Shakers : compendium of the origin, history, princicples, rules and regulations, government, and doctrines of the United Society of Believers in Christ's Second Appearing : with biographies of Ann Lee, William Lee, Jas. Whittaker, J. Hocknell, J. Meacham, and Lucy Wright

by F. W. Evans

Studies on behavioral regulations of morphine tolerance in rats

Opioids remain the drugs of choice in chronic pain treatment, but opioid tolerance, defined as a decrease in analgesic effect after prolonged or repeated use, dramatically limits their clinical utility. Opioid tolerance has classically been studied by implanting spinal catheters in animals for drug administration. This procedure has significant morbidity and mortality, as well as causing an inflammatory response which decreases the potency of opioid analgesia and possibly affects tolerance development. Therefore, we developed and validated a new method, intermittent lumbar puncture (Dautzenberg et al.), for the study of opioid analgesia and tolerance. Using this method, opioid tolerance was reliably induced without detectable morbidity. The dose of morphine needed to induce analgesia and tolerance using this method was about 100-fold lower than that required when using an intrathecal catheter. Only slight inflammation was found at the injection site, dissipated within seven mm. ^ DAMGO, an opioid μ receptor agonist, has been reported to inhibit morphine tolerance, but results from different studies are inconclusive. We evaluated the effect of DAMGO on morphine tolerance using our newly-developed ILP method, as well as other intrathecal catheter paradigms. We found that co-administration of sub-analgesic DAMGO with morphine using ILP did not inhibit morphine tolerance, but instead blocked the analgesic effects of morphine. Tolerance to morphine still developed. Tolerance to morphine can only be blocked by sub-analgesic dose of DAMGO when administered in a lumbar catheter, but not in cervical catheter settings. ^ Finally, we evaluated the effects of Gabapentin (GBP) on analgesia and morphine tolerance. We demonstrated that GBP enhanced analgesia mediated by both subanalgesic and analgesic doses of morphine although GBP itself was not analgesic. GBP increased potency and efficacy of morphine. GBP inhibited the expression, but not the development, of morphine tolerance. GBP blocked tolerance to analgesic morphine but not to subanalgesic morphine. GBP reversed the expression of morphine tolerance even after tolerance was established. These studies may begin to provide new insights into mechanisms of morphine tolerance development and improve clinical chronic pain management. ^

Impact of environmental regulations on lead concentrations in Texas ambient air and water: 1970--1990

In the last two decades, the significance of lead has been addressed in a number of environmental regulations at the national and state levels. This project investigated the environmental regulations (Clean Air Act and Amendments, 1970-1990 and Clean Water Act of 1977) and their cumulative effects on lead in ambient air and water in the state of Texas. For this purpose, historical records from the Texas Water Development Board, Texas Natural Resources Conservation Commission, and the United States Geological Survey have been assembled and analyzed for temporal and spatial trends. These trends might correspond to the phase out of lead in gasoline and other regulations.^ This study concluded that there is a significant correlation (p $\leq$.001) between environmental regulations of lead in gasoline and the concentration of lead in ambient air. Lead concentrations in ambient air have been reduced by over 90 percent in the past twenty years. An overall significant difference (p $\leq$.001) was found in mean (94, 15 respectively) lead concentrations in surface water between two time periods, one at the beginning of the twenty year period and one at the end of the study period. There has been an overall reduction of lead concentrations in surface water in Texas of approximately 84 percent. However, this reduction cannot be statistically associated with any one regulation. Groundwater data could not be analyzed for lead concentrations because of limitations of reporting data as "less than". Approximately two percent of the groundwater data was analyzed by Oneway ANOVA and no significant difference was found between the means (18, 19 respectively) of two time periods, 1977-1979 and 1988-1990. This data is consistent with the regulations having a contributory affect on declining concentrations, but other factors cannot be ruled out as having added to these declines. This study can also serve as a starting point for a more in-depth study of environmental regulations and their impact on the environment. ^

Impact of traffic pollution on telomere length and chronic diseases: Results from the multi-ethnic study of atherosclerosis and the Mexican-American cohort study

