Dissection of class III major histocompatibility complex haplotypes associated with rheumatoid arthritis

Objective. We have previously identified a single-nucleotide polymorphism (SNP) haplotype involving the lymphotoxin α (LTA) and tumor necrosis factor (TNF) loci (termed haplotype LTA-TNF2) on chromosome 6 that shows differential association with rheumatoid arthritis (RA) on HLA-DRB1*0404 and *0401 haplotypes, suggesting the presence of additional non-HLA-DRB1 RA susceptibility genes on these haplotypes. To refine this association, we performed a case-control association study using both SNPs and microsatellite markers in haplotypes matched either for HLA-DRB1*0404 or for HLA-DRB1*0401. Methods. Fourteen SNPs lying between HLA-DRB1 and LTA were genotyped in 87 DRB1*04-positive families. High-density microsatellite typing was performed using 24 markers spanning 2,500 kb centered around the TNF gene in 305 DRB1*0401 or *0404 cases and 400 DRB1*0401 or *0404 controls. Single-marker, 2-marker, and 3-marker minihaplotypes were constructed and their frequencies compared between the DRB1*0401 and DRB1*0404 matched case and control haplotypes. Results. Marked preservation of major histocompatibility complex haplotypes was seen, with chromosomes carrying LTA-TNF2 and either DRB1*0401 or DRB1*0404 both carrying an identical SNP haplotype across the 1-Mb region between TNF and HLA-DRB1. Using microsatellite markers, we observed two 3-marker minihaplotypes that were significantly overrepresented in the DRB1*0404 case haplotypes (P = 0.00024 and P = 0.00097). Conclusion. The presence of a single extended SNP haplotype between LTA-TNF2 and both DRB1*0401 and DRB1*0404 is evidence against this region harboring the genetic effects in linkage disequillbrium with LTA-TNF2. Two RA-associated haplotypes on the background of DRB1*0404 were identified in a 126-kb region surrounding and centromeric to the TNF locus.

Hydrothermal liquefaction of bagasse using ethanol and black liquor as solvents

The objective of this study was to examine the hydrothermal liquefaction of sugarcane bagasse using ethanol and black liquor (BL) in a pilot scale. Combinations of co-solvents (ethanol/ water, ethanol/BL) were studied at various concentrations and reaction conditions. The maximum oil yield of 61% was achieved with a reaction temperature of 300 °C for 30 min and using pure BL as a solvent, while the highest higher heating value (HHV) was obtained from a 50:50 ethanol-BL mixture. The oils contained alcohols, esters, phenolic compounds, aromatics, and heterocyclics. The O/C and H/C ratios of the oil were comparable with traditional biodiesel and commercial diesel. Although this study showed there are some improvements to be made to improve the chemical composition, the approach has potential for large-scale production of a substitute for fossil-fuel-based diesel.

'Black international business': Critical issues and ethical dilemmas

In this chapter, we explore the 'darker' faces of international business (IB). Over a decade ago, Eden and Len way (2001) raised the need for examining both the 'bright' and the 'dark' side of globalization in order to achieve a better understanding of the concept and of its impact on IB activities. In doing this, they posited the multinational enterprise (MNE) as the 'key agent' and 'f.1ee' of globalization and discussed, primarily, the relationship between MNEs and nation-states as the central interf.1ce of its impact. Additionally, they posited that, by and large, the community of IB scholars positioned themselves at the bright end of the globalization spectrum, seeing it as essentially positive, whilst most non-governmental organizations (NGOs) and international political economy (IPE) academics set themselves at the dark end. Whilst they acknowledged their own 'bright side' tendencies, they called for a more nuanced consideration of MNEs as what they referred to as the Janus bee' of globalization.

