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The controversies in international legal scholarship on the permissible modalities of use of self-defence by states have not ceased since the adoption of the Charter of the United Nations, which em...

The functional characteristics of the co-expression of connexin43, connexin40, and connexin45 proteins in human myocardium are thought to play an important role in governing normal propagation of the cardiac electrical impulse and in generating the myocardial substrate for some arrhythmias and conduction disturbances. A rat liver epithelial cell line, that endogenously expresses connexin43, was used to induce also expression of connexin40 or connexin45 after stable transfection using an inducible ecdysone system. Electrical coupling was estimated from measurement of the input resistance of transfected cells using an intracellular microelectrode to inject current and record changes to membrane potential. However, varied expression of the transfected connexin40 or connexin45 did not change electrical coupling, although connexin43/40 co-expression led to better coupling than connexin43/45 co-expression. Quantification of endogenous connexin43 expression, at both mRNA and protein levels, showed that it was altered in a manner dependent on the transfected connexin isotype. The data using rat liver epithelial cells indicate an increased electrical coupling upon expression of connexin40 and connexin43 but decreased coupling with connexin45 and connexin43 co-expression.

International audience; Suicide prevention is a major worldwide public health goal. In Martinique Island (French West Indies), suicide rates are lower than France’s national ratio of suicide but it’s probably severely underestimated. In order to understand social representation’s (SR) of suicide in the general population but also in professionals of health in Martinique, the ReSCU (Representation of Suicide in Ultramarines Community) began in 2016. SR are the bridge between the individual and the social world. Studies point to the fact that personal experience of suicide causes an alteration of general attitudes toward suicide which can’t be separated from SR. This study tries to highlight SR of suicide in Martinique especially in professionals of health in general or psychiatric hospital and general practionners in order to understand basement from their attitudes, stereotypes, behaviour toward suicide. The goal of this study is to adapt a prevention strategy and communication, to modify health behaviours, in particular through the SR. A questionnaire was created to study SR of suicide with a word free-association task according to simple directives. It is a classic tool in SR studies. We disseminated a questionnaire via email for general practionners and face-to-face using digital tablet for hospital professionals. Two analysis of answers were made. First, we analysed the structure of SR using Vergès’s method of double analysis of evocation rank. Secondly, we made a collective mind mapping of word association to understand the most frequent and strongest association to target those inconscient links in communication strategy. The sample for this study is composed of 70 general practionners and 399 health professionals working in general and psychiatric hospital in Fort de France. First results show that most people were directly and personally concerned by suicide. Traumatic impact of suicide exists. Some judgement appears such as braveness and weakness. A difference exists between comprehension of general risk factors of suicide and causal assignment for specific causes of suicide in Martinique. People have two readings of causes of suicide: a general one and a territorial one. We propose in this communication to explain more specifically those results and propose to show how this kind of study allows local analysis and local adaptation of a suicide prevention strategy in particular to change attitudes and behaviour toward suicide.

We study oscillations in quantum cascade lasers due to traveling electric field domains, which are observed both in simulations and experiments. These oscillations occur in a range of negative differential resistance and we clarify the condition determining whether the boundary between domains of different electric field can become stationary., Comment: 6 pages. Accepted manuscript for publication in The European Physical Journal B Topical issue: Non-Linear and Complex Dynamics in Semiconductors and Related Materials

Quantum Cascade Lasers (QCLs) are generally designed to avoid negative differential conductivity (NDC) in the vicinity of the operation point in order to prevent instabilities. We demonstrate, that the threshold condition is possible under an inhomogeneous distribution of the electric field (domains) and leads to lasing at an operation point with a voltage bias normally attributed to the NDC region. For our example, a Terahertz QCL operating up to the current maximum temperature of 199 K, the theoretical findings agree well with the experimental observations. In particular, we experimentally observe self-sustained oscillations with GHz frequency before and after threshold. These are attributed to traveling domains by our simulations. Overcoming the design paradigm to avoid NDC may allow for the further optimization of QCLs with less dissipation due to stabilizing background current., 22 pages

The contact cardiac electrogram is derived from the extracellular manifestation of cellular action potentials and cell-to-cell communication. It is used to guide catheter based clinical procedures. Theoretically, the contact electrogram and the cellular action potential are directly related, and should change in conjunction with each other during arrhythmogenesis, however there is currently no methodology by which to concurrently record both electrograms and action potentials in the same preparation for direct validation of their relationships and their direct mechanistic links. We report a novel dual modality apparatus for concurrent electrogram and cellular action potential recording at a single cell level within multicellular preparations. We further demonstrate the capabilities of this system to validate the direct link between these two modalities of voltage recordings.

