TLR9 Agonist Protects Mice from Radiation-Induced Gastrointestinal Syndrome

Radiation-induced gastrointestinal syndrome (RIGS) is due to the clonogenic loss of crypt cells and villi depopulation, resulting in disruption of mucosal barrier, bacterial invasion, inflammation and sepsis. Intestinal macrophages could recognize invading bacterial DNA via TLR9 receptors and transmit regenerative signals to the neighboring crypt. We therefore investigated whether systemic administration of designer TLR9 agonist could ameliorate RIGS by activating TLR9.Male C57Bl6 mice were distributed in four experimental cohorts, whole body irradiation (WBI) (8.4-10.4 Gy), TLR9 agonist (1 mg/kg s.c.), 1 h pre- or post-WBI and TLR9 agonist+WBI+iMyd88 (pretreatment with inhibitory peptide against Myd88). Animals were observed for survival and intestine was harvested for histological analysis. BALB/c mice with CT26 colon tumors in abdominal wall were irradiated with 14 Gy single dose of whole abdominal irradiation (AIR) for tumor growth study.Mice receiving pre-WBI TLR9 agonist demonstrated improvement of survival after 10.4 Gy (p<0.03), 9.4 Gy (p<0.008) and 8.4 Gy (p<0.002) of WBI, compared to untreated or iMyd88-treated controls. Post-WBI TLR9 agonist mitigates up to 8.4 Gy WBI (p<0.01). Histological analysis and xylose absorption test demonstrated significant structural and functional restitution of the intestine in WBI+TLR9 agonist cohorts. Although, AIR reduced tumor growth, all animals died within 12 days from RIGS. TLR9 agonist improved the survival of mice beyond 28 days post-AIR (p<0.008) with significant reduction of tumor growth (p<0.0001).TLR9 agonist treatment could serve both as a prophylactic or mitigating agent against acute radiation syndrome and also as an adjuvant therapy to increase the therapeutic ratio of abdominal Radiation Therapy for Gastro Intestinal malignancies

Political fragmentation and land use changes in the Interior Plains

Recent years have witnessed growing interest in the critical role of local/regional governance structures in shaping physical land development and associated natural resource management processes. This article investigates how political fragmentation in local governance can affect land use patterns through a watershed-level analysis of population and employment density changes in the Interior Plains, the largest physiographic division of the US. Population density change rates are found to be negatively associated with a higher degree of political fragmentation, while employment density does not show such a clear relationship with political fragmentation. This finding shows that political fragmentation may present significant challenges to land and water resource management, a result consistent with the previous empirical research

COSTLY INTERMEDIATION AND THE POVERTY OF NATIONS

This article has two goals: (i) to reduce the 7-fold productivity differential required to explain the observed 33-fold income difference between the richest and poorest countries of the world; and (ii) to explain cross-country differences in the capital-output ratio. To achieve the first goal we modify the production function of the standard neoclassical growth model to include public capital whose provision is subject to intermediation costs. For the second goal we distort private investment by introducing credit frictions. The model, quantified using cross-country data, generates an income gap of 33 with productivity differences of "only" 3 under the measured variations in public and private capital. The required productivity gap declines even further, to 2.1, when we introduce a home-production sector. On the second goal, however, credit frictions do a poor job of explaining cross-country variations in the capital-output ratio. Copyright 2007 by the Economics Department Of The University Of Pennsylvania And Osaka University Institute Of Social And Economic Research Association.

The Siting of Livestock Facilities and Environmental Regulations

"The significant variation in the stringency of environmental regulations across Ontario municipalities in the late 1990s created the possibility of pollution havens where expanding livestock operations would locate in those municipalities with the lowest regulatory compliance costs. Using actual building permit data rather than aggregate regional production numbers, the study examined the factors affecting spatial changes. Instead of locating to reduce environmental compliance costs as suggested by the pollution haven hypothesis, barns are being built largely where the livestock sector is concentrated suggesting the existence of agglomeration economies. The result suggests that the normalization of standards across the province through the new Nutrient Management Act will not significantly influence the location decisions of expanding or new livestock facilities which are largely determined by economic factors associated with livestock infrastructure support." Copyright 2006 Canadian Agricultural Economics Society.