Serum Urate Concentrations and the Risk of Hyperuricemia

Serum Urate Concentrations and the Risk of Hyperuricemia Common UCP2 variants contribute to serum urate concentrations and the risk of hyperuricemia Luyu Yang, Zheng Dong, Jingru zhou, Yanyun Ma, Weilin Pu, Dongbao Zhao, Hongjun He, Hengdong Ji, Yajun Yang, Xiaofeng Wang, Xia Xu, Yafei Pang, Hejian Zou,  Li Jin,  Chengde Yang*, Jiucun Wang* *Corresponding author These authors equally contributed to this study.   Abstract Elevated serum urate, which is regulated at multiple levels including genetic variants, is a risk factor for gout and other metabolic diseases. This study aimed to investigate the association between UCP2 variants and serum urate as well as hyperuricemia in a Chinese population. In total, 4332 individuals were genotyped for two common UCP2 variants, -866G/A and Ala55Val. These loci were not associated either serum urate level or with a risk of hyperuricemia in the total group of subjects. However, in females, -866G/A and Ala55Val were associated with a lower serum urate (P = 0.006 and 0.014à ¯Ã‚ ¼Ã…’seperately) and played a protective role against hyperuricemia (OR = 0.80, P = 0.018; OR = 0.79, P = 0.016). These associations were not observed in the males. After further stratification, the two loci were associated with serum urate in overweight, but not underweight females. The haplotype A-T (-866G/A-Ala55Val) was a protective factor for hyperuricemia in the female subgroup (OR = 0.80, P=0.017). This present study identified a novel gene, UCP2, that influences the serum urate concentration and the risk of hyperuricemia, and the degree of association varies with gender and BMI levels.   Introduction Uric acid is the final product of purine oxidation in humans. Elevated serum urate, or hyperuricemia, has long been recognized as an independent risk factor for gout [1-2]. There is a renewed interest in hyperuricemia and its association with a number of other clinical disorders including hypertension, atherosclerosis, cardiovascular disease, chronic kidney diseases, and abdominal obesity, glucose intolerance, insulin resistance, and dyslipidemia, which are often subsumed under the term metabolic syndrome [3]. Serum urate is balanced between uric acid production in the liver and its disposal via the kidney and gut [4]. The occurrence of hyperuricemia could be caused by disruptions in any part of this metabolic process. Both genetic and environmental factors, such as gender and body mass index (BMI), have a strong effect on the risk of hyperuricemia [3]. Among those factors, the attribution of genetic factors is estimated to be as high as 73% [5]. Recent genome-wide association studies (GWAS) have identified 28 loci associated with serum urate concentration [6]. However, only approximately 7% of the variation in serum urate concentration could be explained by those reported loci, suggesting the missing heritability remained to be explored [6]. Human uncoupling proteins (UCPs) are mitochondrial transporters present in the inner membrane of mitochondria [7]. UCPs are capable of uncoupling ATP production from mitochondrial respiration by causing proton leak and preventing mitochondrial hyperpolarization and the formation of reactive oxygen species (ROS) [8]. Among the five identified UCPs, UCP2 is widely expressed in almost all mammalian tissues including white adipose tissue, liver, kidney, pancreatic islets, macrophages and retinal endothelial cells, indicating its involvement in a variety of physiologic or pathologic events [9-12]. Two of the most common polymorphisms of this gene, -866G/A (rs659366) in the promoter and Ala55Val (rs660339) in codon 55, were identified as being associated with different phenotypes [7, 12], including obesity, insulin resistance, type 2 diabetes mellitus (T2D), low-density lipoprotein (LDL) particle size, coronary incidence and other metabolic disorders [9-10, 13-21]. Given the involvement of UCP2 and hyperuricemia in a variety of metabolic disorders, we selected the two common loci -866G/A and Ala55Val to explore the association between genetic UCP2 variants and hyperuricemia in a Chinese population, offering a new diagnostic or therapeutic target for hyperuricemia. Results There was no  association between SNPs and serum urate The two loci were proven in Hardy-Weinberg equilibrium (-866G/A: P = 0.990; Ala55Val: P = 0.690). For -866G/A, AA, AG, and GG genotypes accounted for 21.6%, 49.9%, and 28.6% of hyperuricemic patients, respectively; in healthy controls, the distribution was 21.2%, 49.6%, and 29.3%, respectively. As shown in Table 1, the -866G/A polymorphism was not found to be associated with serum urate (AA/GG: Beta = -0.008, P = 0.644; AG/GG:Beta = -0.012, P = 0.474) or with the risk of hyperuricemia (AA/GG: OR = 1.05, P = 0.603; AG/GG:OR = 1.03, P = 0.667). For Ala55Val, the TT, TC, and CC genotype distribution was 21.5%, 50.5% and 28.0% in hyperuricemic patients, respectively, and the distribution was 21.5%, 49.8% and 28.6% in healthy controls, respectively. No association was observed between Ala55Val polymorphism and serum urate (TT/CC: Beta = -0.013, P = 0.460; TC/CC:Beta = -0.017, P = 0.324). There was no difference in the distribution of the genotypes or alleles among hyperuricemic patients a nd healthy controls (TT/CC: OR = 1.02, P = 0.824; TC/CC:OR = 1.04, P = 0.652). Therefore, no statistically solid evidence supported the genetic effect of -866G/A and Ala55Val on serum urate or the risk of hyperuricemia in the total group of subjects. UCP2 variants were associated withserum urate andhyperuricemia in female subgroups As shown in Table 1, we stratified all subjects into male and female subgroups to further explore the gender-related genetic effects of the two polymorphisms. In the male subgroups, there were no significant associations between the two loci and serum urate or the risk of hyperuricemia (all P > 0.025). However, some nominal significant associations were found between -866G/A and the hyperuricemia risk (genotype AA: OR = 1.26, P = 0.038; allele A: OR = 1.12, P = 0.035), indicating a possible risky effect of the -866G/A variant on hyperuricemia incidence in males. A significant association was found between SNPs and serum urate and hyperuricemia in the female subgroups. The -866G/A genotypes were associated with a lower serum urate (AA/GG: Beta = -0.078, P = 0.015; AG/GG: Beta = -0.104, P = 0.001) and a decreased risk of hyperuricemia (AG/GG: OR = 0.71, P = 0.025). The subjects carrying allele A had a lower serum urate and a decreased risk of hyperuricemia (A/G: Beta = -0.054, P = 0.006; OR = 0.80, P = 0.018). For Ala55Val, genotype TT carriers showed a lower serum urate (TT/CC: Beta = -0.075, P = 0.022) and a decreased risk of hyperuricemia (TT/CC: OR = 0.64, P = 0.020). Genotype TC carriers only had a lower serum urate (TC/CC: Beta = -0.082, P = 0.012) but no decreased risk of hyperuricemia (TC/CC: OR = 0.77, P = 0.093). Allele T was associated with a lower serum urate (T/C: Beta = -0.049, P = 0.016) and a decreased risk of hyperuricemia (T/C: OR = 0.79, P = 0.016). Further analysis of associationin females  with different BMI levels Further analysis was performed regarding the genetic effect of UCP2 variants on serum urate and the risk of hyperuricemia among females with different BMI levels (Table 2). The majority of the females enrolled were stratified into normal- or overweight group (Table 2). In the underweight subgroup, whose sample size was limited after stratification, no significant association was observed between the two loci and serum urate or hyperuricemia risk (all P > 0.025, Table 2). In the normal weight subgroup, -866G/A genotype AA+AG carriers were associated with a lower serum urate (AA+AG/GG: Beta = -0.095, P = 0.022) but not with