9,046 research outputs found

    Haplotype analysis of the PPARgamma Pro12Ala and C1431T variants reveals opposing associations with body weight.

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    BACKGROUND: Variation at the PPARG locus may influence susceptibility to type 2 diabetes and related traits. The Pro12Ala polymorphism may modulate receptor activity and is associated with protection from type 2 diabetes. However, there have been inconsistent reports of its association with obesity. The silent C1431T polymorphism has not been as extensively studied, but the rare T allele has also been inconsistently linked to increases in weight. Both rare alleles are in linkage disequilibrium and the independent associations of these two polymorphisms have not been addressed. RESULTS: We have genotyped a large population with type 2 diabetes (n = 1107), two populations of non-diabetics from Glasgow (n = 186) and Dundee (n = 254) and also a healthy group undergoing physical training (n = 148) and investigated the association of genotype with body mass index. This analysis has demonstrated that the Ala12 and T1431 alleles are present together in approximately 70% of the carriers. By considering the other 30% of individuals with haplotypes that only carry one of these polymorphisms, we have demonstrated that the Ala12 allele is consistently associated with a lower BMI, whilst the T1431 allele is consistently associated with higher BMI. CONCLUSION: This study has therefore revealed an opposing interaction of these polymorphisms, which may help to explain previous inconsistencies in the association of PPARG polymorphisms and body weight

    ALTERED PATTERN OF INSULIN-RECEPTOR ISOTYPES IN SKELETAL-MUSCLE MEMBRANES OF TYPE-2 (NON-INSULIN-DEPENDENT) DIABETIC SUBJECTS

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    The human insulin receptor exists in two isoforms (HIR-A alpha-subunit 719 amino acids and HIR-B alpha-subunit 731 amino acids) which are generated by alternative splicing of a small exon and display distinct patterns of tissue-specific expression. Using the polymerase chain reaction we have recently shown that skeletal muscle of non-diabetic individuals contains predominantly mRNA encoding HIR-A while in skeletal muscle derived from subjects with Type 2 (non-insulin-dependent) diabetes mellitus similar amounts of each mRNA are expressed. We used a polyclonal antibody which discriminates between HIR-A and HIR-B to assess the isoform expression at the protein level. The antibody showed clearly distinct displacement of insulin binding in skeletal muscle membranes of non-diabetic subjects compared to Type 2 diabetic subjects (displacement of specific I-125-insulin binding: 13 non-diabetic subjects 70.0 % +/- 14.34, 12 Type 2 diabetic subjects 32.6 % +/- 17.45). A control antibody which does not discriminate between both isoforms showed similar displacement of I-125-insulin in membranes of non-diabetic and Type 2 diabetic subjects. These data suggest that the altered expression of receptor isotype mRNA in the skeletal muscle of Type 2 diabetic subjects leads to an altered receptor isoform pattern in the plasma membrane. While skeletal muscle membranes of non-diabetic subjects contain predominantly HIR-A, membranes of Type 2 diabetic subjects show an increased level of HIR-B in addition to HIR-A

    Performance Evaluation of Distributed-Antenna Communications Systems Using Beam-Hopping

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    Digital beamforming (DBF) techniques are capable of improving the performance of communications systems significantly. However, if the transmitted signals are conflicted with strong interference, especially, in the direction of the transmitted beams , these directional jamming signals will severely degrade the system performance. In order to efficiently mitigate the interference of the directional jammers, in this contribution a beam-hopping (BH) communications scheme is proposed. In the proposed BH communications scheme, only one pair of the beams is used for transmission and it hops from one to the next according to an assigned BH pattern. In this contribution a range of expressions in terms of the average SINR performance have been derived, when both the uplink and downlink are considered. The average SINR performance of the proposed BH scheme and that of the conventional single-beam (SB) as well as multiple-beam (MB) assisted beam-processing schemes have been investigated. Our analysis and results show that the proposed BH scheme is capable of efficiently combating the directional jamming, with the aid of utilizing the directional gain of the beams generated by both the transmitter and the receiver. Furthermore, the BH scheme is capable of reducing the intercept probability of the communications. Therefore, the proposed BH scheme is suitable for communications, when several distributed antenna arrays are available around a mobile

    Tun hu: (du mu ju ji).

