Wire Driven Mechanisms for Deployable Components for Optical Payloads

Large empty volumes in optical payloads like telescopes and baffles take up significant, potentially useful space to package within a launcher volume, and can limit the minimum size of a spacecraft, having major implications on launch options and costs. Volume can be saved by using telescopic structures which can be deployed in-orbit. In previous work a light-weight wire-driven telescope was developed, which employed a constant torque spring motor with a damper to achieve a controlled deployment. This work focusses on the application of a similar deployment scheme to an optical baffle and the further development of the driving, tension-balancing and hold-down and release mechanisms required to achieve a usable sub-system package. In order to compensate for in orbit deformations, a tension balancing mechanism is proposed. A hold down release mechanism is also proposed for the launch. Preliminary FE analysis confirms the modal shapes of the deployed baffle are well beyond 100 Hz and validates the design concept. Initial functional and environmental testing has revealed minor issues, and redesign of the baffle structure will be done to conduct further tests. Future work will involve exploring other methods of manufacturing, using light absorbing materials/coatings and another round of design iteration and testing

Design Comparison of Outer- and Inner-Rotor Permanent Magnet Motors for Hydrofoil Boat

This paper presents the design criteria of a permanent magnet motor for hydrofoil boat applications. Based on the dynamic analysis of hydrofoil boat, the constraints of propulsion motor are derived and therefore the surface-mounted permanent magnet motor is chosen as the competitive candidate. In order to have large power density in the permanent magnet motor, the outer- and inner-rotor motors are investigated and compared to demonstrate their advantages at different design constraints, which will provide the theoretical basis to improve the propulsion system in the hydrofoil boat from the perspective of motor design

Deployable Optics for CubeSats

Since the beginning of the space age, many structures with different levels of complexity have been proposed for the deployment of equipment such as solar arrays, antennae, and scientific instruments. By increasing the packaging efficiency, stowing during launch and then deploying in orbit provides an opportunity for the improvement of the capabilities of small satellites payloads while maintaining a contained launch volume. The latter is particularly important when considering the launch of future constellations and, in particular, CubeSats where the volume is significantly constrained by the size of the pod. The focus of this work is the development of a camera/telescope barrel ideally suited for a Cassegrain configured space instrument, hosting the primary mirror at one (satellite side) end and the secondary mirror supported by a cruciform element at the other end (aperture). The barrel is stowed and deployed using a telescopic approach with three coaxial large diameter hollow cylinders making up the segments of the barrel. For an optical telescope, one of the most important challenges is in maintaining a highly accurate distance between the optical elements (in this case, primary and secondary mirrors which are positioned with an accuracy of a few micron). Thermo-mechanical distortions due to on orbit temperature variations and any micro-vibration excitation from sources on the spacecraft can cause significant degradation of the optical performance. To maintain the required shape stability, the main structural parts are made in a thermally invariable material and incorporate features to provide alignment and locking out. The large diameter of the structure, and low coefficient of thermal expansion, give the assembly excellent resilience to thermal and micro-vibration disturbances whilst keeping mass to a minimum. This “tube” arrangement also naturally fulfils the light baffling requirements of the telescope. Another significant challenge is the apparatus to drive the sequential deployment of the cylinders. Systems that use lead screws and gears have been proposed, however they present significant complexities and their mass has a substantial impact on the mass budget of the overall assembly. Here, a novel robust and simple wire-driven system is proposed to operate the deployment. The main advantages being the simplicity, light weight, and robustness with respect to severe vibration environments. This article will describe the development of the device and the testing of the proof of concept/qualification model

Cancer stem cell markers in breast cancer: pathological, clinical and prognostic significance

INTRODUCTION: The cancer stem cell (CSC) hypothesis states that tumours consist of a cellular hierarchy with CSCs at the apex driving tumour recurrence and metastasis. Hence, CSCs are potentially of profound clinical importance. We set out to establish the clinical relevance of breast CSC markers by profiling a large cohort of breast tumours in tissue microarrays (TMAs) using immunohistochemistry (IHC). METHODS: We included 4, 125 patients enrolled in the SEARCH population-based study with tumours represented in TMAs and classified into molecular subtype according to a validated IHC-based five-marker scheme. IHC was used to detect CD44/CD24, ALDH1A1, aldehyde dehydrogenase family 1 member A3 (ALDH1A3) and integrin alpha-6 (ITGA6). A 'Total CSC' score representing expression of all four CSC markers was also investigated. Association with breast cancer specific survival (BCSS) at 10 years was assessed using a Cox proportional-hazards model. This study was complied with REMARK criteria. RESULTS: In ER negative cases, multivariate analysis showed that ITGA6 was an independent prognostic factor with a time-dependent effect restricted to the first two years of follow-up (hazard ratio (HR) for 0 to 2 years follow-up, 2.4; 95% confidence interval (95% CI), 1.2 to 4.8; P = 0.009). The composite 'Total CSC' score carried independent prognostic significance in ER negative cases for the first four years of follow-up (HR for 0 to 4 years follow-up, 1.3; 95% CI, 1.1 to 1.6; P = 0.006). CONCLUSIONS: Breast CSC markers do not identify identical subpopulations in primary tumours. Both ITGA6 and a composite Total CSC score show independent prognostic significance in ER negative disease. The use of multiple markers to identify tumours enriched for CSCs has the greatest prognostic value. In the absence of more specific markers, we propose that the effective translation of the CSC hypothesis into patient benefit will necessitate the use of a panel of markers to robustly identify tumours enriched for CSCs

