Strictly positive-definite spike train kernels for point-process divergences

Exploratory tools that are sensitive to arbitrary statistical variations in spike train observations open up the possibility of novel neuroscientific discoveries. Developing such tools, however, is difficult due to the lack of Euclidean structure of the spike train space, and an experimenter usually prefers simpler tools that capture only limited statistical features of the spike train, such as mean spike count or mean firing rate. We explore strictly positive-definite kernels on the space of spike trains to offer both a structural representation of this space and a platform for developing statistical measures that explore features beyond count or rate. We apply these kernels to construct measures of divergence between two point processes and use them for hypothesis testing, that is, to observe if two sets of spike trains originate from the same underlying probability law. Although there exist positive-definite spike train kernels in the literature, we establish that these kernels are not strictly definite and thus do not induce measures of divergence. We discuss the properties of both of these existing nonstrict kernels and the novel strict kernels in terms of their computational complexity, choice of free parameters, and performance on both synthetic and real data through kernel principal component analysis and hypothesis testing.     

A model for radar images and its application to adaptive digital filtering of multiplicative noise

Standard image processing techniques which are used to enhance noncoherent optically produced images are not applicable to radar images due to the coherent nature of the radar imaging process. A model for the radar imaging process is derived in this paper and a method for smoothing noisy radar images is also presented. The imaging model shows that the radar image is corrupted by multiplicative noise. The model leads to the functional form of an optimum (minimum MSE) filter for smoothing radar images. By using locally estimated parameter values the filter is made adaptive so that it provides minimum MSE estimates inside homogeneous areas of an image while preserving the edge structure. It is shown that the filter can be easily implemented in the spatial domain and is computationally efficient. The performance of the adaptive filter is compared (qualitatively and quantitatively) with several standard filters using real and simulated radar images.     

Development of a high resolution and high dispersion Thomson parabola

Here, we report on the development of a novel high resolution and high dispersion Thomson parabola for simultaneously resolving protons and low-Z ions of more than 100 MeV/nucleon necessary to explore novel laser ion acceleration schemes. High electric and magnetic fields enable energy resolutions of ΔE∕E < 5% at 100 MeV/nucleon and impede premature merging of different ion species at low energies on the detector plane. First results from laser driven ion acceleration experiments performed at the Trident Laser Facility demonstrate high resolution and superior species and charge state separation of this novel Thomson parabola for ion energies of more than 30 MeV/nucleon.     

Achieving precision and reproducibility for writing patterns of n-alkanethiol self-assembled monolayers with automated nanografting

Nanografting is a high-precision approach for scanning probe lithography, which provides unique advantages and capabilities for rapidly writing arrays of nanopatterns of thiol self-assembled monolayers (SAMs). Nanografting is accomplished by force- induced displacement of molecules of a matrix SAM, followed immediately by the self-assembly of n-alkanethiol ink molecules from solution. The feedback loop used to control the atomic force microscope tip position and displacement enables exquisite control of forces applied to the surface, ranging from pico to nanonewtons. To achieve high-resolution writing at the nanoscale, the writing speed, direction, and applied force need to be optimized. There are strategies for programing the tip translation, which will improve the uniformity, alignment, and geometries of nanopatterns written using open-loop feedback control. This article addresses the mechanics of automated nanografting and demonstrates results for various writing strategies when nanografting patterns of n-alkanethiol SAMs.     

Streak camera measurement of subnanosecond plastic scintillator properties

A streak camera technique with temporal resolution of 20 ps has been used to measure the fluorescence properties of several subnanosecond plastic scintillators. The method employs a vacuum light pipe coupled to an optical streak camera. The scintillators are excited by a 200-ps x-ray pulse generated by a 1.06-microm Nd:YAG laser focused onto an iron target. The time history of the low-energy x-ray pulse is measured with an x-ray streak camera. Results are given for NElll plastic scintillators doped with benzophenone or acetophenone, for PVT doped with butyl-PBD, and for a ZnO phosphor doped with Ga.     

Sensitivity of CFP/YFP and GFP/mCherry pairs to donor photobleaching on FRET determination by fluorescence lifetime imaging microscopy in living cells