a decreased risk of hyperuricemia (AA+AG/GG: OR = 0.65, P = 0.076). However, the Ala55Val genotypes or alleles showed no statistical association with serum urate (TT+TC/CC: Beta = -0.070, P = 0.091; T/C: Beta = -0.047, P = 0.106) or hyperuricemia (TT+TC/CC: OR = 0.72, P = 0.173; T/C: OR = 0.72, P = 0.051). In the overweight subgroup, the genotypes of both loci were associated a lower serum urate (AA+AG/GG: Beta = -0.138, P = 0.001; TT+TC/CC: Beta = -0.130, P = 0.003) and a significant, or at least marginal, decreased risk of hyperuricemia (AA+AG/GG: OR = 0.62, P = 0.015; TT+TC/CC: OR = 0.74, P = 0.027). However, the alleles of the loci were associated with a lower serum urate level (A/G: Beta = -0.072, P = 0.019; T/C: Beta = -0.072, P = 0.019) but not with a decreased risk of hyperuricemia (A/G: OR = 0.75, P = 0.036; T/C: OR = 0.74, P = 0.027). Our results suggested a stronger effect of UCP2 variants on overweight females than on normal weight females (Table 2). Association between haplotypes and risk of hyperuricemia As listed in Table 3, the haplotypes of the two loci were estimated in the total group of subjects and after stratification by gender. The -866G/A and Ala55Val variants were in strong linkage disequilibrium (D = 0.974, r2 = 0.936). The wild type haplotype G-C (-866G/A-Ala55Val) was applied as the reference one. Haplotype A-T made up for the most frequent one, while single mutation at -866G/A or Ala55Val each accounted for less than 1 percent (Table 3). In the total group of subjects, no haplotypes were correlated with susceptibility of hyperuricemia. In the female subgroups, haplotype A-T (-866G/A-Ala55Val) was associated with a decreased risk of hyperuricemia; however, this association was null in males. No further significant associations between hyperuricemia and other two rare haplotypes were found in our study, partly due to the limited size of the rare haplotypes carriers (Table 3). These results correlated with the association between genotypes or alleles and hyperuricemia (Ta ble 1). Discussion Uncoupling protein 2 (UCP2) is present in the inner mitochondrial membrane and mainly decreases the ATP level and ROS produced by electron transport; therefore, UCP2 is involved in a board range of pathological processes. In the present study, we first focused on the relationship between UCP2 variants and serum urate and hyperuricemia, potentially examining the scope of the loci related to hyperuricemia. The present study revealed no association between the two polymorphisms of UCP2 and serum urate or hyperuricemia in the total group of subjects. However, because serum urate is extensively influenced by gender differences, we stratified the total group of subjects and determined that -866G/A and Ala55Val were associated with serum urate and hyperuricemia in females [25-26]. Females with the -866G/A genotype AA+AG or allele A had lower serum urate and a decreased risk of hyperuricemia, indicating a protective role of -866G/A for hyperuricemia in females. The -866G/A variant is a functional polymorphism located in the promoter region and putatively changes the transcription factor binding sites [7]. The wild type G allele in -866G/A was associated with lower UCP2 mRNA expression [19, 27]. Increased UCP2 mRNA expression from the A allele was translated into an increased amount of UCP2 protein, with corresponding induced proton leak, decreased ATP/ADP ratio and enhanced elimination of ROS [10, 19]. Hypermethylation in the promoter region could affect the binding of transcripation factors, causing aberrant gene expression. Consistent with our expectations, we found a typical CpG island in the UCP2 promoter region, which included the locus of the -866G/A variant, using information from the University of California-Santa Cruz (UCSC; Santa Cruz, CA, USA) database (http://genome.ucsc.edu/cgi-bin/hgGateway). We believe the UCP2 promoter variant -866G/A could shape this CpG island and protect the UCP2 promoter region from DNA methylation, unco vering a novel underlying mechanism that determines -866G/A increases UCP2 transcription. Uric acid accumulation is caused by the acceleration of ATP degradation to AMP, a precursor of uric acid, and UCP2 could decrease the ATP level and lower redundant AMP for uric acid formation [7, 28]. Moreover, an elevation of serum urate concentration occurs as a physiologic response to increased oxidative stress [31]. Because the ROS level could be down-regulated by UCP2, a counter-regulatory increase of serum urate as an antioxidant defense is less urgent. Therefore, the -866G/A variant in the promoter region might serve as a protective factor through a higher UCP2 mRNA level and increased translation of the UCP2 protein, which might regulate ROS and modify the ATP/ADP ratio. The other locus, Ala55Val, is a missense variant in exon 4 and is associated with an altered degree of uncoupling [7]. In our study, a protective effect for hyperuricemia and lower serum urate were observed in genotype TT and allele T in the female subgroups. However, the genetic effect of the Ala55Val variant was less clear. Several researchers identified an association of Ala55Val with the BMI level and type 2 diabetes mellitus (T2D), with controversial conclusions within cohorts, and few functional studies were performed [14, 32-33]. Similar to -866G/A, the protective role of the Ala55Val variant for hyperuricemia might also be attributed to altered UCP2 transcription. In the male subgroups, a less statistically significant but possible effect of -866G/A and Ala55Val was observed for hyperuricemia risk and higher serum urate. Similar gender-associated genetic effects of UCP2 variants were more or less observed for diseases other than hyperuricemia [7]. For example, Heidema et al. suggested a genetic effect of UCP2 on weight gain was regulated through different mechanism in males and females [34]. Lee, et al. demonstrated that the association between UCP2 variants and BMI was more apparent among female subjects [35]. Cheurfa et al. confirmed the association of UCP2 variants with coronary artery diseases in males but not females [36]. In the present study, we found UCP2 variants -866G/A and Ala55Val had a stronger effect on females with hyperuricemia. One possible explanation for the gender-associated genetic effects of UCP2 might be a regulation role of sex hormones such as estrogen. Estrogen was reported to repress UCP2 in a breast cancer cell line and papillary thyroid cancer cells [37-38]. Taken together, these results suggest the UCP2 protein level was down-regulated by estrogen in females but reversed by the variants of -866G/A and Ala55Val, providing a plausible explanation for the specific protective effects of UCP2 variants on females [37]. Genetic effects on hyperuricemia and obesity have been widely recognized [3]. In the present study, we found that -866G/A and Ala55Val were associated with lower serum urate and a decreased risk of hyperuricemia in overweight, but not underweight, females (Table 2). The relative small sample size might limit the correlation analysis in the underweight group. However, we did observe females with higher BMI level were more likely to benefit from the protective genetic effect of -866G/A and Ala55Val, where the association was significant between the two SNPs and serum urate level of risk of hyperuricemia. In the contrast, among the normal weight females, -866G/A, but not Ala55Val, showed a significant association with a low risk of hyperuricemia, indicating a less contribution from the protective effect of UCP2 variants than seen in overweight females. It was also implied from our results that the [tw1]functional à ¢Ã‹â€ Ã¢â‚¬â„¢866G>A promoter variant displayed a stronger effect. The interactions between obesity, uric acid and UCP2 