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Radioactive contamination of the Pacific Ocean following the Fukushima nuclear accident has raised public concern about seafood safety, particularly in coastal Indigenous communities. To address this, Health Canada and partners have collected and analyzed a total of 621 samples of commonly consumed salmon, ground fish, and shellfish from the Canadian west coast from 2011 to 2018. While the vast majority of the 137 Cs and 134 Cs levels were below the Minimum Detectable Concentration (MDC, typically 0.7-1.0 Bq kg -1 fw for a 6 h counting), further examination of 19 fish samples revealed 137 Cs concentrations of 0.17-0.53 Bq kg -1 fw with an average value and uncertainty (k = 1) of 0.29 ± 0.02 Bq kg -1 fw. Of these, only two samples were found to have trace levels of 134 Cs likely derived from the Fukushima accident. The global fallout contribution from atmospheric nuclear weapons testing to the observed 137 Cs in these two samples was determined to be 0.26 ± 0.08 Bq kg -1 fw (49 ± 14%) and 0.12 ± 0.02 Bq kg -1 fw (24 ± 4%) for collection years 2015 and 2016, respectively. The annual average level of 137 Cs in fish and shellfish was also determined by spectral summation for collection years 2014-2018. In fish, 137 Cs levels determined through spectral summation were relatively constant (0.18-0.25 Bq kg -1 fw) with an average value and uncertainty of 0.21 ± 0.02 Bq kg -1 fw. By contrast, 38 shellfish samples (bivalves) were measured and revealed no radiocesium or other anomalies in either tissue or shell. In all, measurements over eight years showed that the radioactivity in fish and shellfish was dominated by natural radionuclides and that the level of anthropogenic radionuclides, as indicated by the radioactive cesium content, remained small. An upper bound for ingested dose from 137 Cs was determined to be approximately 0.26 μSv per year, far below the worldwide average annual effective dose of 2400 μSv from exposure to natural background radiation. We can therefore conclude that fish, such as salmon, ground fish, and shellfish from the Canadian west coast are of no radiological health concern despite the Fukushima Dai-ichi nuclear accident of 2011., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We study some effective transmission conditions able to reproduce the effect of a periodic array of Dirichlet wires on wave propagation, in particular when the array delimits an acoustic Faraday cage able to resonate. In the study of Hewett & Hewitt (2016 Proc. R. Soc. A 472 , 20160062 (doi:10.1098/rspa.2016.0062)) different transmission conditions emerge from the asymptotic analysis whose validity depends on the frequency, specifically the distance to a resonance frequency of the cage. In practice, dealing with such conditions is difficult, especially if the problem is set in the time domain. In the present study, we demonstrate the validity of a simpler unified model derived in Marigo & Maurel (2016 Proc. R. Soc. A 472 , 20160068 (doi:10.1098/rspa.2016.0068)), where unified means valid whatever the distance to the resonance frequencies. The effectiveness of the model is discussed in the harmonic regime owing to explicit solutions. It is also exemplified in the time domain, where a formulation guaranteeing the stability of the numerical scheme has been implemented., Competing Interests: We declare we have no competing interests., (© 2021 The Author(s).)

In response to public concern in Canada regarding health impacts attributable to the Fukushima Daiichi nuclear accident, oceanic seawater samples from the north Pacific and Arctic oceans, coastal seawater samples from 16 locations along the British Columbia coastline, and seafood samples (salmon, steelhead trout, and shellfish) from British Columbia coastal waters were collected and analyzed. This paper reports radiological analysis results of Pacific salmon samples (Oncorhynchus species) obtained from summer 2013 to fall 2016. While radioactive cesium from the Fukushima disaster was not detectable in most salmon samples, naturally occurring Po was measured in almost all individual samples in varying activity concentrations, from below the detection limit of 0.2 Bq kg fresh weight up to 4.7 Bq kg fresh weight. The average Po concentration among 297 salmon samples was 0.73 Bq kg fresh weight. The average ingested radiation dose per kilogram of salmon from Po is estimated to be 0.88 μSv, and the average dose from Cs is estimated to be 0.0026 μSv. The annual dose from ingested salmon would be only a fraction of the worldwide average annual effective dose from exposure to natural background radiation (2,400 μSv y) (). The measurement results showed clearly that radiation doses to people consuming fish (such as salmon) from the Canadian west coast pose no health concern.

The influence of the spacing on the resonance of a periodic arrangement of Helmholtz resonators is inspected. An effective problem is used which accurately captures the properties of the resonant array within a large range of frequencies, and whose simplified version leaves an impedance condition. It is shown that the strength of the resonance is enhanced when the array becomes sparser. This degree of freedom on the radiative damping is of particular interest since it does not affect the resonance frequency nor the damping due to losses within each resonator; in addition, it does not affect the total thickness of the array. It is shown that it can be used for the design of a perfect absorbing wall.

Historical results of natural radioactivity in drinking water were reviewed for a total of 21 communities across Canada from 1975 to 2016. Analyses for 226Ra, 210Pb and total uranium were carried out on monthly composite samples of drinking water from selected Canadian municipalities. Generally speaking, levels of 226Ra, 210Pb and total uranium were found to be low compared to national and international standards for drinking water quality. Because levels were low, federal monitoring programs were discontinued in most communities in 1986 except for Regina, Elliot Lake and Port Hope. The population-weighted average levels for these three communities, using data from the most recent 5 years, are <1 mBq/L for 226Ra, <5 mBq/L for 210Pb and <0.4 μg/L for total uranium. The average effective dose resulting from drinking water intake at these levels would be <4.3 μSv per year.

