Discusses the current state-of-the-art in an area of electrical Research Paper

Discusses the current state-of-the-art in an area of electrical engineering and computer science that you are interested - Research Paper Example nd mobile software, however, every mobile application has specific mobile software that defines its characteristics and requirements depending on the data processing need at hand. Generally, with the availability of the Internet, intranet or any other respective communication links, mobile devices enable a user to take a computer and all crucial files, folders, and software out into the field and to work as if he/she were in the office (Masco et al, 17). Mobile computing relies on the principle of mobile voice communication whose technology has been recently extended to include the ability for one to send and receive data across cellular networks. A number of hardware that support mobile computing are available and include mobile devices and device components like Personal Digital Assistants (PDAs), Smartphone, tablet computers, ultra-mobile PCs, and wearable computers to name but a few (Mascolo et al, 19). With these devices, there is efficiency in communication and for business people who are constantly on the move, the concept of mobile computing serves to solve the problem of mobility through the transmission of data from remote locations. The dominant technology in the mobile data communication market today that enables mobile computing is the Cellular Digital Packet Data (CDPD), though; a number of alternative technologies are available such as the Circuit Switched Cellular, Specialized Mobile Radio, and Wireless Data Networks. The basic principle of the CDPD technology is the usage of idle time that is available in between existing signals sent across the cellular networks. This technology usually comes with the advantage of low cost of data transmission since the idle time is not chargeable. Fixed users are provided with a fixed physical link to the CDPD network allowing them to connect to the network while mobile users connect to the network using a packet-switched system. In case the CDPD facilities do not exist, this technology utilizes the concept of

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. Jarmuszkiewicz W, Woyda-Ploszczyca A. [Mitochondrial uncoupling proteins: regulation and physiological role]. Postepy Biochem 2008;54(2):179-87. 13. Yu X, Wieczorek S, Franke A, Yin H, Pierer M, Sina C, et al.. Association of UCP2 -866 G/A polymorphism with chronic inflammatory diseases. In; 2009. p. 601-5. 14. Rosmond R, Bouchard C, Bjorntorp P. Lack of association between the uncoupling protein-2 Ala55Val gene polymorphism and phenotypic features of the Metabolic Syndrome. Biochim Biophys Acta 2002;1588(2):103-5. 15.  Heidari J, Akrami SM, Heshmat R, Amiri P, Fakhrzadeh H, Pajouhi M. Association study of the -866G/A UCP2 gene promoter polymorphism with type 2 diabetes and obesity in a Tehran population: a case control study. Arch Iran Med 2010;13(5):384-90. 16.  Emre Y, Nà ¼bel T. Uncoupling protein UCP2: When mitochondrial activity meets immunity. In; 2010. p. 1437-1442. 17. Toda C, Diano S. Mitochondrial UCP2 in the central regulation of metabolism. 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

Regulatory Issues of VoIP :: essays research papers

Regulatory issues of VoIP The Federal Communications Commission (FCC) has worked to create an environment promoting competition and innovation to benefit consumers. Historically, the FCC has not regulated the Internet or the services provided over it. On February 12, 2004, the FCC found that an entirely Internet-based VoIP service was an unregulated information service. Currently, the FCC is not regulating VoIP, however there are still major concerns that need to be addressed. There are three main issues that are of the utmost importance to the telecommunications industry. The Tax Freedom act, E-911, and Calea are three most imperative issues concerning VoIP.   Ã‚  Ã‚  Ã‚  Ã‚  The Internet Tax Freedom Act was authored by Rep. Christopher Cox and Sen. Ron Wyden, and signed into law on October 21, 1998 by President Bill Clinton. This law bars state and local governments from taxing Internet access service. In 2003 the House of Representatives approved bill H.R. 49, the â€Å"Internet Tax Non-Discrimination Act of 2003.† This bill would expand and make permanent a federally imposed â€Å"moratorium† on state and local taxation of sales of â€Å"Internet access† services. States and local governments would be permanently prohibited from charging sales taxes on the monthly service charge that households and businesses pay to be able to access the World Wide Web.   Ã‚  Ã‚  Ã‚  Ã‚  VoIP rides a fine line between being a telephone service and an internet service. This is due to the fact that a call is initiated from a phone in an analog format, transmitted over the internet in a digital format and finally converted back to analog format typically across the same lines that traditional phones operate on. In addition many states rely on the taxes received from telephone service to run programs to low income areas. VoIP is seen as threat to these programs because taxes will not be imposed on this service due to current legislative language. Many opponents of the non-taxation of VoIP feel that exemption from taxation is not needed to spur investments in this type of telecommunication. They also feel it singles out one type of telecommunications service for favorable treatment, which will lead to other types of services asking for similar treatment at the expense of the state and local tax base. E-911 short for Enhanced 911, is a location technology that will enable phones to process 911 emergency calls and enable emergency services to locate the geographic position of the caller. When a person makes a 911 call using a traditional phone with ground wires, the call is routed to the nearest public safety answering point (PSAP) that then distributes the emergency call to the proper services.