were complicated. BMI has long been viewed as an essential factor influencing uric acid [3]. UCP2 transcription was activated by fatty acids [16]. A recent meta-analysis revealed that UCP2 -866G/A and Ala55Val are associated with a risk of obesity [32]. Subtle intermediary obesity related phenotypes such as elevated triglycerides, total cholesterol concentrations, increased the risk of dyslipidemia and circulating leptin levels were also observed to be correlated with UCP2 variants [40]. Based on these results, we assumed lipid metabolism material such as fatty acids participated in and enhanced the genetic effect of UCP2 variants on serum urate regulation, explaining the stronger genetic effect of UCP2 variants on females with higher BMI levels observed in the present study. The -866G/A and Ala55Val variants were in strong linkage disequilibrium (D = 0.974, r2 = 0.936). The haplotype frequency analysis revealed that variants of the two loci were more in co-variant haplotype A-T (-866G/A-Ala55Val) compared with the single variant forms of G-T or A-C (Table 3). Haplotype A-T was associated with a decreased risk of hyperuricemia only in females, which was consistent with the genotype or alleles results. However, the small size of the two rare haplotypes might limit the power of association analysis with hyperuricemia risk to a certain extent. The susceptibility of hyperuricemia in the two rare haplotype carriers required validation in a larger cohort. Conclusion The present study identified a novel gene, UCP2, with two loci, -866G/A and Ala55Val; this gene influenced the serum urate concentrations and the risk of hyperuricemia in females. The associations of those loci were affected by gender and BMI. This study supported the potential involvement of this gene in the prevention, prediction and treatment of hyperuricemia. Materials and methods Experimental design A total of 4332 subjects were enrolled from the Taizhou Longitudinal Study [22] and included 1387 hyperuricemic patients and 2945 healthy controls. The associations of common UCP2 variants with serum urate and hyperuricemia were tested by linear regression and logistic regression with or without gender stratification, respectively. A body mass index (BMI) subgroup was also used for further analysis. Participants All subjects were enrolled from Taizhou Longitudinal Study [22], of which 1387 individuals had serum urate level over 7 mg/dl and were treated as hyperuricemic patients, and 2945 individuals had normal serum urate (à ¢Ã¢â‚¬ °Ã‚ ¤ 7 mg/dl) and were treated as healthy controls [23]. The subjects were divided into subgroups (underweight: BMI à ¯Ã¢â€š ¬Ã‚ ¼ 18.5; normal weight: 18.50 à ¯Ã¢â‚¬Å¡Ã‚ £ BMI Genetic analysis Genetic analysis was carried out in accordance with the written informed consent and guideline offered by the Ethical Committees of the School of Life Science of Fudan University. For genetic analysis, peripheral blood was collected from all the individuals included in this study. Genomic DNA was extracted from whole blood using the QIAamp DNA Blood Mini kit (QIAGEN, Germany) and was stored at -20à ¢Ã¢â‚¬Å¾Ã†â€™. The DNA concentration and quality (including optical density (OD) 260/280 and 260/230 measurements) were determined using a Nanodrop Lite spectrophotometer (Thermo Fisher Scientific, Waltham, MA, USA). Genotyping of -866G/A and Ala55Val in UCP2 were performed by SNPscan according to the manufacturers instructions. Statistical analysis The clinical characteristics were presented as the mean à ¯Ã¢â‚¬Å¡Ã‚ ± SD. Students t-test was used to test for a significant difference in the mean age, BMI and serum urate between hyperuricemic patients and healthy controls. The chi-square test was used to describe the gender distribution difference between hyperuricemic patients and healthy controls. The chi-square test was used to test Hardy-Weinberg equilibrium (HWE) of the two loci. We conducted a logistic regression analysis to calculate adjusted odd ratio (OR) with 95% confidence interval (95% CI) and P-values to describe the distribution of -866G/A and Ala55Val adjusted for age and gender between hyperuricemic patients and healthy controls. A linear regression was performed to calculate Beta and P-values to estimate the effect on serum urate in different genotypes and alleles. Genotype GG, allele G of -866G/A and genotype CC, allele C of Ala55Val were used as references, respectively. Stratification into subgroups was performed on the basis of gender and different BMI values for further analysis. Haplotype frequencies between the hyperuricemic patients and controls were estimated by OR (95% CI) and chi-square test. The haplotype of the most frequent (-866G/A-Ala55Val, G-C) was used as the reference. A 2-sided P-value less than 0.025 was considered statistically significant after multiple correlation by Bonferroni method. The PHASE program (V2.1) was used for haplotype frequencies estimation, and SPSS 19.0 was used for the statistical analysis. References 1. Choi HK, Mount DB, Reginato AM. Pathogenesis of gout. Ann Intern Med 2005;143(7):499-516. 2.  Weaver AL. Epidemiology of gout. Cleve Clin J Med 2008;75 Suppl 5:S9-12. 3.  Billiet L, Doaty S, Katz JD, Velasquez MT. Review of hyperuricemia as new marker for metabolic syndrome. ISRN Rheumatol 2014;2014:852954. 4.  Hediger MA, Johnson RJ, Miyazaki H, Endou H. Molecular physiology of urate transport. Physiology (Bethesda) 2005;20:125-33. 5.  Kolz M, Johnson T, Sanna S, Teumer A, Vitart V, Perola M, et al.. Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations. PLoS Genet 2009;5(6):e1000504. 6.  Kà ¶ttgen A, Albrecht E, Teumer A, Vitart V, Krumsiek J, Hundertmark C, et al.. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nature Genetics 2012;45(2):145-154. 7.  Donadelli M, Dando I, Fiorini C, Palmieri M. UCP2, a mitochondrial protein regulated at multiple levels. In; 2014. p. 1171-90. 8.  Azzu V, Jastroch M, Divakaruni AS, Brand MD. The regulation and turnover of mitochondrial uncoupling proteins. Biochimica et Biophysica Acta (BBA) Bioenergetics 2010;1797(6-7):785-791. 9.  Dalgaard LT, Andersen G, Larsen LH, Sorensen TI, Andersen T, Drivsholm T, et al.. Mutational analysis of the UCP2 core promoter and relationships of variants with   obesity. Obes Res 2003;11(11):1420-7. 10. Dalgaard LT. Genetic Variance in Uncoupling Protein 2 in Relation to Obesity, Type 2 Diabetes, and Related Metabolic Traits: Focus on the Functional -866G>A Promoter Variant (rs659366). J Obes 2011;2011:340241. 11. Rousset S, Mozo J, Dujardin G, Emre Y, Masscheleyn S, Ricquier D, et al.. UCP2 is a mitochondrial transporter with an unusual very short half-life. FEBS Lett 2007;581(3):479-82. 12. 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Best Pract Res Clin Endocrinol Metab 2014;28(5):757-64. 18. Shen Y, Wen Z, Wang N, Zheng Z, Liu K, Xia X, et al.. Investigation of variants in UCP2 in Chinese type 2 diabetes and diabetic retinopathy. PLoS One 2014;9(11):e112670. 19. Sesti G, Cardellini M, Marini MA, Frontoni S, DAdamo M, Del GS, et al.. A common polymorphism in the promoter of UCP2 contributes to the variation in insulin secretion in glucose-tolerant subjects. Diabetes 2003;52(5):1280-3. 20.  Otaegui D, Saenz A, Ruiz-Martinez J, Olaskoaga J, Lopez DMA. UCP2 and mitochondrial haplogroups as a multiple sclerosis risk factor. In; 2007. p. 454-8. 21.  Oktavianthi S, Trimarsanto H, Febinia CA, Suastika K, Saraswati MR, Dwipayana Pà ¦Ã¢â‚¬ ºÃ‚ ´AW, et al.. Uncoupling protein 2 gene polymorphisms are associated with obesity. Cardiovascular diabetology 2012;11(1):41. 22.  Wang X, Lu M, Qian J, Yang Y, Li S, Lu D, et al.. Rationales, design and recruitment of the Taizhou Longitudinal Study. BMC Public Health 2009;9:223. 23.  Mandell BF. Clinical manifestations of hyperuricemia and gout. Cleve Clin J Med 2008;75 Suppl 5:S5-8. 