (LBMTV) is discussed. Goals set in the project include a payload of 50 cubic feet of lunar soil with a lunar of approximately 800 moon-pounds, a speed of 15 mph, and the ability to handle a grade of 20 percent. Thermal control, an articulated steering mechanism, a dump mechanism, a self-righting mechanism, viable power sources, and a probable control panel are analyzed. The thermal control system involves the use of small strip heaters to heat the housing of electronic equipment in the absence of sufficient solar radiation and multi-layer insulation during periods of intense solar radiation. The entire system uses only 10 W and weighs about 60 pounds, or 10 moon-pounds. The steering mechanism is an articulated steering joint at the center of the vehicle. It utilizes two actuators and yields a turning radius of 10.3 feet. The dump mechanism rotates the bulk material container through an angle of 100 degree using one actuator. The self-righting mechanism consists of two four bar linkages, each of which is powered by the same size actuator as the other linkages. The LBMTV is powered by rechargeable batteries. A running time of at least two hours is attained under a worst case analysis. The weight of the batteries is 100 pounds. A control panel consisting of feedback and control instruments is described. The panel includes all critical information necessary to control the vehicle remotely. The LBMTV is capable of handling many types of cargo. It is able to interface with many types of removable bulk material containers. These containers are made to interface with the three-legged walker, SKITTER. The overall vehicle is about 15 feet in length and has a weight of about 1000 pounds, or 170 lunar pounds

A Services\u27 Frameworks And Support Services For Environmental Information Communities

For environmental datasets to be used effectively via the Internet, they must present standardized data and metadata services and link the two. The Open Geospatial Consortium\u27s (OGC) web services (WFS, WMS, CSW etc.), have seen widespread use over many years however few organizations have deployed information architectures based solely on OGC standards for all their datasets. Collections of organizations within a thematically-based community certainly cannot realistically be expected to do so. To enable service use flexibility we present a services framework - a Data Brokering Layer (DBL). A DBL presents access to data and metadata services for datasets, and links between them, in a standardized manner based on Linked Data and Semantic Web principles. By specifying regular access methods to any data or metadata service relevant for a dataset, community organizers allow a wide range of services for use within their community. Additionally, a community service profile testing service – a Conformance Service – may be run that reveals the day-to-day status of all of a community’s services to be known allowing both better end-user experiences and also that data providers’ data is acceptable to a community and continues to remains available for use. We present DBL and Conformance Service designs as well as a whole-of-community architecture that facilitates the use of the two. We describe implementations of them within two Australian environmental information communities: eReefs and Bioregional Assessments and plans for wider deployment

Concert Choir Early Music Ensemble Madrigal Singers

Center for the Performing Arts Sunday Afternoon November 10, 2002 3:00p.m

Photostatistics Reconstruction via Loop Detector Signatures

Photon-number resolving detectors are a fundamental building-block of optical quantum information processing protocols. A loop detector, combined with appropriate statistical processing, can be used to convert a binary on/off photon counter into a photon-number-resolving detector. Here we describe the idea of a signature of photon-counts, which may be used to more robustly reconstruct the photon number distribution of a quantum state. The methodology is applied experimentally in a 9-port loop detector operating at a telecommunications wavelength and compared directly to the approach whereby only the number of photon-counts is used to reconstruct the input distribution. The signature approach is shown to be more robust against calibration errors, exhibit reduced statistical uncertainty, and reduced reliance on a-priori assumptions about the input state.Comment: 13 pages, 12 figure

Incest in the 1990s: reading Anais Nin's 'Father Story'

In the summer of 1933, diarist, author and critic Anaïs Nin joined her father for a short vacation in France. Nin wrote about the trip in her diary afterwards, referring to it as the ‘Father Story.’ In the story, she details how, aged 30, she embarked upon an affair with her father which would last for several months. Rather than displaying the signs of trauma that we have come to expect from the incest narrative such as dissociation, blame and recrimination, the ‘Father Story’ is more ambiguous in its tone. Part-tribute to the father, part-seduction narrative, part-confession, this is a story that resists categorisation – a resistance that has ethical, critical and formal ramifications for our reading of incest narratives. Upon its publication in the early 1990s, critics responded to the ‘Father Story’ as fantastical, excessive and vulgar. These responses form part of a wider American father story during this period; a story about memory, therapy culture, family values and the concealed rules of testimony. This article reads Anaïs Nin’s narrative as a text which raises fundamental questions about why certain father (and daughter) stories are culturally acceptable and others are not

RobotAssist - A platform for human robot interaction research

This paper presents RobotAssist, a robotic platform designed for use in human robot interaction research and for entry into Robocup@Home competition. The core autonomy of the system is implemented as a component based software framework that allows for integration of operating system independent components, is designed to be expandable and integrates several layers of reasoning. The approaches taken to develop the core capabilities of the platform are described, namely: path planning in a social context, Simultaneous Localisation and Mapping (SLAM), human cue sensing and perception, manipulatable object detection and manipulation

Physician Executive Leadership: Student-Led Curriculum to Fill Gaps in Traditional Medical Education

Students at Sidney Kimmel Medical College (SKMC) have identified a gap in the traditional medical curriculum surrounding topics such as telehealth, the patient experience, health policy, medical malpractice, and health care entrepreneurship and innovation, and in response have initiated a student-centered, student-led, student-driven program called Physician Executive Leadership (PEL). PEL provides students with a variety of avenues to engage with these topics, such as lectures from leaders in each of these fields, easy access to weekly news articles on current events in health care, targeted review sessions on the US health care system, and the opportunity to voice and develop ideas through an online publication. To identify the gaps in medical education PEL is best suited to fill, we administered a survey to 174 students at Sidney Kimmel Medical College.The survey contained 20 multiple-choice questions to assess general knowledge on health insurance and reimbursement, health care policy and reform, and care quality and patient experience. It also included a subjective self-assessment of students’ understanding of and interest in these topics. Overall, we found that although the traditional medical school curriculum improved students\u27 understanding of these topics from year to year, it is not sufficient on it\u27s own: on average, students failed to achieve a passing score of 70% in any of the categories tested. Further illustrating the importance of this program, students self-identified a gap between their current level of understanding and what they want to know. Please visit our website www.physicianexecutiveleadership.com to learn more!https://jdc.jefferson.edu/pel/1000/thumbnail.jp