Illuminating the BOLD signal: combined fMRI-fNIRS studies

Functional magnetic resonance imaging (fMRI) is currently combined with electrophysiological methods to identify the relationship between neuronal activity and the blood oxygenation level-dependent (BOLD) signal. Several processes like neuronal activity, synaptic activity, vascular dilation, blood volume and oxygenation changes underlie both response modalities, that is, the electrophysiological signal and the vascular response. However, accessing single process relationships is absolutely mandatory when aiming at a deeper understanding of neurovascular coupling and necessitates studies on the individual building blocks of the vascular response. Combined fMRI and functional near-infrared spectroscopy studies have been performed to validate the correlation of the BOLD signal to the hemodynamic changes in the brain. Here we review the current status of the integration of both technologies and judge these studies in the light of recent findings on neurovascular coupling.     

Exploring structure–selectivity relationships of biogenic amine GPCR antagonists using similarity searching and dynamic compound mapping

We design and analyze compound selectivity sets of antagonists with differential selectivity against seven biogenic amine G-protein coupled receptors. The selectivity sets consist of a total of 267 antagonists and contain a spectrum of in part closely related molecular scaffolds. Each set represents a different selectivity profile. Using these com- pound sets, a systematic computational analysis of structure-selectivity relationships is carried out with different 2D similarity methods including fingerprints, recursive partitioning, clustering, and dynamic compound mapping. Screening calculations are performed in a background database containing nearly four million molecules. Fingerprint searching and compound mapping are found to enrich target-selective antagonists over family-selective ones. Dynamic compound mapping effectively discriminates database compounds from GPCR antagonists and consistently retains target-selective antagonists during the final dimension extension levels. Furthermore, the widely used MACCS key fingerprint displays a strong tendency to distinguish between target- and family-selective GPCR antagonists. Taken together, the results indicate that different types of 2D similarity methods are capable of distinguishing closely related molecules having different selectivity. The reported compound benchmark system is made freely available in order to enable selectivity-oriented analyses using other computational approaches.     

Bending insensitivity of fiber Bragg gratings in suspended-core optical fibers

This Letter presents simulation and experimental results that explore bending insensitivity of fiber Bragg gratings in suspended-core optical fibers. The implementation of thin silica bridge in the fibers enhances index contrast of the fiber core and reduces bending-induced strain transfer to the fiber core. This fiber design lead to a reduction of over 7 times in strain-induced fiber Bragg grating resonant peak shifts in the suspended-core fiber compared with that in standard telecommunication fiber, and an 0.14 dB bending loss at a bending radius of 6.35 mm.     

Towards Nanoscale Biomedical Devices in Medicine: Biofunctional and Spectroscopic Characterization of Superparamagnetic Nanoparticles

Medical interest in nanotechnology originates from a belief that nanoscale therapeutic devices can be constructed and directed towards its target inside the human body. Such nanodevices can be engineered by coupling superparamagnetic nanoparticle to biomedically active proteins. We hereby report the immobilization of a PhEst, a S-formylglutathione hydrolase from the psychrophilic P. haloplanktis TAC125 onto the gold coated surface of modified superparamagnetic core-shell nanoparticles (Fe₃O₄@Au). The synthesis of the nanoparticles is also reported. S-formylglutathione hydrolases constitute a family of ubiquitous enzymes which play a key role in formaldehyde detoxification both in prokaryotes and eukaryotes. PhEst was originally annotated as a putative feruloyl esterase, an enzyme that releases ferulic acid (an antioxidant reactive towards free radicals such as reactive oxygen species) from polysaccharides esters. Dynamic light scattering, scanning electron microscopy with energy dispersive X-ray spectroscopy, UV–visible absorption spectroscopy, fluorescence spectroscopy, magnetic separation technique and enzyme catalytic assay confirmed the chemical composition of the gold covered superparamagnetic nanoparticles, the binding and activity of the enzyme onto the nanoparticles. Activity data in U/ml confirmed that the immobilized enzyme is approximately 2 times more active than the free enzyme in solution. Such particles can be directed with external magnetic fields for bio-separation and focused towards a medical target for therapeutical as well as bio-sensor applications.     

High-power all-normal-dispersion femtosecond pulse generation from a Yb-doped large-mode-area microstructure fiber laser

We report on an all-normal-dispersion mode-locked fiber laser based on a large-mode-area Yb-doped microstructure fiber and using a high nonlinear modulation depth semiconductor saturable absorber mirror. The laser delivers 3.3 W of average output power with positively chirped 5.5 ps pulses at a center wavelength of 1033 nm. The pulse repetition rate is 46.4 MHz, which results in an energy per pulse of 71 nJ. These pulses are extracavity dechirped down to 516 fs by using bulk gratings. The average power of the dechirped pulses is 2.3 W, which corresponds to a peak power of more than 96 kW.     

Objective and subjective evaluations of the multi-channel auralization technique as applied to solo instruments

Auralizations are commonly used today by architectural acousticians as a tool to model acoustically sensitive spaces. This paper presents investigations employing an auralization methodology known as multi-channel auralizations, to determine the benefits of using an increasing number of channels in such auralizations. First an objective evaluation was conducted to examine how acoustic parameters, such as reverberation time, vary when using “quadrant” (one fourth of a spherical source) or “thirteenth” sources to create the binaural room impulse responses. Large differences in the values were found between the different sections of the sphere, on the order of several just noticeable differences. Two subjective studies were then pursued, first to determine if auralizations made with an increasing number of channels sound more realistic and have an increased perceived source size, using solo musical instruments of varying directivity indices as the sources. Overall, subjects perceived the auralizations made with an increasing number of channels as more realistic, whereas results for perceived source size are less clear. The second subjective study assessed the ease with which subjects could identify the source orientation from the auralizations as a function of number of channels. Results indicate that more channels made it easier for subjects to differentiate between source orientations.     