24.  WHO Global Database on Body Mass Index (BMI): an interactive surveillance tool for monitoring nutrition transition. Public Health Nutr. 2006; 9(5):658-. doi:10.1079/Phn2006967. ISI:000239972300019.. 25. Terkeltaub RA. Clinical practice. Gout. N Engl J Med 2003;349(17):1647-55. 26.  Neogi T. Clinical practice. Gout. N Engl J Med 2011;364(5):443-52.   Ã‚   27.  Lapice E, Pinelli M, Pisu E, Monticelli A, Gambino R, Pagano G, et al.. Uncoupling protein 2 G(-866)A polymorphism: a new gene polymorphism associated with C-reactive protein in type 2 diabetic patients. Cardiovasc Diabetol 2010;9:68. 28.  Richette P, Bardin T. Gout. Lancet 2010;375(9711):318-28. 29. Waring WS, Webb DJ, Maxwell SR. Systemic uric acid administration increases serum antioxidant capacity in healthy volunteers. J Cardiovasc Pharmacol 2001;38(3):365-71. 30. Zhang M, Wang M, Zhao Z. Uncoupling protein 2 gene polymorphisms in association with overweight and obesity susceptibility: A meta-analysis. Meta Gene 2014;2:143-159. 31.Vogler S, Goedde R, Miterski B, Gold R, Kroner A, Koczan D, et al.. Association of a common polymorphism in the promoter of UCP2 with susceptibility to multiple sclerosis. J Mol Med (Berl) 2005;83(10):806-11. 32.Heidema AG, Wang P, van Rossum CT, Feskens EJ, Boer JM, Bouwman FG, et al.. Sex-specific effects of CNTF, IL6 and UCP2 polymorphisms on weight gain. Physiol Behav 2010;99(1):1-7. 33.Lee YH, Kim W, Yu BC, Park BL, Kim LH, Shin HD. Association of the ins/del polymorphisms of uncoupling protein 2 (UCP2) with BMI   in a Korean population. Biochem Biophys Res Commun 2008;371(4):767-71. 34.Cheurfa N, Dubois-Laforgue D, Ferrarezi DA, Reis AF, Brenner GM, Bouche C, et al.. The common -866G>A variant in the promoter of UCP2 is associated with decreased risk of coronary artery disease in type 2 diabetic men. Diabetes 2008;57(4):1063-8. 35.Nadal-Serrano M, Sastre-Serra J, Pons DG, Miro AM, Oliver J, Roca P. The ERalpha/ERbeta ratio determines oxidative stress in breast cancer cell lines in response to 17beta-estradiol. J Cell Biochem 2012;113(10):3178-85. 36.Hima S, Sreeja S. Regulatory role of estrogen-induced reactive oxygen species in the modulatory function of UCP 2 in papillary thyroid cancer cells. IUBMB Life 2015. 37.Hamada T, Kotani K, Fujiwara S, Sano Y, Domichi M, Tsuzaki K, et al.. The UCP2-866 A/A genotype is associated with low density lipoprotein particle sizes in the general population. Med Sci Monit 2008;14(3):CR107-11. Acknowledgements This research was supported by grants from the Science and Technology Committee of Shanghai Municipality (11DJ1400100), International ST Cooperation Program of China (2013DFA30870), Ministry of Science and Technology (2011BAI09B00), and Program for 2012 Outstanding Medical Academic Leader for Hejian Zou. The computations involved in this study were supported by Fudan University High-End Computing Center. Author contributions statement

Plagiarism and the Casual Plagiarist Essay -- Exploratory Essays Resea

Plagiarism and the Casual Plagiarist It is a random Thursday night on the first floor of Brewster Hall and the Campus of State University when a frazzled young girl wanders into the room of a fellow student inquiring about The Stranger by Albert Camus. She needs to have a three page paper completed by tomorrow and cannot find a kick start on the essay writing process. Since her peers are on the level of the common doormat concerning Camus, she was left without any further help. However, had she just typed â€Å"the stranger, camus† into Google, three of the first ten sites listed would have directed her to either free or paid essay sites. While this student simply sat down and worked on her paper, the option to find a pre-made research paper was dangerously accessible to this time strapped student. However, it is these emotions that paper sites play up along with a general apathy towards plagiarism among students that make a stressed student deciding whether to plagiarize or not more inclined to go forward with the plagiaristic activity. One of the sites that the aforementioned student could have found a Camus essay on is megaessays.com. This site boasts a four page paper about freedom and death in The Stranger. However, upon signing up for the site, one must register and accept the terms and acceptable use policy, but this policy is a separate page that is not shown when the essay abstract comes up. So, the site that claims â€Å"immediate access to thousands of high quality papers and essays† on its main page also has the following in its acceptable use policy (note the spelling of plagiarism on this website): You acknowledge and agree that the license granted under these terms does not pe... ...ttp://libwww.syr.edu/research/ej/index.html>. â€Å"Questions† and â€Å"Acceptable Use Policy.† Megaessays.com. 19 September 2004. 2001-2004 Mega Essays LLC. â€Å"School Sucks: Download Your Workload (homepage)† 19 September 2004. 1996-2004 School Sucks. . Schoolsucks.com. â€Å"School Sucks- Info-Students.† 19 September 2004. 1996-2004 School Sucks. . Rosenfeld, Jesse. â€Å"Students Turned off by Turnitin.† The McGill Daily. 8 September 2003. The Daily Publication Society. . Witherspoon, Abigail. â€Å"This Pen for Hire.† Harper's. June 1995: 49-57. WilsonSelectPlus. E-Journals. State University. 19 September 2004. .

A Comparison of Satire in Catch-22 and Good as Gold :: comparison compare contrast essays

Satire in Catch-22 and Good as Gold    Joseph Heller who is perhaps one of the most famous writers of the 20th century writes on some emotional issues such as war. He does not deal with these issues in the normal fashion instead he criticizes them and the institutions that help carry these things out. Heller in fact goes beyond criticizing he satirizes. Throughout his two major novels Catch-22 and Good as Gold he satirizes almost all of America's respectful institutions.    Catch-22 is a satire on World War II. This novel takes place on the small island of Pianosa in the Mediterranean sea late in the war when Germany is no longer a threat. It is the struggle of one man, Yossarian, to survive the war. Throughout this novel Yossarian is trying to escape the war, and in order to do so he does many improper things. Good as Gold is about a Jewish man named Gold. It is about Gold's experiences with the government while being employed in the White House. It also deals in detail with Gold's family problems and Gold's struggle to write a book on the contemporary Jewish society. Throughout these two novels, Catch-22 and Good as Gold, Heller criticizes many institutions. In Good as Gold it is the White House and government as a whole, and in Catch-22 it is the military and medical institutions.    In Catch-22 the military is heavily satirized. Heller does this by criticizing it. Karl agrees with this statement by offering an example of the satire of both the military and civilian institutions in Catch-22:    The influence of mail clerk Wintergreen, the computer foul-up that promotes Major Major, and the petty rivalries among officers satirizes the communication failures and the cut-throat competition Heller saw within both the civilian and military bureaucracies of the 1950's. Even the Civil Rights movement, not yet widespread in the 1950's, is satirized in Colonel Cathcart attitudes toward enlisted men. (23)    Karl summarizes the satirazation of the military with this:    The enemy in Heller's book is not simply the chaos of war, but also the deadly inhuman bureaucracy of the military-economic establishment which clams to be a stay against chaos while it threatens human life more insidiously then battle itself.    Heller also questions the need for the death and carnage throughout the novel asking if it is really necessary.

