Population Changes of North Dakota\u27s Rural Trade Centers, 1960-1970

Research in trade relationships and hinterland analysis has shown that rural trade centers do not exist in isolation, but exhibit an interdependence with other rural and urban places. The purpose of this study is to examine relationships among trade centers by measuring their potential for growth. The construct selected for growth analysis examines rural trade center population changes in relation to the size of rural trade centers, distance from urban centers, and the size of neighboring trade centers, both urban and rural. Trade centers having populations greater than 2,500 in 1970, were defined as urban. All trade centers considered were located within the politically defined boundaries of the State of North Dakota. Detailed examinations of rural trade center relationships were made with respect to urban centers, and regional urban centers. The Fargo-Moorhead urbanized area located in Cass County was used as a case study. Urban centers were differentiated by size—2,500 to 5,000 (Category I) and 5,000 and over (Category II). Regional center population size was 10,000 and over. Population change of rural trade centers was selected as a measurement indicator. A positive population change from 1960 to 1970 was assumed to be indicative of a potential for future population growth and a symbiotic relationship. A negative population change was assumed to be indicative of a lack of growth potential and a competitive relationship. The hypothesis selected for testing assumed rural trade centers to be at a disadvantage when located within 20 miles of urban centers. Underlying this assumption is the postulate that rural trade centers are integrated elements of a hierarchial system and function in association with urban centers. The methodology utilized tabular analysis to identify the relationships and correlation coefficients to measure the degree of association. Results of the tabular and statistical analyses were supplemented with field observations concerning the factors related to population change. The results indicated weak associations between population change and distance to urban centers. It was found that Category I urban centers compete with rural trade centers. Also, a stronger association exists between growth of rural centers and distance to Category II and regional urban centers. Symbiotic relationships are most strongly developed in Cass County, however, growth patterns cannot be fully explained by the relationship between rural trade centers and the City of Fargo. The correlation between rural trade center population change and distance to other rural trade centers was positive. Lack of statistical significance, however, prevented statistical verification of a competitive relationship. The correlation between size of rural trade center and population change was .18 and significant. In comparison to correlations between population change and distance to urban centers, this indicated that size of a rural trade center is a more important variable associated with growth in an area where relationships between urban and rural trade centers are weakly developed

Peripheral and central mechanisms in chronic human inflammatory and neuropathic pain and associated animal models

Imperial Users onl

A Manual for Computer Graphics and Animation Using the CSL Line and Half-Tone Graphic Systems

Coordinated Science Laboratory was formerly known as Control Systems Laborator

Ultrastructural distribution of the S100A1 Ca2+-binding protein in the human heart

Impaired calcium homeostasis and altered expression of Ca2+-binding proteins are associated with cardiomyopathies, myocardial hypertrophy, infarction or ischemia. S100A1 protein with its modulatory effect on different target proteins has been proposed as one of potential candidates which could participate in these pathological processes. The exact localization of S100A1 in human heart cells on the ultrastructural level accompanied with biochemical determination of its target proteins may help clarify the role of S100A1 in heart muscle. In the present study the distribution of the S100A1 protein using postembedding (Lowicryl K4M) immunocytochemical method in human heart muscle has been determined quantitatively, relating number of antigen sites to the unit area of a respective structural component. S100A1 antigen sites have been detected in elements of sarcoplasmic reticulum (SR), in myofibrils at all levels of sarcomere and in mitochondria, the density of immunolabeling at Z-lines being about 3 times and at SR more than 5 times higher than immunolabeling of remaining structural components. The presence of the S100A1 in SR and myofibrils may be related to the known target proteins for S100A1 at these sites

Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF

© 2016 BMJ Publishing Group Ltd & British Thoracic Society.Rationale Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal of all fibrotic conditions with no curative therapies. Common pathomechanisms between IPF and cancer are increasingly recognised, including dysfunctional pan-PI3 kinase (PI3K) signalling as a driver of aberrant proliferative responses. GSK2126458 is a novel, potent, PI3K/mammalian target of rapamycin (mTOR) inhibitor which has recently completed phase I trials in the oncology setting. Our aim was to establish a scientific and dosing framework for PI3K inhibition with this agent in IPF at a clinically developable dose. Methods We explored evidence for pathway signalling in IPF lung tissue and examined the potency of GSK2126458 in fibroblast functional assays and precision-cut IPF lung tissue. We further explored the potential of IPF patient-derived bronchoalveolar lavage (BAL) cells to serve as pharmacodynamic biosensors to monitor GSK2126458 target engagement within the lung. Results We provide evidence for PI3K pathway activation in fibrotic foci, the cardinal lesions in IPF. GSK2126458 inhibited PI3K signalling and functional responses in IPF-derived lung fibroblasts, inhibiting Akt phosphorylation in IPF lung tissue and BAL derived cells with comparable potency. Integration of these data with GSK2126458 pharmacokinetic data from clinical trials in cancer enabled modelling of an optimal dosing regimen for patients with IPF. Conclusions Our data define PI3K as a promising therapeutic target in IPF and provide a scientific and dosing framework for progressing GSK2126458 to clinical testing in this disease setting. A proof-ofmechanism trial of this agent is currently underway. Trial registration number NCT01725139, pre-clinical

Both MC1 and MC3 Receptors Provide Protection From Cerebral Ischemia-Reperfusion-Induced Neutrophil Recruitment.

Objective Neutrophil recruitment is a key process in the pathogenesis of stroke, and may provide a valuable therapeutic target. Targeting the melanocortin receptors (MC) has previously shown to inhibit leukocyte recruitment in peripheral inflammation, however it is not known whether treatments are effective in the unique cerebral microvascular environment. Here, we provide novel research highlighting the effects of the melanocortin peptides on cerebral neutrophil recruitment, demonstrating important yet discrete roles for both MC1 and MC3. Approach and Results Using intravital microscopy, in two distinct murine models of cerebral ischemia-reperfusion (I/R) injury we have investigated melanocortin control over neutrophil recruitment. Following global I/R, pharmacological treatments suppressed pathological neutrophil recruitment. MC1 selective treatment rapidly inhibited neutrophil recruitment while a non-selective MC agonist provided protection even when co-administered with an MC3/4 antagonist, suggesting the importance of early MC1 signaling. However by 2h reperfusion, MC1 mediated effects were reduced, and MC3 anti-inflammatory circuits predominated. Mice bearing a non-functional MC1 displayed a transient exacerbation of neutrophil recruitment following global I/R, which diminished by 2h. However importantly, enhanced inflammatory responses in both MC1 mutant and MC3 -/- mice resulted in increased infarct size and poor functional outcome following focal I/R. Furthermore we utilized an in vitro model of leukocyte recruitment to demonstrate these anti-inflammatory actions are also effective in human cells. Conclusions These studies reveal for the first time melanocortin control over neutrophil recruitment in the unique pathophysiological context of cerebral I/R, whilst also demonstrating the potential therapeutic value of targeting multiple MCs in developing effective therapeutics

Signals, Systems, and Environment in Industrial Food Production

This paper explores characteristics of the “alternative medicine” or ecological paradigm and some of its implications for health po9licies. This paradigm suggests that many degenerative diseases (including cancer) are "caused" or accellerated by the building of industrial toxins and that effective public policies should encourage wholistic preventative changes, including in food and water systems, rather than primarily addressing symptoms. Key Words: disease, health, industrialization, pollution, ecology, alternative medicine, ecological pressure, health policy