We present a model based on a two-scale asymptotic analysis for resonant arrays of the Helmholtz type, with resonators open at a single extremity (standard resonators) or open at both extremities (double-sided resonators). The effective behaviour of such arrays is that of a homogeneous anisotropic slab replacing the cavity region, associated with transmission, or jump, conditions for the acoustic pressure and for the normal velocity across the region of the necks. The coefficients entering in the effective wave equation are simply related to the fraction of air in the periodic cell of the array. Those entering in the jump conditions are related to near field effects in the vicinity of the necks and they encapsulate the effects of their geometry. The effective problem, which accounts for the coupling of the resonators with the surrounding air, is written in the time domain which allows us to question the equation of energy conservation. This is of practical importance if the numerical implementations of the effective problem in the time domain is sought., Competing Interests: We have no competing interests.

The resonance of a Helmholtz resonator is studied with a focus on the influence of the neck shape. This is done using a homogenization approach developed for an array of resonators, and the resonance of an array is discussed when compared to that of a single resonator. The homogenization makes a parameter B appear which determines unambiguously the resonance frequency of any neck. As expected, this parameter depends on the length and on the minimum opening of the neck, and it is shown to depend also on the surface of air inside the neck. Once these three geometrical parameters are known, B has an additional but weak dependence on the neck shape, with explicit bounds.

Concern from northern communities following the Fukushima Daiichi nuclear accident of March 2011 has prompted a reassessment of the safety of their traditional foods with respect to radioactivity levels. To this end, a study was conducted to measure the levels of radionuclides in Arctic caribou (Rangifer tarandus) and beluga (Delphinapterus leucas). The main radionuclide of concern is cesium-137, which is easily transferred through the lichen-caribou food chain. Previous studies have been conducted on the cesium-137 levels in Canadian caribou herds from 1958 to 2000, allowing researchers to determine the amount of cesium-137 in caribou specifically attributable to atmospheric weapons testing and the Chernobyl nuclear accident in 1986. In this study, samples of lichens, mushrooms, caribou, beluga and beluga prey collected before and after the Fukushima accident were analyzed for radioactivity levels. Samples were processed and measured using gamma ray spectroscopy to identify the radionuclides present and determine the radioactivity concentration. Both calibration standards and Monte Carlo simulations were used to determine the efficiency of the detectors for the samples, taking into account differences in individual sample sizes as well as matrices. In particular, a careful analysis of the atomic composition of lichens and mushrooms was performed to ensure the efficiencies for these sample types were correct. A comparison of the concentrations from before and after the accident indicated that there was no increase in radioactivity as a result of the atmospheric plume from the Fukushima accident. Some cesium-137, likely attributable to fallout from atmospheric weapons testing of the 1950s and 1960s (since there was no cesium-134 measured in the samples), was measured in the post Fukushima caribou and beluga whale samples; however, this amount was determined to be insignificant for any radiological concern (9.1 ± 1.8 and 0.63 ± 0.23 Bq kg -1  ww respectively). The activity concentrations of cesium-137 was about 200 times smaller than that of natural radioactive potassium in the beluga samples. Both the caribou and beluga results showed that these foods continue to be a healthy food choice for northern Canadians with respect to radioactivity, and this result has been communicated to the nearby northern communities and stakeholders., (Copyright © 2016. Published by Elsevier Ltd.)

We present an efficient multimodal method to describe the acoustic propagation in the presence of a uniform flow in a waveguide with locally a wall impedance treatment. The method relies on a variational formulation of the problem, which allows to derive a multimodal formulation within a rigorous mathematical framework, notably to properly account for the boundary conditions on the walls (being locally the Myers condition and the Neumann condition otherwise). Also, the method uses an enriched basis with respect to the usual cosine basis, able to absorb the less converging part of the modal series and thus, to improve the convergence of the method. Using the cosine basis, the modal method has a low convergence, 1/ N , with N the order of truncation. Using the enriched basis, the improvement in the convergence is shown to depend on the Mach number, from 1/ N 5 to roughly 1/ N 1.5 for M =0 to M close to unity. The case of a continuously varying wall impedance is considered, and we discuss the limiting case of piecewise constant impedance, which defines pressure edge conditions at the impedance discontinuities.

Health Canada's Radiation Protection Bureau has identified trace quantities of (134)Cs and (137)Cs in commercially available green tea products of Japanese origin. Referenced to March 11, 2011, the activity ratio ((134)Cs/(137)Cs) has been determined to be 1:1, which supports an origin from the Fukushima Dai-ichi Nuclear Power Plant accident. The upper limits of typical tea beverage preparation conditions were applied to the most contaminated of these green tea samples to determine the proportion of radiocesium contamination that would be available for human consumption. The distribution of radiocesium among the components of the extraction experiments (water, residual tea solid, and filter media) was determined by both conventional and Compton-suppressed gamma spectroscopy. The latter aided tremendously in providing a more complete radiocesium distribution profile, particularly for the shorter-lived (134)Cs. Cesium extraction efficiencies of 64 ± 7% and 64 ± 5% were determined based on (134)Cs and (137)Cs, respectively. Annual, effective dose estimates from ingestion of (137)Cs and (134)Cs (1.8-3.7 μSv), arising from the consumption of tea beverages prepared from the most contaminated of these samples, are insignificant relative to both total (∼ 2.4 mSv) and ingested (∼ 0.28 mSv) annual effective doses received from naturally occurring radioactive sources. As such, there is no health concern arising from the consumption of green tea beverages contaminated with radiocesium at the levels encountered in this study., (Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.)