Disasters Do Not Cause Effects. The Effects Are What We Call a Disaster

Humans are the most developed of all the living beings. They think and learn. It is in human nature to minimize the errors in anything and everything as much as possible and to try to reach as near to perfection as can be. However, humans are creatures of mistakes. No matter how small or how large, every individual makes many mistakes in their lives on personal, social, environmental, educational, professional or other levels.In this world, there is a set process and procedure for everything and for things to remain in a balance and keep functioning and working properly and appropriately, it is important that these processes and procedures keep going on in the normal usual way. When there is a disruption in these processes and procedures, disasters occur. These disasters may be on personal level, national level or global level. They may be social, political, economic, natural or of some other type. Technically, a disaster is any event, whether natural or caused by humans, that has a negative impact on the society or the world.The word â€Å"disaster† is derived from two Greek words â€Å"dis† meaning â€Å"bad† and â€Å"astro† meaning stars. It means that when the stars are in a bad state or are aligned in a wrong manner, bad things will happen. In a disaster, the victims suffer. People die or huge losses are incurred or both take place. When classified under broad categories, disasters can be divided in two types; natural disasters and disasters caused by humans. A natural disaster is any event that occurs naturally and humans have a very little or absolutely no control over it.Some examples include earthquakes, tsunamis, volcanic eruptions, floods, typhoons, cyclones, tornados, natural fires, etc. however, human vulnerability plays a great part for a natural hazard to turn into a natural disaster, that is, a natural hazard like an earthquake, fire, tsunami etc will not be considered a â€Å"disaster† if it occurs in such an area that is not occupied by humans or no human is affected by it or both. The greater the impact of the hazard on the human environment or the humans themselves, the greater is the disaster.In such a calamity, a good emergency management system (also known as a disaster management system) can help save lives and reduce the losses incurred, while a weak or unplanned emergency management system or the lack of one can result in huge financial, economic, social and human losses. It has however been observed that the developed nations tend to have considerably better emergency management systems and therefore incur less losses be it on the financial and economic front or the social and human front.Researches show that about 90 to 95 percent of the losses incurred due to these natural disasters every year are incurred by the underdeveloped or the developing nations especially the South East Asian countries. The second type of disasters is the disaster caused by humans. A human-made disa ster is any disaster that is caused by the mistake or misunderstanding of processes by humans. The causes may be human negligence or ignorance, a mechanical failure or any other human action. Human made disasters are further divided into two types; technological disasters and sociological disasters.Technological disasters are all those disasters that are caused by a mechanical, engineering or technical failure and include disasters like a transportation disaster (like a plane crash) or a collapse of a building or bridge (due to engineering or technical faults etc) etc that causes loss of lives or resources or both. Sociological disasters are all those disasters that are backed by a powerful human motive (be it criminal acts, revenge, religious reasons, terrorism, wars etc. ).In recent times, terrorism and wars are the types of such disasters that are most prevalent and claim most of the lives of people dying these days. The powerful are trying to suppress and oppress the weak and in order to take over them and their resources, attack on them (a good example of that would be the on-going America-Iraq war), while on the other hand, the suppressed and oppressed try to defend themselves and raise their voice, which results in riots and similar incidences. Another type of the disasters can be a combination of both human-made and natural disasters.That would include any disasters that have both the human reasons as well as the natural hazards behind them. An example of such a disaster would be an aircraft crash due to sudden turbulence in weather. The natural factor here would be the bad weather while the human error would be the lack of a proper contingency plan. When defined broadly, a disaster is any event or occurrence that has a negative impact on at least one human being. Keeping this definition in mind, a disaster can be on many levels.The lowest level of a disaster would be on a personal level. This may include events like a divorce, loss or death of someone very close and beloved like parents or spouse, heavy losses in business etc that can have immense effects on an individual’s life, and in some cases, can even change the entire course or outlook of one’s life, and can revolutionize that individual’s mentality and thinking. A higher level would be on the organizational basis which might include failure of business projects or liquidation or bankruptcy etc. hen there might be some other levels like national, regional and global as well. According to Wolf Dombrowski, â€Å"Disasters do not cause effects.The effects are what we call a Disaster. † What he means to say is that it is not the disaster in itself in totality that is harmful for us; the humans, it is not just the very incident that has a negative impact on our lives and it is not just a particular event that causes a severe blow to the masses. It is actually a whole series of after effects of any particular event that decide if that event is a disa ster or not.This can easily be understood by the fact that if a hazard (a natural disaster in this example, like an earthquake) hits an uninhabited area, it will not be considered a disaster; the reason being that it did not have any â€Å"effect† on any human or human environment. On the other hand, had the same earthquake hit a largely populated urban area, it would have been the source of massive destruction and would have claimed several human lives. In addition to this, it would have caused huge financial and economic losses as well.All these negative impacts are the â€Å"effects† of the earthquake, which made it a disaster or else, it would have been just an earthquake in a distant uninhabited piece of land. Consider another example of the personal level of damage. What is wrong with a divorce? A divorce is nothing but a separation between spouses who no longer wish to live with one another. This should have been a good thing with positive impacts since the peop le who do not want to stay with each other can now live the way they want.However, this is not the case. Not at least most of the times. The reason being that a divorce always, or most of the times, has many negative â€Å"effects† on the separated spouses, their children and other closely related individuals like parents of the two spouses, and thus the whole family suffers. Therefore, a divorce was not bad in its essence and could not have been classified as a disaster on a personal level, but, due to its â€Å"effects† it turned into a disaster.The examples described above and many other examples make it pretty clear that the disaster and its effects are very closely linked and there is such a thin boundary between then that it is almost impossible to clearly differentiate between them. The disaster is due to its effects and the effects are due to the disaster. So it shows that there is no clear distinction between a disaster and its effects and that they are nothin g but two faces of the same coin and it is the effects that we actually call a disaster.One thing that with the disasters be it natural or human, which renders the humans helpless in this regard, is the very low predictability of these disasters. Moreover, the disasters are not under much of human control, even if they are human made disasters. Due to this fact, the losses incurred are greater and more lives are wasted. The availability and functionality of a proper emergency management system can, however, help minimize the damage, if not eliminate it. When talking about emergency management, which is also called disaster management, there is a step to step process that is involved.There are four phases to establish an emergency management system, being, mitigation, preparedness, response, and recovery. Discussing briefly, mitigation is the long-term planning to prevent a hazard from turning into a disaster or to reduce the impact on the masses as much as possible. The elimination or reduction of potential risks is also included in mitigation. Mitigation may either be structural (technological solutions etc) or non-structural (like insurance etc). Contingency planning is a major part of the mitigation phase of emergency management.The second phase, preparedness, deals with the strategies to prepare the masses in case of a hazardous situation to minimize the disaster. It includes strategies like first-aid training and inventory management and stock piling, etc. Casualty prediction (prediction of deaths that should be expected from the catastrophe) is another important aspect of preparedness phase. Coming to response, the third phase of emergency management, this phase explains how one should respond or react to the calamity on hand in the first place.It requires emergency services, NGOs and other voluntary organizations, rescue teams and other relevant departments to have a complete plan of how to respond to a particular disaster, but the volunteers should be really committed to help in times of disasters or else they can prove to be a hindrance instead of help. The last phase of disaster management (or emergency management) is the recovery phase that actually takes place after the disaster when the effects have spread and its time to try bringing things back to normal as soon as possible.While response phase helps to deal with the impacts of the disaster during the disaster, the recovery phase deals with facing the aftermath and restoring the affected area or people to the previous state (that is the state before the disaster). It includes