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    復工之前 -- 母女們 -- 囤戶.吳天著.Drama.Wu Tian zhu.Fu gong zhi qian -- Mu nü men -- Tun hu

    Flow dynamics on a U shaped channel flow: a numerical study

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    The paper deals with the numerical simulation of river channel flows at laboratory scale. The adopted geometry consists of a U shaped trapezoidal smooth open channel with fixed slope. The branches, 3m of length each, are linked with a joint, 0.40m long, realizing two 90 degrees bends. The system is fed upstream with a water discharge under critical conditions while a Cipolletti weir is set downstream to control flow profiles. Steady flow movements are obtained by means of two different softwares: a pure Lagrangian developed by the author, based on the Weakly Compressible Smoothed Particle Hydrodynamics (WCSPH) technique and Flow3D®, a commercial CFD software based on a Finite Volume formulation of the Navier Stokes equations in the Eulerian framework. Depending on the assumed boundary conditions, velocity profiles and water interfaces at certain cross sections are deducted by using the codes. Results are discussed and compared, showing a satisfactory agreement

    HU Protein Induces Incoherent DNA Persistence Length

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    HU is a highly conserved protein that is believed to play an important role in the architecture and dynamic compaction of bacterial DNA. Its ability to control DNA bending is crucial for functions such as transcription and replication. The effects of HU on the DNA structure have been studied so far mainly by single molecule methods that require us to apply stretching forces on the DNA and therefore may perturb the DNA-protein interaction. To overcome this hurdle, we study the effect of HU on the DNA structure without applying external forces by using an improved tethered particle motion method. By combining the results with DNA curvature analysis from atomic force microscopy measurements we find that the DNA consists of two different curvature distributions and the measured persistence length is determined by their interplay. As a result, the effective persistence length adopts a bimodal property that depends primarily on the HU concentration. The results can be explained according to a recently suggested model that distinguishes single protein binding from cooperative protein binding.Imaging Science and TechnologyApplied Science

    EVIDENCE THAT 2 NATURALLY-OCCURRING HUMAN INSULIN-RECEPTOR ALPHA-SUBUNIT VARIANTS ARE IMMUNOLOGICALLY DISTINCT

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    The IgG from a patient (Italy 2 [I-2]) with hypoglycemia, due to autoantibodies to the insulin receptor, was purified on protein A Sepharose into two fractions that were tested in various human tissues and cells. The IgG fraction that bound protein A (absorbed IgG [IgGa]) nearly completely inhibited the binding of I-125-labeled insulin to various cells or tissues (placenta, IM-9, adipocytes, HEp-2-larynx cells, Epstein-Barr virus lymphocytes) but not > 50% of I-125-labeled insulin binding to human liver membranes. Conversely, both the IgG fraction from this patient, which did not bind protein A (flow-through IgG [IgGb]), and the IgGa fraction from a second similar patient (Italy 1 [I-1]) almost completely inhibited the binding of I-125-labeled insulin to liver membranes. The IgGa fraction from patient 1-2 did not change receptor affinity because 50% inhibition of I-125-labeled insulin binding was not affected by either the presence or absence of these IgG fractions. Furthermore, liver binding data were not due to cross-reaction of I-125-labeled insulin to the insulinlike growth factor I receptor, and treatment of liver membranes with neuraminidase did not alter the inhibitory effect of the IgGa fraction from patient I-2 on I-125-labeled insulin binding to liver. Binding inhibition experiments performed with cells transfected with and overexpressing the -12 (human insulin receptor [HIR]-A) or the +12 (HIR-B) variant of HIR revealed that the IgGa fraction from patient I-2 inhibited I-125-labeled insulin binding to the HIR-A receptor but not to the HIR-B receptor. The data reported herein demonstrate that the two naturally occurring insulin-receptor variants are immunologically distinct and indicate that the HIR-B variant is predominantly expressed in liver compared with other human tissues
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