A multimodal method based on a generalization of the admittance matrix is used to analyze wave propagation in heterogeneous two-dimensional anisotropic media. The heterogeneity of the medium can be due to the presence of anisotropic inclusions with arbitrary shapes, to a succession of anisotropic media with complex interfaces between them, or both. Using a modal expansion of the wave field, the problem is reduced to a system of two sets of first-order differential equations for the modal components of the field, similar to the system obtained in the rigorous coupled wave analysis. The system is solved numerically, using the admittance matrix, which leads to a stable numerical method, the basic properties of which are discussed. The convergence of the method is discussed, considering arrays of anisotropic inclusions with complex shapes, which tend to show that Li's rules are not concerned within our approach. The method is validated by comparison with a subwavelength layered structure presenting an effective anisotropy at the wave scale.

A multimodal method is used to analyze the wave propagation in waveguides containing restrictions (or corrugations) with circular arc shapes. This is done using a geometrical transformation which transforms the waveguide with complex geometry in the real space to a straight waveguide in the transformed space, or virtual space. In this virtual space, the Helmholtz equation has a modified structure which encapsulates the complexity of the geometry. It is solved using an improved modal method, which was proposed in a paper by A. Maurel, J.-F. Mercier, and S. Félix [Proc. R. Soc. A 470, 20130743 (2014)], that increases the accuracy and convergence of usual multimodal formulations. Results show the possibility to solve the wave propagation in a waveguide with a high density of circular arc shaped scatterers.

Even though many studies have shown that radioactive caesium levels in fish caught outside of Japan were below experimental detection limits of a few Bq kg(-1), significant public concern has been expressed about the safety of consuming seafood from the Pacific Ocean following the Fukushima-Daiichi nuclear accident. To address the public concerns, samples of commonly consumed salmon and groundfish harvested from the Canadian west coast in 2013 were analysed for radioactive caesium. None of the fish samples analysed in this study contained any detectable levels of (134)Cs and (137)Cs under given experimental setting with the average detection limit of ∼2 Bq kg(-1). Using a conservative worst-case scenario where all fish samples would contain (137)Cs exactly at the detection limit level and (134)Cs at half of the detection limit level (to account for much shorter half-life of (134)Cs), the resulting radiation dose for people from consumption of this fish would be a very small fraction of the annual dose from exposure to natural background radiation in Canada. Therefore, fish, such as salmon and groundfish, from the Canadian west coast are of no radiological health concern., (© The Author 2014. Published by Oxford University Press.)

Background and Purpose: The prognostic value of dynamic contrast-enhanced MR imaging-derived plasma volume obtained in tumor and the contrast transfer coefficient has not been well-established in patients with gliomas. We determined whether plasma volume and contrast transfer coefficient in tumor correlated with survival in patients with gliomas in addition to other factors such as age, type of surgery, preoperative Karnofsky score, contrast enhancement, and histopathologic grade., Materials and Methods: This prospective study included 46 patients with a new pathologically confirmed diagnosis of glioma. The contrast transfer coefficient and plasma volume obtained in tumor maps were calculated directly from the signal-intensity curve without T1 measurements, and values were obtained from multiple small ROIs placed within tumors. Survival curve analysis was performed by dichotomizing patients into groups of high and low contrast transfer coefficient and plasma volume. Univariate analysis was performed by using dynamic contrast-enhanced parameters and clinical factors. Factors that were significant on univariate analysis were entered into multivariate analysis., Results: For all patients with gliomas, survival was worse for groups of patients with high contrast transfer coefficient and plasma volume obtained in tumor (P < .05). In subgroups of high- and low-grade gliomas, survival was worse for groups of patients with high contrast transfer coefficient and plasma volume obtained in tumor (P < .05). Univariate analysis showed that factors associated with lower survival were age older than 50 years, low Karnofsky score, biopsy-only versus resection, marked contrast enhancement versus no/mild enhancement, high contrast transfer coefficient, and high plasma volume obtained in tumor (P < .05). In multivariate analysis, a low Karnofsky score, biopsy versus resection in combination with marked contrast enhancement, and a high contrast transfer coefficient were associated with lower survival rates (P < .05)., Conclusions: In patients with glioma, those with a high contrast transfer coefficient have lower survival than those with low parameters., (© 2015 by American Journal of Neuroradiology.)

Electromagnetic or acoustic metamaterials can be described in terms of equivalent effective, in general anisotropic, media and several techniques exist to determine the effective permeability and permittivity (or effective mass density and bulk modulus in the context of acoustics). Among these techniques, retrieval methods use the measured reflection and transmission coefficients (or scattering coefficients) for waves incident on a metamaterial slab containing few unit cells. Until now, anisotropic effective slabs have been considered in the literature but they are limited to the case where one of the axes of anisotropy is aligned with the slab interface. We propose an extension to arbitrary orientations of the principal axes of anisotropy and oblique incidence. The retrieval method is illustrated in the electromagnetic case for layered media, and in the acoustic case for array of tilted elliptical particles.

We present an efficient Fourier modal method for wave scattering by perfectly conducting gratings (in the two polarizations). The method uses a geometrical transformation, similar to the one used in the C-method, that transforms the grating surface into a flat surface, thus avoiding to question the Rayleigh hypothesis; also, the transformation only affects a bounded inner region that naturally matches the outer region; this allows applying a simple criterion to select the ingoing and outgoing waves. The method is shown to satisfy reciprocity and energy conservation, and it has an exponential rate of convergence for regular groove shapes. Besides, it is shown that the size of the inner region, where the solution is computed, can be reduced to the groove depth, that is, to the minimal computation domain.

