2,311 research outputs found

    Analysis and design of a capsule landing system and surface vehicle control system for Mars exploration

    Get PDF
    Problems related to the design and control of a mobile planetary vehicle to implement a systematic plan for the exploration of Mars are reported. Problem areas include: vehicle configuration, control, dynamics, systems and propulsion; systems analysis, terrain modeling and path selection; and chemical analysis of specimens. These tasks are summarized: vehicle model design, mathematical model of vehicle dynamics, experimental vehicle dynamics, obstacle negotiation, electrochemical controls, remote control, collapsibility and deployment, construction of a wheel tester, wheel analysis, payload design, system design optimization, effect of design assumptions, accessory optimal design, on-board computer subsystem, laser range measurement, discrete obstacle detection, obstacle detection systems, terrain modeling, path selection system simulation and evaluation, gas chromatograph/mass spectrometer system concepts, and chromatograph model evaluation and improvement

    Imaging of lumpectomy surface with large field-of-view confocal laser scanning microscope for intraoperative margin assessment - POLARHIS study

    Get PDF
    Introduction: Breast-conserving surgery (BCS) in case of breast cancer and/or in-situ-carcinoma lesions (DCIS) intends to completely remove breast cancer while saving healthy tissue as much as possible to achieve better aesthetic and psychological outcomes for the patient. Such modality should result in postoperative tumor-free margins of the surgical resection in order to carry on with the next therapeutical steps of the patient care. However, 10–40% of patients undergo more than one procedure to achieve acceptable cancer-negative margins. A 2nd operation or further operation (re-operation) has physical, psychological, and economic consequences. It also delays the administration of adjuvant therapy, and has been associated with an elevated risk of local and distant disease relapse. In addition, a high re-operation rate can have significant economic effects - both for the service provider and for the payer. A more efficient intraoperative assessment of the margin may address these issues. Recently, a large field-of-view confocal laser scanning microscope designed to allow real-time intraoperative margin assessment has arrived on the market - the Histolog Scanner. In this paper, we present the first evaluation of lumpectomy margins assessment with this new device. Materials and methods: 40 consecutive patients undergoing BCS with invasive and/or DCIS were included. The whole surface of the surgical specimens was imaged right after the operation using the Histolog Scanner (HLS). The assessment of all the specimen margins was performed intraoperatively according to the standard-of-care of the center which consists of combined ultrasound (IOUS) and/or conventional specimen radiography (CSR), and gross surgical inspection. Margin assessment on HLS images was blindly performed after the surgery by 5 surgeons and one pathologist. The capabilities to correctly determine margin status in HLS images was compared to the final histopathological assessment. Furthermore, the potential reduction of positive-margin and re-operation rates by utilization of the HLS were extrapolated. Results: The study population included 7/40 patients with DCIS (17.5%), 17/40 patients with DCIS and invasive ductal cancer (IDC NST) (42.5%), 10/40 patients with IDC NST (25%), 4/40 with invasive lobular cancer (ILC) (10%), and 1/40 patients with a mix of IDC NST, DCIS, and ILC. Clinical routine resulted in 13 patients with positive margins identified by final histopathological assessment, resulting in 12 re-operations (30% re-operation rate). Amongst these 12 patients, 10 had DCIS components involved in their margin, confirming the importance of improving the detection accuracy of this specific lesion. Surgeons, who were given a short familiarization on HLS images, and a pathologist were able to detect positive margins in 4/12 and 7/12 patients (33% and 58%), respectively, that were missed by the intraoperative standard of care. In addition, a retrospective analysis of the HLS images revealed that cancer lesions can be identified in 9/12 (75%) patients with positive margins. Conclusion: The present study presents that breast cancer can be detected by surgeons and pathologists in HLS images of lumpectomy margins leading to a potential reduction of 30% and 75% of the re-operations. The Histolog Scanner is easily inserted into the clinical workflow and has the potential to improve the intraoperative standard-of-care for the assessment of breast conserving treatments. In addition, it has the potential to increase oncological safety and cosmetics by avoiding subsequent resections and can also have a significant positive economic effect for service providers and cost bearers. The data presented in this study will have to be further confirmed in a prospective phase–III–trial