Exposure to air pollutants in urban locales has been associated with increased risk for chronic diseases including cardiovascular disease (CVD) and pulmonary diseases in epidemiological studies. The exact mechanism explaining how air pollution affects chronic disease is still unknown. However, oxidative stress and inflammatory pathways have been posited as likely mechanisms. ^ Data from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Mexican-American Cohort Study (2003-2009) were used to examine the following aims, respectively: 1) to evaluate the association between long-term exposure to ambient particulate matter (PM) (PM10 and PM2.5) and nitrogen oxides (NO x) and telomere length (TL) among approximately 1,000 participants within MESA; and 2) to evaluate the association between traffic-related air pollution with self-reported asthma, diabetes, and hypertension among Mexican-Americans in Houston, Texas. ^ Our results from MESA were inconsistent regarding associations between long-term exposure to air pollution and shorter telomere length based on whether the participants came from New York (NY) or Los Angeles (LA). Although not statistically significant, we observed a negative association between long-term air pollution exposure and mean telomere length for NY participants, which was consistent with our hypothesis. Positive (statistically insignificant) associations were observed for LA participants. It is possible that our findings were more influenced by both outcome and exposure misclassification than by the absence of a relationship between pollution and TL. Future studies are needed that include longitudinal measures of telomere length as well as focus on effects of specific constituents of PM and other pollutant exposures on changes in telomere length over time. ^ This research provides support that Mexican-American adults who live near a major roadway or in close proximity to a dense street network have a higher prevalence of asthma. There was a non-significant trend towards an increased prevalence of adult asthma with increasing residential traffic exposure especially for residents who lived three or more years at their baseline address. Even though the prevalence of asthma is low in the Mexican-origin population, it is the fastest growing minority group in the U.S. and we would expect a growing number of Mexican-Americans who suffer from asthma in the future. Future studies are needed to better characterize risks for asthma associated with air pollution in this population.^

Regulations of SOX9 activity during chondrogenesis

Sox9 is a transcription factor required for chondrocyte differentiation and cartilage formation. In an effort to identify SOX9 interacting protein(s), we screened a chondrocyte cDNA library with a modified yeast two-hybrid method, Son of Sevenless (SOS) recruitment system (SRS). The catalytic subunit of cyclic AMP-dependent protein kinase A (PKA-Cα) and a new long form of c-Maf transcription factor (Lc-Maf) were found to interact specifically with SOX9. We showed here that two PKA phosphorylation consensus sites of SOX9 could be phosphorylated by PKA in vitro as well as in vivo. PKA phosphorylation of SOX9 increases its DNA binding and transcriptional activities on a Col2a1 chondrocyte-specific enhancer. Mutations of these two PKA phosphorylation sites markedly decreased the activation of SOX9 by PKA. ^ To test whether parathyroid hormone-related peptide (PTHrP) signaling results in SOX9 phosphorylation, we generated a phosphospecific antibody that specifically recognizes SOX9 that is phosphorylated at serine 181 (S 181) one of the two consensus PKA phosphorylation sites. Addition of PTHrP to COS7 cells cotransfected with SOX9 and PTH/PTHrP receptor strongly increased phosphorylation of SOX9 at S181; this phosphorylation was blocked by a PKA-specific inhibitor. In similar experiments we showed that PTHrP increased the activity of a SOX9-dependent Col2a1 enhancer. This increase in activity was abolished when a SOX9 mutant was used containing serine-to-alanine substitution in the two consensus PKA phosphorylation sites of SOX9. Using our phosphospecific SOX9 antibody we showed by immunohistochemistry of mouse embryos that Sox9 phosphorylated at S181 was localized almost exclusively in the pre-hypertrophic zone of the growth plate, an area corresponding to the major site of expression of PTH/PTHrP receptor. In contrast, no phosphorylation of Sox9 at S181 was detected in growth plates of PTH/PTHrP receptor null mutant mice. Sox9, regardless of phosphorylation state, was present in all chondrocytes of both genotypes except in hypertrophic chondrocytes. Thus, Sox9 is a target of PTHrP signaling and the PTHrP-dependent phosphorylation of SOX9 enhances its transcriptional activity. ^ In order to investigate the in vivo function of Sox9 phosphorylation by PKA, we are generating a mouse model of mutant Sox9 harboring point mutations in two PKA phosphorylation sites. Preliminary results indicated that heterozygous mice containing half amount of mutant Sox9 that can not be phosphorylated by PKA have normal skeletal phenotype and homozygous mice are being generated. ^ Lc-Maf encodes an extra ten amino acids at the carboxyl terminus of c-Maf and contains a completely different 3′ untranslated region. The interaction between SOX9 and Lc-Maf was further confirmed by co-immunoprecipitation and GST-pull down assays, which mapped the interacting domains of SOX9 to HMG DNA binding domain and that of Lc-Maf to basic leusine zipper motif. In situ hybridizations showed that RNA of Lc-Maf coexpressed with those of Sox9 and Col2a1 in areas of mesenchymal condensation during the early stages of mouse embryo development. A DNA binding site of Lc-Maf was identified at the 5′ part of a 48-bp Col2a1 enhancer element near the HMG binding site of SOX9. Lc-Maf and SOX9 synergistically activated a luciferase reporter plasmid containing a Col2al enhancer and increased the transcription of endogenous Col2a1 gene. In summary, Lc-Maf is the first identified SOX9-interating protein during chondrogenesis and may be an important activator of Col2a1 gene. ^

Legal Abortion: A Comparative Analysis of Health Regulations

This publication is the result of a comparative analysis of laws and health regulations governing access to legal abortion in 13 countries: Bolivia, Brazil, Canada, Colombia, Guyana, Italy, Mexico, Norway, Panama, Peru, Puerto Rico, South Africa, and Spain. It seeks to promote access to safe and legal abortion services by developing health regulations and guidelines that are grounded in a human rights framework.