We address the problem of the transmission through subwavelength dielectric gratings. Following Maurel et al. [Phys. Rev. B 88, 115416 (2013)], the problem is reduced to the transmission by an homogeneous slab, either anisotropic (for transverse magnetic waves, TM) or isotropic (for transverse electric waves, TE), and an explicit expression of the transmission coefficient is derived. The optimum angle realizing perfect impedance matching (Brewster angle) is shown to depend on the contrasts of the dielectric layers with respect to the air. Besides, we show that the Fabry-Perot resonances may be dependent on the incident angle, in addition to the dependence on the frequency. These facts depart from the case of metallic gratings usually considered; they are confirmed experimentally both for TE and TM waves in the microwave regime.

We present an efficient multi-modal method to describe the acoustic propagation in waveguides with varying curvature and cross section. A key feature is the use of a flexible geometrical transformation to a virtual space in which the waveguide is straight and has unitary cross section. In this new space, the pressure field has to satisfy a modified wave equation and associated modified boundary conditions. These boundary conditions are in general not satisfied by the Neumann modes, used for the series representation of the field. Following previous work, an improved modal method (MM) is presented, by means of the use of two supplementary modes. Resulting increased convergences are exemplified by comparison with the classical MM. Next, the following question is addressed: when the boundary conditions are verified by the Neumann modes, does the use of supplementary modes improve or degrade the convergence of the computed solution? Surprisingly, although the supplementary modes degrade the behaviour of the solution at the walls, they improve the convergence of the wavefield and of the scattering coefficients. This sheds a new light on the role of the supplementary modes and opens the way for their use in a wide range of scattering problems.

An improved version of the multimodal admittance method in acoustic waveguides with varying cross sections is presented. This method aims at a better convergence with respect to the number of transverse modes that are taken into account. It is based on an enriched modal expansion of the pressure: the N first modes are the local transverse modes and a supplementary ( N +1)th mode, called boundary mode, is a well-chosen transverse function orthogonal to the N first modes. This expansion leads to the classical form of the coupled mode equations where the component of the boundary mode is of evanescent character. Under this form, the multimodal admittance method based on the Riccati equation on the admittance matrix (the Dirichlet-to-Neumann operator) is straightforwardly implemented. With this supplementary mode, in addition to the improvement of the convergence of the pressure field, results show a superconvergence of the scattered field outside of the varying cross sections region.

A multimodal method based on the admittance matrix is used to analyze wave propagation through scatterers of arbitrary shape. Two cases are considered: a waveguide containing scatterers, and the scattering of a plane wave at oblique incidence to an infinite periodic row of scatterers. In both cases, the problem reduces to a system of two sets of first-order differential equations for the modal components of the wavefield, similar to the system obtained in the rigorous coupled wave analysis. The system can be solved numerically using the admittance matrix, which leads to a stable numerical method, the basic properties of which are discussed (convergence, reciprocity, energy conservation). Alternatively, the admittance matrix can be used to get analytical results in the weak scattering approximation. This is done using the plane wave approximation, leading to a generalized version of the Webster equation and using a perturbative method to analyze the Wood anomalies and Fano resonances.

The identification of novel antiretroviral agents is required to provide alternative treatment options for HIV-1-infected patients. The screening of a phenotypic cell-based viral replication assay led to the identification of a novel class of 4,5-dihydro-1H-pyrrolo[3,4-c]pyrazol-6-one (pyrrolopyrazolone) HIV-1 inhibitors, exemplified by two compounds: BI-1 and BI-2. These compounds inhibited early postentry stages of viral replication at a step(s) following reverse transcription but prior to 2 long terminal repeat (2-LTR) circle formation, suggesting that they may block nuclear targeting of the preintegration complex. Selection of viruses resistant to BI-2 revealed that substitutions at residues A105 and T107 within the capsid (CA) amino-terminal domain (CANTD) conferred high-level resistance to both compounds, implicating CA as the antiviral target. Direct binding of BI-1 and/or BI-2 to CANTD was demonstrated using isothermal titration calorimetry and nuclear magnetic resonance (NMR) chemical shift titration analyses. A high-resolution crystal structure of the BI-1:CANTD complex revealed that the inhibitor bound within a recently identified inhibitor binding pocket (CANTD site 2) between CA helices 4, 5, and 7, on the surface of the CANTD, that also corresponds to the binding site for the host factor CPSF-6. The functional consequences of BI-1 and BI-2 binding differ from previously characterized inhibitors that bind the same site since the BI compounds did not inhibit reverse transcription but stabilized preassembled CA complexes. Hence, this new class of antiviral compounds binds CA and may inhibit viral replication by stabilizing the viral capsid.

