Field structure and electron life times in the MEFISTO Electron Cyclotron Resonance Ion Source

The complex magnetic field of the permanent-magnet electron cyclotron resonance (ECR) ion source MEFISTO located at the University of Bern have been numerically simulated. For the first time the magnetized volume qualified for electron cyclotron resonance at 2.45 GHz and 87.5 mT has been analyzed in highly detailed 3D simulations with unprecedented resolution. New results were obtained from the numerical simulation of 25211 electron trajectories. The evident characteristic ion sputtering trident of hexapole confined ECR sources has been identified with the field and electron trajectory distribution. Furthermore, unexpected long electron trajectory lifetimes were found.Comment: 11 pages, 18 figure

Problems of resort hotel management

This item was digitized by the Internet Archive. Thesis (M.B.A.)--Boston Universityhttps://archive.org/details/problemsofresort00she

Flexible and stretchable electrodes for dielectric elastomer actuators

Dielectric elastomer actuators (DEAs) are flexible lightweight actuators that can generate strains of over 100%. They are used in applications ranging from haptic feedback (mm-sized devices), to cm-scale soft robots, to meter-long blimps. DEAs consist of an electrode-elastomer-electrode stack, placed on a frame. Applying a voltage between the electrodes electrostatically compresses the elastomer, which deforms in-plane or out-of plane depending on design. Since the electrodes are bonded to the elastomer, they must reliably sustain repeated very large deformations while remaining conductive, and without significantly adding to the stiffness of the soft elastomer. The electrodes are required for electrostatic actuation, but also enable resistive and capacitive sensing of the strain, leading to self-sensing actuators. This review compares the different technologies used to make compliant electrodes for DEAs in terms of: impact on DEA device performance (speed, efficiency, maximum strain), manufacturability, miniaturization, the integration of self-sensing and self-switching, and compatibility with low-voltage operation. While graphite and carbon black have been the most widely used technique in research environments, alternative methods are emerging which combine compliance, conduction at over 100% strain with better conductivity and/or ease of patternability, including microfabrication-based approaches for compliant metal thin-films, metal-polymer nano-composites, nanoparticle implantation, and reel-to-reel production of μm-scale patterned thin films on elastomers. Such electrodes are key to miniaturization, low-voltage operation, and widespread commercialization of DEA

Shape Memory Polymer Resonators as Highly Sensitive Uncooled Infrared Detectors

Uncooled InfraRed (IR) detectors have enabled the rapid growth of thermal imaging applications. These detectors are predominantly bolometers, where the heating of pixel from incoming IR radiation is read out as a resistance change. Another uncooled sensing method is to transduce the IR radiation into the frequency shift of a mechanical resonator. We present here a highly sensitive, simple to fabricate resonant IR sensor, based on thermo-responsive Shape Memory Polymers (SMPs). By exploiting the phase-change polymer as the transduction mechanism, our approach provides 2 orders of magnitude improvement of the temperature coefficient of frequency (TCF). The SMP has very good absorption in IR wavelengths, obviating the need for an absorber layer. A Noise Equivalent Temperature Difference (NETD) of 22 mK in vacuum and 112 mK in air are obtained using f/2 optics. Such high performance in air eliminates the need for vacuum packaging, paving a path towards flexible IR sensors

EFFECTS OF RESVERATROL ON PACLITAXEL-SENSITIVE AND –RESISTANT TRIPLE NEGATIVE BREAST CANCER CELLS

poster abstractTreatment of drug-resistant cancer cells remains a difficult problem in cancer therapy because most resistant cells can pump out drugs or upregulate other survival pathways to bypass a targeted therapy. The poly-phenol natural compound, resveratrol, has been shown to inhibit cell growth of multiple cancer types, but it is not cytotoxic to normal cells. However, the effects of resveratrol in triple negative breast cancer cells as well as cancers that are resistant to the common cancer drug, paclitaxel, are not well under-stood. In this study, the effects of resveratrol were investigated in the triple negative breast cancer cell line MDA-MB-231 as well as a novel paclitaxel-resistant MDA-MB-231 derived line generated in our laboratory. Both cell lines exhibited a reduction in cell proliferation after resveratrol treatment, with the paclitaxel-resistant cells to a greater extent. In addition, resveratrol decreased the ability of both cell lines to form colonies when plated at low density indicating reduced cell survival capacity. Resveratrol treatment also increased the amount of DNA fragmentation associated with cell death in both cell lines, again with the paclitaxel resistant cells being more sensitive. By protein expression analyses, we observed that in both the parental and resistant cell lines, resveratrol may be acting by through NAD-dependent deacetylase sirtuin (SIRT1) activity by decreasing the expression of the in-hibitor-of-apoptosis protein, survivin, as well as increasing the activator-of-cell death, caspase 7. These data suggest that resveratrol can inhibit prolif-eration and induce cell death in triple negative breast cancer cells, including paclitaxel-resistant cells. In addition, these results provide rationale for the use of resveratrol as an important starting point for the development of a novel anti-cancer agent for drug resistant, aggressive cancers as well as in combination with other anti-cancer drugs without significant toxicity to nor-mal cells

The telomerase inhibitor imetelstat alone, and in combination with trastuzumab, decreases the cancer stem cell population and self-renewal of HER2+ breast cancer cells

