Singing training predicts increased insula connectivity with speech and respiratory sensorimotor areas at rest.

The insula contributes to the detection of salient events during goal-directed behavior and participates in the coordination of motor, multisensory, and cognitive systems. Recent task-fMRI studies with trained singers suggest that singing experience can enhance the access to these resources. However, the long-term effects of vocal training on insula-based networks are still unknown. In this study, we employed resting-state fMRI to assess experience-dependent differences in insula co-activation patterns between conservatory-trained singers and non-singers. Results indicate enhanced bilateral anterior insula connectivity in singers relative to non-singers with constituents of the speech sensorimotor network. Specifically, with the cerebellum (lobule V-VI) and the superior parietal lobes. The reversed comparison showed no effects. The amount of accumulated singing training predicted enhanced bilateral insula co-activation with primary sensorimotor areas representing the diaphragm and the larynx/phonation area-crucial regions for cortico-motor control of complex vocalizations-as well as the bilateral thalamus and the left putamen. Together, these findings highlight the neuroplastic effect of expert singing training on insula-based networks, as evidenced by the association between enhanced insula co-activation profiles in singers and the brain's speech motor system components.

Hanbury Brown-Twiss effect with electromagnetic waves.

The classic Hanbury Brown-Twiss experiment is analyzed in the space-frequency domain by taking into account the vectorial nature of the radiation. We show that as in scalar theory, the degree of electromagnetic coherence fully characterizes the fluctuations of the photoelectron currents when a random vector field with Gaussian statistics is incident onto the detectors. Interpretation of this result in terms of the modulations of optical intensity and polarization state in two-beam interference is discussed. We demonstrate that the degree of cross-polarization may generally diverge. We also evaluate the effects of the state of polarization on the correlations of intensity fluctuations in various circumstances.

Strategies for the structural analysis of multi-protein complexes: lessons from the 3D-Repertoire project.

Structural studies of multi-protein complexes, whether by X-ray diffraction, scattering, NMR spectroscopy or electron microscopy, require stringent quality control of the component samples. The inability to produce 'keystone' subunits in a soluble and correctly folded form is a serious impediment to the reconstitution of the complexes. Co-expression of the components offers a valuable alternative to the expression of single proteins as a route to obtain sufficient amounts of the sample of interest. Even in cases where milligram-scale quantities of purified complex of interest become available, there is still no guarantee that good quality crystals can be obtained. At this step, protein engineering of one or more components of the complex is frequently required to improve solubility, yield or the ability to crystallize the sample. Subsequent characterization of these constructs may be performed by solution techniques such as Small Angle X-ray Scattering and Nuclear Magnetic Resonance to identify 'well behaved' complexes. Herein, we recount our experiences gained at protein production and complex assembly during the European 3D Repertoire project (3DR). The goal of this consortium was to obtain structural information on multi-protein complexes from yeast by combining crystallography, electron microscopy, NMR and in silico modeling methods. We present here representative set case studies of complexes that were produced and analyzed within the 3DR project. Our experience provides useful insight into strategies that are more generally applicable for structural analysis of protein complexes.

Large-scale comparison of Liberase HI and collagenase NB1 utilized for human islet isolation.

For more than a decade Liberase HI was commonly used as the standard enzyme blend for clinical human islet isolation until enforced replacement by collagenase NB1 (NB1). This change resulted initially in a reduction in islet isolation outcome and transplant activities worldwide. This retrospective study was initiated to compare the efficiency of NB1 premium grade with Liberase in 197 human islet isolations. All pancreata were processed between January 2006 and June 2008 utilizing the same procedures for isolation and quality assessment except the administration of preselected lots of either Liberase (n = 101) or NB1 (n = 96). Utilizing Liberase, significantly more digested tissue and purified islet yield was produced compared to NB1. In contrast, the use of NB1 was associated with significantly higher purity and glucose stimulation index during dynamic perifusion. The expression of proinflammatory markers was almost identical except tissue factor expression, which was higher after utilization of Liberase. No difference was found in the percentage of pancreata fulfilling the criteria for clinical islet transplantation. The results suggest that Liberase is more efficient for pancreas dissociation than collagenase NB1 but seems to be more harmful to exocrine cells and islet tissue.

Human islet separation utilizing a closed automated purification system.

A central step within the human islet isolation process is the separation of islets from contaminating exocrine tissue utilizing linear, continuous density gradients manufactured by means of manually controlled standard gradient makers (SGM). The present study was performed to develop a closed, automated purification system (APS) that customizes density gradient profiles aiming to standardize and optimize human islet purification. Digested human pancreata were pooled, split evenly, and incubated in UW solution according to our standard protocol (n = 11). Continuous density gradient centrifugation was performed in parallel in two refrigerated COBE 2991 cell separators loaded with light (1.076 g/ml) and heavy (1.097 g/ml) Ficoll utilizing either an SGM or two computer-controlled pumps connected to Ficoll-containing bags. Quality control included islet equivalent (IE) yield, purity, in vitro function, and islet cytokine expression. Gradient profiles demonstrated that the APS readily customizes linear and nonlinear gradients. In comparison to the SGM, the APS recovered a higher percentage of the expected volume of continuous gradients (90.0 +/- 1.1% vs. 98.2 +/- 2.0%, p < 0.05). Islet yield (120,468 +/- 15,970 vs. 114,570 +/- 15,313 IE, NS) and purity (51.7 +/- 4.8% vs. 54.4 +/- 4.9%, NS) were nearly identical utilizing the SGM or APS. Decreased MCP-1, IL-6, and IL-8 expression indicated that APS-purified islets were possibly exposed to less proinflammatory stress. Compared to standard procedures, similar success and gentle continuous density gradient separation of human islets is feasible utilizing the APS. The APS facilitates the standardization of this complex procedure according to cGMP standards.