The HIV-1 capsid (CA) protein, a domain of Gag, which participates in formation of both the mature and immature capsid, represents a potential target for anti-viral drug development. Characterization of hits obtained via high-throughput screening of an in vitro capsid assembly assay led to multiple compounds having this potential. We previously presented the characterization of two inhibitor series that bind the N-terminal domain of the capsid (CA(NTD)), at a site located at the bottom of its helical bundle, often referred to as the CAP-1 binding site. In this work we characterize a novel series of benzimidazole hits. Initial optimization of this series led to compounds with improved in vitro assembly and anti-viral activity. Using NMR spectroscopy we found that this series binds to a unique site on CA(NTD), located at the apex of the helical bundle, well removed from previously characterized binding sites for CA inhibitors. 2D (1)H-(15)N HSQC and (19)F NMR showed that binding of the benzimidazoles to this distinct site does not affect the binding of either cyclophilin A (CypA) to the CypA-binding loop or a benzodiazepine-based CA assembly inhibitor to the CAP-1 site. Unfortunately, while compounds of this series achieved promising in vitro assembly and anti-viral effects, they also were found to be quite sensitive to a number of naturally occurring CA(NTD) polymorphisms observed among clinical isolates. Despite the negative impact of this finding for drug development, the discovery of multiple inhibitor binding sites on CA(NTD) shows that capsid assembly is much more complex than previously realized.

The emergence of resistance to existing classes of antiretroviral drugs underlines the need to find novel human immunodeficiency virus (HIV)-1 targets for drug discovery. The viral capsid protein (CA) represents one such potential target. Recently, a series of benzodiazepine inhibitors was identified via high-throughput screening using an in vitro capsid assembly assay (CAA). Here, we demonstrate how a combination of NMR and X-ray co-crystallography allowed for the rapid characterization of the early hits from this inhibitor series. Ligand-based (19)F NMR was used to confirm inhibitor binding specificity and reversibility as well as to identify the N-terminal domain of the capsid (CA(NTD)) as its molecular target. Protein-based NMR ((1)H and (15)N chemical shift perturbation analysis) identified key residues within the CA(NTD) involved in inhibitor binding, while X-ray co-crystallography confirmed the inhibitor binding site and its binding mode. Based on these results, two conformationally restricted cyclic inhibitors were designed to further validate the possible binding modes. These studies were crucial to early hit confirmation and subsequent lead optimization., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background and Purpose: The accuracy of tumor plasma volume and K(trans) estimates obtained with DCE MR imaging may have inaccuracies introduced by a poor estimation of the VIF. In this study, we evaluated the diagnostic accuracy of a novel technique by using a phase-derived VIF and "bookend" T1 measurements in the preoperative grading of patients with suspected gliomas., Materials and Methods: This prospective study included 46 patients with a new pathologically confirmed diagnosis of glioma. Both magnitude and phase images were acquired during DCE MR imaging for estimates of K(trans)&#95;φ and V(p&#95;)φ (calculated from a phase-derived VIF and bookend T1 measurements) as well as K(trans)&#95;SI and V(p&#95;)SI (calculated from a magnitude-derived VIF without T1 measurements)., Results: Median K(trans)&#95;φ values were 0.0041 minutes(-1) (95 CI, 0.00062-0.033), 0.031 minutes(-1) (0.011-0.150), and 0.088 minutes(-1) (0.069-0.110) for grade II, III, and IV gliomas, respectively (P ≤ .05 for each). Median V(p&#95;)φ values were 0.64 mL/100 g (0.06-1.40), 0.98 mL/100 g (0.34-2.20), and 2.16 mL/100 g (1.8-3.1) with P = .15 between grade II and III gliomas and P = .015 between grade III and IV gliomas. In differentiating low-grade from high-grade gliomas, AUCs for K(trans)&#95;φ, V(p&#95;φ), K(trans)&#95;SI, and V(p&#95;)SI were 0.87 (0.73-1), 0.84 (0.69-0.98), 0.81 (0.59-1), and 0.84 (0.66-0.91). The differences between the AUCs were not statistically significant., Conclusions: K(trans)&#95;φ and V(p&#95;)φ are parameters that can help in differentiating low-grade from high-grade gliomas.

The emergence of resistance to existing classes of antiretroviral drugs necessitates finding new HIV-1 targets for drug discovery. The viral capsid (CA) protein represents one such potential new target. CA is sufficient to form mature HIV-1 capsids in vitro, and extensive structure-function and mutational analyses of CA have shown that the proper assembly, morphology, and stability of the mature capsid core are essential for the infectivity of HIV-1 virions. Here we describe the development of an in vitro capsid assembly assay based on the association of CA-NC subunits on immobilized oligonucleotides. This assay was used to screen a compound library, yielding several different families of compounds that inhibited capsid assembly. Optimization of two chemical series, termed the benzodiazepines (BD) and the benzimidazoles (BM), resulted in compounds with potent antiviral activity against wild-type and drug-resistant HIV-1. Nuclear magnetic resonance (NMR) spectroscopic and X-ray crystallographic analyses showed that both series of inhibitors bound to the N-terminal domain of CA. These inhibitors induce the formation of a pocket that overlaps with the binding site for the previously reported CAP inhibitors but is expanded significantly by these new, more potent CA inhibitors. Virus release and electron microscopic (EM) studies showed that the BD compounds prevented virion release, whereas the BM compounds inhibited the formation of the mature capsid. Passage of virus in the presence of the inhibitors selected for resistance mutations that mapped to highly conserved residues surrounding the inhibitor binding pocket, but also to the C-terminal domain of CA. The resistance mutations selected by the two series differed, consistent with differences in their interactions within the pocket, and most also impaired virus replicative capacity. Resistance mutations had two modes of action, either directly impacting inhibitor binding affinity or apparently increasing the overall stability of the viral capsid without affecting inhibitor binding. These studies demonstrate that CA is a viable antiviral target and demonstrate that inhibitors that bind within the same site on CA can have distinct binding modes and mechanisms of action.