We read with great interest the article by Feola et al1 on investigating the mechanisms of rotor-guided ablation through optogenetic stimulation in monolayers of neonatal rat atrial cardiomyocytes. The authors optically map single stable rotors which could be reliably initiated in their homogeneous monolayers and report on the success rate of different light ablation approaches to terminate the rotors by localized conduction block. We previously studied similar rotor activity using high spatiotemporal resolution optical mapping in monolayers …

On 16 April 2013, the International Court of Justice (icj) rendered an unanimous Judgment in the case regarding the boundary dispute between Burkina Faso and the Republic of Niger. This note will review the findings of the Court against the background of the previous judgments which the icj has rendered regarding land boundaries in this region, formed by the former French colonial territories of West Africa (Burkina Faso/Mali and Benin/Niger). It will also examine current trends and future prospects for the delimitation of frontiers in Africa, where it is estimated that at present only 35% of land boundaries have been subject to delimitation and demarcation. Many African frontiers, while theoretically defined by means of treaties, are insufficiently (if at all) demarcated on the ground, which causes confusion concerning the actual physical location of (or at least parts of) boundaries. In the recent period, several factors have contributed to a greater awareness of concerned States and stakeholders of the urgent need for the completion of outstanding delimitations. The author argues that the icj is likely to remain a popular venue for African States willing to settle boundary disputes.

Objectives The purpose of this study was to investigate the effects of enhancing gap junction (GJ) coupling during acute myocardial infarction (MI) on the healed infarct scar morphology and late post-MI arrhythmia susceptibility. Background Increased heterogeneity of myocardial scarring after MI is associated with greater arrhythmia susceptibility. We hypothesized that short-term enhancement of GJ coupling during acute MI can produce more homogeneous infarct scars, reducing late susceptibility to post-MI arrhythmias. Methods Following arrhythmic characterization of a rat 4-week post-MI model (n = 24), another 27 Sprague-Dawley rats were randomized to receive rotigaptide to enhance GJ coupling (n = 13) or to saline control (n = 14) by osmotic minipump immediately prior to and for the first 7 days following surgically induced MI. At 4 weeks post-MI, hearts were explanted for ex vivo programmed electrical stimulation (PES) and optical mapping. Heterogeneity of infarct border zone (IBZ) scarring was quantified by histomorphometry. Results Despite no detectable differences in infarct size at 4 weeks post-MI, rotigaptide-treated hearts had reduced arrhythmia susceptibility during PES (inducibility score for rotigaptide: 2.4 ± 0.8; for control: 5.0 ± 0.6; p = 0.02) and less heterogeneous IBZ scarring (dispersion of IBZ complexity score: rotigaptide: 1.1 ± 0.1; control: 1.4 ± 0.1; p = 0.04), associated with an improvement in IBZ conduction velocity (rotigaptide: 43.1 ± 3.4 cm/s; control: 34.8 ± 2.0 cm/s; p = 0.04). Conclusions Enhancement of GJ coupling for only 7 days at the time of acute MI produced more homogeneous IBZ scarring and reduced arrhythmia susceptibility at 4 weeks post-MI. Short-term GJ modulation at the time of MI may represent a novel treatment strategy to modify the healed infarct scar morphology and reduce late post-MI arrhythmic risk., Graphical abstract Image 1

The controversy over the Iranian nuclear programme is probably one of most sensitive contemporary instances of a situation involving legal issues related to compliance and enforcement of non-proliferation treaty obligations. The allegations put forward against Iran in this context are rarely formulated or substantiated in legal terms, nor grounded in a clearly identifiable legal basis or framework. This article aims at the identification of the specific international obligations that Iran would have breached or failed to comply with, whether contained in the NPT or in other non-proliferation agreements, and at the evaluation of the criteria or standards under which the occurrence of a failure or a breach of treaty commitments by Iran is to be assessed. It begins with an overview of the instruments comprising the safeguards system established pursuant to the NPT and monitored by the IAEA, then provides an account of the treatment by the IAEA of the Iranian nuclear program since 2002, which led the IAEA to declare that Iran was in non-compliance with its safeguards agreement, before assessing the IAEA’s findings, in light of relevant rules pertaining to both general international law and the NPT/IAEA legal framework for nuclear safeguards as lex specialis.

