Carbon nanotube - Based cold cathodes: Field emission angular properties and temporal stability

The field emission (FE) properties of carbon nanotube (CNT)-based cathodes have been investigated on nanostructured surfaces grown by plasma enhanced chemical vapor deposition. The FE angular properties and temporal stability of the emergent electron beam have been determined using a dedicated apparatus for cathodes of various architectures and geometries, characterized by scanning electron microscopy and I-V measurements. The angular electron beam divergence and time instability at the extraction stage, which are crucial parameters in order to obtain high brilliance of FE-based-cathode electron sources, have been measured for electrons emitted by several regular architectures of vertically aligned arrays and critically compared to conventional disordered cathodes. The measured divergences strongly depend on the grid mesh. For regular arrays of individual CNT, divergences from 2° to 5° have been obtained; in this specific case, measurements together with ray-tracing simulations suggest that the maximum emission angle is of the order of ±30° about the tube main axis. Larger divergences have been measured for electron beams emitted from honeycomb-structured cathodes (6°) and significantly broader angle distributions (10°) from disordered CNT surfaces. Emission current instabilities of the order of 1% for temporal stability studies conducted across a medium time scale (hours) have been noted for all cathodes consisting of a high number (10$^{4}$ and larger) of aligned CNTs, with the degree of stability being largely independent of the architecture.The European AXIS project (FP7-SME-1-2007) is acknowledged for financial support

Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer's disease

Alterations of the dopaminergic (DAergic) system are frequently reported in Alzheimer’s disease (AD) patients and are commonly linked to cognitive and non-cognitive symptoms. However, the cause of DAergic system dysfunction in AD remains to be elucidated. We investigated alterations of the midbrain DAergic system in the Tg2576 mouse model of AD, overexpressing a mutated human amyloid precursor protein (APPswe). Here, we found an age-dependent DAergic neuron loss in the ventral tegmental area (VTA) at pre-plaque stages, although substantia nigra pars compacta (SNpc) DAergic neurons were intact. The selective VTA DAergic neuron degeneration results in lower DA outflow in the hippocampus and nucleus accumbens (NAc) shell. The progression of DAergic cell death correlates with impairments in CA1 synaptic plasticity, memory performance and food reward processing. We conclude that in this mouse model of AD, degeneration of VTA DAergic neurons at pre-plaque stages contributes to memory deficits and dysfunction of reward processing

Some Secrets of Fluorescent Proteins: Distinct Bleaching in Various Mounting Fluids and Photoactivation of cyan fluorescent proteins at YFP-Excitation

Background
The use of spectrally distinct variants of green fluorescent protein (GFP) such as cyan or yellow mutants (CFP and YFP, respectively) is very common in all different fields of life sciences, e.g. for marking specific proteins or cells or to determine protein interactions. In the latter case, the quantum physical phenomenon of fluorescence resonance energy transfer (FRET) is exploited by specific microscopy techniques to visualize proximity of proteins.

Methodology/Principal Findings
When we applied a commonly used FRET microscopy technique - the increase in donor (CFP)-fluorescence after bleaching of acceptor fluorophores (YFP), we obtained good signals in live cells, but very weak signals for the same samples after fixation and mounting in commercial microscopy mounting fluids. This observation could be traced back to much faster bleaching of CFP in these mounting media. Strikingly, the opposite effect of the mounting fluid was observed for YFP and also for other proteins such as Cerulean, TFP or Venus. The changes in photostability of CFP and YFP were not caused by the fixation but directly dependent on the mounting fluid. Furthermore we made the interesting observation that the CFP-fluorescence intensity increases by about 10 - 15% after illumination at the YFP-excitation wavelength – a phenomenon, which was also observed for Cerulean. This photoactivation of cyan fluorescent proteins at the YFP-excitation can cause false-positive signals in the FRET-microscopy technique that is based on bleaching of a yellow FRET acceptor.