Fluorescent protein-based FRET is a powerful method for visualizing protein-protein interactions and biochemical reactions in living cells. It can be difficult, however, to avoid photobleaching when observing fluorescent cells under the microscope, especially those expressing CFP. We compared the sensitivity of two protein-based FRET pairs to light-induced fluorescence changes in the donor, on FRET determination by fluorescence lifetime imaging microscopy (FLIM). Thanks to the very low excitation light levels of the time- and space-correlated single photon counting (TSCSPC) method, FLIM acquisitions were achieved without donor photobleaching. Here, we show that photobleaching of CFP by a mercury lamp under the microscope induced a decrease in the mean fluorescence lifetime, which interfered with FRET determination between CFP and YFP. Importantly, the range of light-induced variation of the mean fluorescence lifetime of CFP was not proportional to the decrease in the steady state fluorescence intensity and varied from cell to cell. The choice of the CFP/YFP pair therefore requires that the cells be observed and analyzed at very low light levels during the whole FRET experiment. In contrast, the GFP/mCherry pair provided an accurate FRET measurement by FLIM, even if some GFP photobleaching took place. We thus demonstrate that CFP can be an unreliable donor for FRET determination in living cells, due to its photosensitivity properties. We demonstrate that the GFP/mCherry pair is better suited for FRET measurement by FLIM in living cells than the CFP/YFP pair.     

Cysteine tagging for MS-based proteomics

Amino acid-tagging strategies are widespread in proteomics. Because of the central role of mass spectrometry (MS) as a detection technique in protein sciences, the term "mass tagging" was coined to describe the attachment of a label, which serves MS analysis and/or adds analytical value to the measurements. These so-called mass tags can be used for separation, enrichment, detection, and quantitation of peptides and proteins. In this context, cysteine is a frequent target for modifications because the thiol function can react specifically by nucleophilic substitution or addition. Furthermore, cysteines present natural modifications of biological importance and a low occurrence in the proteome that justify the development of strategies to specifically target them in peptides or proteins. In the present review, the mass-tagging methods directed to cysteine residues are comprehensively discussed, and the advantages and drawbacks of these strategies are addressed. Some concrete applications are given to underline the relevance of cysteine-tagging techniques for MS-based proteomics.     

Relationships between glucose, energy intake and dietary composition in obese adults with type 2 diabetes receiving the cannabinoid 1 (CB1) receptor antagonist, rimonabant

ABSTRACT: BACKGROUND: Weight loss is often difficult to achieve in individuals with type 2 diabetes and anti-obesity drugs are often advocated to support dietary intervention. Despite the extensive use of centrally acting anti-obesity drugs, there is little evidence of how they affect dietary composition. We investigated changes in energy intake and dietary composition of macro- and micronutrients following therapy with the endocannabinoid receptor blocker, rimonabant. METHODS: 20 obese patients with type 2 diabetes were studied before and after 6 months dietary intervention with rimonabant. Dietary intervention was supervised by a diabetes dietician. Five-day food diaries were completed at baseline and at 6 months and dietary analysis was performed using computer software (Dietplan 6). RESULTS: After 6 months, (compared with baseline) there were reductions in weight (107+/-21Kg versus 112+/-21, p<0.001, 4% body weight reduction), and improvements in HbA1c (7.4+/-1.7 versus 8.0+/-1.6%, p<0.05) and HDL cholesterol. Intake of energy (1589+/-384 versus 2225+/-1109kcal, p<0.01), carbohydrate (199+/-74 versus 273+/-194g, p<0.05), protein (78+/-23 versus 98+/-36g, p<0.05), fats (55+/-18 versus 84+/-39g, p<0.01) and several micronutrients were reduced. However, relative macronutrient composition of the diet was unchanged. Improvement in blood glucose was strongly correlated with a reduction in carbohydrate intake (r = 0.76, p<0.001). CONCLUSIONS: In obese patients with type 2 diabetes, rimonabant in combination with dietary intervention led to reduced intake of energy and most macronutrients. Despite this, macronutrient composition of the diet was unaltered. These dietary changes (especially carbohydrate restriction) were associated with weight loss and favourable metabolic effects.     

Individual cell lag time distributions of Cronobacter (Enterobacter sakazakii) and impact of pooling samples on its detection in powdered infant formula

Cells of six strains of Cronobacter were subjected to dry stress and stored for 2.5 months at ambient temperature. The individual cell lag time distributions of recovered cells were characterized at 25 °C and 37 °C in non-selective broth. The individual cell lag times were deduced from the times taken by cultures from individual cells to reach an optical density threshold. In parallel, growth curves for each strain at high contamination levels were determined in the same growth conditions. In general, the extreme value type II distribution with a shape parameter fixed to 5 (EVIIb) was the most effective at describing the 12 observed distributions of individual cell lag times. Recently, a model for characterizing individual cell lag time distribution from population growth parameters was developed for other food-borne pathogenic bacteria such as Listeria monocytogenes. We confirmed this model’s applicability to Cronobacter by comparing the mean and the standard deviation of individual cell lag times to populational lag times observed with high initial concentration experiments. We also validated the model in realistic conditions by studying growth in powdered infant formula decimally diluted in Buffered Peptone Water, which represents the first enrichment step of the standard detection method for Cronobacter. Individual lag times and the pooling of samples significantly affect detection performances.