efforts like rebuilding of the destroyed property and estate, reemployment of the affected masses and the rehabilitation of those who are psychologically struck by the incident, etc. The International Organizations that respond in emergency situations include United Nations, World Bank, Red Cross, Red Crescent, International Association of Emergency Managers, etc.Let us now take some examples and disc uss the notion â€Å"Disasters do not cause effects. The effects are what we call a Disaster† further, in the light of those devastating events. The events that the discussion would be focused on would be: a) Indian Ocean Tsunami – 2004 b) The 9/11 incident of The World Trade Centers – 2001 South East Asia, especially the coastal areas, is the part of the world which is gifted by nature’s great bounties.Hundreds of thousands of tourists, especially from Australian and European nations, travel to this region every year to spend their vacations in the beautiful days and the peaceful nights of these God-gifted lands and these tourist activities contribute a major chunk to the revenue generated by these underdeveloped or developing countries, annually. December 26, 2004 was a nice sunny day of the beautiful winters of this South East Asian region. The sea shores were crowded with both, he locals and the tourists and everyone was enjoying the amazing winter of f the coast when suddenly, there appeared a wall of water right at the shore.Within seconds, the huge wall-like wave of water crashed on the shore engulfing numerous people who were peacefully having fun in the sun not very long ago. The fun and peaceful environment turned into a sight of immense chaos and destruction and the gigantic waves did not take longer than a few minutes to travel up to kilometers inside the cities. A tsunami had hit the shores of the Indian Ocean. Let us first shed some light on what a Tsunami actually is. The word tsunami is derived from two Japanese words; â€Å"tsu† meaning â€Å"harbor† and â€Å"nami† meaning â€Å"waves†.A Tsunami can be described as an immediate immense after effect of an earthquake or mass movements in the land under the ocean. When an earthquake or mass movements occur in the ocean bed, due to any reason (being a volcanic eruption, underwater explosions, landslides or underwater earthquakes themselves), they generate huge amounts of energy that causes the water waves to move at large mean and extreme positions and thus create gigantic waves that appear to be walls of water when the strike the shore before the crash down on land and engulf everything that there is.The height or the amplitude of the waves of a Tsunami off the shore is much smaller than what it suddenly becomes the instant it strikes the shore. This is because while the water under the surface of the ocean is full of energy emitted by the earthquake or mass movements in the ocean bed and continues to undergo very fast movements, the water of the surface is comparatively very calm. The moment the water reaches the shore, these two layers merge and give rise to the gigantic waves of water capable of engulfing the whole area in a matter of mere minutes and thus create the walls of water, a characteristic the Tsunamis are famous for.In the Tsunami that occurred in the Indian Ocean in 2004, the cause was determined to be a n earthquake, with its epicenter (point of generation) off the west coast of the Sumatra Island of Indonesia. That is why Indonesia was the country to suffer from this calamity the most. The magnitude of the earthquake was recorded to be between 9. 1 and 9. 3 by different sources on the Richter scale or a Seismograph. The earthquake was so powerful that it generated a series of tsunami waves that hit various shores along the Indian Ocean and created many powerful gigantic waves that caused a lot of destruction.The Tsunami affected about eleven countries and created waves up to a hundred feet in height. The earthquake was of the second highest magnitude to be recorded on a seismograph, ever, and the tsunami was recorded to be one of the deadliest natural disasters in history claiming lives of more that 350,000 individuals and causing losses of billions of dollars.The countries most affected include Indonesia, Sri Lanka, India, Thailand, the Maldives, Somalia, Myanmar, Malaysia, Seych elles, etc. n addition to this, many citizens of various Australian and European nations lost their lives while spending their vacations on the shores where the disaster struck. The disaster did not end here. The actual problems started after the major outbreak when the rescue mission started. Many were saved yet many lost their lives. Many were left missing who would have died eventually hoping and praying, waiting for a rescue team to come and save them.The areas where the calamity hit were totally destroyed and needed to be rebuilt. As the days passed, the temperature dropped further. This caused more casualties due to the chilling effect of winters. There was an outburst of many epidemics and other diseases while the health resources were minimal and the hygiene conditions were adverse. Food, clothing, shelter, water, medicines and other health supplies and other basic necessities of life were needed immediately in huge quantities.Many were injured and needed medical facilities to be treated quickly in order to prevent more casualties while those who remained safe were now reaching adverse conditions due to lack of resources. These and many other immediate after effects needed to be looked after as early as possible to prevent further losses. This clearly shows that the disaster was not â€Å"just† the Tsunami waves but the effects that it left on the areas that it hit, were equally disastrous.Another event that can easily be deemed disastrous is the 9/11 incident that took place in 2001. It was a peaceful morning, a regular American day in New York. Many people had already reached their workplaces while others were in a hurry to reach theirs when a plane smashed straight into one of the two tallest towers of the World Trade Center, New York. Not much time had passed when another plane crashed in the second tower. Fire broke out in the two towers and a state of emergency was created.In the mean while, an attack on the Pentagon took place as well. It was a series of attacks by Al-Qaeda (a terrorist organization) on America in which they used passenger airplanes as their weapons. The whole world’s attention was diverted towards America, the Super Power in the world, since no body could imagine something like this happening there. No matter what the motives and the caused were, thousands of innocent people lost their lives and it took months for even a country like America to overcome the immediate devastating effects of this incident.However, this incident, in the long run, changed the complete outlook of the world. America started a war against terrorism which resulted in attacks on Afghanistan, Iraq, Lebanon, etc, some of which are still going on. Various treaties and agreements took place between various nations and many alliances were formed. Many Strategies were formulated and the concept of Emergency Management, Crisis Management and other similar concepts changed altogether, which is very evident from the compariso n of the books published before and after the disaster.All in all, this incident had a huge impact on almost the entire world and it’s after effects were, and still are, actually greater and more devastating than what it was that day. This example too, clearly shows that the disaster was not just what happened that particular day, but also what happened after it and what is still happening, especially in the regions that were and/or are the subject of the war against terrorism. Thus the statement of Wolf Dombrowski, that â€Å"Disasters do not cause effects. The effects are what we call a Disaster† holds true

Would Juluis caesar be a good king

Would Julius Caesar be a good king? Julius Caesar takes place in ancient Rome in 44 B. C. He was never technically king, but he came close to having the powers of a king, but he got killed before he could become one. He is very arrogant throughout the story while he is still alive. He is pretty stubborn while being p retty manipulative Just like almost every character in the play. I don't feel like he will be a good king just because of his arrogance. He also had his good qualities like being a military astermind.Caesar shows us his arrogance throughout the play. For example in Act 1 Scene 2 he says â€Å"Such men as he be never at heart's ease Whiles they behold a greater than themselves, and therefore are they very dangerous. I rather tell thee what is to be fear'd than what I fear, for always I am Caesar† . In this quote we can see that is Caesar unashamed of how arrogant he is being. This arrogance would cause him to do other errors like he did later in the story like igno ring his wife's dreamHe was great ruler because he led Rome in the right direction, but by doing so, in the process he was an arrogant and selfish ruler. He was great for Rome as a ruler but not for the people. Just like Brutus said in Act 2 Scene 1 â€Å"And therefore think him as a serpent's egg which, natch'd, would, as his kind, grow mischievous, and ill shell. † Here Brutus is comparing Caesar to a â€Å"Serpent's Egg† that is should be destroyed before it hatches and becomes dangerous if he becomes king.They are not afraid of him ecause he is a tyrant but will become one if he becomes the king of Rome. In the book Julius Caesar manipulation seems like a varsity sport. In Act 2 Scene 1 Caesar really deceives the Romans. He is putting a show and refusing that he doesn't want the crown, even though he would secretly love it deep inside. He thinks that refusal to the crown in front of the public is a smart political tactic to get people to love him and think he less ambitious or for lack of better word desperate.This is also a form of reverse hycology as Caesar is using it to make the crowd like him and even consider making him king as he is not greedy and hungry for it. In conclusion Caesar would be a great king for Rome but not for the Romans. He is a genius in warfare but is very arrogant which cost him his life. If he was king his arrogance would definitely be his downfall. And the romans would find out that he was manipulating them, it was Just a matter of time. He would be a very good war chief of be a ruler with Pompey but not a king all by himself.

