Linear free vibration analysis of tapered Timoshenko beams using coupled displacement field method

Every structure which is having some mass and elasticity is said to vibrate. Natural frequency is the one of the most important parameter associated with engineering vibration. In nature every structure has its own natural frequency. Whenever the natural frequency of the structure coincides with the frequency of external applied load, excessive deflections will occur and the structure will be failed. To avoid such condition one must be aware of the operating frequencies of the materials or structures under various conditions like simply supported, clamped and cantilever boundary conditions. There are many methods to evaluate the natural frequency of the structures. in this method the authors developed a method called “coupled displacement field method” which reduces computational efforts compared with the other methods and which is successfully applied for the Hinged-Hinged boundary condition of a tapered (rectangular cross section) Timoshenko beam and calculated the fundamental frequency parameter values and compared the results with existing literature. The results obtained in this method are very close to the existing literature

IN UTERO GENE DELIVERY OF AAV VECTORS FOR EFFICIENT TREATMENT OF MUSCLE DISORDERS

Duchenne muscular dystrophy (DMD) is a devastating primary muscle disease with pathological changes in skeletal muscle that are ongoing at the time of birth. Progressive deterioration in striated muscle function in affected individuals ultimately results in early death due to cardio-pulmonary failure. Since affected individuals can be identified prior to birth by prenatal genetic testing for DMD, gene replacement treatment can be started in utero. This approach offers the possibility of preventing pathological changes in muscle that begin early in life. Previous studies with systemic in utero adenoassociated viral (AAV) vector serotype 1 gene delivery to embryonic day 16 (E-16) pups resulted in high levels of transduction in diaphragm and intercostal muscles, but no detectable levels in limb muscle. Recently newer AAV serotypes such as AAV8 have demonstrated widespread and high transgene expression in skeletal muscles and diaphragm by systemic delivery in adults and neonatal mice. In this study I tested AAV8 vector gene delivery by intraperitoneal administration in E-16 mice in utero. Using an AAV8 vector carrying a lacZ transgene, I observed high level transduction of diaphragm and more moderate transduction of multiple limb muscles and heart. Encouraged with these results I tested in utero gene transfer in the mdx mouse model of DMD, a minidystrophin gene driven by the human cytomegalovirus promoter was delivered systemically by an intraperitoneal injection to the fetus at embryonic day 16. Treated mdx mice studied at 9 weeks after birth demonstrated widespread expression of recombinant dystrophin in skeletal muscle, restoration of the dystrophin associated glycoprotein complex in dystrophin-expressing muscle fibers, improved muscle pathology, and functional benefit to the transduced diaphragm compared to untreated littermate controls. In order to further extend these studies, AAV9 carrying a minidytsrophin gene was also tested. Robust expression in heart and muscles were seen at 4 weeks post treatment by in utero gene delivery. Furthermore robust heart expression persisted as long as 3 months post treatment. These results support the potential of AAV8 and AAV9 vectors to efficiently cross the blood vessel barrier to achieve systemic gene transfer to skeletal muscle in utero in a mouse model of muscular dystrophy, to significantly improve the dystrophic phenotype and to ameliorate the processes that lead to exhaustion of the skeletal muscle regenerative capacity

Linear free vibration analysis of tapered Timoshenko beams using coupled displacement field method

Every structure which is having some mass and elasticity is said to vibrate. Natural frequency is the one of the most important parameter associated with engineering vibration. In nature every structure has its own natural frequency. Whenever the natural frequency of the structure coincides with the frequency of external applied load, excessive deflections will occur and the structure will be failed. To avoid such condition one must be aware of the operating frequencies of the materials or structures under various conditions like simply supported, clamped and cantilever boundary conditions. There are many methods to evaluate the natural frequency of the structures. in this method the authors developed a method called “coupled displacement field method” which reduces computational efforts compared with the other methods and which is successfully applied for the Hinged-Hinged boundary condition of a tapered (rectangular cross section) Timoshenko beam and calculated the fundamental frequency parameter values and compared the results with existing literature. The results obtained in this method are very close to the existing literature

Systemic delivery of AAV8 in utero results in gene expression in diaphragm and limb muscle: treatment implications for muscle disorders