    Discovery of macrocyclic inhibitors of apurinic/apyrimidinic endonuclease 1

    Get PDF
    Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential base excision repair enzyme that is upregulated in a number of cancers, contributes to resistance of tumors treated with DNA-alkylating or -oxidizing agents, and has recently been identified as an important therapeutic target. In this work, we identified hot spots for binding of small organic molecules experimentally in high resolution crystal structures of APE1 and computationally through the use of FTMAP analysis (http://ftmap.bu.edu/). Guided by these hot spots, a library of drug-like macrocycles was docked and then screened for inhibition of APE1 endonuclease activity. In an iterative process, hot-spot-guided docking, characterization of inhibition of APE1 endonuclease, and cytotoxicity of cancer cells were used to design next generation macrocycles. To assess target selectivity in cells, selected macrocycles were analyzed for modulation of DNA damage. Taken together, our studies suggest that macrocycles represent a promising class of compounds for inhibition of APE1 in cancer cells.This work was supported by grants from the National Institutes of Health (Grant R01CA205166 to M.R.K. and M.M.G. and Grant R01CA167291 to M.R.K.) and by the Earl and Betty Herr Professor in Pediatric Oncology Research, Jeff Gordon Children's Foundation, and the Riley Children's Foundation (M.R.K.). Work at the BU-CMD (J.A.P., L.E.B., R.T.) is supported by the National Institutes of Health, Grant R24 GM111625. D.B. and S.V. were supported by the National Institutes of Health, Grant R35 GM118078. (R35 GM118078 - National Institutes of Health; R01CA205166 - National Institutes of Health; R01CA167291 - National Institutes of Health; R24 GM111625 - National Institutes of Health; Earl and Betty Herr Professor in Pediatric Oncology Research; Jeff Gordon Children's Foundation; Riley Children's Foundation)Accepted manuscriptSupporting documentatio

    SU(2) chiral perturbation theory low-energy constants from staggered 2+1 flavor simulations

    Get PDF
    We extract the NLO low-energy constants \bar\ell_3 and \bar\ell_4 of SU(2) chiral perturbation theory, based on precise lattice data for the pion mass and decay constant on ensembles generated by the Wuppertal-Budapest collaboration for QCD thermodynamics. These ensembles feature 2+1 flavors of 2-fold stout-smeared dynamical staggered fermions combined with Symanzik glue, with pion masses varying from 135 MeV to 435 MeV, lattice scales between 0.7 GeV and 2.0 GeV, while m_s is kept fixed at its physical value. Moderate taste splittings and the scale being set through the pion decay constant allow us to restrict ourselves to the taste pseudoscalar state and to use formulae from continuum ChPT. Finally, by dropping the data points near 135 MeV from the fits, we can explore the range of pion masses that is needed in SU(2) ChPT to reliably extrapolate to the physical point

    Adrenalectomy promotes a permanent decrease of plasma corticoid levels and a transient increase of apoptosis and the expression of Transforming Growth Factor β1 (TGF-β1) in hippocampus: effect of a TGF-β1 oligo-antisense

    Get PDF
    BACKGROUND: Corticosterone reduction produced by adrenalectomy (ADX) induces apoptosis in dentate gyrus (DG) of the hippocampus, an effect related to an increase in the expression of the pro-apoptotic gene bax. However it has been reported that there is also an increase of the anti-apoptotic gene bcl-2, suggesting the promotion of a neuroprotective phenomenon, perhaps related to the expression of transforming growth factor β1 (TGF-β1). Thus, we have investigated whether TGF-β1 levels are induced by ADX, and whether apoptosis is increased by blocking the expression of TGF-β1 with an antisense oligonucleotide (ASO) administered intracerebrally in corticosterone depleted rats. RESULTS: It was observed an increase of apoptosis in DG, 2 and 5 days after ADX, in agreement with a reduction of corticosterone levels. However, the effect of ADX on the number of apoptotic positive cells in DG was decreased 5 days after the lesion. In CA1–CA3 regions, the effect was only observed 2 days after ADX. TGF-β1 mRNA levels were increased 2 days after ADX. The sustained intracerebro-ventricular administration of a TGF-β1 ASO via an osmotic mini pump increased apoptosis levels in CA and DG regions 5 days after ADX as well as sham-operated control animals. No significant effect was observed following a scrambled-oligodeoxynucleotide treatment. CONCLUSION: The changes in both the pattern and the magnitude of apoptotic-cell morphology observed 2 and 5 days after ADX suggest that, as a consequence of the reduction of corticosteroids, some trophic mechanisms restricting cell death to a particular time window are elicited. Sustained intracerebral administration of TGF-β1 ASO increased the apoptosis promoted by ADX, suggesting that TGF-β1 plays an anti-apoptotic role in vivo in hippocampus