Race and Crime Essay

Are minorities continually being unfairly arrested, tried and punished as a result of racial discrimination or do minorities just commit more crimes? In order to determine if disparity or discrimination is the cause of current over representation of minorities in the criminal justice system we have to study race, ethnicity and past discriminatory judicial practices. Are the historical discriminatory practices and past laws the cause of the systematic imbalance of power in relation to race, class and discrimination within our society that leads to more crime among minorities today? There are many theories on why, how and even if race discrimination plays a significant role in explaining the current arrest and incarceration rates of minorities in the United States. Social strain theory, because it also involves the most restriction to important social aspects of society is the one I most agree with. In my experience restricted access to social and cultural capital is the cause for higher than expected crime rates among our citizens who lack these two important aspects of crime control. The inability to achieve success based on societies’ definition causes stain and alternative ways of thinking to achieve that level of success, which is sometimes outside the confines of the law. The term race has traditionally referred to the biological differences of mankind. The differences that distinguish us by the color of our skin, hair texture and certain physical features determine what race we are. Some experts contend that race is just a social construct and people are classified and labeled by the culturally dominant group in that society. This type of classification system tends to imply that one race is inferior to another (Walker et al pg 6). The term minority is used for any race that is less in numbers than the race in power. Currently in the United States the â€Å"majority† is considered to be Caucasian and the â€Å"minorities† are African Americans, Hispanics, Arab Americans, etc. There have been many historical examples of minorities being unfairly treated within the confines of our judicial system. â€Å"Race discrimination and social and economical inequality have a direct impact on crime and criminal justice† (Walker et al, pg 78). In the southern states during the 1800’s barriers were created in the laws to separate nonwhite persons from the majority, white persons called the Black Codes. These codes created a legal line of separation stating where blacks could and could not go in public, what land they could own and how they could earn a living. The term, Color Line encompassed everything involving what water fountains and bathrooms â€Å"coloreds† could use and where they could stand or sit in public spaces. The Jim Crow laws of the 1900 were also racist laws and actions that deprived African Americans civil rights, claiming blacks were inferior to the whites and were lower class people. â€Å"The colored sign was the most visible mark of inferiority imposed upon African Americans by the Jim Crow laws† (Davis PhD). The punishment for breaking these laws and codes were mob lynching, serving prison time on chain gangs and debilitating debt imposed by sharecropping attempts to make a living (Davis PhD). Previous laws and codes set the stage for economic inequality of minorities in the United States. Income, wealth, unemployment are the standard measure of economic inequality. â€Å"All of these measures indicate deep and persistent inequality in society generally and with respect to race and ethnicity† (Walker et al pg, 79). In order to determine if race discrimination has the major contributor to minority over representation in the criminal justice system we must rule out the idea of disparity being the cause of overrepresentation. The concept of disparity in the criminal justice system refers to differences in say incarceration rates of a certain race but not because of systematic race discrimination. Disparity is a way to explain the high numbers of minorities as criminal perpetrators with legitimate factors. These factors could include, minorities commit more crimes, not because police officers, judges and juries are racists. Crime arrest and convictions could be solely based on legal factors. These legal factors include the seriousness of offense, mitigating circumstances and previous criminal records. These factors opposed to extralegal factors that include race, class, gender and lifestyle (Walker et al, pg 18). If arrest and conviction rates were based solely on legal factors with no weight given to extralegal factors, a high minority count would be considered disparity not systematic discrimination on part of the criminal justice system. To determine if only legal factors and not extralegal factors are the cause of an overrepresentation of minorities in the criminal justice system much more research needs to be conducted. If the cause of high incarceration rates is because of disparity instead of discrimination there is one theory I feel explains why there is disparity. The Social Strain Theory explains the causes of disparity among minorities that leads to higher rates of arrests and incarceration rates. â€Å"Robert Merton’s social stain theory holds that each society has a dominant set of values and goals along with acceptable means of achieving them† (Walker et al, pg 92). If success in life is measured by your social status, involving what you own, where you live and who you know then that is your personal goals for success. The ways to achieve this success are seen as hard work, education, self-control and as individual achievements (Walker et al, pg 92). If the American dream is not realized by a group of people because of societies inability to provide equal levels of educational and work opportunities to achieve success it results in what Merton’s calls social strain. Merton’s theory of social strain addresses the gap between what society views as success and a persons circumstances are for trying to achieve that success. (Walker et al, pg 92). Social strain helps to explain high rates of criminal activity among minorities because minorities are more likely to be denied legal opportunities to obtain the American dream by legal means. â€Å"The high levels of economic inequality experienced by minorities, together with continuing discrimination based on race and ethnicity, mean that minorities are far less likely to be able to achieve approved social goals through conventional means† (Walker et al, pg 93). In conclusion I believe minorities do commit more crimes today, but that is because of a history of discrimination and blocked opportunities to achieve social and cultural capital. The ruling class, the majority, because of past-institutionalized and systematic discrimination has created what we have today, a disparity among minorities involved in our criminal justice system. Therefore even though we have curbed contextual and individual acts of discrimination we have yet to address past discrimination in a meaningful way while still upholding the law. Bibliography Davis, Ronald L. F. Ph. D. California State University, Northridge. Creating Jim Crow. History of Jim Crow retrieved on June 2, 2011 from http://jimcrowhistory. org/history/creating. htm Lafree, G. & Russell, K. K. (1993). The argument for studying race and crime. Journal of Criminal Justice Education. 4, 273-289. Walker, S, Spohn, C, & DeLone, M. (2007). The Color of Justice: Race, Ethnicity, and Crime in America. Wadsworth Publishing Co.

