A Design Method for Flexure-Based Compliant Mechanisms on the Basis of Stiffness and Stress Characteristics

Geometric nonlinearities of flexure hinges introduced by large deflections often complicate the analysis of compliant mechanisms containing such members, and therefore, Pseudo-Rigid-Body Models (PRBMs) have been well proposed and developed by Howell [1994] to analyze the characteristics of slender beams under large deflection. These models, however, fail to approximate the characteristics for the deep beams (short beams) or the other flexure hinges. Lobontiu's work [2001] contributed to the diverse flexure hinge analysis building on the assumptions of small deflection, which also limits the application range of these flexure hinges and cannot analyze the stiffness and stress characteristics of these flexure hinges for large deflection. Therefore, the objective of this thesis is to analyze flexure hinges considering both the effects of large-deflection and shear force, which guides the design of flexure-based compliant mechanisms. The main work conducted in the thesis is outlined as follows. 1. Three popular types of flexure hinges: (circular flexure hinges, elliptical flexure hinges and corner-filleted flexure hinges) are chosen for analysis at first. 2. Commercial software (Comsol) based Finite Element Analysis (FEA) method is then used for correcting the errors produced by the equations proposed by Lobontiu when the chosen flexure hinges suffer from large deformation. 3. Three sets of generic design equations for the three types of flexure hinges are further proposed on the basis of stiffness and stress characteristics from the FEA results. 4. A flexure-based four-bar compliant mechanism is finally studied and modeled using the proposed generic design equations. The load-displacement relationships are verified by a numerical example. The results show that a maximum error about the relationship between moment and rotation deformation is less than 3.4% for a flexure hinge, and it is lower than 5% for the four-bar compliant mechanism compared with the FEA results.

The biological basis of autism spectrum disorders: evaluation of oxidative stress and erytrocyte membrane alterations

This case-control study involved a total of 29 autistic children (Au) aged 6 to 12 years, and 28 gender and age-matched typically developing children (TD). We evaluated a high number of peripheral oxidative stress parameters, erythrocyte and lymphocyte membrane functional features and membrane lipid composition of erythrocyte. Erythrocyte TBARS, Peroxiredoxin II, Protein Carbonyl Groups and urinary HEL and isoprostane levels were elevated in AU (confirming an imbalance of the redox status of Au); other oxidative stress markers or associated parameters (urinary 8-oxo-dG, plasma Total antioxidant capacity and plasma carbonyl groups, erythrocyte SOD and catalase activities) were unchanged, whilst peroxiredoxin I showed a trend of elevated levels in red blood cells of Au children. A very significant reduction of both erythrocyte and lymphocyte Na+, K+-ATPase activity (NKA), a reduction of erythrocyte membrane fluidity, a reduction of phospatydyl serine exposition on erythrocyte membranes, an alteration in erythrocyte fatty acid membrane profile (increase in MUFA and in ω6/ω3 ratio due to decrease in EPA and DHA) and a reduction of cholesterol content of erythrocyte membrane were found in Au compared to TD, without change in erythrocyte membrane sialic acid content and in lymphocyte membrane fluidity. Some Au clinical features appear to be correlated with these findings; in particular, hyperactivity score appears to be related with some parameters of the lipidomic profile and membrane fluidity, and ADOS and CARS score are inversely related to peroxiredoxin II levels. Oxidative stress and erythrocyte structural and functional alterations may play a role in the pathogenesis of Autism Spectrum Disorders and could be potentially utilized as peripheral biomarkers.

Regularization methods for the solution of a nonlinear least-squares problem in tomography

In this work we study a polyenergetic and multimaterial model for the breast image reconstruction in Digital Tomosynthesis, taking into consideration the variety of the materials forming the object and the polyenergetic nature of the X-rays beam. The modelling of the problem leads to the resolution of a high-dimensional nonlinear least-squares problem that, due to its nature of inverse ill-posed problem, needs some kind of regularization. We test two main classes of methods: the Levenberg-Marquardt method (together with the Conjugate Gradient method for the computation of the descent direction) and two limited-memory BFGS-like methods (L-BFGS). We perform some experiments for different values of the regularization parameter (constant or varying at each iteration), tolerances and stop conditions. Finally, we analyse the performance of the several methods comparing relative errors, iterations number, times and the qualities of the reconstructed images.

Percutaneous access of the epicardial space for mapping ventricular and supraventricular arrhythmias in patients with and without prior cardiac surgery

There is a paucity of data on the success rates of achieving percutaneous epicardial access in different groups of patients.

The genetic basis of craniofacial and dental abnormalities

The embryonic head development, including the formation of dental structures, is a complex and delicate process guided by specific genetic programs. Genetic changes and environmental factors can disturb the execution of these programs and result in abnormalities in orofacial and dental structures. Orofacial clefts and hypodontia/ oligodontia are examples of such abnormalities frequently seen in dental clinics. An insight into the mechanisms and genes involved in the formation of orofacial and dental structures has been gradually gained by genetic analysis of families and by the use of experimental vertebrate models such as the mouse and chick models. The development of novel clinical therapies for orofacial and dental pathological conditions depends very much on a detailed knowledge of the molecular and cellular processes that are involved in head formation.

