The black silicon method: a universal method for determining the parameter setting of a fluorine-based reactive ion etcher in deep silicon trench etching with profile control

Very deep trenches (up to 200 µm) with high aspect ratios (up to 10) in silicon and polymers are etched using a fluorine-based plasma (SF6/O2/CHF3). Isotropic, positively and negatively (i.e. reverse) tapered as well as fully vertical walls with smooth surfaces are achieved by controlling the plasma chemistry. A convenient way to find the processing conditions needed for a vertical wall is described: the black silicon method. This new procedure is checked for three different reactive ion etchers (RIE), two parallel-plate reactors and a hexode. The influence of the RF power, pressure and gas mixture on the profile will be shown. Scanning electron microscope (SEM) photos are included to demonstrate the black silicon method, the influence of the gases on the profile, and the use of this method in fabricating microelectromechanical systems (MEMS)

Anisotropic reactive ion etching of silicon using SF₆/O₂/CHF₃ gas mixtures

Reactive ion etching of silicon in an RF parallel plate system, using SF6/O2/CHF3, plasmas has been studied. Etching behavior was found to be a function of loading, the cathode material, and the mask material. Good results with respect to reproducibility and uniformity have been obtained by using silicon as the cathode material and silicon dioxide as the masking material for mask designs where most of the surface is etched. Etch rate, selectivity, anisotropy, and self-bias voltage have been examined as a function of SF6 flow, O2 flow, CHF3 flow, pressure, and the RF power, using response surface methodology, in order to optimize anisotropic etching conditions. The effects of the variables on the measured responses are discussed. The anisotropic etch mechanism is based on ion-enhanced inhibitor etching. SF6 provides the reactive neutral etching species, O2 supplies the inhibitor film forming species, and SF6 and CHF3 generate ion species that suppress the formation of the inhibitor film at horizontal surfaces. Anisotropic etching of high aspect ratio structures with smooth etch surfaces has been achieved. The technique is applied to the fabrication of three-dimensional micromechanical structures

Explicit kinetic heterogeneity: mechanistic models for interpretation of labeling data of heterogeneous cell populations

Estimation of division and death rates of lymphocytes in different conditions is vital for quantitative understanding of the immune system. Deuterium, in the form of deuterated glucose or heavy water, can be used to measure rates of proliferation and death of lymphocytes in vivo. Inferring these rates from labeling and delabeling curves has been subject to considerable debate with different groups suggesting different mathematical models for that purpose. We show that the three models that are most commonly used are in fact mathematically identical and differ only in their interpretation of the estimated parameters. By extending these previous models, we here propose a more mechanistic approach for the analysis of data from deuterium labeling experiments. We construct a model of "kinetic heterogeneity" in which the total cell population consists of many sub-populations with different rates of cell turnover. In this model, for a given distribution of the rates of turnover, the predicted fraction of labeled DNA accumulated and lost can be calculated. Our model reproduces several previously made experimental observations, such as a negative correlation between the length of the labeling period and the rate at which labeled DNA is lost after label cessation. We demonstrate the reliability of the new explicit kinetic heterogeneity model by applying it to artificially generated datasets, and illustrate its usefulness by fitting experimental data. In contrast to previous models, the explicit kinetic heterogeneity model 1) provides a mechanistic way of interpreting labeling data; 2) allows for a non-exponential loss of labeled cells during delabeling, and 3) can be used to describe data with variable labeling length

Resistance to different classes of drugs is associated with impaired apoptosis in childhood acute lymphoblastic leukemia

Resistance of leukemic cells to chemotherapeutic agents is associated with an unfavorable outcome in pediatric acute lymphoblastic leukemia (ALL). To investigate the underlying mechanisms of cellular drug resistance, the activation of various apoptotic parameters in leukemic cells from 50 children with ALL was studied after in vitro exposure with 4 important drugs in ALL therapy (prednisolone, vincristine, l-asparaginase, and daunorubicin). Exposure to each drug resulted in early induction of phosphatidylserine (PS) externalization and mitochondrial transmembrane (Deltapsim) depolarization followed by caspase-3 activation and poly(ADP-ribose) polymerase (PARP) inactivation in the majority of patients. For all 4 drugs, a significant inverse correlation was found between cellular drug resistance and (1) the percentage of cells with PS externalization (<.001 < P <.008) and (2) the percentage of cells with Deltapsim depolarization (.002 < P <.02). However, the percentage of cells with caspase-3 activation and the percentage of cells with PARP inactivation showed a significant inverse correlation with cellular resistance for prednisolone (P =.001; P =.001) and l-asparaginase (P =.01; P =.001) only. This suggests that caspase-3 activation and PARP inactivation are not essential for vincristine- and daunorubicin-induced apoptosis. In conclusion, resistance to 4 unrelated drugs is associated with defect(s) upstream or at the level of PS externalization and Deltapsim depolarization. This leads to decreased activation of apoptotic parameters in resistant cases of pediatric AL