One of the major challenges in the treatment of primary muscle disorders, which often affect many muscle groups, is achieving efficient, widespread transgene expression in muscle. In utero gene transfer can potentially address this problem by accomplishing gene delivery when the tissue mass is small and the immune system is immature. Previous studies with systemic in utero adeno-associated viral (AAV) vector serotype 1 gene delivery to embryonic day 16 (E-16) pups resulted in high levels of transduction in diaphragm and intercostal muscles, but no detectable transgene expression in limb muscles. Recently newer AAV serotypes such as AAV8 have demonstrated widespread and high transgene expression in skeletal muscles and diaphragm by systemic delivery in adult and neonatal mice. We tested AAV8 vector gene delivery by intraperitoneal administration in E-16 mice in utero. Using an AAV8 vector carrying a lacZ reporter gene, we observed high level transduction of diaphragm and intercostal muscles and more moderate transduction of multiple limb muscles and heart. Our current studies demonstrate the potential of AAV8 to achieve widespread muscle transduction in utero and suggest its therapeutic potential for primary muscle disorders

Improvement of the mdx mouse dystrophic phenotype by systemic in utero AAV8 delivery of a minidystrophin gene

Duchenne muscular dystrophy (DMD) is a devastating primary muscle disease with pathological changes in skeletal muscle that are ongoing at birth. Progressive deterioration in striated muscle function in affected individuals ultimately results in early death due to cardio-pulmonary failure. Since affected individuals can be identified prior to birth by prenatal genetic testing for DMD, gene replacement treatment could be started in utero. This approach offers the possibility of preventing pathological changes in muscle that begin early in life. To test in utero gene transfer utilizing the AAV8 vector in the mdx mouse model of DMD, a minidystrophin gene driven by the human cytomegalovirus promoter was delivered systemically by intraperitoneal injection to the fetus at embryonic day 16. Treated mdx mice studied at 9 weeks after birth demonstrated widespread expression of recombinant dystrophin in skeletal muscle, restoration of the dystrophin associated glycoprotein complex in dystrophin-expressing muscle fibers, improved muscle pathology, and functional benefit to the transduced diaphragm compared to untreated littermate controls. These results support the potential of the AAV8 vector to efficiently cross the blood vessel barrier to achieve systemic gene transfer to skeletal muscle in utero in a mouse model of muscular dystrophy, to significantly improve the dystrophic phenotype and to ameliorate the processes that lead to exhaustion of skeletal muscle regenerative capacity

Free Vibrations of Uniform Timoshenko Beams on Pasternak Foundation Using Coupled Displacement Field Method

Complex structures used in various engineering applications are made up of simple structural members like beams, plates and shells. The fundamental frequency is absolutely essential in determining the response of these structural elements subjected to the dynamic loads. However, for short beams, one has to consider the effect of shear deformation and rotary inertia in order to evaluate their fundamental linear frequencies. In this paper, the authors developed a Coupled Displacement Field method where the number of undetermined coefficients 2n existing in the classical Rayleigh-Ritz method are reduced to n, which significantly simplifies the procedure to obtain the analytical solution. This is accomplished by using a coupling equation derived from the static equilibrium of the shear flexible structural element. In this paper, the free vibration behaviour in terms of slenderness ratio and foundation parameters have been derived for the most practically used shear flexible uniform Timoshenko Hinged-Hinged, Clamped-Clamped beams resting on Pasternak foundation. The findings obtained by the present Coupled Displacement Field Method are compared with the existing literature wherever possible and the agreement is good

Large amplitude free vibration analysis of tapered timoshenko hinged-hinged beam using coupled displacement field method

Tapered beams are more efficient compared to uniform beams as they provide a better distribution of mass and strength and also meet special functional requirements in many engineering applications like architecture, aeronautical, civil, mechanical, automobile, nuclear and robotics. The authors proposed a new method called Coupled Displacement Field (CDF) method in which the displacement field such as total rotation is assumed such that the assumed displacement must satisfy the kinematic and force boundary condition of the beam. The lateral transverse displacement is derived from the coupling equation which is derived from the static equilibrium conditions of the beam. By the application of principle of minimum total potential energy for different beam boundary conditions, the fundamental frequency parameter value is calculated in terms of taper ratio and slenderness ratio for various maximum amplitude ratios of the tapered Timoshenko shear flexible hinged-hinged beam boundary condition