Compound C prevents Hypoxia-Inducible Factor-1α protein stabilization by regulating the cellular oxygen availability via interaction with Mitochondrial Complex I

The transcription factor Hypoxia-Inducible Factor-1α is a master regulator of the cellular response to low oxygen concentration. Compound C, an inhibitor of AMP-activated kinase, has been reported to inhibit hypoxia dependent Hypoxia-Inducible Factor-1α activation via a mechanism that is independent of AMP-activated kinase but dependent on its interaction with the mitochondrial electron transport chain. The objective of this study is to characterize the interaction of Compound C with the mitochondrial electron transport chain and to determine the mechanism through which the drug influences the stability of the Hypoxia-Inducible Factor-1α protein

Applications of a non-interferometric x-ray phase contrast imaging method with both synchrotron and conventional sources

We have developed a totally incoherent, non-interferometric x-ray phase contrast imaging (XPCI) method. This is based on the edge illumination (EI) concept developed at the ELETTRA synchrotron in Italy in the late ‘90s. The method was subsequently adapted to the divergent beam generated by a conventional source, by replicating it for every detector line through suitable masks. The method was modelled both with the simplified ray-tracing and with the more rigorous wave-optics approach, and in both cases excellent agreement with the experimental results was found. The wave-optics model enabled assessing the methods’ coherence requirements, showing that they are at least an order of magnitude more relaxed than in other methods, without this having negative consequences on the phase sensitivity. Our masks have large pitches (up to 50 times larger than in grating interferometry, for example), which allows for manufacturing through standard lithography, scalability, cost-effectiveness and easiness to align. When applied to a polychromatic and divergent beam generated by a conventional source, the method enables the detection of strong phase effects also with uncollimated, unapertured sources with focal spots of up to 100 mm, compatible with the state-of-the-art in mammography. When used at synchrotrons, it enables a contrast increase of orders of magnitude over other methods. Robust phase retrieval was proven for both coherent and incoherent sources, and additional advantages are compatibility with high x-ray energies and easy implementation of phase sensitivity in two directions simultaneously. This paper briefly summarizes these achievements and reviews some of the key results

Edge illumination and coded-aperture X-ray phase-contrast imaging: Increased sensitivity at synchrotrons and lab-based translations into medicine, biology and materials science

The edge illumination principle was first proposed at Elettra (Italy) in the late nineties, as an alternative method for achieving high phase sensitivity with a very simple and flexible set-up, and has since been under continuous development in the radiation physics group at UCL. Edge illumination allows overcoming most of the limitations of other phase-contrast techniques, enabling their translation into a laboratory environment. It is relatively insensitive to mechanical and thermal instabilities and it can be adapted to the divergent and polychromatic beams provided by X-ray tubes. This method has been demonstrated to work efficiently with source sizes up to 100m, compatible with state-of-the-art mammography sources. Two full prototypes have been built and are operational at UCL. Recent activity focused on applications such as breast and cartilage imaging, homeland security and detection of defects in composite materials. New methods such as phase retrieval, tomosynthesis and computed tomography algorithms are currently being theoretically and experimentally investigated. These results strongly indicate the technique as an extremely powerful and versatile tool for X-ray imaging in a wide range of applications

Method for automatization of the alignment of a laboratory based x-ray phase contrast edge illumination system

Here we present a general alignment algorithm for an edge illumination x-ray phase contrast imaging system, which is used with the laboratory systems developed at UCL. It has the flexibility to be used with all current mask designs, and could also be applied to future synchrotron based systems. The algorithm has proved to be robust experimentally, and can be used for the automatization of future commercial systems through automatic alignment and alignment correction

Edge illumination X-ray phase-contrast imaging: nanoradian sensitivity at synchrotrons and translation to conventional sources

Edge illumination is an X-ray phase-contrast imaging technique that can be efficiently applied to both synchrotron radiation and laboratory sources. Its implementation with these two types of setups is here described, and a recently developed method to perform quantitative retrieval of the object attenuation and refraction properties is presented. We report results obtained at two synchrotron radiation facilities and with one of the setups installed in our laboratories at University College London, which show that very high angular sensitivities can be obtained with this technique. The effect of different experimental parameters on the achievable sensitivity is also analyzed. The obtained results will be a useful guide for the design and optimization of future experimental layouts

Medicine, material science and security: the versatility of the coded-aperture approach

The principal limitation to the widespread deployment of X-ray phase imaging in a variety of applications is probably versatility. A versatile X-ray phase imaging system must be able to work with polychromatic and non-microfocus sources (for example, those currently used in medical and industrial applications), have physical dimensions sufficiently large to accommodate samples of interest, be insensitive to environmental disturbances (such as vibrations and temperature variations), require only simple system set-up and maintenance, and be able to perform quantitative imaging. The coded-aperture technique, based upon the edge illumination principle, satisfies each of these criteria. To date, we have applied the technique to mammography, materials science, small-animal imaging, non-destructive testing and security. In this paper, we outline the theory of coded-aperture phase imaging and show an example of how the technique may be applied to imaging samples with a practically important scale

Protocol for the Cognitive Interventions and Nutritional Supplements (CINS) trial: A randomized controlled multicenter trial of a brief intervention (BI) versus a BI plus cognitive behavioral treatment (CBT) versus nutritional supplements for patients with long-lasting muscle and back pain