The present article aims at revisiting the relationship between countermeasures and the collective security system embodied in the UN Charter, through the case study of the economic measures targeting Iran agreed by the EU Member States in early 2012. This case concerns a very specific situation: that of measures enacted motu proprio in the framework of a regional organization against a country which has already been targeted by sanctions adopted by the UN Security Council. The unprecedented extent of these new EU measures raises various issues regarding their lawfulness under international law. Beginning with a brief overview of the factual background of the Iranian nuclear controversy, our assessment of the measure’s lawfulness consists of a two-fold primary process; first, it is necessary to characterize these measures, in order to determine the applicable legal framework. Then, depending upon the conclusion reached as to the legal nature of the measures, their lawfulness is to be assessed with respect to the relevant rules governing their use. As regards the first step, the measures under consideration may prima facie qualify either as measures of retorsion, as sanctions (whether emanating from the UN Security Council or ‘autonomous’), or as countermeasures. The article examines what legal category adequately describes the EU measures, and concludes with reasonable certainty that they display the general characteristics of countermeasures. This finding entails the applicability of the law of State responsibility (as well as the law of responsibility of international organization), which is relevant to assess in the case considered the lawfulness of the measures, both from a procedural and a substantive perspective.

Cardiac connexin 43 (Cx43), Cx40 and Cx45 are co-expressed at distinct ratios in myocytes. This pattern is considered a key factor in regulating the gap junction channels composition, properties and function and remains poorly understood. This work aims to correlate gap junction function with the connexin composition of the channels at accurate ratios Cx43:Cx40 and Cx43:Cx45. Rat liver epithelial cells that endogenously express Cx43 were stably transfected to induce expression of accurate levels of Cx40 or Cx45 that may be present in various areas of the heart (e.g. atria and ventricular conduction system). Induction of Cx40 does not increase the amounts of junctional connexins (Cx43 and Cx40), whereas induction of Cx45 increases the amounts of junctional connexins (Cx43 and Cx45). Interestingly, the non-junctional fraction of Cx43 remains unaffected upon induction of Cx40 and Cx45. Co-immunoprecipitation studies show low level of Cx40/Cx43 heteromerisation and undetectable Cx45/Cx43 heteromerisation. Functional characterisation shows that induction of Cx40 and Cx45 decreases Lucifer Yellow transfer. Electrical coupling is decreased by Cx45 induction, whereas it is decreased at low induction of Cx40 and increased at high induction. These data indicate a fine regulation of the gap junction channel make-up in function of the type and the ratio of co-expressed Cxs that specifically regulates chemical and electrical coupling. This reflects specific gap junction function in regulating impulse propagation in the healthy heart, and a pro-arrhythmic potential of connexin remodelling in the diseased heart.

The thermal dynamic behaviors of terahertz quantum cascade lasers are investigated using a spectrally matching terahertz quantum-well photodetector. The THz output power of a lasing device under a pulse excitation is found to decrease with time, which is attributed to the increase of active-region temperature. The measurements show that the duration of output lasing pulse ranges from a few microseconds up to 77 ?s, depending on device bias and heat-sink temperature. A theoretical analysis based on a two-dimensional heat diffusion model is presented. The model calculates lasing quenching time based on an ?average active-region temperature? criterion as well as a ?reserve of gain? criterion. The best fit for quenching time is found when the vertical thermal conductivity in the quantum well region is two orders of magnitude lower than that of substrate. The measured lasing quenching time is in very good agreement with theoretical modeling calculated using both criteria.

In the human heart connexin(Cx)40, Cx43 and Cx45-containing gap junctional channels electrically couple cardiomyocytes, forming a functional syncytium. In the mouse heart, additionally, Cx30.2-containing gap junctions have been detected in the atrioventricular node where they are implicated, together with Cx45, in impulse delay. However, whether the human ortholog of Cx30.2, Cx31.9, is expressed in the human heart has not previously been investigated. We therefore generated Cx31.9 specific antibodies to test for the expression of Cx31.9 in the human heart. These antibodies recognized the Cx31.9 protein in HeLaCx31.9 transfectants by immunofluorescence and immunoblot analyses. However, we did not find punctate Cx31.9 specific immunofluorescence signals in the working myocardium or in the impulse generation and conduction system of adult or fetal human heart. Complementary immunoblot analyses did not reveal Cx31.9 protein in the adult atrial or ventricular myocardium. We conclude that the Cx31.9 protein, unlike its counterpart in the mouse, is not expressed in detectable quantities and is thus unlikely to contribute to the impulse generation and conduction system or the working myocardium of the human heart.

This paper investigates the heat conduction behavior of a terahertz (THz) quantum-cascade laser (QCL) active region by measuring its temperature using in-situ microprobe band-to-band photoluminescence (PL) technique. The heat resistance of different regions in QCL structure is derived from the temperature measurement. Experimental results show that thinning the substrate from 300 mum thick to 140 mum lowers thermal resistance of the device by 21%, which helps achieving continuous-wave operation. A thermodynamic differential equation was numerically solved and the temperature profiles and thermal behavior of various regions within actively biased QCL devices under various conditions were obtained. The simulation confirms the measured results that the substrate accounts for 59% of the total device thermal resistance.

Gap junctions form the cell-to-cell pathways for propagation of the precisely orchestrated patterns of current flow that govern the regular rhythm of the healthy heart. As in most tissues and organs, multiple connexin types are expressed in the heart: connexin43 (Cx43), Cx40 and Cx45 are found in distinctive combinations and relative quantities in different, functionally-specialized subsets of cardiac myocyte. Mutations in genes that encode connexins have only rarely been identified as being a cause of human cardiac disease, but remodelling of connexin expression and gap junction organization are well documented in acquired adult heart disease, notably ischaemic heart disease and heart failure. Remodelling may take the form of alterations in (i) the distribution of gap junctions and (ii) the amount and type of connexins expressed. Heterogeneous reduction in Cx43 expression and disordering in gap junction distribution feature in human ventricular disease and correlate with electrophysiologically identified arrhythmic changes and contractile dysfunction in animal models. Disease-related alterations in Cx45 and Cx40 expression have also been reported, and some of the functional implications of these are beginning to emerge. Apart from ventricular disease, various features of gap junction organization and connexin expression have been implicated in the initiation and persistence of the most common form of atrial arrhythmia, atrial fibrillation, though the disparate findings in this area remain to be clarified. Other major tasks ahead focus on the Purkinje/working ventricular myocyte interface and its role in normal and abnormal impulse propagation, connexin-interacting proteins and their regulatory functions, and on defining the precise functional properties conferred by the distinctive connexin co-expression patterns of different myocyte types in health and disease.

This chapter addresses an interpretative issue concerning the scope of safeguards applied by the IAEA under comprehensive safeguards agreements (CSAs) concluded by non-nuclear-weapon States pursuant to the obligation set out in Article III of the NPT. It aims at assessing the way rules for treaty interpretation ought to be applied, and have de facto been applied, in the context of a controversy surrounding the interpretation of para 2 of IAEA document INFCIRC/153 (Corr.), which provides the basis for CSAs, concerning the scope of safeguards under such agreements. The controversial issue is whether this provision is to be read as implying that the IAEA is authorized to verify the absence of ‘undeclared’ nuclear activities in the State subject to safeguards under CSAs, i.e. the ‘completeness’ of the declarations made by the State on the extent of its nuclear activities. I argue that existing rules of interpretation, including an enquiry into subsequent agreement and practice, do not lend unconditional support to the interpretation according to which such provision is to be read as implying that the IAEA under CSAs is entitled to verify the ‘completeness’ of declarations made by States. It appears that a textual approach, together with examination of the context and the object and purpose of CSAs and recourse to the travaux preparatoires gives some weight to the ‘completeness’ argument; and it may be assumed that this embodies a correct interpretation of the disputed provision. But this position is in turn weakened by the consideration of other relevant elements. Indeed, various sources point to the fact that, at the time of entry into force of the NPT and of negotiation of the INFCIRC/153 safeguards system—and at least until the 1990s—there was no shared understanding on the disputed interpretation of para 2 of INFCIRC/153. The various decisions of the IAEA Board of Governors in 1992–1995 often invoked as supporting the ‘completeness’ argument do not in fact embody a common unequivocal endorsement by the Board. As a matter of fact, such disagreements on interpretation have persisted to date, with a few States expressing reservations on the ‘completeness’ argument. The present author has been unable to identify relevant subsequent agreement or subsequent practice that would confirm the ‘completeness’ argument. Therefore, he expresses the view that the confirmation by the IAEA of the ‘completeness’ of declarations of States can only derive, practically if not even legally, from the application of an Additional Protocol.

The impacts of interface roughness (IR) scattering on device performance of indirectly-pumped (IDP) terahertz quantum cascade lasers are studied. Three different active region designs with almost the same lasing frequency at threshold and comparable oscillator strength are experimentally investigated and the measurement data are analyzed and compared with numerical simulation. The simulation results show that all structures suffer from the detrimental effect of intersubband roughness scattering in terms of threshold current density, and probably operating temperature. The intrasubband IR scattering time could also to be a limiting factor in the IDP structures due to the employed high energetic barrier., ICOOPMA2014, Sixth International Conference on Optical, Optoelectronic and Photonic Materials and Applications, July 27-Aug. 1, 2014, Leeds, U.K.

Interband cascade (IC) lasers have been demonstrated based on type-I InGaAsSb/AlAsSb quantum well (QW) active regions. These type-I IC lasers are composed of 6-cascade stages and InAs/AlSb superlattice cladding layers. In contrast to the use of quinary AlGaInAsSb barriers for active region in previous type-I QW lasers, the type-I QW active region in each stage is sandwiched by digitally graded multiple InAs/AlSb QW electron injector and GaSb/AlSb QW hole injector. The fabricated type-I IC lasers were able to operate in continuous wave and pulsed modes at temperatures up to 306 and 365 K, respectively. The threshold current densities of broad-area lasers were around 300 A/cm2 at 300 K with a lasing wavelength near 3.2 μm. The implications and prospects of these initial results are discussed.

Interband cascade lasers with type-I InGaAsSb/AlAsSb quantum well active regions were demonstrated. Ridge-waveguide devices exhibit room-temperature continuous-wave emission at 3.2μm, providing a potential alternative to quantum cascade and diode lasers in this wavelength range., CLEO: Science and Innovations, CLEO-SI 2015, 10 May 2015 through 15 May 2015

We study the impact of interface roughness on the operation of mid-IR and THz quantum cascade lasers. Particular emphasis is given towards the differences between the Gaussian and exponential roughness distribution functions, for which we present results from simulation packages based on nonequilibrium Green's functions and density matrices. The Gaussian distribution suppresses scattering at high momentum transfer which enhances the lifetime of the upper laser level in mid-IR lasers. For THz lasers, a broader range of scattering transitions is of relevance, which is sensitive to the entire profile of the interface fluctuations. Furthermore we discuss the implementation of interface roughness within a two band model.

Scanning voltage microscopy results clearly show that the formation of electric field domains is responsible for the missing of lasing operation in a resonant-phonon based terahertz quantum cascade laser with a highly diagonal transition., CLEO: Science and Innovations, CLEO-SI 2015, 10 May 2015 through 15 May 2015

This chapter argues that in some cases, there may be a reasonable chance of success for those companies targeted by unilateral sanctions to prevail in an investor-State arbitration against a targeting State where the companies are in a position to rely on a BIT in force between their home country and this State. The chapter begins with a consideration of the jurisdictional basis of claims for damages suffered by investments. It emphasizes that affected companies considering such an option shall first assess the likelihood of an arbitral tribunal’s determination that such company has actually made an investment in the targeting State. The chapter then turns to the standards of investment protection found in BITs that could be invoked in cases of application of unilateral sanctions. It is submitted that the prohibition of expropriation is prima facie the most relevant but that other standards of investment protection such as fair and equitable treatment, full protection and security, and the prohibition of unreasonable and discriminatory measures, may at times come into play. It finally examines the probable defenses that a respondent State faced with such a claim would likely raise. These arguments could be based either on the law of countermeasures or on specific provisions in BITs such as clauses on ‘essential security interests’ and ‘non-precluded measures’ or, in the case of EU measures, on the principle of primacy of EU law. The author argues that none of these lines of argument could operate as to exclude ipso facto the international responsibility of the targeting State.

Generation of terahertz (THz), and sub-THz, coherent waves has been demonstrated at room temperature in GaAs-AlGaAs asymmetric quantum wells by mixing two CO2 laser beams. Two overlapping regimes were studied: the double resonance regime where three states are involved and the optical rectification which relies on two states only. The measured conversion efficiency of ~10-7 W-1 is in reasonable agreement with theoretical predictions. In addition, this technique of THz generation provides a model system to study the emission profile from an ensemble of radiating dipoles. For instance, backward emission and strong diffraction effects have been observed

Gap junction expression is considered to influence myocardial conduction and arrhythmogenesis, but studies in patients with atrial fibrillation (AF) have reported inconsistent results. We used human atrial conduction and arrhythmogenicity to provide clinical parameters with which to correlate quantification of connexin40 (Cx40) by different techniques to address the hypothesis that antibody-epitope binding properties may influence quantification methods.Atrial conduction properties were studied in patients undergoing coronary artery bypass grafting (N = 27) using multi-electrode array mapping. Patients were defined as having a vulnerable atrial substrate if pacing-induced AF lasted for more than 30 s. Using antibodies targeted at two different epitopes of the cytoplasmic carboxyl tail, Cx40 signal was quantified by immunoconfocal microscopy in biopsies taken from the mapped atria. Only patients with a vulnerable substrate subsequently developed post-operative AF (P0.02). Immunoconfocal Cx40 signal measured by one antibody, designated S15C(R85), was lower in patients with sustained induced AF (0.013 +/- 0.009 microm(2)/microm(2) vs. 0.024 +/- 0.010 microm(2)/microm(2), P = 0.005) and was negatively correlated with atrial conduction velocity during sinus rhythm (P0.05). However, these relationships did not exist when the Cx40 signal was measured using a different antibody (Y21Y(R968)). Further studies suggested that quantification technique was reproducible against the same epitope (P0.001) but not against different epitopes indicating variable exposure of Cx40 epitopes.Quantification of Cx40 by immunoconfocal microscopy appears to be epitope dependent and evidence of epitope masking raises the possibility of more than one conformational form of the Cx40 carboxyl tail, suggesting functionally important conformations of the protein.

Up-regulation of the gap-junctional protein connexin43 (Cx43) in arterial smooth muscle cells (SMCs) features in response to injury and in atherosclerosis, in parallel with phenotypic transition to the synthetic state. TGF-beta1 is known to have a role in SMC differentiation and extracellular matrix (ECM) synthesis, key characteristics of phenotypic state. Here, we set out to examine the effects of TGF-beta1 on Cx43-gap junction expression in relation to SMC differentiation, ECM synthesis and growth. Cx43 expression was analysed by immunoconfocal microscopy and Western blotting in primary human aortic SMCs treated with TGF-beta1 over a 48-h period, with assessment of gap-junctional communication by cell-to-cell transfer of microinjected ethidium bromide. In parallel, synthetic activity was analysed by Northern blotting for ECM components alpha-1(I) and alpha1(III) procollagen transcripts, contractile differentiation was assessed by immunoconfocal microscopy and Western blotting of the markers smooth muscle alpha-actin, calponin and smooth muscle heavy chain isoform 1 (SM1), and growth was measured by BrdU incorporation. Our results demonstrate that TGF-beta1 significantly up-regulates Cx43 expression and intercellular communication, in concert with increased expression of alpha-actin, calponin and SM1. Concomitant with contractile protein expression, ECM synthesis was increased rather than decreased, TGF-beta1 inducing a significant up-regulation of both procollagen transcripts. These effects were independent of growth. We conclude that in human aortic SMCs, TGF-beta1 treatment leads to up-regulation of Cx43-mediated gap-junctional communication and increased synthetic activity yet, somewhat paradoxically, also enhanced contractile differentiation.

We report planar integration of tapered terahertz (THz) frequency quantum cascade lasers (QCLs) with metasurface waveguides that are designed to be spoof surface plasmon (SSP) out-couplers by introducing periodically arranged SSP scatterers. The resulting surface-emitting THz beam profile is highly collimated with a divergence as narrow as ~4° × 10°, which indicates a good waveguiding property of the metasurface waveguide. In addition, the low background THz power implies a high coupling efficiency for the THz radiation from the laser cavity to the metasurface structure. Furthermore, since all the structures are in-plane, this scheme provides a promising platform where well-established surface plasmon/metasurface techniques can be employed to engineer the emitted beam of THz QCLs controllably and flexibly. More importantly, an integrated active THz photonic circuit for sensing and communication applications could be constructed by incorporating other optoelectronic devices such as Schottky diode THz mixers, and graphene modulators and photodetectors. Published version

Background— We tested the hypothesis that alterations to action potential conduction velocity (CV) and conduction anisotropy in left ventricular hypertrophy are associated with topographical changes to gap-junction coupling and intracellular conductance by measuring these variables in the same preparations. Methods and Results— Left ventricular papillary muscles were excised from aortic-banded or sham-operated guinea-pig hearts. With intracellular stimulating and recording microelectrodes, CV was measured in 3 dimensions with simultaneous conductance mapping with subthreshold stimuli and correlated with quantitative histomorphometry of myocardial architecture and connexin 43 distribution. In hypertrophied myocardium, CV in the longitudinal axis was smaller and transverse velocity was greater compared with control; associated with similar differences of intracellular conductance, consistent with more cell contacts per cell (5.7±0.2 versus 8.1±0.5; control versus hypertrophy), and more intercalated disks mediating side-to-side coupling (8.2±0.2 versus 10.2±0.4 per cell). Intercalated disk morphology and connexin 43 immunolabelling were not different in hypertrophy. Hypertrophied preparations showed local submillimeter (≈250 μm) regions with slow conduction and low intracellular conductance, which, although not affecting CV on the millimeter scale, were consistent with discontinuities from increased microscopical connective tissue content. Conclusions— With myocardial hypertrophy, altered longitudinal and transverse CV, and greater nonuniformity of CV anisotropy correspond to changes of intracellular conductance. These are associated with alteration of myocardial architecture, specifically the topography of cell–cell coupling and gap-junction connectivity.

The external performance of quantum optoelectronic devices is governed by the spatial profiles of electrons and potentials within the active regions of these devices. For example, in quantum cascade lasers (QCLs), the electric field domain (EFD) hypothesis posits that the potential distribution might be simultaneously spatially nonuniform and temporally unstable. Unfortunately, there exists no prior means of probing the inner potential profile directly. Here we report the nanoscale measured electric potential distribution inside operating QCLs by using scanning voltage microscopy at a cryogenic temperature. We prove that, per the EFD hypothesis, the multi-quantum-well active region is indeed divided into multiple sections having distinctly different electric fields. The electric field across these serially-stacked quantum cascade modules does not continuously increase in proportion to gradual increases in the applied device bias, but rather hops between discrete values that are related to tunneling resonances. We also report the evolution of EFDs, finding that an incremental change in device bias leads to a hopping-style shift in the EFD boundary – the higher electric field domain expands at least one module each step at the expense of the lower field domain within the active region., Natural Sciences and Engineering Research Council of Canada, Canadian Foundation for Innovation, CMC Microsystems (Firm), Ontario Research Foundation

The optimization of diffraction gratings for pixelless thermal imagers based on the epitaxial integration of a 9-μm quantum-well infrared photodetector (QWIP) and a near-infrared light-emitting diode (LED) is reported. It is found that the thickness of the reflecting layer deposited onto the grating should be carefully controlled to reach a good tradeoff between high infrared responsivity of the QWIP and reasonable external efficiency of the LED. In addition, on a non-optimized device we demonstrated thermal images with a temperature sensitivity below 100 mK and a noise equivalent temperature difference of 57 mK.

Three of this month's Scientific Discovery papers highlight the importance of collaboration in delivering high quality scientific research. As scientific technology increases in power and cost, and specific areas of interest become more specialized, it is becoming more difficult to cover all aspects of a completeresearch story. Collaborating with other experts in the field or other fields, including industry, allows strong scientific proof to be generated for the hypothesis and aims. Building strong collaborative,inter-disciplinary, multi-institutional, international groups with academic and industrial partners is the way forward for all discovery. We look forward to publishing more of these collaborative papersin future issues of the BJU International. OBJECTIVES To test the hypothesis that intercellular electrical coupling is altered in human detrusor smooth muscle from patients with unstable bladders. MATERIALS AND METHODS Human detrusor biopsy samples were obtained from patients with stable and unstable bladders. Intracellular electrical impedance was measured with alternating current (20 Hz−300 kHz) across the ends of detrusor strips in an oil-gap, after correcting for extracellular space resistance. Gap junctions were identified by localization of connexins (Cx), specifically Cx45, Cx43 and Cx40 transcripts, using immunoconfocal microscopy. RESULTS Total intracellular resistivity was greater in strips from unstable than from stable bladders (median 1246 vs 817 Ω.cm). The increase was attributed to an increase in junctional resistance; cytoplasmic resistance was unchanged. Cx43 was localized to a submucosal layer and to connective tissue; Cx40 label was confined to endothelial cells of blood vessels. Cx45 labelling was localized to detrusor bundles and appeared to be less marked in samples from unstable bladders. Semi-quantitative analysis of Northern blots showed that Cx45 expression in unstable was less than that in stable bladders. CONCLUSIONS These data suggest that intercellular coupling is reduced in detrusor from unstable bladders. Cx45 was localized to the detrusor layer, with Cx 43 more evident in the suburothelial mucosa. Cx45 labelling was less intense in detrusor samples from unstable bladders. These results are consistent with reduced gap junction coupling in detrusor from unstable bladders.

For the majority of applications involving detection of weak signals or thermal imaging, the quantum well infrared photodetector (QWIP) is designed to have the highest possible detectivity and operating temperature. The device parameters, such as the doping density, are chosen accordingly. In a different direction, the intrinsic short carrier lifetime (~ 5 ps) makes QWIPs well suited for high speed and high frequency applications. In such cases, since lasers are normally used, a high dark current can be tolerated. The most important parameter is then the absorption efficiency. For system simplicity and potential wide use, room temperature or near room temperature (reachable by thermo-electric cooling) operations are desirable. This paper discusses the QWIP design for high absorption and elevated temperature operation, and present a systematic experimental study on a set of GaAs/AlGaAs QWIPs with different doping densities. High absorption (~ 100%) and up to room temperature operation are achieved in devices having high doping densities and 100 quantum wells.

Objective To determine whether suburothelial interstitial cells of the human bladder express gap junctions, and if so, to establish their extent and composition, using immunocytochemistry, confocal microscopy and electron microscopy. Materials and methods Bladder tissue was obtained at cystectomy; the tissue was: (i) frozen for cryosectioning and Northern blot analysis; (ii) fixed and embedded for standard thin-section electron microscopy; and (iii) processed using low-denaturation conditions in Lowicryl for immunogold-label electron microscopy. Cryosections were immunofluorescently labelled using antibodies against connexins 43, 40 and 45, vimentin, desmin and c-Kit ligand, and examined by confocal microscopy. Double labelling was used to determine the spatial relationship of labelling for connexin43 with that of vimentin and desmin. Thin-section electron microscopy was used to investigate interstitial cell ultrastructure and permit unequivocal identification of gap junctions, and immunogold labelling of Lowicryl sections was applied to localize connexin43. Results Immunoconfocal microscopy showed prominent labelling for the gap junction protein, connexin43, in a suburothelial band of cells that was also strongly positive for vimentin. The connexin43/vimentin-positive cells showed only weak labelling for desmin and c-Kit ligand, and were immunonegative for connexins 40 and 45. Northern blotting showed a corresponding abundance of connexin43 transcript in the mucosal layer but not the detrusor layer of the bladder wall. Electron microscopy revealed abundant gap junctions, recognized by their pentalaminar structure, between the cell processes of interstitial cells in the suburothelial zone. That these interstitial cell gap junctions were the source of the connexin43 immunolabelling observed by immunoconfocal microscopy was confirmed by immunogold labelling in sections of Lowicryl-embedded tissue examined by electron microscopy. Conclusion A network of interstitial cells, extensively linked by connexin43-containing gap junctions, is located beneath the urothelium in human bladder. As gap junctions provide pathways for direct cell-to-cell communication, the interstitial cellular network may operate as a functional syncytium, integrating signals and responses in the bladder wall.

Absorption spectra of strongly coupled intersubband cavity polaritons have been measured, using a tunable midinfrared quantum cascade laser, with high angular and spectral resolution. Pronounced linewidth narrowing of the polaritons around the anticrossing was found, with polariton linewidths narrower (4.2 meV) than both the bare intersubband transition linewidth and empty cavity linewidth (6.2 and 6 meV, respectively), at room temperature. This is due to variations in the degree of spatial averaging of the in-plane quantum-well disorder as the polariton's extended coherence length is increased by the photonic coupling over the value corresponding to the bare intersubband transition coherence length.

The HL-1 atrial line contains cells blocked at various developmental stages. To obtain homogeneous sub-clones and correlate changes in gene expression with functional alterations, individual clones were obtained and characterised for parameters involved in conduction and excitation-contraction coupling. Northern blots for mRNAs coding for connexins 40, 43 and 45 and calcium handling proteins (sodium/calcium exchanger, L- and T-type calcium channels, ryanodine receptor 2 and sarco-endoplasmic reticulum calcium ATPase 2) were performed. Connexin expression was further characterised by western blots and immunofluorescence. Inward currents were characterised by voltage clamp and conduction velocities measured using microelectrode arrays. The HL-1 clones had similar sodium and calcium inward currents with the exception of clone 2 which had a significantly smaller calcium current density. All the clones displayed homogenous propagation of electrical activity across the monolayer correlating with the levels of connexin expression. Conduction velocities were also more sensitive to inhibition of junctional coupling by carbenoxolone (∼80%) compared to inhibition of the sodium current by lidocaine (∼20%). Electrical coupling by gap junctions was the major determinant of conduction velocities in HL-1 cell lines. In summary we have isolated homogenous and stable HL-1 clones that display characteristics distinct from the heterogeneous properties of the original cell line.

The effect of interface roughness scattering on performance of indirectly-pumped terahertz quantum cascade lasers is studied and a dual-barrier structure is proposed to improve its performance in terms of threshold current density and operating temperature., CLEO : Science and Innovations, 2014, June 8-13, 2014, San Jose, California