The scattering of a scalar wave propagating in a waveguide containing weak penetrable scatterers is inspected in the Born approximation. The scatterers are of arbitrary shape and present a contrast both in density and in wavespeed (or bulk modulus), a situation that can be translated in the context of SH waves, water waves, or transverse electric/transverse magnetic polarized electromagnetic waves. For small size inclusions compared to the waveguide height, analytical expressions of the transmission and reflection coefficients are derived, and compared to results of direct numerical simulations. The cases of periodically and randomly distributed inclusions are considered in more detail, and compared with unbounded propagation through inclusions. Comparisons with previous results valid in the low frequency regime are proposed., (© 2012 Acoustical Society of America)

It has long been observed that the environmental gamma-ray dose rate increases noticeably during precipitation intervals. This increase, due to the presence of radon progeny in the rain droplets (or snow flakes), can affect the reliability of the monitoring of artificial radioactivity and long term estimates of exposure to ambient natural radionuclides in surveillance network. Predicting the amplitude of the dose increase has been shown to be surprisingly challenging. In this work, standard air mass back trajectory analysis is used to show that the amplitude of the increase can be quantitatively linked to the history of the air mass where the precipitation is occurring. Furthermore, we show how back trajectory analysis, environmental gamma and rain data can be used to obtain estimations of relative radon emanation rates for locations far from the actual point of detection.

2-D DNA display is a simple separation method that provides a fast and economical way of visualizing polymorphism and comparing genomes. The DNA fragments are separated first according to their size by standard gel electrophoresis and then according to their sequence composition using denaturing gradient gel electrophoresis. First developed by Fischer and Lerman (Cell 1979, 16, 191-200), this method has recently been used to distinguish strains within a bacterial species. The genomic restriction fragments are displayed as spots on a 2-D surface. Although most of the relevant physical mechanisms are understood, this technique is mostly empirical and remains essentially qualitative. In view of optimizing this procedure, we combine our understanding of the different physical mechanisms at play to develop a complete numerical model to predict the relative coordinates of the spots as a function of the corresponding DNA sequence and of the experimental conditions. We experimentally validate our model by predicting the outcome of a 2-D display of the lambda phage genome. It thus becomes possible to optimize in silico the experimental parameters, to predict whether specific mutations as well as yet undescribed genetic polymorphisms can be resolved, and to assist in interpreting the experimental data.

We derive a mean-field expression for the effective diffusion coefficient of a probe molecule in a two-phase medium consisting of a hydrogel with large gel-free solvent inclusions, in terms of the homogeneous diffusion coefficients in the gel and in the solvent. Upon comparing with exact numerical lattice calculations, we find that our expression provides a remarkably accurate prediction for the effective diffusion coefficient, over a wide range of gel concentration and relative volume fraction of the two phases. Moreover, we extend our model to handle spatial variations of viscosity, thereby allowing us to treat cases where the solvent viscosity itself is inhomogeneous. This work provides robust grounds for the modeling and design of multiphase systems for specific applications, e.g., hydrogels as novel food agents or efficient drug-delivery platforms.

The separation of DNA fragments by (slab or capillary) gel electrophoresis has been studied extensively. To characterize the separation achieved by such systems, one needs to understand the impact (and their dependency upon the experimental quantities) of two physical parameters: the electrophoretic mobility mu and the diffusion coefficient D. Three different regimes have been shown to exist for both mu and D: the Ogston regime, the reptation regime and the reptation with orientation regime (note that separation is only possible for the first two regimes). In the small electric field limit, both mu and D are apparently well described by theories for all three regimes. Unfortunately this results in disjointed scaling laws and no theory-based general equations can apply to all regimes. Recently, an empirical interpolating formula has been proposed that adequately fits the low electric field mobility mu of dsDNA fragments across all three regimes and is compatible with accepted theories. In this article we review and clarify the current state of knowledge regarding the size dependence of the mobility and the diffusion coefficient and propose an interpolating formula for molecular size dependence of the low field diffusion coefficient D. With formulas for both the mobility and the diffusion coefficient as a function of the experimental conditions one could, in principle, optimize any gel/polymer matrix-based electrophoresis system for a wide range of DNA molecular sizes.

Solid phase amplification (SPA), a new method to amplify DNA, is characterized by the use of surface-bound primers. This limits the amplification to two-dimensional surfaces and therefore allows the easy parallelization of DNA amplification in a single system. SPA leads to the formation of small but dense DNA brushes, called DNA colonies. For a molecule to successfully duplicate itself, it needs to bend so that its free end can find a matching primer, located on the surface. We used Brownian dynamics simulations (with a united-atom model) to model the basic kinetics of an SPA experiment. The simulations mimic the temperature cycles and the molecule duplication process found in SPA. Our results indicate that the steric interaction between molecules leads to a decreased duplication probability for molecules in the center of a colony and to an outward leaning for the molecules on the perimeter. These effects result in slower amplification (compared to solution PCR) and indicate that steric interaction alone can explain the loss of the exponential growth (characteristic of solution PCR) of the number of molecules in an SPA experiment. Furthermore, the growth of the colony as a function of the number of thermal cycles is found to be similar to the one obtained with a simple Monte Carlo simulation.