Biological background of pediatric medulloblastoma and ependymoma: A review from a translational research perspective

Survival rates of pediatric brain tumor patients have significantly improved over the years due to developments in diagnostic techniques, neurosurgery, chemotherapy, radiotherapy, and supportive care. However, brain tumors are still an important cause of cancer-related deaths in children. Prognosis is still highly dependent on clinical characteristics, such as the age of the patient, tumor type, stage, and localization, but increased knowledge about the genetic and biological features of these tumors is being obtained and might be useful to further improve outcome for these patients. It has become clear that the deregulation of signaling pathways essential in brain development, for example, sonic hedgehog (SHH), Wnt, and Notch pathways, plays an important role in pathogenesis and biological behavior, especially for medulloblastomas. More recently, data have become available about the cells of origin of brain tumors and the possible existence of brain tumor stem cells. Newly developed array-based techniques for studying gene expression, protein expression, copy number aberrations, and epigenetic events have led to the identification of other potentially important biological abnormalities in pediatric medulloblastomas and ependymomas. Copyright 2008 by the Society for Neuro-Oncology

Endoscopic colorectal cancer screening: a cost-saving analysis

BACKGROUND: Comprehensive analyses have shown that screening for cancer usually induces net costs. In this study, the possible costs and savings of endoscopic colorectal cancer screening are explored to investigate whether the induced savings may compensate for the costs of screening. METHODS: A simulation model for evaluation of colorectal cancer screening, MISCAN-COLON, is used to predict costs and savings for the U.S. population, assuming that screening is performed during a period of 30 years. Plausible baseline parameter values of epidemiology, natural history, screening test characteristics, and unit costs are based on available data and expert opinion. Important parameters are varied to extreme but plausible values. RESULTS: Given the expert opinion-based assumptions, a program based on every 5-year sigmoidoscopy screenings could result in a net savings of direct health care costs due to prevention of cancer treatment costs that compensate for the costs of screening, diagnostic follow-up, and surveillance. This result persists when costs and health effects are discounted at 3%. The "break-even" point, the time required before savings exceed costs, is 35 years for a screening program that terminates after 30 years and 44 years for a screening program that continues on indefinitely. However, net savings increase or turn into net costs when alternative assumptions about natural history of colorectal cancer, costs of screening, surveillance, and diagnostics are considered. CONCLUSIONS: Given the present, limited knowledge of the disease process of colorectal cancer, test characteristics, and costs, it may well be that the induced savings by endoscopic colorectal cancer screening completely compensate for the costs

How cost-effective is breast cancer screening in different EC countries?

Should the decision to start breast cancer screening in the Netherlands and in the U.K. be followed by other EC countries? This question has been addressed in an exploratory analysis of the differences in cost-effectiveness of breast cancer screening in Spain, France, the U.K. and the Netherlands. A detailed cost-effectiveness analysis of breast cancer screening in the Netherlands has been used as the starting point. Country specific data on incidence, mortality, demography, screening organisation and price levels in health care have been used to predict the costs and effects of nationwide screening programmes, in which women aged 50–70 are invited for 2-yearly mammographic screening. The relative effect of screening is highest in the U.K. (16.55 life-years gained per 1000 screens) and lowest in Spain (8.23 life-years gained per 1000 screens). The cost per screen is highest in Spain (£38) and lowest in the U.K. (£18). In comparison with the yearly health expenditures per capita, the cost per life-year gained is 2.8 times higher in the Netherlands, 3.1 times higher in the U.K., 6.5 times higher in France and 20.6 times higher in Spain. These marked differences show that no uniform policy recommendations for breast cancer screening can be made for all countries of the EC