Conclusions/Significance
Our results show that photostability of fluorescent proteins differs significantly for various media and that CFP bleaches significantly faster in commercial mounting fluids, while the opposite is observed for YFP and some other proteins. Moreover, we show that the FRET microscopy technique that is based on bleaching of the YFP is prone to artifacts due to photoactivation of cyan fluorescent proteins under these conditions

User-centered virtual environment design for virtual rehabilitation

<p>Abstract</p> <p>Background</p> <p>As physical and cognitive rehabilitation protocols utilizing virtual environments transition from single applications to comprehensive rehabilitation programs there is a need for a new design cycle methodology. Current human-computer interaction designs focus on usability without benchmarking technology within a user-in-the-loop design cycle. The field of virtual rehabilitation is unique in that determining the efficacy of this genre of computer-aided therapies requires prior knowledge of technology issues that may confound patient outcome measures. Benchmarking the technology (e.g., displays or data gloves) using healthy controls may provide a means of characterizing the "normal" performance range of the virtual rehabilitation system. This standard not only allows therapists to select appropriate technology for use with their patient populations, it also allows them to account for technology limitations when assessing treatment efficacy.</p> <p>Methods</p> <p>An overview of the proposed user-centered design cycle is given. Comparisons of two optical see-through head-worn displays provide an example of benchmarking techniques. Benchmarks were obtained using a novel vision test capable of measuring a user's stereoacuity while wearing different types of head-worn displays. Results from healthy participants who performed both virtual and real-world versions of the stereoacuity test are discussed with respect to virtual rehabilitation design.</p> <p>Results</p> <p>The user-centered design cycle argues for benchmarking to precede virtual environment construction, especially for therapeutic applications. Results from real-world testing illustrate the general limitations in stereoacuity attained when viewing content using a head-worn display. Further, the stereoacuity vision benchmark test highlights differences in user performance when utilizing a similar style of head-worn display. These results support the need for including benchmarks as a means of better understanding user outcomes, especially for patient populations.</p> <p>Conclusions</p> <p>The stereoacuity testing confirms that without benchmarking in the design cycle poor user performance could be misconstrued as resulting from the participant's injury state. Thus, a user-centered design cycle that includes benchmarking for the different sensory modalities is recommended for accurate interpretation of the efficacy of the virtual environment based rehabilitation programs.</p

Virtual Reality Applications in Rehabilitation

The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-39510-4_1One of the most valuable applications of virtual reality (VR) is in the domain of rehabilitation. After brain injuries or diseases, many patients suffer from impaired physical and/or cognitive capabilities, such as difficulties in moving arms or remembering names. Over the past two decades, VR has been tested and examined as a technology to assist patients’ recovery and rehabilitation, both physical and cognitive. The increasing prevalence of low-cost VR devices brings new opportunities, allowing VR to be used in practice. Using VR devices such as head-mounted displays (HMDs), special virtual scenes can be designed to assist patients in the process of re-training their brain and reorganizing their functions and abilities. However, such VR interfaces and applications must be comprehensively tested and examined for their effectiveness and potential side effects. This paper presents a review of related literature and discusses the new opportunities and challenges. Most of existing studies examined VR as an assessment method rather than a training/exercise method. Nevertheless, promising cases and positive preliminary results have been shown. Considering the increasing need for self-administered, home-based, and personalized rehabilitation, VR rehabilitation is potentially an important approach. This area requires more studies and research effort

Predicting lymphoma in Sjogren's syndrome and the pathogenetic role of parotid microenvironment through precise parotid swelling recording

Objective Parotid swelling (PSW) is a major predictor of non-Hodgkin's lymphoma (NHL) in primary SS (pSS). However, since detailed information on the time of onset and duration of PSW is scarce, this was investigated to verify whether it may lead to further improved prediction. NHL localization was concomitantly studied to evaluate the role of the parotid gland microenvironment in pSS-related lymphomagenesis. Methods A multicentre study was conducted among patients with pSS who developed B cell NHL during follow-up and matched controls that did not develop NHL. The study focused on the history of salivary gland and lachrymal gland swelling, evaluated in detail at different times and for different durations, and on the localization of NHL at onset. Results PSW was significantly more frequent among the cases: at the time of first referred pSS symptoms before diagnosis, at diagnosis and from pSS diagnosis to NHL. The duration of PSW was evaluated starting from pSS diagnosis, and the NHL risk increased from PSW of 2-12 months to >12 months. NHL was prevalently localized in the parotid glands of the cases. Conclusion A more precise clinical recording of PSW can improve lymphoma prediction in pSS. PSW as a very early symptom is a predictor, and a longer duration of PSW is associated with a higher risk of NHL. Since lymphoma usually localizes in the parotid glands, and not in the other salivary or lachrymal glands, the parotid microenvironment appears to be involved in the whole history of pSS and related lymphomagenesis