Although homodimerization has been demonstrated for a large number of G protein-coupled receptors (GPCRs), no general role has been attributed to this process. Because it is known that oligomerization plays a key role in the quality control and endoplasmic reticulum (ER) export of many proteins, we sought to determine if homodimerization could play such a role in GPCR biogenesis. Using the beta2-adrenergic receptor (beta2AR) as a model, cell fractionation studies revealed that receptor homodimerization is an event occurring as early as the ER. Supporting the hypothesis that receptor homodimerization is involved in ER processing, beta2AR mutants lacking an ER-export motif or harboring a heterologous ER-retention signal dimerized with the wild-type receptor and inhibited its trafficking to the cell surface. Finally, in addition to inhibiting receptor dimerization, disruption of the putative dimerization motif, 276GXXXGXXXL284, prevented normal trafficking of the receptor to the plasma membrane. Taken together, these data indicate that beta2AR homodimerization plays an important role in ER export and cell surface targeting.

Recently, a new way to amplify DNA, called solid phase amplification (SPA), has been introduced. SPA differs from the traditional polymerase chain reaction (PCR) in the use of surface-bound instead of freely-diffusing primers to amplify DNA. This limits the amplification to two-dimensional surfaces and therefore allows the easy parallelization of DNA amplification in a single system. Furthermore, SPA could provide an alternate route to DNA target implantation on DNA chips for genomic studies. Standard PCR processes are usually characterized (at least initially) by an exponential growth and a broad population distribution, and they are well described by the theory of branching processes, wherein a generating function can be used to obtain the probability distribution function for the population of offspring. This theoretical approach is not appropriate for SPA because it cannot properly take into account the many-body (steric) and geometric effects in a quenched two-dimensional environment. In this article, we propose a simple Lattice Monte Carlo technique to model SPA. We study the growth, stability, and morphology of isolated DNA colonies under various conditions. Our results indicate that, in most cases, SPA is characterized by a geometric growth and a rather sharp size distribution. Various non-ideal effects are studied, and we demonstrate that such effects do not generally change the nature of the process, except in extreme cases.

Quantitative bioluminescence resonance energy transfer (BRET) analysis was applied to the study of beta(1)- and beta(2)-adrenergic receptor homo- and heterodimerization. To assess the relative affinity between each of the protomers, BRET saturation experiments were carried out in HEK-293T cells. beta(1)- and beta(2)-adrenergic receptors were found to have similar propensity to engage in homo- and heterotropic interactions suggesting that, at equivalent expression levels of the two receptor subtypes, an equal proportion of homo- and heterodimers would form. Analysis of the data also revealed that, at equimolar expression levels of energy donor and acceptor, more than 80% of the receptor molecules exist as dimers and that this high incidence of receptor dimerization is insensitive to receptor density for expression levels varying between 1.4 and 26.9 pmol of receptor/mg of membrane protein. Taken together, these results indicate that most of the receptors expressed in cells exist as constitutive dimers and that, at least in undifferentiated fibroblasts, the proportion of homo- and heterodimers between the closely related beta(1)- and beta(2)-adrenergic receptors is determined by their relative levels of expression.

Over the last two decades, the introduction of new methods such as pulsed-field gel electrophoresis and capillary array electrophoresis has made it possible to map and sequence entire genomes, including our own. The development of these experimental methods has been helped by the progress of theoretical and computational sciences, and the interactions between these three modi operandi of modern science are still pushing the limits of our technologies. We now see a clear trend towards proteomics and microfluidic (even nanofluidic!) devices. In this review, we take a look at the progress of the field over the last 3 years using the glasses of the theoretical scientist and focusing mostly on new ideas and concepts. About a dozen different subfields are discussed and reviewed. We conclude by giving a commented list of some of the best review articles published over the last 2-3 years.

Beta(1)- and beta(2)-adrenergic receptors (beta(1)AR and beta(2)AR) are co-expressed in numerous tissues where they play a central role in the responses of various organs to sympathetic stimulation. Although the two receptor subtypes share some signaling pathways, each has been shown to have specific signaling and regulatory properties. Given the recent recognition that many G protein-coupled receptors can form homo- and heterodimers, the present study was undertaken to determine whether the beta(1)AR and beta(2)AR can form dimers in cells and, if so, to investigate the potential functional consequences of such heterodimerization. Using co-immunoprecipitation and bioluminescence resonance energy transfer, we show that beta(1)AR and beta(2)AR can form heterodimers in HEK 293 cells co-expressing the two receptors. Functionally, beta-adrenergic stimulated adenylyl cyclase activity was found to be identical in cells expressing beta(1)AR, beta(2)AR, or both receptors at similar levels, indicating that heterodimerization did not affect this signaling pathway. When considering ERK1/2 MAPK activity, a significant agonist-promoted activation was detected in beta(2)AR- but not beta(1)AR-expressing cells. Similarly to what was observed in cells expressing the beta(1)AR alone, no beta-adrenergic stimulated ERK1/2 phosphorylation was observed in cells co-expressing the two receptors. A similar inhibition of agonist-promoted internalization of the beta(2)AR was observed upon co-expression of the beta(1)AR, which by itself internalized to a lesser extent. Taken together, our data suggest that heterodimerization between beta(1)AR and beta(2)AR inhibits the agonist-promoted internalization of the beta(2)AR and its ability to activate the ERK1/2 MAPK signaling pathway.

