The KRN mouse model of inflammatory arthritis

Abstract.: In 1996 a new murine model of spontaneous arthritis was described by the group of Benoist and Mathis. Mice transgenic for a T cell receptor recognizing an epitope of bovine RNase and bred onto a NOD background developed severe destructive arthritis, which resembles human rheumatoid arthritis in many respects. The development of disease requires the presence of T and B lymphocytes and is dependent on the MHC class II molecule I-Ag7. B cell activation by antigen and an additional CD40-CD40 ligand interaction was found to give rise to the production of autoantibodies. Glucose-6-phosphate isomerase was identified as the target of the autoantibodies; moreover, the transgenic T cells were demonstrated to exhibit a dual specificity for both bovine RNase and glucose-6-phosphate isomerase. Importantly, the arthritis is serum transferable to normal recipients, enabling the examination of the pathogenic mechanisms of joint inflammation and destruction. Recent studies suggest the crucial involvement of the innate immune system in the development of antibody-induced arthritis. Complement components, Fc receptors and neutrophils are indispensable for disease induction. An overview of the existing data is given and the emerging concepts of the pathogenesis of the K/BxN arthritis are discussed with respect to their relevance for human rheumatoid arthritis. Because of the reliable and robust induction of joint inflammation by serum transfer this new disease model has been and will be a valuable means to address the as-yet-unanswered key questions related to the development of arthriti

Fast track to growth? Railway access, population growth and local displacement in 19th century Switzerland

We study the effect of railway access on population growth in 19th century Switzerland. Our analysis is based on geo-referenced railway network information and an inconsequential units IV approach. Gaining direct railway access increased annual population growth by 0.4 percentage points, while municipalities in close vicinity but no direct access (i.e. 2-10 km distance) experienced a growth slump of similar magnitude. We interpret these findings as evidence of highly localised displacement effects related to railway connections

Cohesive institutions and political violence

Can institutionalized transfers of resource rents be a source of civil conflict? Are cohesive institutions better in managing distributive conflicts? We study these questions exploiting exogenous variation in revenue disbursements to local governments together with new data on local democratic institutions in Nigeria. We make three contributions. First, we document the existence of a strong link between rents and conflict far away from the location of the actual resource. Second, we show that distributive conflict is highly organized involving political militias and concentrated in the extent to which local governments are non-cohesive. Third, we show that democratic practice in form having elected local governments significantly weakens the causal link between rents and political violence. We document that elections (vis-a-vis appointments), by producing more cohesive institutions, vastly limit the extent to which distributional conflict between groups breaks out following shocks to the available rents. Throughout, we confirm these findings using individual level survey data

White County Highway Garage Project Development and outcomes

In this presentation we will discuss the conducted project needs assessment; site search and selection process; ancillary benefits to the county and the surrounding communities; site challenges; design development strategies and lessons learned; the anticipated time line to duplicate this project; and the contractual methods used to deliver the project. We will then wrap up with a photographic campus tour of the final outcomes and improvements

Life on the Quarry Wall Vs the Quarry Floor: Parthenocissus quinquefolia

Parthenocissus quinquefolia, Virginia creeper, is found in two parts of the DePauw Nature Park quarry: vertically along the quarry wall and on large rock piles on the quarry floor. I looked into how these different habitats influenced the growth form, stress responses, and fitness of the P. quinquefolia growing in them. P. quinquefolia on the wall has higher chlorophyll a content and higher water content. There was also a higher percentage of flowering individuals on the quarry wall than on the floor. Lastly, the two habitats had vastly different morphological growth forms, with those on the wall having very long internodes compared to those on the floor. The data shows that P. quinquefolia on the quarry floor was more water and light stressed and had lower fitness; this suggests the quarry wall is a more suitable habitat for P. quinquefolia than the floor

The role of the yeast cleavage and polyadenylation factor subunit Ydh1p/Cft2p in pre‐mRNA 3′‐end formation

Cleavage and polyadenylation factor (CPF) is a multi‐protein complex that functions in pre‐mRNA 3′‐end formation and in the RNA polymerase II (RNAP II) transcription cycle. Ydh1p/Cft2p is an essential component of CPF but its precise role in 3′‐end processing remained unclear. We found that mutations in YDH1 inhibited both the cleavage and the polyadenylation steps of the 3′‐end formation reaction in vitro. Recently, we demonstrated that an important function of CPF lies in the recognition of poly(A) site sequences and RNA binding analyses suggesting that Ydh1p/Cft2p interacts with the poly(A) site region. Here we show that mutant ydh1 strains are deficient in the recognition of the ACT1 cleavage site in vivo. The C‐terminal domain (CTD) of RNAP II plays a major role in coupling 3′‐end processing and transcription. We provide evidence that Ydh1p/Cft2p interacts with the CTD of RNAP II, several other subunits of CPF and with Pcf11p, a component of CF IA. We propose that Ydh1p/Cft2p contributes to the formation of important interaction surfaces that mediate the dynamic association of CPF with RNAP II, the recognition of poly(A) site sequences and the assembly of the polyadenylation machinery on the RNA substrat

Exchanging Appointment Data Among Healthcare Institutions

The introduction of national electronic patient records such as the electronic patient dossier EPD in Switzerland provides a new basis for digitizing healthcare processes at a national level. One process however, that is currently neglected within the Swiss EPD, is the scheduling process in healthcare. The objective of this work is to analyze the appointment scheduling process and the involved IT systems in order to develop an appointment data structure and a concept for cross-institutional exchange of appointment data. The analysis showed that various outpatient and inpatient information systems support appointment booking through proprietary solutions. A true standard for appointment data exchange is missing. We suggest an appointment data structure and a corresponding data exchange process based on the FHIR standard. In its current implementation, the Swiss EPD does not support this proposed appointment scheduling process. We discuss how potential additions such as the IHE Care Services Discovery (CSD) profile can provide better compatibility