    Winegrowers’ decision-making: A pan-European perspective on pesticide use and inter-row management

    Get PDF
    European viticultural landscapes not only support a significant share of rural livelihoods and cultural traditions, but also conserve biodiversity and sustain various ecosystem services. Winegrowers' practices of inter-row management (including whether to have vegetation in the inter-rows, type of vegetation, duration of vegetation cover, and soil tillage) and pesticide use (including herbicides in the inter-rows, fungicides, insecticides, and pheromone dispensers as an alternative) can affect these services. This study aims to understand winegrowers' decision-making driven by their personal characteristics, attitudes and beliefs towards viticultural practices, physical properties of vineyards, and farm management characteristics in five European winegrowing regions. These include Palatinate in Germany, Leithaberg in Austria, Tarnave in Romania, Bordeaux in France, and Montilla-Moriles in Spain. Based on a questionnaire survey, we constructed decision trees for each behaviour per case study as well as in a generic European model. We found factors that best explain how winegrowers manage their inter-rows and use pesticides. Results showed that not only do behaviours of winegrowers vary drastically across the case studies, but also the factors that explain most behaviours: farmers' attitudes and beliefs and farm management characteristics. This implies the importance of attitudes and beliefs – which are under-researched as compared to other factors – in understanding farmers’ behaviour. With the driving factors found to vary per case study, our results also imply the need for locally-adapted policies. Furthermore, our results suggest that the effects of climate change on European viticultural landscapes concern not only shifting production regions and changes in yields, but also changing pressure of pests and diseases. Any long-term behavioural change requires efforts from many stakeholders.This research was funded by the research project SECBIVIT which was funded through the 2017–2018 Belmont Forum and BiodivERsA joint call for research proposals, under the BiodivScen ERA-Net COFUND programme, with the funding organisations: Agencia Estatal de Investigación (Ministerio de ciencia e innovación/Spain), Austrian Science Fund (FWF) (grant number I 4025-B32), Federal Ministry of Education and Research (BMBF/Germany) through VDI/VDE Innovation + Technik GmbH, DLR Projektträger, French National Research Agency (ANR), Netherlands Organisation for Scientific Research (NWO), National Science Foundation (Grant #1850943) and Romanian Executive Agency for Higher Education, Research, Development and Innovation Funding (UEFISCDI). We would like to thank all winegrowers who participated in the focus groups, online questionnaires and personal interviews and the extension services who distributed our online questionnaire through their e-mail distribution list (DLR-Rheinpfalz)

    A comparison of statistical hadronization models

    Full text link
    We investigate the sensitivity of fits of hadron spectra produced in heavy ion collisions to the choice of statistical hadronization model. We start by giving an overview of statistical model ambiguities, and what they tell us about freeze-out dynamics. We then use Montecarlo generated data to determine sensitivity to model choice. We fit the statistical hadronization models under consideration to RHIC data, and find that a comparison χ2\chi^2 fits can shed light on some presently contentious questions.Comment: Proceedings for SQM2003 [7th Int. Conf. on Strangeness in Quark Matter (Atlantic Beach, NC, USA, Mar 12-17, 2003)], to be published in Journal of Physics G (Typos corrected, reference added

    Information Presentation: Human Research Program - Space Human Factors and Habitability, Space Human Factors Engineering Project

    Get PDF
    The goal of the Information Presentation Directed Research Project (DRP) is to address design questions related to the presentation of information to the crew. The major areas of work, or subtasks, within this DRP are: 1) Displays, 2) Controls, 3) Electronic Procedures and Fault Management, and 4) Human Performance Modeling. This DRP is a collaborative effort between researchers atJohnson Space Center and Ames Research Center.
    • …
    corecore