Bulk and quantum well semiconductor lasers by nature display fundamentally different physical characteristics relative to multilevel gas and solid state lasers. In particular, the refractive index is nonzero at peak gain and the peak gain can shift strongly with varying carrier density or temperature. Moreover, a quantum well laser gain may be strongly asymmetric if more than the lowest subband is populated. Rigorously computed and experimentally validated, gain and refractive index spectra are now available for a variety of quantum well structures emitting from the infrared to the visible. Active devices can be designed and grown such that the gain spectrum remains approximately parabolic for carrier density variations typically encountered in above threshold pumped broad area edge-emitting semiconductor lasers. Under this assumption, we derive a robust optical propagation model that tracks the important peak gain shifts and broadening as long as the gain remains approximately parabolic over the relevant energy range in a running laser. We next derive a multimode model where the longitudinal modes are projected out of the total field. The next stage is to derive a mean-field single longitudinal mode model for a wide aperture semiconductor laser. The mean-field model allows for significant cavity losses and widely different facet reflectivities such as occurs with antireflection- and high-reflectivity-coated facets. The single mode mean-field model is further reduced using an asymptotic expansion of the relevant physical fields with respect to a small parameter. The end result is a complex semiconductor Swift-Hohenberg description of a single longitudinal mode wide aperture laser. The latter should provide a useful model for studying scientifically and technologically important lasers such as vertical cavity surface emitting semiconductor lasers.

In this article, we examine the low-field electrophoretic migration of infinitely small analytes in dilute sieving media made of nonconducting gel fibers. Using an Ogston obstruction model, we show that the electrophoretic mobility is not affected by the presence of curved field lines. In other words, the Nernst-Einstein relation between the mobility and the diffusion coefficient is valid regardless of the electrical properties of the gel fibers. Although this finding may greatly simplify the development of obstruction models of electrophoretic sieving, it also represents a critical test for any analytical or computational approach.

Although electrophoresis is one of the basic methods of the modern molecular biology laboratory, new ideas are being suggested at an accelerated rate, in large part because of the pressing demands of the biomedical community. Although we now have, at least for some methods, a fairly good theoretical understanding of the physical mechanisms that lead to the observed peak spacings, widths and shapes, this knowledge is often too qualitative to be used to guide further technical developments and improvements. In this article, we review some selected elements of the current state of our theoretical ignorance, focusing mostly on DNA electrophoresis, and we offer several suggestions for further theoretical investigations.

We examine the effect of attractive analyte-gel interactions within the framework of our recently developed lattice model of gel electrophoresis. We show that it is possible to take into account such interactions and still calculate exact mobilities for various analytes and gel structures. Our study then focuses on two main issues: (i) the effect of these interactions on the separation efficiency of the Ogston regime; and (ii) the presence of inflection points (changes of curvature) in Ferguson plots. We establish some general principles, and we describe the results for selected two- and three-dimensional model systems. Numerous practical problems, such as chiral separations and affinity electrophoresis, can be treated using this approach.

In this article, we extend our recently developed lattice model of gel electrophoresis to periodic three-dimensional gels made of either isolated obstacles or infinitely long fibers. Exact mobilities are calculated using a much improved numerical method that allows us to treat very large systems. A comparison of the exact mobilities and free available volumes indicates that the main assumption of the Ogston-Morris-Rodbard-Chrambach model (OMRCM), which postulates that the mobility (mu) of charged particles is directly related to the fractional gel volume available to them, is not valid. However, a study of the gel concentration and analyte size dependence of the zero-field mobility indicates that the OMRCM and the Ferguson plots can indeed be used to obtain useful, semi-quantitative information about the gel properties. A procedure to study more realistic three-dimensional gel systems is discussed.

After removal, the maxilla and the mandible are placed on a standard radiologic cassette and a X-ray is performed with a low energy beam. Different views can be obtained if required. These radiographic images provide a complete, permanent and detailed record of dental anatomy and restorations, for comparison with antemortem radiographies. Two examples are provided. Moreover, this technique enables the determination of the dental age of children.

The role of radiologic imaging studies in the forensic medical procedure following an airborne disaster is now well established. This report summarizes the experience and the results acquired with a recent air crash, and insists on three suggestions: the necessity of a prepared identification team consisting of specialist in forensic medicine, in forensic odontology and specialist in forensic radiology, and the usefulness of a suitable structure for the study and the storage of the dead bodies, the need for a compilation of radiological informations, notably dental X-Ray examinations for the flying personnel.

Cadmium exposure is known to induce hypertension, but development of hypertension is not universal in exposed animals. However, the cellular uptake of cadmium could also exert renal cytotoxic effects which have been, until now, essentially only studied at the proximal tubule level. Kallikrein is an enzyme synthetized in renal cortex and excreted in the urine in the distal tubule. Therefore, to evaluate the distal renal effect of cadmium, we studied the daily urinary kallikrein excretion (UKE) in conscious unrestrained female Brown Norway rats during long-term chronic exposure to 2 dosages of cadmium given subcutaneously 3 times a week, a low dose (LD): 0.25 mg/kg and a high dose (HD): 1 mg/kg. Neither dose of cadmium was able to induce significant hypertension in the treated animals. HD administration for 24 weeks resulted in a decreased UKE associated with an increase in plasma renin activity and sodium and potassium excretions. LD administration had no significant effect on UKE. Twenty weeks after stopping cadmium administration, a persistent reduction in UKE was still observed; furthermore, the group which had been previously administered a LD of cadmium, now also exhibited a reduced UKE. During this re-examination period in both groups, the UKE reductions were associated with normal systolic blood pressure, glycosuria, natriuresis. Our data show that cadmium administration can influence UKE, plasma renin activity, plasma aldosterone concentration and electrolyte excretion without inducing any variation of blood pressure. This may reflect a nephrotoxic, non-hypertensive effect. Since this effect persisted after stopping cadmium administration, it may indicate a prolonged irreversible nephrotoxic effect at the distal nephron level. Thus, UKE may be a useful non-invasive index to evaluate distal nephrotoxicity.