123 research outputs found
Free piston linear generator in comparison to other range-extender technologies
The free piston linear generator is a new range-extender technology. It converts chemical energy into electrical energy by means of a combustion process and linear generator. Thereby the technology aims to have better properties than other range extenders. Therefore this publication deals with the explanation of the concept and the characteristics of a free piston linear generator and a comparison to other technologies. In order to compare the range extender systems, fuel cells, micro gas turbine and otto/wankel combustion, will briefly be presented, before being compared to the free piston linear generator
Free-piston linear generator and the development of a solid lubrication system
The free piston linear generator is a new electromechanical generator. It converts chemical energy into electrical energy by means of a combustion process, a linear generator and a gas spring. Thereby the technology aims to have better properties than other electromechanical generators. Therefore this publication deals with the explanation of the concept, the characteristics of a free piston linear generator and one of the challenges in the development. In order to use a port scavenging the emission issue is the challenge and has to be solved. One possible solution is the use of solid lubricants to substitute motor oil. The development methodology and one aspect of the development will be explained
Zero-inflated regression models for radiation-induced chromosome aberration data: A comparative study
Within the field of cytogenetic biodosimetry, Poisson regression is the classical approach for modeling the number of chromosome aberrations as a function of radiation dose. However, it is common to find data that exhibit overdispersion. In practice, the assumption of equidispersion may be violated due to unobserved heterogeneity in the cell population, which will render the variance of observed aberration counts larger than their mean, and/or the frequency of zero counts greater than expected for the Poisson distribution. This phenomenon is observable for both full- and partial-body exposure, but more pronounced for the latter. In this work, different methodologies for analyzing cytogenetic chromosomal aberrations datasets are compared, with special focus on zero-inflated Poisson and zero-inflated negative binomial models. A score test for testing for zero inflation in Poisson regression models under the identity link is also developed
Studies of the dose-effect relation
Dose-effect relations and, specifically, cell survival curves are surveyed with emphasis on the interplay of the random factors — biological variability, stochastic reaction of the cell, and the statistics of energy deposition —that co-determine their shape. The global parameters mean inactivation dose, , and coefficient of variance, V, represent this interplay better than conventional parameters. Mechanisms such as lesion interaction, misrepair, repair overload, or repair depletion have been invoked to explain sigmoid dose dependencies, but these notions are partly synonymous and are largely undistinguishable on the basis of observed dose dependencies. All dose dependencies reflect, to varying degree, the microdosimetric fluctuations of energy deposition, and these have certain implications, e.g. the linearity of the dose dependence at small doses, that apply regardless of unresolved molecular mechanisms of cellular radiation action
Radiation-induced cell transformation: transformation efficiencies of different types of ionizing radiation and molecular changes in radiation transformants and tumor cell lines
This study aims to compare the efficiencies of 5.4 keV soft X-rays, alpha-particles, and gamma-rays in transforming C3H 10T1/2 cells and to assess the sequence of cellular and molecular changes during the process of radiation-induced transformation of Syrian hamster embryo (SHE) cells. The somewhat more densely ionizing soft X-rays are more effective than gamma-rays both for cell inactivation and cell transformation. The relative biological effectiveness (RBE) appears to be independent of dose; it is approximately 1.3 for either end point. The RBE of alpha-particles versus gamma-rays, on the other hand, increases with decreasing dose; the dose dependence is somewhat more apparent for cell transformation than for cell inactivation. SHE cells transformed by different types of ionizing radiation and related tumor cell lines isolated from nude mice tumors were found to have a distinct growth advantage compared to primary SHE cells, documented by higher plating efficiencies, shorter doubling times, and higher cloning efficiencies in semisolid medium. Most transformed and tumor cell lines that were investigated have elevated mRNA levels for the H-ras gene, some of them show restriction fragment length polymorphisms of the H-ras gene, and some exhibit a substantially amplified c-myc gene. In a sequence analysis of the Syrian hamster H-ras gene of eight tumor cell lines from radiation transformants, we have not found any mutation in codons 12, 13, 59, 61, nor in the flanking regions of these codons. The transformed and tumor cell lines tend to have lower chromosome numbers than primary SHE cells