Modelling of a city canyon problem in a turbulent atmosphere using an equivalent sources approach

The sound propagation into a courtyard shielded from direct exposure is predicted using an equivalent sources approach. The problem is simplified into that of a two-dimensional city canyon. A set of equivalent sources are used to couple the free half-space above the canyon to the cavity inside the canyon. Atmospheric turbulence causes an increase in the expected value of the sound pressure level compared to a homogeneous case. The level increase is estimated using a von Kármán turbulence model and the mutual coherences of all equivalent sources' contributions. For low frequencies the increase is negligible, but at 1.6 kHz it reaches 2-5 dB for the geometries and turbulence parameters used here. A comparison with a ray-based model shows reasonably good agreement.     

Correction of spin diffusion during iterative automated NOE assignment

Indirect magnetization transfer increases the observed nuclear Overhauser enhancement (NOE) between two protons in many cases, leading to an underestimation of target distances. Wider distance bounds are necessary to account for this error. However, this leads to a loss of information and may reduce the quality of the structures generated from the inter-proton distances. Although several methods for spin diffusion correction have been published, they are often not employed to derive distance restraints. This prompted us to write a user-friendly and CPU-efficient method to correct for spin diffusion that is fully integrated in our program ambiguous restraints for iterative assignment (ARIA). ARIA thus allows automated iterative NOE assignment and structure calculation with spin diffusion corrected distances. The method relies on numerical integration of the coupled differential equations which govern relaxation by matrix squaring and sparse matrix techniques. We derive a correction factor for the distance restraints from calculated NOE volumes and inter-proton distances. To evaluate the impact of our spin diffusion correction, we tested the new calibration process extensively with data from the Pleckstrin homology (PH) domain of Mus musculus beta-spectrin. By comparing structures refined with and without spin diffusion correction, we show that spin diffusion corrected distance restraints give rise to structures of higher quality (notably fewer NOE violations and a more regular Ramachandran map). Furthermore, spin diffusion correction permits the use of tighter error bounds which improves the distinction between signal and noise in an automated NOE assignment scheme.     

Profiling of generic anti-phosphopeptide antibodies and kinases with peptide microarrays using radioactive and fluorescence-based assays

Kinases represent one of the largest enzyme families and key regulatory proteins in the cell. Only a small subset of these enzymes has been characterised so far. We have prepared different types of phosphopeptide and peptide microarrays displaying peptides deduced from annotated human phosphorylation sites and cytoplasmic domains of all annotated human membrane proteins. This approach was enabled by fully-automated high throughput micro-scale synthesis of peptides by the SPOT technology combined with chemo-selective immobilisation on modified glass slides. The phosphopeptide microarrays displaying 2923 peptides in total have been used for the characterisation of commercially available generic anti-phosphopeptide antibodies. This enabled us to detect Abl kinase activity on a microarray with anti-phosphotyrosine antibodies yielding results comparable to those obtained from a radioactive assay. More than 13 000 peptides deposited on six glass slides were used to profile casein kinase 2 (CK2) using a radioactive assay, since no generic antibody for the reliable detection of serine or threonine phosphorylation could be identified. All previously identified substrates were detected in the microarray experiment. In order to confirm whether substrates on the microarray are substrates in solution phase assays, more than 700 peptides were synthesised and tested with CK2 in a solution phase assay. All substrates identified in the solution phase assay were also detected on the microarray.     

Elemental composition of fine particulate matter (PM2.5) in Skopje,FYR of Macedonia

Aerosol samples were collected at an urban background site in Skopje, Former Yugoslavic Republic of Macedonia, during four measurement campaigns from December 2006 to October 2007. An impactor was used to collect particulate matter (PM_2.5) aerosol particles and the samples were analyzed for the concentrations of particulate mass, black carbon (BC), and 17 elements. The 12‐h average PM_2.5 concentrations varied in the range 10–140 µg m^?3 with the highest concentrations measured during wintertime pollution episodes and during the summer period. Pair‐wise correlations and crustal enrichment were studied and the data set was analyzed by factor analysis and positive matrix factorization. Major aerosol components were identified as mineral dust (main observed tracers Si, K, Ca, Ti, Fe, Sr, and Rb), combustion (BC, S, K, V, and Ni), traffic‐related aerosol (Pb and Zn), and secondary sulfate combined with mineral dust. Combustion sources dominated during wintertime and were likely due to heavy oil combustion, biomass burning, and other industrial activities within the city area. Mineral dust was observed throughout the year, but the concentrations peaked during the unusually hot and dry summer of 2007. It is concluded that Skopje suffers from serious air pollution due to central and residential heating, the transport sector, and industrial activities within the city, and contributions from mineral dust increase the PM_2.5 concentrations under dry periods. Topography and meteorological conditions aggravate the problems and make the air quality comparable with the conditions in other highly polluted cities in Southern Europe and worldwide. Copyright © 2011 John Wiley & Sons, Ltd.