Growth and Fiscal Health in Wisconsin Cities

The intent of the applied research reported in this paper is to examine the relationship between growth and the fiscal health of a subset of local governments (incorporated cities) over the last decade. While any number of researchers has raised this question, the literature has tended to focus on larger urban areas during economic downturns. Ladd's (1994) most recent research looking at the fiscal effects of growth has become perhaps the most influential in this line of work. Ladd's research, however, is limited in that she focused on per capita spending, a variable of interest in itself and because it can be conceptually linked to service quality and tax burden. While the data used in her analysis do not reflect a period of economic downturn, the data are for large counties from across the U.S. The analysis presented in this paper is intended to explore of the impact of growth on the fiscal health of smaller local governments. Annual data for Wisconsin cities from 1991 to 1998 are analyzed in this study. Six measures are used to capture different aspects of fiscal health. Changes in these measures in relation to changes in population, property values, and income are evaluated through a series of tests of subsample equivalence and regression analysis.

Surgical Sterilization

Surgical sterilization as it now is practiced in Veterinary Medicine varies from careful technics carried out in an environment which would do credit to a human hospital, to the dipping of unclean instruments into a bucket of sheep dip solution of unknown strength. Even though economic considerations militate against the employment of expensive equipment and time-consuming technics, attention to a few simple details will greatly assist our approach to surgical asepsis

Alien Registration- Mccullough, June C. (Portland, Cumberland County)

https://digitalmaine.com/alien_docs/21477/thumbnail.jp

Purified venom components inhibit EGFR phosphorylation in triple negative breast cancer

Abstract: EACR22-0963 Introduction Breast cancer remains the most commonly diagnosed type of cancer in both menopausal age women and adolescent/young adults. 10-20% of diagnosed breast cancers are deemed to be triple negative (TN), lacking expression of hormone receptors and HER2. Triple negative breast cancers (TNBC) present with poor patient prognosis, through their lack of effective treatment options. Studies report that epidermal growth factor receptor (EGFR) is expressed in 15–45% of all breast tumours and its expression is inversely related to hormone receptor expression. Expression of EGFR is indicative of poor prognosis, making it an attractive target for treatment in both TN and receptor expressing cancer subtypes. Development of resistance to current EGFR targeted therapeutics is common, leading to treatment failure and patient relapse, thus novel compound classes are needed. Venom peptides have evolved to be secreted into the lumen of the venom gland and stored ready for rapid delivery; therefore they are exceptionally stable. These proteins naturally act as ligands for a large variety of receptors and ion channels, making them a rich source of potentially novel drug like molecules. Material and Methods In this study the Venomtech Targeted-Venom Discovery ArrayEGFR (T-VDA™) containing 320 venom 2D HPLC fractions was screened using Abcam Human EGFR (pY1086) + total EGFR ELISA Kits to identify venom peptides with antagonistic activity against EGFR pY1086 phosphorylation. Optimal cell number, dosing and lysate concentrations were determined empirically. MDA-MB-468 TNBC cells were dosed at 20ug/ml for 2h with fractions, before being stimulated with 1x10-7M EGF for 5 mins. Further assay protocol was carried out as per manufacturer’s instructions. TMB Absorbance signal was measured using a CLARIOstarPLUS plate reader at 450nm (BMG LabTech). Results and Discussions Screening of the TVDAEGFR array (N=2) identified 7 hit fractions (2.2% hit rate) from the venoms of three distinct rattlesnake genera from Northern, Central and southern America, and 1 viper species from Northern Africa. These fractions were followed up with dose response, mass spec and drug like properties. Conclusion Purified protein components from the venoms of pit vipers and vipers show the capacity to antagonistically inhibit the phosphorylation of EGFR at specific tyrosine residues linked to downstream signalling pathways in TNBC cells. Thus, representing a novel chemical class for targeting EGF

Dendritic Cell Endocytosis Essential for Viruses and Vaccines

Protective immune defences are dependent upon critical roles played by dendritic cells (DCs), rendering them important targets for both vaccine delivery and virus infection. Studies in these areas led to successful development of targeted vaccine delivery, including synthetic virus-like particle (SVLP) and nanoparticulate RNA vaccines. A major consideration is DC endocytosis, whereby the different endocytic routes influencing the outcome. Rapid clathrin-mediated endocytosis likely favours degradative pathways. Slower processes such as macropinocytosis, caveolar endocytosis and retrograde transport to endoplasmic reticulum relate more to the processing rates leading to antigen presentation by DCs. These pathways are also influential in promoting the initiation of virus replication following infection. DC endocytosis of RNA viruses and RNA vaccines must lead to cytosolic translocation of the RNA for translation, relating to the process of antigen cross-presentation. One can learn from observations on both virus infections and cross-presentation for delivering RNA vaccines. Accordingly, recent advances in nanoparticulate delivery have been applied with self-amplifying replicon RNA (RepRNA), providing efficient delivery to DCs and promoting replicon-encoded antigen translation. Through realising the important relationships between DC endocytic pathways and induction of immune responses, delivery of SVLP and RepRNA vaccines to DCs offers high value for the development of future synthetic vaccine platforms