Topology Based Optimization of Suspension and Steering Mechanisms of Automobiles

This thesis proposes a kinematic based optimization of the characteristics of suspension and steering systems by focusing on their dynamics interaction. Two of the most important suspension mechanisms are modeled. A new approach based on combining transformation matrix and vector analysis is used resulting in less time and memory consumption during optimization. Modelling is verified by comparing the results with multi-body dynamics software. Further, the steering importance and its effects on the suspension are discussed, along with modelling and analysis of the rack and pinion steering mechanism. The optimization aims at the road holding and vehicle stability considering the effects of steering mechanism on the suspension. Therefore, the cost function is defined based on both steering and wheel travel. Moreover, the effect of wheel travel in different steering angles is shown to be important and has been considered in the cost function. In regards to some behaviors of the suspension, static constraints are defined and their importance is discussed. Lastly, case studies are presented to provide analysis and optimization of the suspension characteristics including steering error and track alterations. Optimization is performed to design suspensions for particular vehicle classification, such as, family cars and SUVs. The results show that optimization can be used to arrive at desired behaviors when the steering and suspension interaction is considered in the optimization

Polymorphisms of the methylene tetrahydrofolate reductase and susceptibility to acute lymphoblastic leukemia in children

Background: Correlation between epigenetic factors and their effects on hematopoietic cells has led to a study of 2 common functional polymorphisms (C677T and A1298C) of 5,10-methylene tetrahydrofolate reductase (MTHFR) enzyme. The aim of this study was to assess the individual and/or combined roles of these 2 polymorphisms in pediatric acute lymphoblastic leukemia (ALL). Methods: Using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses, we studied the frequencies of the C677T and A1298C MTHFR genotypes in 103 pediatric ALL patients and 160 age-sex matched controls. We calculated the odds ratio (OR) of MTHFR genotypes to determine if 1 or both of these polymorphisms may be associated with childhood ALL. Results: The T allele frequency for MTHFR 677C>T was 22.2 and 18.45 in controls and cases, respectively. The C allele frequency for MTHFR 1298 A>C was 40.65 and 40.72 in controls and cases, respectively. The OR for MTHFR 677CT was 1.08 (95CI 0.58-1.95) and OR for MTHFR 677TT was 0.25 (95CI 0.05-10.24). The OR for MTHFR 1298 AC was 0.57 (0.95 CI 0.57-1.95) and for MTHFR CC was 0.96 (0.95 CI 0.37-2.45). The OR for the combined heterozygous status (677CT and 1298AC) was 1.08 (95 CI 0.41-2.82). Conclusion: Our findings suggest that the MTHFR C677T and A1298C gene variants lack a major influence on the susceptibility for pediatric ALL. Another result was that the C allele frequency for MTHFR 1298 A>C was significantly higher than those reported for most Asian and European populations. The C677T prevalence seems to be similar to those reported in most Asian populations. © 2011 by The American Society for Clinical Pathology

Fucoidan and cancer: A multifunctional molecule with anti-tumor potential

There is a wide variety of cancer types yet, all share some common cellular and molecular behaviors. Most of the chemotherapeutic agents used in cancer treatment are designed to target common deregulated mechanisms within cancer cells. Many healthy tissues are also affected by the cytotoxic effects of these chemical agents. Fucoidan, a natural component of brown seaweed, has anti-cancer activity against various cancer types by targeting key apoptotic molecules. It also has beneficial effects as it can protect against toxicity associated with chemotherapeutic agents and radiation. Thus the synergistic effect of fucoidan with current anti-cancer agents is of considerable interest. This review discusses the mechanisms by which fucoidan retards tumor development, eradicates tumor cells and synergizes with anti-cancer chemotherapeutic agents. Challenges to the development of fucoidan as an anti-cancer agent will also be discussed

Detection of nucleophosmin and FMS-like tyrosine kinase-3 gene mutations in acute myeloid leukemia

BACKGROUND AND OBJECTIVES: Nucleophosmin gene mutations are frequently reported in acute myeloid leukemia (AML) patients with normal karyotype, which is also frequently associated with internal tandem duplication mutations in the FMS-like tyrosine kinase-3 gene. We sought to detect the nucleophosmin and FMS-like tyrosine kinase-3 (FLT3) internal tandem duplication (ITD) mutations among Iranian patients with AML and to assess the relationship between these mutations and the subtypes of the disease. DESIGN AND SETTING: Cross-sectional study of patients referred during 2007 through 2009. PATIENTS AND METHODS: Bone marrow and peripheral blood samples of 131 AML patients were randomly collected at the time of diagnosis and prior to treatment and the DNA extracted. After amplifying the nucleophosmin and FLT3 gene regions, positive cases were screened by conformation-sensitive gel electrophoresis and agarose gel electrophoresis techniques. RESULTS: Of 131 patients, 23 (17.5) (0.95 CI=0.107-0.244) had nucleophosmin gene mutations. The highest frequency of such mutations was found among the subtypes of M4 (30.4), M3 (21.7) and M5 (17.4). There was a high frequency of these mutations in the M3 subtype as well as a high frequency of allele D in all subtypes. Also, 21 (16.0) samples (0.95 CI=0.092-0.229) had FLT3/ITD mutation, of which 8 samples had mutant nucleophosmin (8 of 23, 35), and another 13 samples had wild-type nucleophosmin gene (13 of 108, 12). There was a high degree of association between the occurrence of nucleophosmin and FLT3/ITD mutations (P=.012). CONCLUSION: Our data showed a high frequency of NPM1 mutations in the monocytic subtypes of AML, as well as a high degree of association between the occurrence of NPM1 and FLT3/ITD mutations