Common variants in the HLA-DRB1-HLA-DQA1 HLA class II region are associated with susceptibility to visceral leishmaniasis

To identify susceptibility loci for visceral leishmaniasis, we undertook genome-wide association studies in two populations: 989 cases and 1,089 controls from India and 357 cases in 308 Brazilian families (1,970 individuals). The HLA-DRB1-HLA-DQA1 locus was the only region to show strong evidence of association in both populations. Replication at this region was undertaken in a second Indian population comprising 941 cases and 990 controls, and combined analysis across the three cohorts for rs9271858 at this locus showed P combined = 2.76 × 10 -17 and odds ratio (OR) = 1.41, 95% confidence interval (CI) = 1.30-1.52. A conditional analysis provided evidence for multiple associations within the HLA-DRB1-HLA-DQA1 region, and a model in which risk differed between three groups of haplotypes better explained the signal and was significant in the Indian discovery and replication cohorts. In conclusion, the HLA-DRB1-HLA-DQA1 HLA class II region contributes to visceral leishmaniasis susceptibility in India and Brazil, suggesting shared genetic risk factors for visceral leishmaniasis that cross the epidemiological divides of geography and parasite species. © 2013 Nature America, Inc. All rights reserved.

Fine mapping of the MHC Class III region demonstrates association of AIF1 and rheumatoid arthritis

Objective. The heritability of RA has been estimated to be ∼55%, of which the MHC contributes about one-third. HLA-DRB1 alleles are strongly associated with RA, but it is likely that significant non-DRB1 MHC genetic susceptibility factors are involved. Previously, we identified two three-marker haplotypes in a 106-kb region in the MHC class III region immediately centromeric to TNF, which are strongly associated with RA on HLA-DRB1*0404 haplotypes. In the present study, we aimed to refine these associations further using a combination of genotyping and gene expression studies. Methods. Thirty-nine nucleotide polymorphisms (SNPs) were genotyped in 95 DRB1*0404 carrying unrelated RA cases, 125 DRB1*0404 - carrying healthy controls and 87 parent-case trio RA families in which the affected child carried HLA-DRB1*04. Quantitative RT-PCR was used to assess the expression of the positional candidate MHC class III genes APOM, BAT2, BAT3, BAT4, BAT5, AIF1, C6orf47, CSNK2β and LY6G5C, and the housekeeper genes, hypoxanthine-guanine phosphoribosyltransferase (HPRT) and β2-microglobulin (B2M) in 31 RA cases and 21 ethnically, age- and sex-matched healthy controls. Synovial membrane specimens from RA, PsA and OA cases were stained by an indirect immunoperoxidase technique using a mouse-anti-human AIF1 monoclonal antibody. Results. Association was observed between RA and single markers or two marker haplotypes involving AIF1, BAT3 and CSNK. AIF1 was also significantly overexpressed in RA mononuclear cells (1.5- to 1.9-fold difference, P = 0.02 vs HPRT, P = 0.002 vs B2M). AIF1 protein was clearly expressed by synovial macrophages in all the inflammatory synovial samples in contrast to the non-inflammatory OA samples. Conclusions. The results of the genotyping and expression studies presented here suggest a role for AIF1 in both the aetiology and pathogenesis of RA.

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1–3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region4, 5, 6, 7, 8, 9, 10, 11. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods—recursive partitioning and regression...

A New Class Of Photo-Cross-Linkable Side-Chain Liquid Crystalline Polymers Containing Bis(Benzylidene)Cyclohexanone Units