Constant Critics of Monopolies

Monopolies are under constant critics from the public and other producers of being polutive, straining to competition and they are accused of worsening resource allocation. Whether this is true or not, depends on the specific company, but certain characteristics are possible to define. It is these I will describe in the following, and hence conclude if monopolies worsen or improve It is important to distinguish between competition and monopoly before describing advantages and disadvantages of both. Many monopolies are government owned. This means that the incentive to trive for more profit, better conditions etc. is gone. This is due to the fact that, if there is a loss, the government will cover it, and government owned companies seldom strive to achieve maximum profits. A lot of the characteristics are also seen in privately owned monopolizing firms. When they become so big, that competition is practically gone, the incentive to make even more profits, and In a competitive industry this is not the case. The fear of loosing your job, not being able to compete, your products becoming obsolete etc. re important factors, which stimulate productivity. It is therefor obvious that the competitive industry will try harder to allocate their resources in the most efficient way. To land, the external costs in a competitive industry will often be pollution, seeing that the firm will strive hard to diminish their costs resulting in the firm ignoring ‘unnecessary' costs. The monopoly owned by the government, would never be able to ignore such a serious matter, and they would have to pay the costs. A monopoly would also have to be careful not to damage its image, seeing that is, in many cases, already is unpopular. Capital, on the other hand, is often to the benefit of a monopoly, since they produce at a large scale. To fully utilize capital, a lot of labour is needed, labour which a monopoly is expected to have, and a smaller competitive firm may lack. For example, a blast furnace might need a crew of 24 men working night and day, to fully utilize it. The monopolizing company may be able to provide the men, but the smaller firm might not have the money to hire all the 24 men at night, seeing wages are much higher at then. The question then is if the competitive company is so much more efficient due to ard work, that they still can produce more than the monopoly. When it comes to labour, it is obvious that a competitive industry will strive to utilize the workers at a maximum level, due to the desire of minimizing costs, and workers will in general be very efficient due the reasons mentioned above. The workers in a monopoly, often loose the feeling, that their work makes a difference in the firm, making it hard for managers to fully In my opinion, the characteristics described above are not as valid any more. Companies, which enjoyed monopoly status in the eginning of the 80's, like IBM, are now realizing that nothing lasts forever, and they have be innovative, even if the competition is not a great threat. Bill Gates, owner of MicroSoft, has very admirable policies concerning this. His firm is not a monopoly, but it is definably a cutting-edge firm, which is shaping the future. One rule he has, is that every six months the bottom five percent of the company's workforce (in terms of performance) get firedo. It is his goal to make his own products obsolete, not letting others do it, and it seems he is achieving that goal.

The Place of Factor X in Friedman and Albright’s Conflict

Three scholars namely Thomas L. Friedman, Madeleine Albright and Francis Fukuyama have offered related thoughts which policy-makers could learn to use in conflict resolution. To all of them, respecting human dignity is apparently the key to conflict resolution. Also, they all try to explain moral choices as the type of choice that must surface in the society to create a harmonious society. However, they have presented different sources for which people reflect on in making moral judgments like identity, rationality and freedom. The articles they have written which are; The Dell Theory of Conflict Resolution, Faith and Diplomacy and The Posthuman Future, respectively have tackled distinct issues but they derive their arguments from human nature. The first article for example discusses about the impacts of economic globalization on state and group collaboration; the second deals with how expertise and consideration of religion could facilitate in the understanding of cultural and religious differences to arrive at peace and settlements thus preventing wars; the third concerns itself with dissecting human nature to prove that technological and scientific development should be regulated to preserve the innate characteristics of humans and maintain their aspirations for unity. I would like to emphasize however that using the third article, Posthuman Future by Francis Fukuyama, the two articles are similar in that they refer to some aspects of human nature that Fukuyama referred to in his study as part of Factor X. But at the same time, I would like to present a personal analysis that Friedman and Albright in their discussions of economic-political behaviour and religious beliefs, are able to introduce although implicitly another aspect of human nature that Fukuyama might have not fully underscored- the human interactions that produce, mould, shape and influence beliefs, behavior, ideologies that yields to mobilization, organization, even conflict and its resolution. Let me begin by sharing what Fukuyama has to say about human dignity. How is moral choice determined? Francis Fukuyama in his new book the â€Å"Posthuman Future† tries to give a fresh perspective on the nature of humans and human values that eventually leads to a discussion of a kind of moral choice that is rooted in human dignity. Fukuyama says that human values are rooted in human nature which in turn is rooted in our genes. Fukuyama defines human nature as â€Å"the sum of the behavior and characteristics that are typical of the human species, arising from genetic rather than environmental factors.† Humans as complex wholes with a range of capacities like rationality, moral choice, sociability, sentience, consciousness, language, and so on that exceed those located among non-human animals is what gives humans moral worth. So while non-humans may possess nature as well, only humans possess dignity. Dignity is what gives humans the following: â€Å"superior†¦ moral status that raises us all above the rest of animal creation and yet makes us equals of one another qua human beings.† Fukuyama believes that dignity resides in what he refers below as Factor X: â€Å"a mysterious ‘Factor X' which is the ‘essential human quality' that remains after ‘all of a person's contingent and accidental characteristics' have been stripped away.† Fukuyama claims that: â€Å"Factor X cannot be reduced to the possession of moral choice, or reason, or language, or sociability, or sentience, or emotions, or consciousness, or any other quality that has been put forth as a grounds for human dignity. It is all of these qualities coming together in a human whole that make up Factor X† It is Factor X that Fukuyama wants to conserve from the command of biotechnologists. In this given equation, biotechnology which consists of the alteration of our biological nature would also alter human nature, transforming human values and undermine capitalism. He further notes that: â€Å"What is ultimately at stake with biotechnology is the very grounding of the human moral sense. We therefore need international regulation to obstruct any technological advance that might ‘disrupt either the unity or the continuity of human nature, and thereby the human rights that are based upon it.† (Fukuyama, 2002) Francis Fukuyama seemingly concerned with the natural order of things fears that with artificial actions like those presented in medicines, cloning and genetic engineering, what could have been naturally designed as the end in our society would change as we intervened in the natural course of events. This assumption leads him to some policy prescriptions as regards the limitations of these developments. One can deduce from his assumptions that our morality and our moral choices will also be affected with these perceived changes. The resolution for Fukuyama in all of humans’ worries that provoke biotechnology is seen in his statement, â€Å"There are good prudential reasons to defer to the natural order of things and not to think that human beings can easily improve upon it through casual intervention† Having read the Dell Theory of Conflict Resolution, one can judge at the outset that the intention was to rationalize the behavior of people and organizations which due to globalization and   in the consideration of their best interests have resorted to collaboration, thus making their human nature progress into economically defined configurations and abstain from war and other skirmishes. Richard Cobden said: â€Å"Free trade is God’s diplomacy. There is no other certain way of uniting people in the bonds of peace† (cited in the Dell Theory of Conflict Resolution). If I were to put it simply, I’d say Friedman as he appears a liberal to me wishes to promote for the sake of resolving conflict among groups and states, human’s embedded rationality as the aspect that makes us unique and thinking life-forms. He is saying that economically speaking, we would rather choose the best possible choice- that one that will entail the least costs and risks and the greater benefits. The least harm would be to preserve the freedom of choice and inherent rights of humans -characteristic of a capitalist system and even prospered in free trade. Now, this has become not only a rational choice for him, but also a moral choice; and dignity derives itself from the consideration of other people’s rights to personal property, opportunity to engage in the globalizing system as free and rational beings and appreciation of what others could do to help others at the same time helping their own selves (comparative advantage). In this case, conflict arises when disrespect against other humans in the form of illegal transactions, abuse of power, unfair decisions and agreements take place. Hence, as far as foreign policy is concern, time has come for policy-makers to lose interest in hard security issues like war but focus on meaningful and friendly trade treaties and the like. On the other hand, the article Faith and Diplomacy by Madeleine Albright takes faith in religion as the basis of human’s moral choices. Looking at human’s capacity and nature to reason and feel- this must be provoked to make people make better assessment of their actions and decisions. It is the domination of a common identity as humans created in the likeness of God that could fashion an intensive dislike to killing other humans and hurting them. The ultimate reason to abhor war and fighting must come from the nature of humans to feel sympathy, pain, sadness from the makings of their religious differences. Hence, international diplomatic relations faced with religious-based insurgencies must take this tactic to eliminate the perspective of dehumanization in wars as an opportunity to maintain order. Human dignity in this case is taken away when one treats another human non-human. He says in the article: â€Å"When participants in a conflict claim to be people of faith, a negotiator who has the credentials and the credibility to do so might wish to call their bluff† Humans have the nature to realize mistakes after some moments of reflection based on reason and sentiments. However as Fukuyama states, Factor X is the totality of human natures, the sum of all parts. Although a lot of other scholars still contest and rebut Fukuyama’s exaggeration of the impacts of biotechnology on the human qualities, I may not delve into those criticisms although one thing is clear to me: that all of these scholars have faith in what humans can do both negative and positive. Conflict is caused by human qualities and characteristics as rational, free beings capable of innovation and complex organizing. What must be given emphasis however more than human nature is human interaction. Their social nature is what brings them to form distinct religious groups and organizations, influence each other to develop new traditions, norms and structures, cooperate and not to cooperate depending on mainstream beliefs and ideologies. I would say Friedman and Albright’s thoughts on moral choice, human dignity and conflict resolution are not isolated from the human aspects that Fukuyama is talking about, although in a separate discussion, they have perhaps unintentionally promoted another way of looking at conflict which transcends the explanations made by Fukuyama.       .