Bringing Agriculture into the GATT: Designing Acceptable Agricultural Policies

Agricultural and Food Policy, International Relations/Trade,

Direct comparison of the abilities of bone marrow mesenchymal versus hematopoietic stem cells to reverse hyperglycemia in diabetic NOD.SCID mice

Both bone marrow-derived hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) improve glycemic control in diabetic mice, but their kinetics and associated changes in pancreatic morphology have not been directly compared. Our goal was to examine the time course of improvements in glucose tolerance and associated changes in β-cell mass and proliferation following transplantation of equivalent numbers of HSC or MSC from the same bone marrow into diabetic non-obese diabetic severe combined immune deficiency (NOD.SCID) mice. We used transgenic mice with a targeted expression of yellow fluorescent protein (YFP) driven by the Vav1 gene promoter to genetically tag HSC and progeny. HSC were separated from bone marrow by fluorescence-activated cell sorting and MSC following cell culture. Equivalent numbers of isolated HSC or MSC were transplanted directly into the pancreas of NOD.SCID mice previously made diabetic with streptozotocin. Glucose tolerance, serum insulin, β-cell mass and β-cell proliferation were examined up to 28 days following transplant. Transplantation with MSC improved glucose tolerance within 7 days and serum insulin levels increased, but with no increase in β-cell mass. Mice transplanted with HSC showed improved glucose tolerance only after 3 weeks associated with increased β-cell proliferation and mass. We conclude that single injections of either MSC or HSC transiently improved glycemic control in diabetic NOD.SCID mice, but with different time courses. However, only HSC infiltrated the islets and were associated with an expanded β-cell mass. This suggests that MSC and HSC have differing mechanisms of action

Identification of Unreported Sources of Objects Containing High Release Nickel

Globally, nickel is the leading cause of allergic contact dermatitis (ACD). Nickel is ubiquitous, and published literature continues to index items most frequently associated with Ni-ACD. Unregulated nickel exposure in North America is evident by the unprecedented rates of sensitization seen in patch-tested cohorts, 18.5% in children (ages 0-18 years) and 28.1% in adults.1 Conservative estimates of ACD within the pediatric population suggest at least one million cases in the US yearly with roughly one-quarter of those cases due to nickel.2-3 The United States could potentially save $5.7 billion annually in health care costs, extrapolating current cost-saving data from Denmark post nickel regulation, by implementing similar regulation to that of the European Union (EU).2 To our knowledge, site surveys testing for items releasing nickel in public locations has yet to be performed

DEVELOPMENT OF THE PERMEABLE DESIGN PRO PERMEABLE INTERLOCKING CONCRETE PAVEMENT DESIGN SYSTEM

, [email protected], www.icpi.org Note: The following is the notation used in this paper: ( . ) for decimals and ( ) for thousands. Summary National, state/provincial and municipal legislation regulating stormwater runoff in the United States and Canada have provided increased incentives for using permeable pavements. In addition, regulatory frameworks for implementation of sustainable design have embraced permeable pavement solutions. These regulations are often called low impact development (LID) or sustainable urban drainage systems (SUDS). A logical and technically sound design process using design software can support design professionals and help permeable pavement achieve full potential in North America. In 2008, the Interlocking Concrete Pavement Institute (ICPI) introduced a non-proprietary software program called Permeable Design Pro that integrates hydrological and structural design solutions for permeable interlocking concrete pavement. The hydrological analysis determines if the volume of water from user-selected rainfall events can be stored and released by the pavement structure. User defined parameters determine how much water infiltrates into the soil subgrade, enters pipe subdrains or flows from the pavement surface. The structural capacity of PICP is determined using the American Association of State Highway and Transportation Officials [AASHTO, 1993] structural design equations for base/subbase thickness to support vehicular traffic. This paper describes the development of the structural and hydrological design methodology with an example of its use

TOP2A and EZH2 Provide Early Detection of an Aggressive Prostate Cancer Subgroup.

Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive prostate cancer, defined by the progression from localized disease to metastasis, is responsible for the majority of prostate cancer–associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of prostate cancer patients; however, they have yet to provide targeted therapy approaches that could inhibit a patient\u27s progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary prostate cancer cohorts (n = 1,900), two metastatic castration-resistant prostate cancer datasets (n = 293), and one prospective cohort (n = 1,385) to assess the impact of TOP2A and EZH2 expression on prostate cancer cellular program and patient outcomes. We also performed IHC staining for TOP2A and EZH2 in a cohort of primary prostate cancer patients (n = 89) with known outcome. Finally, we explored the therapeutic potential of a combination therapy targeting both TOP2A and EZH2 using novel prostate cancer–derived murine cell lines. Results: We demonstrate by genome-wide analysis of independent primary and metastatic prostate cancer datasets that concurrent TOP2A and EZH2 mRNA and protein upregulation selected for a subgroup of primary and metastatic patients with more aggressive disease and notable overlap of genes involved in mitotic regulation. Importantly, TOP2A and EZH2 in prostate cancer cells act as key driving oncogenes, a fact highlighted by sensitivity to combination-targeted therapy. Conclusions: Overall, our data support further assessment of TOP2A and EZH2 as biomarkers for early identification of patients with increased metastatic potential that may benefit from adjuvant or neoadjuvant targeted therapy approaches. ©2017 AACR