Age-prioritized use of antivirals during an influenza pandemic

<p>Abstract</p> <p>Background</p> <p>The WHO suggested that governments stockpile, as part of preparations for the next influenza pandemic, sufficient influenza antiviral drugs to treat approximately 25% of their populations. Our aim is two-fold: first, since in many countries the antiviral stockpile is well below this level, we search for suboptimal strategies based on treatment provided only to an age-dependent fraction of cases. Second, since in some countries the stockpile exceeds the suggested minimum level, we search for optimal strategies for post-exposure prophylactic treatment of close contacts of cases.</p> <p>Methods</p> <p>We used a stochastic, spatially structured individual-based model, considering explicit transmission in households, schools and workplaces, to simulate the spatiotemporal spread of an influenza pandemic in Italy and to evaluate the efficacy of interventions based on age-prioritized use of antivirals.</p> <p>Results</p> <p>Our results show that the antiviral stockpile required for treatment of cases ranges from 10% to 35% of the population for <it>R</it>₀in 1.4 – 3. No suboptimal strategies, based on treatment provided to an age-dependent fraction of cases, were found able to remarkably reduce both clinical attack rate and antiviral drugs needs, though they can contribute to largely reduce the excess mortality. Treatment of all cases coupled with prophylaxis provided to younger individuals is the only intervention resulting in a significant reduction of the clinical attack rate and requiring a relatively small stockpile of antivirals.</p> <p>Conclusion</p> <p>Our results strongly suggest that governments stockpile sufficient influenza antiviral drugs to treat approximately 25% of their populations, under the assumption that <it>R</it>₀is not much larger than 2. In countries where the number of antiviral stockpiled exceeds the suggested minimum level, providing prophylaxis to younger individuals is an option that could be taken into account in preparedness plans. In countries where the number of antivirals stockpiled is well below 25% of the population, priority should be decided based on age-specific case fatality rates. However, late detection of cases (administration of antivirals 48 hours after the clinical onset of symptoms) dramatically affects the efficacy of both treatment and prophylaxis.</p

Profiling of the perturbed metabolomic state of mouse spleen during acute and chronic toxoplasmosis

Background Toxoplasma gondii, a common opportunistic protozoan, is a leading cause of illness and mortality among immunosuppressed individuals and during congenital infections. Current therapeutic strategies for toxoplasmosis are not fully effective at curtailing disease progression in these cases. Given the parasite ability to influence host immunity and metabolism, understanding of the metabolic alterations in the host’s immune organs during T. gondii infection may enhance the understanding of the molecular mechanisms that define the pathophysiology of T. gondii infection. Methods We investigated the global metabolic changes in the spleen of BALB/c mice at early and late stage of infection with T. gondii using LC-MS/MS-based metabolomics. Multivariate data analysis methods, principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA), were used to identify metabolites that are influenced by T. gondii infection. Results Multivariate analyses clearly separated the metabolites of spleen of infected and control mice. A total of 132 differential metabolites were identified, 23 metabolites from acutely infected versus control mice and 109 metabolites from chronically infected versus control mice. Lipids, hormones, lactones, acids, peptides, antibiotics, alkaloids and natural toxins were the most influenced chemical groups. There were 12 shared differential metabolites between acutely infected versus control mice and chronically infected versus control mice, of which 4,4-Dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol was significantly upregulated and ubiquinone-8 was significantly downregulated. Major perturbed metabolic pathways included primary bile acid biosynthesis, steroid hormone biosynthesis, biotin metabolism, and steroid biosynthesis, with arachidonic acid metabolism being the most significantly impacted pathway. These metabolic changes suggest a multifactorial nature of the immunometabolic responses of mouse spleen to T. gondii infection. Conclusions This study demonstrated that T. gondii infection can cause significant metabolomic alterations in the spleen of infected mice. These findings provide new insights into the molecular mechanisms that underpin the pathogenesis of T. gondii infection

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications