2,835 research outputs found

    Exploiting metabolic acidosis in solid cancers using a tumor-agnostic pH-activatable nanoprobe for fluorescence-guided surgery

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    Cancer cell metabolism leads to a uniquely acidic microenvironment in solid tumors, but exploiting the labile extracellular pH differences between cancer and normal tissues for clinical use has been challenging. Here we describe the clinical translation of ONM-100, a nanoparticle-based fluorescent imaging agent. This is comprised of an ultra-pH sensitive amphiphilic polymer, conjugated with indocyanine green, which rapidly and irreversibly dissociates to fluoresce in the acidic extracellular tumor microenvironment due to the mechanism of nanoscale macromolecular cooperativity. Primary outcomes were safety, pharmacokinetics and imaging feasilibity of ONM-100. Secondary outcomes were to determine a range of safe doses of ONM-100 for intra-operative imaging using commonly used fluorescence camera systems. In this study (Netherlands National Trial Register #7085), we report that ONM-100 was well tolerated, and four solid tumor types could be visualized both in- and ex vivo in thirty subjects. ONM-100 enables detection of tumor-positive resection margins in 9/9 subjects and four additional otherwise missed occult lesions. Consequently, this pH-activatable optical imaging agent may be clinically beneficial in differentiating previously unexploitable narrow physiologic differences

    NNSA ASC Exascale Environment Planning, Applications Working Group, Report February 2011

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    The scope of the Apps WG covers three areas of interest: Physics and Engineering Models (PEM), multi-physics Integrated Codes (IC), and Verification and Validation (V&V). Each places different demands on the exascale environment. The exascale challenge will be to provide environments that optimize all three. PEM serve as a test bed for both model development and 'best practices' for IC code development, as well as their use as standalone codes to improve scientific understanding. Rapidly achieving reasonable performance for a small team is the key to maintaining PEM innovation. Thus, the environment must provide the ability to develop portable code at a higher level of abstraction, which can then be tuned, as needed. PEM concentrate their computational footprint in one or a few kernels that must perform efficiently. Their comparative simplicity permits extreme optimization, so the environment must provide the ability to exercise significant control over the lower software and hardware levels. IC serve as the underlying software tools employed for most ASC problems of interest. Often coupling dozens of physics models into very large, very complex applications, ICs are usually the product of hundreds of staff-years of development, with lifetimes measured in decades. Thus, emphasis is placed on portability, maintainability and overall performance, with optimization done on the whole rather than on individual parts. The exascale environment must provide a high-level standardized programming model with effective tools and mechanisms for fault detection and remediation. Finally, V&V addresses the infrastructure and methods to facilitate the assessment of code and model suitability for applications, and uncertainty quantification (UQ) methods for assessment and quantification of margins of uncertainty (QMU). V&V employs both PEM and IC, with somewhat differing goals, i.e., parameter studies and error assessments to determine both the quality of the calculation and to estimate expected deviations of simulations from experiments. The exascale environment must provide a performance envelope suitable both for capacity calculations (high through-put) and full system capability runs (high performance). Analysis of the results place shared demand on both the I/O as well as the visualization subsystems

    Study of the reaction pbar p -> phi phi from 1.1 to 2.0 GeV/c

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    A study has been performed of the reaction pbar p -> 4K using in-flight antiprotons from 1.1 to 2.0 GeV/c incident momentum interacting with a hydrogen jet target. The reaction is dominated by the production of a pair of phi mesons. The pbar p -> phi phi cross section rises sharply above threshold and then falls continuously as a function of increasing antiproton momentum. The overall magnitude of the cross section exceeds expectations from a simple application of the OZI rule by two orders of magnitude. In a fine scan around the xi/f_J(2230) resonance, no structure is observed. A limit is set for the double branching ratio B(xi -> pbar p) * B(xi -> phi phi) < 6e-5 for a spin 2 resonance of M = 2.235 GeV and Width = 15 MeV.Comment: 13 pages, 13 figures, 2 tables, Latex. To be published in Phys. Rev.

    Feasibility of ex vivo fluorescence imaging of angiogenesis in (non-) culprit human carotid atherosclerotic plaques using bevacizumab-800CW

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    Vascular endothelial growth factor-A (VEGF-A) is assumed to play a crucial role in the development and rupture of vulnerable plaques in the atherosclerotic process. We used a VEGF-A targeted fluorescent antibody (bevacizumab-IRDye800CW [bevacizumab-800CW]) to image and visualize the distribution of VEGF-A in (non-)culprit carotid plaques ex vivo. Freshly endarterectomized human plaques (n = 15) were incubated in bevacizumab-800CW ex vivo. Subsequent NIRF imaging showed a more intense fluorescent signal in the culprit plaques (n = 11) than in the non-culprit plaques (n = 3). A plaque received from an asymptomatic patient showed pathologic features similar to the culprit plaques. Cross-correlation with VEGF-A immunohistochemistry showed co-localization of VEGF-A over-expression in 91% of the fluorescent culprit plaques, while no VEGF-A expression was found in the non-culprit plaques (p < 0.0001). VEGF-A expression was co-localized with CD34, a marker for angiogenesis (p < 0.001). Ex vivo near-infrared fluorescence (NIRF) imaging by incubation with bevacizumab-800CW shows promise for visualizing VEGF-A overexpression in culprit atherosclerotic plaques in vivo

    Commissioning and performance of the LHCb Silicon Tracker

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    The LHCb Silicon Tracker is a silicon micro-strip detector with a sensitive area of 12 m2 and a total of 272k readout channels. The Silicon Tracker consists of two parts that use different detector modules. The detector installation was completed by early summer 2008 and the commissioning without beam has reached its final stage, successfully overcoming most of the encountered problems. Currently, the detector has more than 99% of the channels fully functioning. Commissioning with particles has started using beam-induced events from the LHC injection tests in 2008 and 2009. These events allowed initial studies of the detector performance. Especially, the detector modules could be aligned with an accuracy of about 20μm. Furthermore, with the first beam collisions that took place end of 2009 we could further study the performance and improve the alignment of the detector

    Emergence of qualia from brain activity or from an interaction of proto-consciousness with the brain: which one is the weirder? Available evidence and a research agenda

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    This contribution to the science of consciousness aims at comparing how two different theories can explain the emergence of different qualia experiences, meta-awareness, meta-cognition, the placebo effect, out-of-body experiences, cognitive therapy and meditation-induced brain changes, etc. The first theory postulates that qualia experiences derive from specific neural patterns, the second one, that qualia experiences derive from the interaction of a proto-consciousness with the brain\u2019s neural activity. From this comparison it will be possible to judge which one seems to better explain the different qualia experiences and to offer a more promising research agenda

    Aging Studies for the Large Honeycomb Drift Tube System of the Outer Tracker of HERA-B

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    The HERA-B Outer Tracker consists of drift tubes folded from polycarbonate foil and is operated with Ar/CF4/CO2 as drift gas. The detector has to stand radiation levels which are similar to LHC conditions. The first prototypes exposed to radiation in HERA-B suffered severe radiation damage due to the development of self-sustaining currents (Malter effect). In a subsequent extended R&D program major changes to the original concept for the drift tubes (surface conductivity, drift gas, production materials) have been developed and validated for use in harsh radiation environments. In the test program various aging effects (like Malter currents, gain loss due to anode aging and etching of the anode gold surface) have been observed and cures by tuning of operation parameters have been developed.Comment: 14 pages, 6 figures, to be published in the Proceedings of the International Workshop On Aging Phenomena In Gaseous Detectors, 2-5 Oct 2001, Hamburg, German
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