Role of supply chains in adopting product related environmental regulations : case studies of Vietnam

This paper shows some findings how product related environmental regulations, especially those that relate to management of chemical substances affect firms in Asia. Interviews were conducted for some firms in Vietnam that are part of global supply chains of electrical and electronic, furniture, and plastic industries. The global supply chains with MNC lead firms have helped local firms in developing countries to adopt technical PRERs overseas. On the other hand, indigenous firms that do not belong to global value chains might face hurdles to keep exporting to the regulated markets. PRERs could become a barrier for firms that attempt to the regulated markets without supports by MNC lead firms.

Impact of product-related environmental regulations / voluntary requirements on Thai firms

The rules governing the trade of goods in global markets have shifted toward non-tariff measures related to environmental and chemical safety. Unlike traditional environmental/safety requirements, the scope of modern regulations covers products’ environmental performance and chemical safety. To comply with these modern regulations, production practices along the entire supply chain must be realigned to manage certain chemical substances incorporated into the final product. This paper examines the implications of product-related environmental and chemical safety regulations on different firms operating in Thailand.

Role of laboratories for adapting product-related environmental regulations (PRERs)

This paper examines how a country which has been successful in creating agglomeration of a manufacturing industry has faced various types of product-related environmental regulations. Then the paper shows how the government and testing laboratory have taken measures to adapt to PRERs overseas in response to the needs by firms affected by regulations. In reaction to the introductions of PRERs overseas, Malaysia also has introduced equivalent policies domestically, proving that PRERs have spread to Malaysia.

Role of laboratories for adapting product-related environmental regulations (PRERs)

This paper examines how a country which has been successful in creating agglomeration of a manufacturing industry has faced various types of product-related environmental regulations. Then the paper shows how the government and testing laboratory have taken measures to adapt to PRERs overseas in response to the needs by firms affected by regulations. In reaction to the introductions of PRERs overseas, Malaysia also has introduced equivalent policies domestically, proving that PRERs have spread to Malaysia.

Role of laboratories for adapting product-related environmental regulations (PRERs)

This paper examines how a country which has been successful in creating agglomeration of a manufacturing industry has faced various types of product-related environmental regulations. Then the paper shows how the government and testing laboratory have taken measures to adapt to PRERs overseas in response to the needs by firms affected by regulations. In reaction to the introductions of PRERs overseas, Malaysia also has introduced equivalent policies domestically, proving that PRERs have spread to Malaysia.

Role of laboratories for adapting product-related environmental regulations (PRERs)

This paper examines how a country which has been successful in creating agglomeration of a manufacturing industry has faced various types of product-related environmental regulations. Then the paper shows how the government and testing laboratory have taken measures to adapt to PRERs overseas in response to the needs by firms affected by regulations. In reaction to the introductions of PRERs overseas, Malaysia also has introduced equivalent policies domestically, proving that PRERs have spread to Malaysia.

Role of laboratories for adapting product-related environmental regulations (PRERs)

This paper examines how a country which has been successful in creating agglomeration of a manufacturing industry has faced various types of product-related environmental regulations. Then the paper shows how the government and testing laboratory have taken measures to adapt to PRERs overseas in response to the needs by firms affected by regulations. In reaction to the introductions of PRERs overseas, Malaysia also has introduced equivalent policies domestically, proving that PRERs have spread to Malaysia.

Impact of product-related environmental regulations in Asia : descriptive statistics from a survey of firms in Penang, Malaysia

This paper summarizes the main results of a unique firm survey conducted in Penang, Malaysia in 2012 on product-related environmental regulations. The results show that firms receiving foreign-direct investment have adapted well to regulations but faced more rejections. Several research questions are addressed and examined by using the survey data. Major findings are as follows. First, adaptation involves changes in input procurement and market diversification, which potentially changes the structure of supply chains. Second, belonging to global supply chains is a key factor in compliance, but this requires firms to meet tougher customer requirements. Third, there is much room for government policy to play a role in assisting firms.