Thymoquinone Induces Telomere Shortening, DNA Damage and Apoptosis in Human Glioblastoma Cells
Background: A major concern of cancer chemotherapy is the side effects caused by the non-specific targeting of both normal and cancerous cells by therapeutic drugs. Much emphasis has been placed on discovering new compounds that target tumour cells more efficiently and selectively with minimal toxic effects on normal cells. Methodology/Principal Findings: The cytotoxic effect of thymoquinone, a component derived from the plant Nigella sativa, was tested on human glioblastoma and normal cells. Our findings demonstrated that glioblastoma cells were more sensitive to thymoquinone-induced antiproliferative effects. Thymoquinone induced DNA damage, cell cycle arrest and apoptosis in the glioblastoma cells. It was also observed that thymoquinone facilitated telomere attrition by inhibiting the activity of telomerase. In addition to these, we investigated the role of DNA-PKcs on thymoquinone mediated changes in telomere length. Telomeres in glioblastoma cells with DNA-PKcs were more sensitive to thymoquinone mediated effects as compared to those cells deficient in DNA-PKcs. Conclusions/Significance: Our results indicate that thymoquinone induces DNA damage, telomere attrition by inhibiting telomerase and cell death in glioblastoma cells. Telomere shortening was found to be dependent on the status of DNA-PKcs. Collectively, these data suggest that thymoquinone could be useful as a potential chemotherapeutic agent in th
Spontaneous and radiation-induced chromosomal instability and persistence of chromosome aberrations after radiotherapy in lymphocytes from prostate cancer patients
The aim of the study was to compare the spontaneous and ex vivo radiation-induced chromosomal damage in lymphocytes of untreated prostate cancer patients and age-matched healthy donors, and to evaluate the chromosomal damage, induced by radiotherapy, and its persistence. Blood samples from 102 prostate cancer patients were obtained before radiotherapy to investigate the excess acentric fragments and dicentric chromosomes. In addition, in a subgroup of ten patients, simple exchanges in chromosomes 2 and 4 were evaluated by fluorescent in situ hybridization (FISH), before the onset of therapy, in the middle and at the end of therapy, and 1 year later. Data were compared to blood samples from ten age-matched healthy donors. We found that spontaneous yields of acentric chromosome fragments and simple exchanges were significantly increased in lymphocytes of patients before onset of therapy, indicating chromosomal instability in these patients. Ex vivo radiation-induced aberrations were not significantly increased, indicating proficient repair of radiation-induced DNA double-strand breaks in lymphocytes of these patients. As expected, the yields of dicentric and acentric chromosomes, and the partial yields of simple exchanges, were increased after the onset of therapy. Surprisingly, yields after 1 year were comparable to those directly after radiotherapy, indicating persistence of chromosomal instability over this time. Our results indicate that prostate cancer patients are characterized by increased spontaneous chromosomal instability. This instability seems to result from defects other than a deficient repair of radiation-induced DNA double-strand breaks. Radiotherapy-induced chromosomal damage persists 1 year after treatment
Rad51 and DNA-PKcs are involved in the generation of specific telomere aberrations induced by the quadruplex ligand 360A that impair mitotic cell progression and lead to cell death
Functional telomeres are protected from non-homologous end-joining (NHEJ) and homologous recombination (HR) DNA repair pathways. Replication is a critical period for telomeres because of the requirement for reconstitution of functional protected telomere conformations, a process that involves DNA repair proteins. Using knockdown of DNA-PKcs and Rad51 expression in three different cell lines, we demonstrate the respective involvement of NHEJ and HR in the formation of telomere aberrations induced by the G-quadruplex ligand 360A during or after replication. HR contributed to specific chromatid-type aberrations (telomere losses and doublets) affecting the lagging strand telomeres, whereas DNA-PKcs-dependent NHEJ was responsible for sister telomere fusions as a direct consequence of G-quadruplex formation and/or stabilization induced by 360A on parental telomere G strands. NHEJ and HR activation at telomeres altered mitotic progression in treated cells. In particular, NHEJ-mediated sister telomere fusions were associated with altered metaphase-anaphase transition and anaphase bridges and resulted in cell death during mitosis or early G1. Collectively, these data elucidate specific molecular and cellular mechanisms triggered by telomere targeting by the G-quadruplex ligand 360A, leading to cancer cell death
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