Increased expression of interleukin-1 receptor characterizes anti-estrogen resistant ALDH+ breast cancer stem cells

Estrogen receptor-positive (ER+) breast tumours are often treated with anti- estrogen (AE) therapies but frequently develop resistance. Cancer Stem Cells (CSCs) with high aldehyde dehydrogenase (ALDH) activity (ALDH+ cells) are reported to be enriched following AE treatment. Here we perform in vitro and in vivo functional CSC assays and gene expression analysis to characterise the ALDH+ population in AE resistant metastatic patient samples and an ER+ cell line. We show that the IL1 signalling pathway is activated in ALDH+ cells and data from single cells reveals that AE treatment selects for IL1R1-expressing ALDH+ cells. Importantly, CSC activity is inhibited by Anakinra, a synthetic IL1R1 antagonist, in AE-resistant models. Moreover, we demonstrate that increased expression of IL1R1 is observed in the tumours of patients treated with AE therapy and predicts for treatment failure. Single-cell gene expression analysis revealed that at least 2 sub-populations exist within the ALDH+ population, one proliferative and one quiescent. Following AE therapy, the quiescent ALDH+IL1R1+ population is expanded, which suggests CSC dormancy as an adaptive strategy that facilitates treatment resistance. Supporting this, analysis of AE resistant dormant tumours reveals significantly increased expression of ALDH1A1, ALDH1A3 and IL1R1 genes. Thus, our work establishes that targeting of ALDH+IL1R1+ cells may reverse AE resistance in patients with minimal residual disease

Number crunching in the cancer stem cell market

Like their normal counterparts, many tumours are thought to have a hierarchical organization, albeit a disorganized one. Accordingly, the concept of cancer stem cells has emerged, and that these cells are responsible for perpetuating tumour existence. Operationally, cancer stem cells are regarded as prospectively purified cells that are the most effective at tumour initiation in an in vivo assay, usually after xenotransplantation to NOD/SCID mice. The conventional wisdom is that such tumour-initiating cells are rare based upon having to xenotransplant large numbers of human tumour cells into immunodeficient mice to propagate the tumour, but new evidence indicates that perhaps these cells are not so rare, at least in malignant melanoma, if a supportive soil is provided for the transplanted cells along with further restriction of the murine host's immune response

CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers

<p>Abstract</p> <p>Background</p> <p>The CD44 cell adhesion molecule is aberrantly expressed in many breast tumors and has been implicated in the metastatic process as well as in the putative cancer stem cell (CSC) compartment. We aimed to investigate potential associations between alternatively spliced isoforms of CD44 and CSCs as well as to various breast cancer biomarkers and molecular subtypes.</p> <p>Methods</p> <p>We used q-RT-PCR and exon-exon spanning assays to analyze the expression of four alternatively spliced CD44 isoforms as well as the total expression of CD44 in 187 breast tumors and 13 cell lines. ALDH1 protein expression was determined by IHC on TMA.</p> <p>Results</p> <p>Breast cancer cell lines showed a heterogeneous expression pattern of the CD44 isoforms, which shifted considerably when cells were grown as mammospheres. Tumors characterized as positive for the CD44⁺/CD24<it>^-</it>phenotype by immunohistochemistry were associated to all isoforms except the CD44 standard (CD44S) isoform, which lacks all variant exons. Conversely, tumors with strong expression of the CSC marker ALDH1 had elevated expression of CD44S. A high expression of the CD44v2-v10 isoform, which retain all variant exons, was correlated to positive steroid receptor status, low proliferation and luminal A subtype. The CD44v3-v10 isoform showed similar correlations, while high expression of CD44v8-v10 was correlated to positive EGFR, negative/low HER2 status and basal-like subtype. High expression of CD44S was associated with strong HER2 staining and also a subgroup of basal-like tumors. Unsupervised hierarchical cluster analysis of CD44 isoform expression data divided tumors into four main clusters, which showed significant correlations to molecular subtypes and differences in 10-year overall survival.</p> <p>Conclusions</p> <p>We demonstrate that individual CD44 isoforms can be associated to different breast cancer subtypes and clinical markers such as HER2, ER and PgR, which suggests involvement of CD44 splice variants in specific oncogenic signaling pathways. Efforts to link CD44 to CSCs and tumor progression should consider the expression of various CD44 isoforms.</p

Quantitative High-Resolution Genomic Analysis of Single Cancer Cells

During cancer progression, specific genomic aberrations arise that can determine the scope of the disease and can be used as predictive or prognostic markers. The detection of specific gene amplifications or deletions in single blood-borne or disseminated tumour cells that may give rise to the development of metastases is of great clinical interest but technically challenging. In this study, we present a method for quantitative high-resolution genomic analysis of single cells. Cells were isolated under permanent microscopic control followed by high-fidelity whole genome amplification and subsequent analyses by fine tiling array-CGH and qPCR. The assay was applied to single breast cancer cells to analyze the chromosomal region centred by the therapeutical relevant EGFR gene. This method allows precise quantitative analysis of copy number variations in single cell diagnostics