Shuttle orbiter S-band payload communications equipment design evaluation

The analysis of the design, and the performance assessment of the Orbiter S-band communication equipment are reported. The equipment considered include: network transponder, network signal processor, FM transmitter, FM signal processor, payload interrogator, and payload signal processor

Issues faced by vision-impaired users of interactive TV search facilities

This paper reports two studies of digital television users. The first study investigates the behaviour of non-impaired users to understand typical usage patterns and problem-solving, attempting three representative tasks using a digital television terrestrial receiver. Videos were analysed to identify problem incidents and attempts at recovery. Patterns observed included misidentifying handset menu options leading to extended guessed action, repeated misspecification of task and repeated re-performance to confirm actions. The results show that interaction with Digital TV in its current handset-based form involves considerable reactive action specification and corrective action, suggesting that interaction endemically difficult for those with various levels of low vision. The second study, a less formal probe of users with visual impairments, suggests that even users with relatively mild visual impairments may struggle with current two-device interaction. However, suitable strategies for supporting vision impaired users may as much to do with user preferences rather than simply accessibility. We conclude by discussing the efficacy of current two-device interaction support and possible future directions

Measurement of the Mitochondrial Membrane Potential and pH Gradient from the Redox Poise of the Hemes of the bc1 Complex

AbstractThe redox potentials of the hemes of the mitochondrial bc1 complex are dependent on the proton-motive force due to the energy transduction. This allows the membrane potential and pH gradient components to be calculated from the oxidation state of the hemes measured with multi-wavelength cell spectroscopy. Oxidation states were measured in living RAW 264.7 cells under varying electron flux and membrane potential obtained by a combination of oligomycin and titration with a proton ionophore. A stochastic model of bc1 turnover was used to confirm that the membrane potential and redox potential of the ubiquinone pool could be measured from the redox poise of the b-hemes under physiological conditions assuming the redox couples are in equilibrium. The pH gradient was then calculated from the difference in redox potentials of cytochrome c and ubiquinone pool using the stochastic model to evaluate the ΔG of the bc1 complex. The technique allows absolute quantification of the membrane potential, pH gradient, and proton-motive force without the need for genetic manipulation or exogenous compounds

Innovation for an inclusive future

This workshop will focus on setting the agenda for research, practice and policy in support of inclusive design for third generation computer-based products. The next generation of technology represents an unprecedented opportunity to improve the quality of life for groups of users who have previously faced exclusion, such as those with impairments and older citizens. At the same time it risks creating a greater digital divide and further exclusion. How we approach design for this new generation will determine whether or not the third wave will provide positive advances towards an inclusive digital world. We therefore need to put forward both a rationale for inclusive design and provide pointers towards technical development and design practice in support of inclusion. It is our belief that there is not only a strong moral case for design for inclusion but also significant commercial incentive, which may be key to persuading influential players to focus on inclusion. Therefore one of our key objectives is to describe and promote the advantages of designing ‘in from the edges’ of the user population rather than designing for a notional ‘average’ user

Measurement of the Oxidation State of Mitochondrial Cytochrome c from the Neocortex of the Mammalian Brain

Diffuse optical remission spectra from the mammalian neocortex at visible wavelengths contain spectral features originating from the mitochondria. A new algorithm is presented, based on analytically relating the first differential of the attenuation spectrum to the first differential of the chromophore spectra, that can separate and calculate the oxidation state of cytochrome c as well as the absolute concentration and saturation of hemoglobin. The algorithm is validated in phantoms and then tested on the neocortex of the rat during an anoxic challenge. Implementation of the algorithm will provide detailed information of mitochondrial oxygenation and mitochondrial function in physiological studies of the mammalian brain

Fumarate Hydratase Loss Causes Combined Respiratory Chain Defects.

Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid (TCA) cycle mutated in hereditary and sporadic cancers. Despite recent advances in understanding its role in tumorigenesis, the effects of FH loss on mitochondrial metabolism are still unclear. Here, we used mouse and human cell lines to assess mitochondrial function of FH-deficient cells. We found that human and mouse FH-deficient cells exhibit decreased respiration, accompanied by a varying degree of dysfunction of respiratory chain (RC) complex I and II. Moreover, we show that fumarate induces succination of key components of the iron-sulfur cluster biogenesis family of proteins, leading to defects in the biogenesis of iron-sulfur clusters that affect complex I function. We also demonstrate that suppression of complex II activity is caused by product inhibition due to fumarate accumulation. Overall, our work provides evidence that the loss of a single TCA cycle enzyme is sufficient to cause combined RC activity dysfunction

Electron mobility and localization in dense He4 gas

The mobility was measured for gas densities 2< rho <40*1020 atoms cm-3, and for gas temperatures 4<T<300K. Refinements of former treatments of electron localization via the bubble model are presented which demonstrate a strong correlation between the mobility 'edge' and a localization criterion. Detailed agreement between theory and experiment is not realized, but the general features of the density and temperature dependence of the mobility are reproduced in a consistent manner.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48846/2/jbv6i5p908.pd

Pharmacological Inhibition of polysialyltransferase ST8SiaII Modulates Tumour Cell Migration

YesPolysialic acid (polySia), an α-2,8-glycosidically linked polymer of sialic acid, is a developmentally regulated posttranslational modification predominantly found on NCAM (neuronal cell adhesion molecule). Whilst high levels are expressed during development, peripheral adult organs do not express polySia-NCAM. However, tumours of neural crest-origin re-express polySia-NCAM: its occurrence correlates with aggressive and invasive disease and poor clinical prognosis in different cancer types, notably including small cell lung cancer (SCLC), pancreatic cancer and neuroblastoma. In neuronal development, polySia-NCAM biosynthesis is catalysed by two polysialyltransferases, ST8SiaII and ST8SiaIV, but it is ST8SiaII that is the prominent enzyme in tumours. The aim of this study was to determine the effect of ST8SiaII inhibition by a small molecule on tumour cell migration, utilising cytidine monophosphate (CMP) as a tool compound. Using immunoblotting we showed that CMP reduced ST8iaII-mediated polysialylation of NCAM. Utilizing a novel HPLC-based assay to quantify polysialylation of a fluorescent acceptor (DMB-DP3), we demonstrated that CMP is a competitive inhibitor of ST8SiaII (Ki = 10 μM). Importantly, we have shown that CMP causes a concentration-dependent reduction in tumour cell-surface polySia expression, with an absence of toxicity. When ST8SiaII-expressing tumour cells (SH-SY5Y and C6-STX) were evaluated in 2D cell migration assays, ST8SiaII inhibition led to significant reductions in migration, while CMP had no effect on cells not expressing ST8SiaII (DLD-1 and C6-WT). The study demonstrates for the first time that a polysialyltransferase inhibitor can modulate migration in ST8SiaII-expressing tumour cells. We conclude that ST8SiaII can be considered a druggable target with the potential for interfering with a critical mechanism in tumour cell dissemination in metastatic cancers.Yorkshire Cancer Research; EPSRC; Association for International Cancer Research; Jordanian Government PhD scholarshi