Connection between electric and magnetic coherence in free electromagnetic fields.

We introduce quantitative measures for the description of the electric and magnetic coherence in a stationary, random electromagnetic field at two points, in a volume, and in the Fourier space. These quantities are applied to free electromagnetic fields, and several theorems regarding the relationship between the two types of coherences in such fields are established. Fields which are statistically homogeneous, and those which, in addition, are statistically isotropic are considered separately. Furthermore, the connection between the electric and magnetic coherence is exemplified for some specific statistically homogeneous fields.

High-density culture of human islets on top of silicone rubber membranes.

Islet culture has emerged as a standard practice prior to clinical transplantation. However, culturing large numbers of islets requires low islet density (number of islets per unit surface area) and, consequently, 20 to 30 flasks per pancreas in order to avoid hypoxia-induced death (HID). There is a need for a simple, practical, small-footprint culture vessel that will accommodate aseptic maintenance of entire human islet isolations while avoiding HID. In this communication, we examine the hypothesis that by improving oxygen transfer through culture of islets on silicone rubber membranes (SRM), we may increase islet surface coverage and reduce the number of flasks required while avoiding HID. Our results demonstrate that islets cultured for up to 48 hours in vessels with SRM bottoms at 2000 to 4000 islet equivalents (IE)/cm(2), a surface coverage 10- to 20-fold higher than the standard culture protocol, displayed no significant loss of viability. In contrast, islets cultured for 48 hours at 4000 IE/cm(2) in flasks with gas-impermeable bottoms suffered a 60% to 70% reduction in viability. The data suggest that it is possible to culture all islets isolated from a human pancreas on SRM in a single, standard-sized vessel while maintaining the same viability as with the current, standard culture protocols that require 20 to 30 flasks. This approach may lead to substantial improvements in islet culture for research and clinical transplantation.

Spectral analysis of resonant transmission of light through a single sub-wavelength slit.

We analyze the spectral properties of resonant transmission of light through a sub-wavelength slit in a metal film. We show that the enhanced transmission can be understood in terms of interfering surface-wave-like modes propagating in the slit. We characterize the effect of geometrical and material properties of the slit on the transmission spectrum. Furthermore, we show that the wavelength of the transmission resonance strongly depends on the surrounding medium. This effect may be utilized in sensors, imaging, and the detection of, e.g. biomolecules.

Universality of electromagnetic-field correlations within homogeneous and isotropic sources.

We investigate the structure of second-order correlations in electromagnetic fields produced by statistically stationary, homogeneous, and isotropic current distributions. We show that the coherence properties of such fields within a low-loss or nondissipative medium do not depend on the source characteristics, but are solely determined by the propagation properties, and that the degree of coherence of the field is given by the sinc law. Our analysis reproduces the known results for blackbody fields, but it applies to a wider class of sources, not necessarily in thermal equilibrium. We discuss the physics behind the universal behavior of the correlations by comparing the results with those obtained by an electromagnetic plane-wave model.

Degree of polarization for optical near fields.

We investigate an extension to the concept of degree of polarization that applies to arbitrary electromagnetic fields, i.e., fields whose wave fronts are not necessarily planar. The approach makes use of generalized spectral Stokes parameters that appear as coefficients, when the full 3 x 3 spectral coherence matrix is expanded in terms of the Gell-Mann matrices. By defining the degree of polarization in terms of these parameters in a manner analogous to the conventional planar-field case, we are led to a formula that consists of scalar invariants of the spectral coherence matrix only. We show that attractive physical insight is gained by expressing the three-dimensional degree of polarization explicitly with the help of the correlations between the three orthogonal spectral components of the electric field. Furthermore, we discuss the fundamental differences in characterizing the polarization state of a field by employing either the two- or the three-dimensional coherence-matrix formalism. The extension of the concept of the degree of polarization to include electromagnetic fields having structures of arbitrary form is expected to be particularly useful, for example, in near-field optics.

Radiation efficiency of partially coherent electromagnetic beams.

We present a general definition of the radiation efficiency of stationary electromagnetic fields and prove that it is bounded between zero and unity for beams of any state of coherence and polarization. The radiation efficiency may be interpreted as a measure of how directed the radiated fields are, and therefore it can be used to assess the allowed spatial coherence and intensity variations across a beam. We consider a class of partially coherent electromagnetic fields that were recently introduced in the literature and evaluate the radiation efficiencies for two particular examples, namely, the azimuthally polarized symmetric beams and the dipolar beams that are nearly linearly polarized in the central region. The results show that the radiation efficiency is fairly insensitive to the state of polarization and that it differs appreciably from unity for only small values of source and correlation widths.