Cancer stem cells (CSCs) are thought to be responsible for tumor progression, metastasis, and recurrence. HER2 overexpression is associated with increased CSCs, which may explain the aggressive phenotype and increased likelihood of recurrence for HER2+ breast cancers. Telomerase is reactivated in tumor cells, including CSCs, but has limited activity in normal tissues, providing potential for telomerase inhibition in anti-cancer therapy. The purpose of this study was to investigate the effects of a telomerase antagonistic oligonucleotide, imetelstat (GRN163L), on CSC and non-CSC populations of HER2+ breast cancer cell lines. The effects of imetelstat on CSC populations of HER2+ breast cancer cells were measured by ALDH activity and CD44/24 expression by flow cytometry as well as mammosphere assays for functionality. Combination studies in vitro and in vivo were utilized to test for synergism between imetelstat and trastuzumab. Imetelstat inhibited telomerase activity in both subpopulations. Moreover, imetelstat alone and in combination with trastuzumab reduced the CSC fraction and inhibited CSC functional ability, as shown by decreased mammosphere counts and invasive potential. Tumor growth rate was slower in combination-treated mice compared to either drug alone. Additionally, there was a trend toward decreased CSC marker expression in imetelstat-treated xenograft cells compared to vehicle control. Furthermore, the observed decrease in CSC marker expression occurred prior to and after telomere shortening, suggesting that imetelstat acts on the CSC subpopulation in telomere length-dependent and -independent mechanisms. Our study suggests addition of imetelstat to trastuzumab may enhance the effects of HER2 inhibition therapy, especially in the CSC population

Li-Fraumeni Syndrome Patient-derived LFS50 Progression Cell Series as an Experimental Model for Breast Cancer Prevention Research

poster abstractLi-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with germline mutations in the tumor suppressor gene TP53. Breast cancer (BC) is the most common tumor amongst women with LFS, who have increased risk for premenopausal BC before age 40 and a lifetime risk of 49% by the age of 60. Non-malignant, human mammary epithelial cells (HMECs) were derived from the contralateral breast tissue of LFS patient (LFS50) undergoing BC surgery. The LFS50 HMEC progression series comprises of pre-immortal (HME50), spontaneously immortalized (HME50-5E), hTERT-immortalized (HME50hTERT or HME50hT), and tumorigenic (HMET) which can be modeled to represent breast cancer progression. Gene expressions of the LFS50 series were profiled using HG-U133_Plus_2 Affymetrix chip. By hierarchical clustering, the LFS50 cells were observed to have significant differential expression of genes and ANOVA results revealed that EMT-related genes (e.g., epithelial membrane protein 3, p= 6.84911E-19; E-cadherin, p= 8.66098E-19; and Keratin 5, p= 9.73095E-19) to be the most differentially expressed amongst the LFS50 cells. Ingenuity Pathway Analysis (IPA) confirmed that Ecadherin and Keratin 5 were the top most differentially expressed genes as well as G2/M DNA Damage Checkpoint Regulation (p= 2.67E-05), Estrogen-mediated S-phase Entry (p=3.32E-04) Mitotic Roles of Polo-Like Kinase (p=5.5E-04) as few of the top canonical pathways. Furthermore, to identify the type of breast cancer that LFS50 series could model, the triple negative breast cancer (TNBC) subtyping database tool predicted that each of the LFS50 strains could be classified as a different subtype. Finally, as a proof of principle for drug targeting, treatment of the LFS50 series with PRIMA-1, a p53 rescue drug, using 3D cultures resulted in a reduction in acini size of the pre-invasive LFS50 cells (p<0.05). Therefore, this progression series can serve as a resource for drug target discovery and breast cancer prevention research

Molecular Mechanisms of Paclitaxel Resistance and Resveratrol Sensitivity in MDA-MB-231 Breast Cancer Cells

poster abstractTreatment of drug-resistant cancer cells remains a difficult problem in cancer therapy because most resistant cells can pump out drugs or upregulate other survival pathways to bypass a targeted therapy. To study cancers that are resistant to the common cancer drug, paclitaxel, a novel paclitaxel-resistant cell line was generated from the breast cancer cell line MDA-MB-231. A “spiking” method of paclitaxel treatment was used to select for a population of cells that are resistant to the drug. This method mimics the development of resistance in recurrent tumors in patients. However, it is difficult to study such a heterogeneous population. To better study these cells, the paclitaxel-resistant cell line was cloned using a limiting dilution method to provide more homogeneous populations of resistant cells. The 29 clones obtained exhibited a paclitaxel IC50 range of 8 μM to 78 μM which was equivalent to a 200- to 2000-fold increase in resistance compared to the parent line. It has been suggested that the polyphenol natural compound, resveratrol, which has been shown to inhibit cell growth of multiple cancer types, may be useful as a combination anti-cancer treatment or novel therapeutic for drug-resistant cancer cells. The parent line, the heterogeneous resistant line, the least paclitaxel-resistant clone and the most paclitaxelresistant clone were similarly sensitive to resveratrol treatment. We observed that treatment with 10-100 μM concentrations of resveratrol in all cell lines showed a reduction in cell proliferation and increased apoptosis within 72 hours (p<0.05), with the paclitaxel-resistant cells to a greater extent. In addition, resveratrol decreased the ability of the parent, heterogeneous resistant and the highest resistant clone cells to form colonies (an indication of reduced cell survival capacity). This resistant cell line and its clones provide a powerful tool to study paclitaxel-resistance in and therapeutics for breast cancer