63 research outputs found

    AAV2/8-hSMAD3 gene delivery attenuates aortic atherogenesis, enhances Th2 response without fibrosis, in LDLR-KO mice on high cholesterol diet

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    BACKGROUND: Inflammation is a key etiologic component in atherogenesis and transforming growth factor beta 1 (TGFβ1) is a well known anti-inflammatory cytokine which potentially might be used to limit it. Yet TGFβ1 is pleiomorphic, causing fibrosis, cell taxis, and under certain circumstances, can even worsen inflammation. SMAD3 is an important member of TGFβ1′s signal transduction pathway, but is a fully intracellular protein. OBJECTIVES: With the hope of attenuating TGFβ1′s adverse systemic effects (eg. fibrosis) and accentuating its anti-inflammatory activity, we proposed the use of human (h)SMAD3 as an intracellular substitute for TGFβ1. STUDY DESIGN: To test this hypothesis adeno-associated virus type 2/8 (AAV)/hSMAD3 or AAV/Neo (control) was tail vein injected into the low density lipoprotein receptor knockout (LDLR-KO) mice, then placed on a high-cholesterol diet (HCD). RESULTS: The hSMAD3 delivery was associated with significantly lower atherogenesis as measured by larger aortic cross sectional area, thinner aortic wall thickness, and lower aortic systolic blood velocity compared with Neo gene-treated controls. HSMAD3 delivery also resulted in fewer aortic macrophages by immunohistochemistry for CD68 and ITGAM, and quantitative reverse transcriptase polymerase chain reaction analysis of EMR and ITGAM. Overall, aortic cytokine expression showed an enhancement of Th2 response (higher IL-4 and IL-10); while Th1 response (IL-12) was lower with hSMAD3 delivery. While TGFβ1 is often associated with increased fibrosis, AAV/hSMAD3 delivery exhibited no increase of collagen 1A2 or significantly lower 2A1 expression in the aorta compared with Neo-delivery. Connective tissue growth factor (CTGF), a mediator of TGFβ1/SMAD3-induced fibrosis, was unchanged in hSMAD3-delivered aortas. In the liver, all three of these genes were down-regulated by hSMAD3 gene delivery. CONCLUSION: These data strongly suggest that AAV/hSMAD3 delivery gave anti-atherosclerosis therapeutic effect without the expected undesirable effect of TGFβ1-associated fibrosis

    On the exponential Diophantine equation x^2+p^{2m}=2y^{n}

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    Let pp be an odd prime. In this paper, we consider the equation x2+p2m=2yn, gcd(x,y)=1,n>2x^{2}+p^{2m}=2y^{n},~\gcd(x,y)=1,n>2 and we give a description for all its solutions. Moreover, we prove that this equation has no solution (x,y,m,n)(x,y,m,n) such that n>3n>3 is an odd prime and yy is not the sum of two consecutive squares. This extends the work of Tengely. DOI: 10.1017/S000497271200010

    Introduction of a guide based on a femoral neck section for fixation with multiple screws: a cadaveric study

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    Abstract Background The design and application of assisted instrumentation for internal fixation of femoral neck fractures with multiple screws are still evolving. A novel guide based on a femoral neck section was designed to improve the accuracy of screw placement, and its efficacy was evaluated. Methods A guide based on a femoral neck section was designed for assisted fixation of femoral neck fractures with multiple screws. Femoral specimens from 10 adults (20 femurs) underwent assisted internal fixation for a femoral neck fracture with 3 cannulated screws using the new guide technique or conventional technique. The accuracy of screw orientation and entry point, the accuracy of optimal screw positioning, and drilling attempts, operative time, and fluoroscopy time were recorded. Results Among all 20 specimens, 60 screws were inserted successfully. Screw parallelism, operative time, and fluoroscopy time showed no statistical difference between the new guide technique and conventional technique (P > 0.05). The accuracy of optimal screw positioning was determined by the contained screw area ratio, distance between screws, distance from the centre of the femoral neck section, distance between screws and the femoral neck cortex, and Drilling attempts were statistical significantly better (data in the first three were larger and in the latter two was smaller) with the new guide technique, than with conventional technique (P < 0.05). Conclusions This new, two-dimensional, fluoroscopy-assisted, percutaneous guide technique enables accurate and optimal screw positioning in internal fixation of femoral neck fractures, compared with conventional technique

    Research on Anti-loosening Technology of Transmission Line Bolts

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    Transmission lines are affected by the natural environment for a long time, and bolts are prone to frequent vibration, resulting in loosening or falling off. In this paper, the loose mechanism of transmission line threaded connection is analysed, and the transverse vibration comparative test of bolt locking method is carried out. A new type of locking nut has been developed, which has good locking performance and convenient installation. According to different operating environments, the principle of differential bolt locking is proposed

    ON THE EXPONENTIAL DIOPHANTINE EQUATION x(2) + p(2m)=2y(n)

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    Fundamental Research Funds for the Central Universities [2011121039]; National Science Foundation of China [10971184]; Purdue University North CentralLet p be an odd prime. In this paper, we consider the equation x(2) + p(2m) = 2y(n), gcd(x, y) = 1, n > 2, and we describe all its solutions. Moreover, we prove that this equation has no solution (x, y, m, n) when n > 3 is an odd prime and y is not the sum of two consecutive squares. This extends the work of Tengely [On the diophantine equation x(2) + q(2m) = 2y(p), Acta Arith. 127(1) (2007), 71-86]
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