Background: Brief intervention programs are clinically beneficial, and cost efficient treatments for low back pain, when offered at 8-12 weeks, compared with treatment as usual. However, about 30% of the patients do not return to work. The European Guidelines for treatment of chronic low back pain recommends Cognitive Behavioral Therapy (CBT), but conclude that further research is needed to evaluate the effectiveness of CBT for chronic low back pain. Methods/Design: The aim of the multicenter CINS trial (Cognitive Interventions and Nutritional Supplements) is to compare the effectiveness of 4 different interventions; Brief Intervention, Brief Intervention and CBT, Brief Intervention and nutritional supplements of seal oil, and Brief Intervention and nutritional supplements of soy oil. All participants will be randomly assigned to the interventions. The nutritional supplements will be tested in a double blind design. 400 patients will be recruited from a population of chronic low back pain patients that have been sick listed for 2-10 months. Four outpatient clinics, located in different parts of Norway, will participate in recruitment and treatment of the patients. The Brief Intervention is a one session cognitive, clinical examination program based on a non-injury model, where return to normal activity and work is the main goal, and is followed by two booster sessions. The CBT is a tailored treatment involving 7 sessions, following a detailed manual. The nutritional supplements consist of a dosage of 10 grams of either soy or seal oil (capsules) per day for 3 months, administered in a double blind design. All patients will be followed up with questionnaires after 3, 6 and 12 months, while sick leave data will be collected up to at least 24 months after randomization. The primary outcome of the study is sick leave and will be based on register data from the National Insurance Administration. Secondary outcomes include self-reported data on disability, pain, and psychological variables. Conclusions: To our knowledge, the CINS trial will be the largest, randomized trial of psychological and nutritional interventions for chronic low back pain patients to date. It will provide important information regarding the effectiveness of CBT and seal oil for chronic low back pain patients

Low-dose phase contrast mammography with conventional x-ray sources

Purpose: To provide an x-ray phase contrast imaging (XPCI) method working with conventional sources that could be readily translated into clinical practice. XPCI shows potential in synchrotron studies but attempts at translating it for use with conventional sources are subject to limitations in terms of field of view, stability, exposure time, and possibly most importantly, delivered dose. Methods: Following the adaptation of our “edge-illumination” XPCI technique for use with conventional x-ray sources through the use of x-ray masks, the authors have further modified the design of such masks to allow further reducing the dose delivered to the sample without affecting the phase sensitivity of the method. Results: The authors have built a prototype based on the new mask design and used it to image ex vivo breast tissue samples containing malignant lesions. The authors compared images acquired with this prototype to those obtained with a conventional system. The authors demonstrate and quantify image improvements, especially in terms of microcalcification detection. On calcifications detected also by the conventional system, the authors measure contrast increases from five to nine fold; calcifications and other features were also detected which are completely invisible in the conventional image. Dose measurements confirmed that the above enhancements were achieved while delivering doses compatible with clinical practice. Conclusions: The authors obtained phase-related image enhancements in mammography by means of a system built with components available off-the-shelf that operates under exposure time and dose conditions compatible with clinical practice. This opens the way to a straightforward translation of phase enhanced imaging methods into clinical practice

Collaborative Brain-Computer Interface for Aiding Decision-Making

We look at the possibility of integrating the percepts from multiple non-communicating observers as a means of achieving better joint perception and better group decisions. Our approach involves the combination of a brain-computer interface with human behavioural responses. To test ideas in controlled conditions, we asked observers to perform a simple matching task involving the rapid sequential presentation of pairs of visual patterns and the subsequent decision as whether the two patterns in a pair were the same or different. We recorded the response times of observers as well as a neural feature which predicts incorrect decisions and, thus, indirectly indicates the confidence of the decisions made by the observers. We then built a composite neuro-behavioural feature which optimally combines the two measures. For group decisions, we uses a majority rule and three rules which weigh the decisions of each observer based on response times and our neural and neuro-behavioural features. Results indicate that the integration of behavioural responses and neural features can significantly improve accuracy when compared with the majority rule. An analysis of event-related potentials indicates that substantial differences are present in the proximity of the response for correct and incorrect trials, further corroborating the idea of using hybrids of brain-computer interfaces and traditional strategies for improving decision making

Characteristic Evolution and Matching

I review the development of numerical evolution codes for general relativity based upon the characteristic initial value problem. Progress in characteristic evolution is traced from the early stage of 1D feasibility studies to 2D axisymmetric codes that accurately simulate the oscillations and gravitational collapse of relativistic stars and to current 3D codes that provide pieces of a binary black hole spacetime. Cauchy codes have now been successful at simulating all aspects of the binary black hole problem inside an artificially constructed outer boundary. A prime application of characteristic evolution is to extend such simulations to null infinity where the waveform from the binary inspiral and merger can be unambiguously computed. This has now been accomplished by Cauchy-characteristic extraction, where data for the characteristic evolution is supplied by Cauchy data on an extraction worldtube inside the artificial outer boundary. The ultimate application of characteristic evolution is to eliminate the role of this outer boundary by constructing a global solution via Cauchy-characteristic matching. Progress in this direction is discussed.Comment: New version to appear in Living Reviews 2012. arXiv admin note: updated version of arXiv:gr-qc/050809