Eye-safe actively Q-switched microchip laser with an electro-absorbing semiconductor modulator.

We present what we believe to be the first actively Q -switched monolithic microchip laser with a wavelength of 1.55 microm that uses an electro-absorbing semiconductor modulator. At an absorbed pump power of 130 mW and a switching voltage of 2.2 V, the laser produces 470-nJ pulses at a repetition rate of 10 kHz. The output is a stable single longitudinal mode with a center wavelength of 1.553 microm, and the transverse beam profile is close to an ideal Gaussian, with an M(2) value of 1.15.

Synthesis of diffractive axicons for partially coherent light based on asymptotic wave theory.

A general, noniterative method for designing diffractive axicons is derived. This new technique clarifies the earlier phenomenological design principle that was used for coherent light and extends it to the domain of partial coherence. The approach is based on the method of stationary phase in fluctuating diffracted wave fields, and it applies to arbitrary axially symmetric radiation of the Schell-model type. It is shown that the general design equation can be solved numerically, in a straightforward way, for any reasonable illumination and image specifications.

Canonical perturbative approach to nonlinear systems with application to optical waves in layered Kerr media.

We investigate electromagnetic wave reflection and propagation in layered Kerr structures by introducing a method based on the application of canonical perturbation theory to fields in nonlinear media. Via the Hamilton-Jacobi formalism of classical mechanics, the waves in linear layers are expressed with constant canonical variables. The nonlinearity is treated as a small perturbation that modifies the constant invariants. We explicitly evaluate the nonlinear fields correct to first order by perturbation and compare the results to a rigorous nonlinear thin-layer model. Both polarizations, TE and TM, are considered separately. An exact quadrature solution of the nonlinear field in TM polarization is derived. We show that with weak nonlinearities the perturbative technique yields simple and accurate analytical expressions for the nonlinear fields. The results give physical insight into the use of nonlinear media for controlling the scattered fields in layered structures.

A reciprocity inequality for Gaussian Schell-model beams and some of its consequences.

A reciprocity inequality is derived, involving the effective size of a planar, secondary, Gaussian Schell-model source and the effective angular spread of the beam that the source generates. The analysis is shown to imply that a fully spatially coherent source of that class (which generates the lowest-order Hermite-Gaussian laser mode) has certain minimal properties.

Conoscopic interferometry of surface-acoustic-wave substrate crystals.

Conoscopic interferometry is applied for determining the crystal orientation of lithium niobate and other commonly employed substrate wafers for integrated-optic and surface-acoustic-wave devices. The method is particularly applicable for detecting the orientation of the optic axes of the strongly birefringent niobate but is less sensitive for lithium tantalate or quartz. Conoscopic interference is a low-cost and easy-to-use method that is especially suitable for laboratory usage.

Design of diffractive axicons for partially coherent light.

We propose a novel method of designing diffractive axicons for use in spatially partially coherent illumination. The design procedure is based on the results obtained by the stationary-phase method. The technique leads to a coherence-dependent differential equation with appropriate boundary conditions for the axicon phase function. We demonstrate the method with annular-aperture axicons generating extended focal line segments of uniform on-axis intensity.

The clinical relevance of the interaction between carbamazepine and dextropropoxyphene in elderly patients in Gothenburg, Sweden.

OBJECTIVES: To evaluate the clinical importance of the interaction between carbamazepine (CBZ) and dextropropoxyphene in elderly patients. METHODS: All patients (n = 7263) in Gothenburg, Sweden, who were part of a drug-dispensing programme, were included in the study. Eight per cent of the patients took CBZ and 18% took dextropropoxyphene, continuously. Patients who used a combination of these drugs were compared with patients who took only CBZ or dextropropoxyphene or neither of the two drugs. These four groups of patients were matched to each other with reference to gender, age and concomitant medication, which finally resulted in 21 patients in each group. A questionnaire with 30 symptoms of well-being, including symptoms typical of adverse effects of CBZ, were answered by the patients with the help of a registered nurse. Venous blood samples were drawn from the patients for the analysis of CBZ, its metabolite CBZ 10,11-epoxide (CBZ-E) and dextropropoxyphene. RESULTS: The doses of CBZ and dextropropoxyphene were lower among patients who used the combination of the two drugs than among those who only used one of the drugs. The mean level of CBZ in serum (S-CBZ) was, however, significantly higher and the level of CBZ-E in serum (S-CBZ-E) significantly lower among the patients who used the combination of CBZ and dextropropoxyphene, thus indicating an inhibition of the metabolism of CBZ. The prevalence of symptoms indicating side effects of CBZ was significantly higher in the group of patients who used both drugs. CONCLUSION: This study has shown that the combination of CBZ and dextropropoxyphene is hazardous in elderly patients and should be used with caution.