This paper reports a new class of photo-cross-linkable side chain liquid crystalline polymers (PSCLCPs) based on the bis(benzylidene)cyclohexanone unit, which functions as both a mesogen and a photoactive center. Polymers with the bis(benzylidene)cyclohexanone unit and varying spacer length have been synthesized. Copolymers of bis(benzylidene)cyclohexanone containing monomer and cholesterol benzoate containing monomer with different compositions have also been prepared. All these polymers have been structurally characterized by spectroscopic techniques. Thermal transitions were studied by DSC, and mesophases were identified by polarized light optical microscopy (POM). The intermediate compounds OH-x, the monomers SCLCM-x, and the corresponding polymers PSCLCP-x, which are essentially based on bis(benzylidene)cyclohexanone, all show a nematic mesophase. Transition temperatures were observed to decrease with increasing spacer length. The copolymers with varying compositions exhibit a cholesteric mesophase, and the transition temperatures increase with the cholesteric benzoate units in the copolymer. Photolysis of the low molecular weight liquid crystalline bis(benzylidene)-cyclohexanone compound reveals that there are two kinds of photoreactions in these systems: the EZ photoisomerization and 2 pi + 2 pi addition. The EZ photoisomerization in the LC phase disrupts the parallel stacking of the mesogens, resulting in the transition from the LC phase to the isotropic phase. The photoreaction involving the 2 pi + 2 pi addition of the bis(benzylidene)cyclohexanone units in the polymer results in the cross-linking of the chains. The liquid crystalline induced circular dichroism (LCICD) studies of the cholesterol benzoate copolymers revealed that the cholesteric supramolecular order remains even after the photo-cross-linking.

Spatial distribution of aerosol black carbon over India during pre-monsoon season

Aerosol black carbon (BC) mass concentrations ([BC]), measured continuously during a multi-platform field experiment, Integrated Campaign for Aerosols gases and Radiation Budget (ICARB, March-May 2006), from a network of eight observatories spread over geographically distinct environments of India, (which included five mainland stations, one highland station, and two island stations (one each ill Arabian Sea and Bay of Bengal)) are examined for their spatio-temporal characteristics. During the period of study, [BC] showed large variations across the country, with values ranging from 27 mu g m(3) over industrial/urban locations to as low as 0.065 mu g m(-3) over the Arabian Sea. For all mainland stations, [BC] remained high compared to highland as well as island stations. Among the island stations, Port Blair (PBR) had higher concentration of BC, compared to Minicoy (MCY), implying more absorbing nature of Bay of Bengal aerosols than Arabian Sea. The highland station Nainital (NTL), in the central Himalayas, showed low values of [BC], comparable or even lower than that of the island station PBR, indicating the prevalence of cleaner environment over there. An examination of the changes in the mean temporal features, as the season advances from winter (December-February) to pre-monsoon (March-May), revealed that: (a) Diurnal variations were pronounced over all the mainland stations, with all afternoon low and a nighttime high: (b) At the islands, the diurnal variations, though resembled those over the mainlands, were less pronounced; and (c) In contrast to this, highland station showed an opposite pattern with an afternoon high and a late night or early morning low. The diurnal variations at all stations are mainly caused by the dynamics of local Atmospheric Boundary Layer (ABL), At the entire mainland as well as island stations (except HYD and DEL), [BC] showed a decreasing trend from January to May, This is attributed to the increased convective mixing and to the resulting enhanced vertical dispersal of species in the ABL. In addition, large short-period modulations were observed at DEL and HYD, which appeared to be episodic, An examination of this in the light of the MODIS-derived fire count data over India along with the back-trajectory analysis revealed that advection of BC from extensive forest fires and biomass-burning regions upwind were largely responsible for this episodic enhancement in BC at HYD and DEL.

Higher-Order Nonlinearity In Accretion Disks: Quasi-Periodic Oscillations Of Black Hole And Neutron Star Sources And Their Spin

We propose a unified model to explain Quasi-Periodic Oscillation (QPO), particularly of high frequency, observed from black hole and neutron star systems globally. We consider accreting systems to be damped harmonic oscillators exhibiting epicyclic oscillations with higher-order nonlinear resonance to explain QPO. The resonance is expected to be driven by the disturbance from the compact object at its spin frequency. The model explains various properties parallelly for both types of the compact object. It describes QPOs successfully for ten different compact sources. Based on this, we predict the spin frequency of the neutron star Sco X-1 and specific angular momentum of black holes GRO J1655–40, XTE J1550–564, H1743–322, and GRS 1915+105.

Novel Functionalised Troger's Bases: Synthesis of a New Class of Troger's Base Analogues Containing Dicarboxyl Functionality

The synthesis of three new Troger's base analogues, each functionalized with two carboxyl groups, is described. Copyright.

A pseudo-dynamical systems approach to a class of inverse problems in engineering

A pseudo-dynamical approach for a class of inverse problems involving static measurements is proposed and explored. Following linearization of the minimizing functional associated with the underlying optimization problem, the new strategy results in a system of linearized ordinary differential equations (ODEs) whose steady-state solutions yield the desired reconstruction. We consider some explicit and implicit schemes for integrating the ODEs and thus establish a deterministic reconstruction strategy without an explicit use of regularization. A stochastic reconstruction strategy is then developed making use of an ensemble Kalman filter wherein these ODEs serve as the measurement model. Finally, we assess the numerical efficacy of the developed tools against a few linear and nonlinear inverse problems of engineering interest.

A Classification of Homogeneous Operators in the Cowen-Douglas Class

A complete list of homogeneous operators in the Cowen-Douglas class B-n(D) is given. This classification is obtained from an explicit realization of all the homogeneous Hermitian holomorphic vector bundles on the unit disc under the action of the universal covering group of the bi-holomorphic automorphism group of the unit disc.

On optimum stratification with proportional allocation for a class of pareto distributions

Cum ./LSTA_A_8828879_O_XML_IMAGES/LSTA_A_8828879_O_ILM0001.gif rule [Singh (1975)] has been suggested in the literature for finding approximately optimum strata boundaries for proportional allocation, when the stratification is done on the study variable. This paper shows that for the class of density functions arising from the Wang and Aggarwal (1984) representation of the Lorenz Curve (or DBV curves in case of inventory theory), the cum ./LSTA_A_8828879_O_XML_IMAGES/LSTA_A_8828879_O_ILM0002.gif rule in place of giving approximately optimum strata boundaries, yields exactly optimum boundaries. It is also shown that the conjecture of Mahalanobis (1952) “. . .an optimum or nearly optimum solutions will be obtained when the expected contribution of each stratum to the total aggregate value of Y is made equal for all strata” yields exactly optimum strata boundaries for the case considered in the paper.

Massive black-hole binary inspirals: results from the LISA parameter estimation taskforce

The LISA Parameter Estimation Taskforce was formed in September 2007 to provide the LISA Project with vetted codes, source distribution models and results related to parameter estimation. The Taskforce's goal is to be able to quickly calculate the impact of any mission design changes on LISA's science capabilities, based on reasonable estimates of the distribution of astrophysical sources in the universe. This paper describes our Taskforce's work on massive black-hole binaries (MBHBs). Given present uncertainties in the formation history of MBHBs, we adopt four different population models, based on (i) whether the initial black-hole seeds are small or large and (ii) whether accretion is efficient or inefficient at spinning up the holes. We compare four largely independent codes for calculating LISA's parameter-estimation capabilities. All codes are based on the Fisher-matrix approximation, but in the past they used somewhat different signal models, source parametrizations and noise curves. We show that once these differences are removed, the four codes give results in extremely close agreement with each other. Using a code that includes both spin precession and higher harmonics in the gravitational-wave signal, we carry out Monte Carlo simulations and determine the number of events that can be detected and accurately localized in our four population models.

Distribution of black nodes at various levels in a linear quadtree

The distribution of black leaf nodes at each level of a linear quadtree is of significant interest in the context of estimation of time and space complexities of linear quadtree based algorithms. The maximum number of black nodes of a given level that can be fitted in a square grid of size 2n × 2n can readily be estimated from the ratio of areas. We show that the actual value of the maximum number of nodes of a level is much less than the maximum obtained from the ratio of the areas. This is due to the fact that the number of nodes possible at a level k, 0≤k≤n − 1, should consider the sum of areas occupied by the actual number of nodes present at levels k + 1, k + 2, …, n − 1.