Frequency of CYP1A1*2C polymorphism in patients with leukemia in the Iranian population

Background: CYP1A1, a member of the cytochrome P450 (CYP) enzymes, plays a very important role in metabolizing carcinogens. The aim of this case-control study was to detect the frequency of CYP1A1*2C polymorphism in Iranian leukemic patients and determine the role of this allele's variants, if any, as a risk factor for developing leukemia. Methods: Thirty-nine patients with chronic myeloid leukemia (CML), 105 with acute myeloid leukemia (AML), 95 healthy volunteers as the adult control group, 85 children with acute lymphoblastic leukemia (ALL), and 94 healthy children as the children control group were studied. Genomic DNA was assayed for restriction fragment length polymorphism (RFLP) in the CYP1A1*2C loci by amplification followed by digestion with BsrDI. Results: The frequencies of AA genotype (wild) were 82.05, 62.85, 84.70, 85.10, and 80 in CML, AML, ALL, the children control group, and the adult control group, respectively. The frequencies of AG genotype (heterogeneous) were 17.95, 36.20, 15.30, 14.90, and 18.95 in CML, AML, ALL, the children control group, and the adult control group, respectively. The frequencies of GG genotype (mutant) were 0.95 and 1.05 in AML and the adult control groups respectively; whereas, it was not observed in CML, ALL, or the children control group. Logistic regression analysis showed a significant correlation between the CYP1A1*2C polymorphism AG and AML patients (OR=2.4, 95 CI=1.3-4.7, P>0.05). Conclusion: A higher frequency of CYP1A1*2C, observed in AML patients, compared with the adult control group indicates an increased risk for AML in individuals carrying the heterozygote allele CYP1A1*2C. However, the results did not show any association between CYP1A1*2C genotypes and risk of ALL or CML. © 2011 by The American Society for Clinical Pathology

The key role of sulfation and branching on fucoidan antitumor activity

There is an urgent need for antitumor bioactive agents with minimal or no side effects over normal adjacent cells. Fucoidan is a marine-origin polymer with known antitumor activity. However, there are still some concerns about its application due to the inconsistent experimental results, specifically its toxicity over normal cells and the mechanism behind its action. Herein, three fucoidan extracts (FEs) have been tested over normal and breast cancer cell lines. From cytotoxicity results, only one of the extracts shows selective antitumor behavior (at 0.2 mg mLâ 1), despite similarities in sulfation degree and carbohydrates composition. Although the three FEs present different molecular weights, depolymerization of selected samples discarded Mw as the key factor in the antitumor activity. Significant differences in sulfates position and branching are observed, presenting FE 2 the higher branching degree. Based on all these experimental data, it is believed that these last two properties are the ones that influence the cytotoxic effects of fucoidan extracts.The authors would like to thank the funding from projects 0687_NOVOMAR_1_P, cofunded by INTERREG 2007-2013/POCTEP, CarbPol_u_Algae (EXPL/MAR-BIO/0165/2013), and IF/00376/2014/CP1212/CT0015, funded by the Portuguese Foundation for Science and Technology, FCT, and ComplexiTE (ERC-2012-ADG 20120216-321266), funded by the European Research Council under the European Union's Seventh Framework Programme for Research and Development. The authors would also like to thank FCT, Portugal, for the scholarship of A.S.F. (SFRH/BD/102471/2014), fellowship of C.N. (SFRH/BPD/100627/2014), Investigator grants of A.M. (IF/00376/2014), R.N.-C. (IF/00373/2014), and I.P. (IF/00032/2013) and the financial support to CICECO-Aveiro Institute of Materials (POCI-01-0145-FEDER-007679, FCT UID/CTM/50011/2013) and OOPNA (UID/OUI/00062/2013), through national founds and cofinanced by the FEDER, within the PT2020 Partnership Agreement

Immunodeficiency, Centromeric Region Instability, and Facial Anomalies Syndrome (ICF) in a Boy with Variable Clinical and Immunological Presentations

Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare primary immunodeficiency disorder characterized by recurrent infections and low immunoglobulin levels due to variable combined immunodeficiency, and centromeric region instability, and facial dysmorphism. We describe a 12-year-old boy with recurrent respiratory tract infections, facial anomalies, scoliosis, and psychomotor retardation. He had recurrent pneumonia with low serum IgG and IgM levels during infancy and preschool age. Later at the age of 10, he developed recurrent ear infections. An IgA and IgM deficiency was found accompanied by a normal B-cell and T-cell count as well as an impaired candida-induced T-cell proliferation. Further evaluations revealed a missense mutation in the DNMT3B gene on chromosome 20. Chromosomal analysis showed a sunburst multi-radial feature on chromosome 1, which is a hallmark of ICF syndrome. The genetic mutation and chromosomal abnormality along with clinical findings are compatible with the diagnosis of ICF syndrome. To the best of our knowledge, this is the first time that scoliosis is observed in an ICF patient. The additional variable clinical symptoms in the case were the presence of spastic gait as well as hypogammaglobulinemia with immunoglobulin isotype switch at different ages