Association of polymorphisms in APOE, p53, and p21 with primary open-angle glaucoma in Turkish patients

Purpose To investigate the association between Apolipoprotein E (APOE), tumor suppressor protein p53 (p53), and cyclin-dependent kinase inhibitor 1A (p21) genes and primary open-angle glaucoma (POAG) in a cohort of Turkish subjects. Methods Seventy-five POAG patients (49 women, 26 men) and 119 healthy subjects (67 women, 52 men) were genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Allele and genotype frequencies between healthy subjects and glaucoma patients were compared by the χ2 test, and intraocular pressure (IOP), cup/disc ratio (C/D) and visual field indices (MD and PSD) were compared among different APOE, p53, and p21 genotypes in POAG group. A p value 0.05). POAG subjects with the ε2ε3 genotype had a worse PSD value (median=2.2) than those with the ε3ε4 genotype (median=1.77; p=0.01) and POAG subjects with the ε3ε3 genotype had worse MD and PSD values (median= -7.4 and 3.4, respectively) than those with the ε3ε4 genotype (median= -4.1 and 1.77, respectively; p=0.034 and 0.028, respectively). Conclusions Our study found no link between polymorphisms in APOE, p53, and p21 genes and POAG in Turkish patients, although a larger sample is required to elucidate the role of these polymorphisms in the pathogenesis and course of glaucoma

On the pp-supports of a holonomic D\mathcal{D}-module

For a smooth variety $Y$ over a perfect field of positive characteristic, the sheaf $D_Y$ of crystalline differential operators on $Y$ (also called the sheaf of $PD$-differential operators) is known to be an Azumaya algebra over $T^*_{Y'},$ the cotangent space of the Frobenius twist $Y'$ of $Y.$ Thus to a sheaf of modules $M$ over $D_Y$ one can assign a closed subvariety of $T^*_{Y'},$ called the $p$-support, namely the support of $M$ seen as a sheaf on $T^*_{Y'}.$ We study here the family of $p$-supports assigned to the reductions modulo primes $p$ of a holonomic $\mathcal{D}$-module. We prove that the Azumaya algebra of differential operators splits on the regular locus of the $p$-support and that the $p$-support is a Lagrangian subvariety of the cotangent space, for $p$ large enough. The latter was conjectured by Kontsevich. Our approach also provides a new proof of the involutivity of the singular support of a holonomic $\mathcal{D}$-module, by reduction modulo $p.$Comment: The article has been rewritten with much improved exposition as well as some additional results, e.g. Corollary 6.3.1. This is the final version, accepted for publication in Inventiones Mathematica

European integration assessed in the light of the 'rules vs. standards debate'

The interplay of various legal systems in the European Union (EU) has long triggered a debate on the tension between uniformity and diversity of Member States' (MS) laws. This debate takes place among European legal scholars and is also paralleled by economic scholars, e.g. in the ambit of the 'theory of federalism'. This paper takes an innovative perspective on the discrepancy between 'centralized' and 'decentralized' law-making in the EU by assessing it with the help of the rules versus standards debate. When should the EU legislator grant the national legislator leeway in the formulation of new laws and when should all be fixed ex ante at European level? The literature on the 'optimal shape of legal norms' shall be revisited in the light of law-making in the EU, centrally dealing with the question how much discretion shall be given to the national legislator; and under which circumstances. This paper enhances the established decisive factors for the choice of a rule or a standard in a national setting (complexity, volatility, judges' specialization and frequency of application) by two new crucial factors (switching costs and the benefit of uniformity in terms of information costs) in order to assess law-making policies at EU level

Understanding and protecting vulnerable financial consumers

This article considers how consumer protection law and policy should address the interests of particularly vulnerable financial consumers. Specifically, the article proposes a taxonomy of vulnerability which helps to identify (a) what makes consumers particularly vulnerable, and (b) how consumer protection law and consumer policy (broadly understood) can respond to these causes in a way that provides such consumers with appropriate protection. Changes to economic conditions, legal requirements on traders and our understanding of consumer behaviour make discussion of these issues particularly topical. There is little doubt that finding solutions is extremely difficult. Trade-offs are necessary and some enduring factors that contribute to vulnerability, in particular poverty, sometimes appear intractable. Nevertheless, it is submitted that by identifying clearly both why consumers are vulnerable and how the factors that lead to such vulnerability can be addressed, it is possible to construct an environment which respects consumer choice while ensuring that the most vulnerable are protected appropriately

Regulatory Constructivism: Application of Q Methodology in Italy and China

Conventional view holds that beliefs play an important role in the development of regulations but there is little evidence to support this claim. We use Comparative Q Methodology to systematically map out and compare the beliefs of public officers in China and Italy, two countries with contrasting sets of institutions but have both adopted similar ideas about integrated water resource management. We find some similarities and differences in the beliefs of public officers in both countries. In particular, we find that in both countries beliefs on the regulation of water utilities are diverse and fragmented on issues such as ownership structure of water utilities, how water infrastructure development should be funded, and how tariffs should be regulated. Our findings have two implications for theory, methods and practice. First, the Q methodology is a useful tool for systematically mapping out the beliefs of regulators and managers. Second, systematically mapping out beliefs will help facilitate the development of an alternative regime of regulation such as negotiated rule making. This alternative regime can provide substantial benefits such as more efficient rule making, more cost effective enforcement and compliance, and more equitable in terms of balancing the interests of stakeholders

Toll-like receptor 2 gene polymorphisms, pulmonary tuberculosis, and natural killer cell counts

<p>Abstract</p> <p>Background</p> <p>To investigate whether the toll-like receptor 2 polymorphisms could influence susceptibility to pulmonary TB, its phenotypes, and blood lymphocyte subsets.</p> <p>Methods</p> <p>A total of 368 subjects, including 184 patients with pulmonary TB and 184 healthy controls, were examined for TLR2 polymorphisms over locus -100 (microsatellite guanine-thymine repeats), -16934 (T>A), -15607 (A>G), -196 to -174 (insertion>deletion), and 1350 (T>C). Eighty-six TB patients were examined to determine the peripheral blood lymphocyte subpopulations.</p> <p>Results</p> <p>We newly identified an association between the haplotype [A-G-(insertion)-T] and susceptibility to pulmonary TB (p = 0.006, false discovery rate q = 0.072). TB patients with systemic symptoms had a lower -196 to -174 deletion/deletion genotype frequency than those without systemic symptoms (5.7% vs. 17.7%; p = 0.01). TB patients with the deletion/deletion genotype had higher blood NK cell counts than those carrying the insertion allele (526 vs. 243.5 cells/μl, p = 0.009). TB patients with pleuritis had a higher 1350 CC genotype frequency than those without pleuritis (12.5% vs. 2.1%; p = 0.004). TB patients with the 1350 CC genotype had higher blood NK cell counts than those carrying the T allele (641 vs. 250 cells/μl, p = 0.004). TB patients carrying homozygous short alleles for GT repeats had higher blood NK cell counts than those carrying one or no short allele (641 vs. 250 cells/μl, p = 0.004).</p> <p>Conclusions</p> <p>TLR2 genetic polymorphisms influence susceptibility to pulmonary TB. TLR2 variants play a role in the development of TB phenotypes, probably by controlling the expansion of NK cells.</p

Migration of myogenic cells in the rat extensor digitorum longus muscle studied with a split autograft model

The ability of myogenic cells to migrate perpendicular to the long axis of freely autografted muscles was examined. Rat extensor digitorum longus muscles were divided, and one half was devitalized by repeated freezing in liquid nitrogen while the other half was kept viable in physiologic saline. The halves were reunited with sutures and grafted back into the original muscle bed. At intervals between 5 and 25 days the grafts were removed and examined histologically for the presence of myotubes within the devitalized region. Myotubes were first seen in the devitalized half 10 days postgrafting with the maximum number of myotubes observed after 12 to 15 days. These results indicate that myogenic cells are capable of migration perpendicular to the long axis of the muscle fibers in an autograft.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47687/1/441_2004_Article_BF00327748.pd

Genetic polymorphisms and susceptibility to lung disease

Susceptibility to infection by bacterium such as Bacillus anthracis has a genetic basis in mice and may also have a genetic basis in humans. In the limited human cases of inhalation anthrax, studies suggest that not all individuals exposed to anthrax spores were infected, but rather, individuals with underlying lung disease, particularly asthma, sarcoidosis and tuberculosis, might be more susceptible. In this study, we determined if polymorphisms in genes important in innate immunity are associated with increased susceptibility to infectious and non-infectious lung diseases, particularly tuberculosis and sarcoidosis, respectively, and therefore might be a risk factor for inhalation anthrax. Examination of 45 non-synonymous polymorphisms in ten genes: p47phox (NCF1), p67phox (NCF2), p40phox (NCF4), p22phox (CYBA), gp91phox (CYBB), DUOX1, DUOX2, TLR2, TLR9 and alpha 1-antitrypsin (AAT) in a cohort of 95 lung disease individuals and 95 control individuals did not show an association of these polymorphisms with increased susceptibility to lung disease