Big Mountain High School Case Study Analysis Education Essay

In this instance survey analysis, I will give a brief sum-up of the instance and the jobs I found along with particulars. I will besides supply recommendations for the territory and school leading that will turn to the awaited barriers to alter. I will establish my recommendations on the needed readings for this class every bit good as other theoreticians and their research applicable to the instance survey. Big Mountain High School serves over 1450 pupils in grades 10-12. Large Mountain is the lone high school in the county, and besides the largest high school in the province. Its geographical location is known for its wilderness and beauty. Because of its location it is mostly a rural territory where many of the attending pupils commute more than 30 stat mis every twenty-four hours to have day-to-day direction. The population of the school ranges from diverse socio-economic backgrounds. As evidenced in the instance, 40 % of the pupils will travel on to go toing 4-year colleges, while 20 % of the pupils attend 2-year colleges. For pupils that are non college edge, as an excess educational option, the territory provides them with a vocational plan ( Smith & A ; Louis, Winter 1999 ) . The Superintendent of the territory is Mr. Bob Carpenter a indigen of the territory. He has been the overseer for four old ages and he is described as being magnetic, a individual who makes determinations and gets things done. He is extremely respected amongst the instructors and staff because he meets straight with the instructors and listens to what they have to state. Mr. Carpenter is besides described as utilizing a bottom-up leading manner doctrine. The chief Mr. Vogel has held the place for 15 old ages. He is known as being a dedicated manager, candid and carnival to his staff. Mr. Vogel besides adopted a bottom-up leading manner doctrine. Some nevertheless, see him to be â€Å" crusty and impersonal † and even unapproachable. He makes hiring determinations, nominates the section chairs, normally communicates with instructors in short staff meetings, and maintains that disposal has full authorization over the processs and policies in the school. The sections at Big Mountain high school were given entire authorization and liberty as how they distribute the instruction assignments, how course of study and direction is designed and they besides make the determinations on budget allotments. Meetings between the principal and section caputs are non regular events, they normally meet one time every three hebdomads and the meetings are normally really short. Finally, there are the instructors. The territory ranks the highest paid among other territories in the province, supplying the territory with a big pool of extremely qualified appliers. Teachers at Big Mountain command how they teach, have small or no treatments over learning methods, the type of direction, and have small or no input in the determination doing procedure that takes topographic point in the school. Faculty is divided and with really small interdisciplinary engagement. There are several leading issues present in the instance. The major issues revolve around the ability of the leading to expeditiously take the school during a much needed alteration. In the instance of the mandated course of study alteration as required by the province, the treatments of the new course of study raised personal and pedagogical differences amongst the module. If the end of the leading is to further growing and alter the way in which the school is traveling, it would be wise for the leading to take a human resource frame attack as discussed in Bolman & A ; Deal, where under the human resource frame, leaders provide and foster equal engagement in the determination devising ( Bolman & A ; Deal, 2008 ) . At Big Mountain, the caputs of section have a significant sum of influence and authorization, and are perceived by the module as decision makers and determination shapers. These differences in power have led to a deficiency of interdisciplinary engagement between section caputs and module members where Hargreaves & A ; Fink refer to as, traditional power blocks ( Hargreaves & A ; Fink, April 2004 ) . This deficiency of interdisciplinary engagement and the misinterpretation of a collaborative leading, as become a top-down hierarchy leading, instead than a sensed bottom-up leading as expressed by the chief Mr. Vogel. It is obvious that the principal in this school will non be developing meaningful relationships with the staff. His neglect for the sentiments of the instructors during his short module meetings, along with his important leading manner resemble what Fullan ( 2001 ) describes as coercive and bossy leading. As the freshly appointed caput for the Language Arts Department, Mr. Chester non merely appointed to the commission merely those who agree with him, he besides restricted the engagement from the instructors that will be implementing the course of study. By making so, he derailed Bolman & A ; Deal ‘s model attack, and the construct of the structural frame where the attempts of groups and persons are coordinated, and besides the human resource frame, where affecting others gives them a sense of belonging and ownership ( Bolman & A ; Deal, 2008 ) . Even though ab initio the principal shared the determination devising with the commission, he rapidly reversed that determination and decided to do the determinations himself. However, subsequently he decided to name Chester to take the new alterations commission to implement the new course of study. One once more his rushed determination was made without the engagement and the input from the instructors, go forthing it small room to win and showing the deficiency of communicating and alliance edifice, necessary when turn toing alteration ( Kanter, Summer 1999 ) . As the overseer, Bob Carpenter was non of much aid to the principal in set uping and developing a successful civilization of committed members within the organisation. Although important and magnetic, his strong interaction accomplishments, the ability to construct relationships while run intoing with instructors and listening to their concerns when the principal was non supportive, have earned him the regard of the instructors, minimising the authorization of the principal. As the overseer, Bob failed as a function theoretical account, and a wise man to the principal. He came across as holding his ain political docket, showing the deficiency of his leading qualities. Qualities required when constructing a successful organisation. Recommendations for ImprovementInspiring leaders have the ability to turn schools about. On the other manus mediocre leaders can alter the civilization of a school and hinder the patterned advance of successful enterprises that may be ongoing within an organisation driven by its members. â€Å" A civilization of alteration consists of great celerity and nonlinearity, on one manus and every bit great potency for originative discoveries on the other. The paradox is that transmutation would non be possible without attach toing muss † ( Fullan, 2001, p. 31 ) . It is obvious that muss is in the hereafter of Big Mountain. Changes are inevitable, and a complete restructuring of the school is recommended. From the overseer, to principal, to section leaders, and to instructors, all fail to develop a collaborative and cohesive work environment. In the instance, the prostration was initiated from the top-down where is lacked sustainable leading. Hargreaves ( 2009 ) describes five obstructions that impede effectual leading and should be addressed in the restructuring procedure of Big Mountain. The obstructions impede the successful execution of the restructuring when sequence is ill planned, sequence passages are severely managed, sequence is frequently on the incorrect frequence, sequence planning fails to see the emotional facets, and in conclusion sequence is non treated as a systemic job. Sequence in leading is an of import facet when reconstituting an organisation and it is frequently overlooked, weakening the long term alterations for a successful turn-around. Large Mountain could profit of an increased stableness in leading. It was evident that neither the overseer nor the principal were wholly dedicated to the school and its vision. The overseer and the principal could hold been more proactive in edifice and set uping a common vision for the school. Constructing a systemic leading is another of import facet that should be taken into consideration. The overseer should work on developing unfastened lines of communicating with other successful schools in the territory, and develop partnerships with the other schools where information is shared, and thoughts are exchanged leting schools to assist each other and ultimately addition accomplishment. Another recommendation involves the development of a distributed leading and the creative activity of managers for the new leading. Bolman & A ; Deal ( 2008 ) depict the human resource frame, where the overseer and the principal would put more accent on constructing personal relationships, and the s chool would profit from the constitution of an unfastened and true bottom-up leading manner doctrine. Because more and more disposal is comprised of first-time leaders, giving support to new leaders will relieve the emotional emphasis associated with the place. Supplying good back uping managers will assist the new leaders with the troubles that come with the new administrative function. A concluding option is to maintain the position quo of the school. However, without alterations in leading, the instability that exists amongst the staff will stay and will go on to decline. Leadership stableness can be improved by leading sequence, and this may be accomplished by administering successful leaders across schools in the territory and developing a support web that will help overseers, principals and instructors throughout the territory. â€Å" Successful sequence is about turning and linking leading throughout a system, non merely happening the right tantrum for single leaders. † And â€Å" Permanent betterment seldom exists without leading stableness or successful sequence. Effective sequence is a strategic challenge but non an unsurmountable 1 † ( Hargreaves & A ; Fink, April 2004 ) . MentionsBolman, L. G. , & A ; Deal, T. E. ( 2008 ) .Reframing organisations. San Francisco: Jossey-Bass. Fullan, M. ( 2001 ) .Leading in a civilization of alteration. San Francisco: Jossey-Bass. Hargreaves, A. ( 2009 ) . Leadership Succession and Sustainable Improvement.School Administrator, 66 ( 11 ) , 10-15. Retrieved from ERIC database. Hargreaves, A. , & A ; Fink, D. ( April 2004 ) . The Seven Principles of Sustainable Leadership.Educational Leadership, 61 ( 7 ) , 8-13. Kanter, M. ( Summer 1999 ) . The Enduring Skill of Change Leaders.Leader to Leader Journal( 13 ) , 15-22. Smith, B. , & A ; Louis, L. ( Winter 1999 ) . Case 2: Changes at Big Mountain High School [ Abstract ] .Journal of Cases in Educational LeadershiP, 2 ( 1 ) , 1-2.