Screening the Structural Space of Bicyclo-DNA: Synthesis and Properties of Bicyclo-DNA Functionalized at C(6’)

The synthesis of a novel bicyclo-thymidine nucleoside bearing an ester functionality at C(6') (bc(alpha-alk)-nucleosides) is reported. This nucleoside was incorporated into oligodeoxynucleotides via solid phase phosphoramidite chemistry, and the ester moiety was post-synthetically converted to an amide or a carboxy group, or was left unchanged. Thermal melting data (T-m) with complementary DNA and RNA were collected and compared to natural DNA and to bc- and bc(ox)-DNA. It was found that single incorporations of bc(alpha-alk)-nucleosides in DNA duplexes were destabilizing by 0.5 to 2.5 degrees C/mod, whereas two consecutive bc(alpha-alk)-residues were less destabilizing, and in some cases even stabilizing by 0.5 degrees C/mod. In duplexes with complementary RNA, isolated bc(alpha-alk)-residues destabilized the duplex by -1.0 to -4.0 degrees C/mod, depending on the chemical nature of the substituent, whereas two consecutive modifications were only destabilizing by 0.3-1.0 degrees C/mod. The pairing selectivity was similar to that of unmodified or bc-DNA.

Placement of coiled catheters into the paravertebral space

There are conflicting results with regard to the use of catheter-based techniques for continuous paravertebral block. Local anaesthetic spread within the paravertebral space is limited and the clinical effect is often variable. Discrepancies between needle tip position and final catheter position can also be problematic. The aim of this proof-of-concept study was to assess the reliability of placing a newly developed coiled catheter in human cadavers. Sixty Tuohy needles and coiled catheters were placed under ultrasound guidance, three on each side of the thoracic vertebral column in 10 human cadavers. Computed tomography was used to assess needle tip and catheter tip locations. No catheter was misplaced into the epidural, pleural or prevertebral spaces. The mean (SD) distance between catheter tips and needle tips was 8.2 (4.9) mm. The median (IQR [range]) caudo-cephalad spread of contrast dye injectate through a subset of 20 catheters was 4 (4-5[3-8]) thoracic segments. All catheters were removed without incident. Precise paravertebral catheter placement can be achieved using ultrasound-guided placement of a coiled catheter.

Structural basis for the regulation of cysteine-protease activity by a new class of protease inhibitors in Plasmodium

Plasmodium cysteine proteases are essential for host-cell invasion and egress, hemoglobin degradation, and intracellular development of the parasite. The temporal, site-specific regulation of cysteine-protease activity is a prerequisite for survival and propagation of Plasmodium. Recently, a new family of inhibitors of cysteine proteases (ICPs) with homologs in at least eight Plasmodium species has been identified. Here, we report the 2.6 A X-ray crystal structure of the C-terminal, inhibitory domain of ICP from P. berghei (PbICP-C) in a 1:1 complex with falcipain-2, an important hemoglobinase of Plasmodium. The structure establishes Plasmodium ICP as a member of the I42 class of chagasin-like protease inhibitors but with large insertions and differences in the binding mode relative to other family members. Furthermore, the PbICP-C structure explains why host-cell cathepsin B-like proteases and, most likely, also the protease-like domain of Plasmodium SERA5 (serine-repeat antigen 5) are no targets for ICP.

Structural basis for the sheddase function of human meprin β metalloproteinase at the plasma membrane

Ectodomain shedding at the cell surface is a major mechanism to regulate the extracellular and circulatory concentration or the activities of signaling proteins at the plasma membrane. Human meprin β is a 145-kDa disulfide-linked homodimeric multidomain type-I membrane metallopeptidase that sheds membrane-bound cytokines and growth factors, thereby contributing to inflammatory diseases, angiogenesis, and tumor progression. In addition, it cleaves amyloid precursor protein (APP) at the β-secretase site, giving rise to amyloidogenic peptides. We have solved the X-ray crystal structure of a major fragment of the meprin β ectoprotein, the first of a multidomain oligomeric transmembrane sheddase, and of its zymogen. The meprin β dimer displays a compact shape, whose catalytic domain undergoes major rearrangement upon activation, and reveals an exosite and a sugar-rich channel, both of which possibly engage in substrate binding. A plausible structure-derived working mechanism suggests that substrates such as APP are shed close to the plasma membrane surface following an "N-like" chain trace.

A 3-center comparison of 1-year mortality outcomes between transcatheter aortic valve implantation and surgical aortic valve replacement on the basis of propensity score matching among intermediate-risk surgical patients

This study sought to compare all-cause mortality in patients at intermediate surgical risk undergoing transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR).