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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. [ABSTRACT FROM AUTHOR]

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 μs, depending on device bias and heat-sink temperature. Atheoretical 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. [ABSTRACT FROM AUTHOR]

Abstract: We report on recent measurements on GaAs/AlGaAs THz quantum well infrared photodetectors (QWIPs), investigating linewidth broadening as function of doping level. Structures with 3% and 2% Al content in the barrier were grown using molecular beam epitaxy (MBE) and metal-organic chemical vapor deposition (MOCVD), respectively. Linewidth widening with increasing doping of the GaAs quantum well could be observed in the detection spectra. The observed shift of peak detection wavelength for different well dopings fits with values obtained from wavefunction calculations, taking into account many-particle effects, namely exchange and correlation energies and the effect of depolarization on the absorption. In addition, activation energies extracted from dark current measurements as function of device temperature are also in agreement with the calculations. [Copyright &y& Elsevier]

The role of gap junction channels on cardiac impulse propagation is complex. This review focuses on the differential expression of connexins in the heart and the biophysical properties of gap junction channels under normal and disease conditions. Structural determinants of impulse propagation have been gained from biochemical and immunocytochemical studies performed on tissue extracts and intact cardiac tissue. These have defined the distinctive connexin coexpression patterns and relative levels in different cardiac tissues. Functional determinants of impulse propagation have emerged from electrophysiological experiments carried out on cell pairs. The static properties (channel number and conductance) limit the current flow between adjacent cardiomyocytes and thus set the basic conduction velocity. The dynamic properties (voltage-sensitive gating and kinetics of channels) are responsible for a modulation of the conduction velocity during propagated action potentials. The effect is moderate and depends on the type of Cx and channel. For homomeric-homotypic channels, the influence is small to medium; for homomeric-heterotypic channels, it is medium to strong. Since no data are currently available on heteromeric channels, their influence on impulse propagation is speculative. The modulation by gap junction channels is most prominent in tissues at the boundaries between cardiac tissues such as sinoatrial node-atrial muscle, atrioventricular node-His bundle, His bundle-bundle branch and Purkinje fibers-ventricular muscle. The data predict facilitation of orthodromic propagation. [ABSTRACT FROM AUTHOR]

The role of gap junction channels on cardiac impulse propagation is complex. This review focuses on the differential expression of connexins in the heart and the biophysical properties of gap junction channels under normal and disease conditions. Structural determinants of impulse propagation have been gained from biochemical and immunocytochemical studies performed on tissue extracts and intact cardiac tissue. These have defined the distinctive connexin coexpression patterns and relative levels in different cardiac tissues. Functional determinants of impulse propagation have emerged from electrophysiological experiments carried out on cell pairs. The static properties (channel number and conductance) limit the current flow between adjacent cardiomyocytes and thus set the basic conduction velocity. The dynamic properties (voltage-sensitive gating and kinetics of channels) are responsible for a modulation of the conduction velocity during propagated action potentials. The effect is moderate and depends on the type of Cx and channel. For homomeric-homotypic channels, the influence is small to medium; for homomeric-heterotypic channels, it is medium to strong. Since no data are currently available on heteromeric channels, their influence on impulse propagation is speculative. The modulation by gap junction channels is most prominent in tissues at the boundaries between cardiac tissues such as sinoatrial node-atrial muscle, atrioventricular node-His bundle, His bundle-bundle branch and Purkinje fibers-ventricular muscle. The data predict facilitation of orthodromic propagation. [ABSTRACT FROM AUTHOR]

Generation of terahertz (THz), and sub-THz, coherent waves has been demonstrated at room temperature in GaAs-AIGaAs 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. [ABSTRACT FROM AUTHOR]

Abstract: Background. – 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. Methods and results. – 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 (P <0.02). Immunoconfocal Cx40 signal measured by one antibody, designated S15C(R85), was lower in patients with sustained induced AF (0.013±0.009 μm2/μm2 vs. 0.024±0.010 μm2/μm2, P =0.005) and was negatively correlated with atrial conduction velocity during sinus rhythm (P <0.05). 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 (P <0.001) but not against different epitopes indicating variable exposure of C×40 epitopes. Conclusions. – 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. [Copyright &y& Elsevier]

Different combinations and relative quantities of three connexins—connexin43, connexin40 and connexin45—are expressed in different subsets of cardiomyocyte. In the healthy heart, gap junctions assembled from these different connexin combinations form the cell-to-cell pathways for the precisely orchestrated patterns of current flow that govern the normal heart rhythm. Remodelling of gap junction organization and connexin expression is a conspicuous feature of human heart disease in which there is an arrhythmic tendency. This remodelling may take the form of structural remodelling, involving disturbances in the distribution of gap junctions (i.e., disruption of the normal ordered pathways for cell-to-cell conduction), and remodelling of connexin expression, involving alteration in the amount or type of connexin(s) present. Most notable among quantitative alterations in connexin expression is a reduction in ventricular connexin43 levels in human congestive heart failure. By correlating data from studies in experimental animal models, gap junction and connexin remodelling emerges as a factor to be considered in understanding the pro-arrhythmic substrate characteristic of many forms of heart disease. However, our knowledge of the functional correlates of the specific patterns of multiple connexin expression found in different regions of the heart in health and disease remains rudimentary, and the development of new experimental cell models heralds advances in this area over the next few years. [Copyright &y& Elsevier]

We set out to develop an in vitro cell model in which connexins 43, 40 and 45 are co-expressed in the same combinations as found in different sub-types of cardiomyocyte in vivo , using inducible promoters of the Tet-Off and Ecdysone systems. In initial studies, a heterogeneous pattern of gene expression was observed. To achieve homogeneous expression, an Internal Ribosome Entry Site (IRES) sequence was employed, ensuring that a single mRNA coded for connexin and antibiotic resistance. We then constructed plasmids that combine the inducibility of the Tet-Off and Ecdysone systems with the homogeneous expression given by the IRES constructs. These were demonstrated to give inducible and homogeneous expression. By using the reporter gene, Enhanced Green Fluorescent Protein (EGFP), it was further shown in the Tet-Off system that expression of the transfected gene was modulated homogeneously in all cells when induction was repressed. The cell model is now at a suitable stage of development for investigation of the functional correlates of the distinctive connexin co-expression found in different regions of the heart. [ABSTRACT FROM AUTHOR]

Immunocytochemical investigations have previously shown that antibodies specific for mammal connexins labeled in situ rat and mouse brain gap junctions. However brain gap-junction proteins have neither been identified with certainty, nor purified. By immunoblotting, anti-peptide antibodies directed against rat heart connexin 43 (CX43) detect a major protein of 41 kDa in rat brain homogenates. The specificity of these antibodies made it possible to establish an affinity-chromatography purification procedure of the 41-kDa protein. Purified antibodies specific for the sequence SAEQNRMGQ (residues 314-322) of rat heart CX43 were covalently bound to a protein-A -- Sepharose-CL-4B matrix. Rat brain homogenates were recycled through the immunomatrix and the material specifically bound to the matrix was then competitively eluted with the peptide SAEQNRMGQY. Analysis by SDS/PAGE of eluates demonstrated that they contain a 41-kDa protein associated with low amounts of high-molecular-mass proteins. By immunoblotting, these proteins were shown to be specifically recognized by antibodies directed against residues 5-17, 55-56 and 314-322 of rat heart CX43. The NH2-terminal partial sequence for the 41-kDa protein was determined by microsequencing and shown to be similar to α1 connexins. This is the first successful purification of a junctional protein from brain tissue and provides direct evidence that the 41-kDa protein is a CX43 gene product. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

HeLa cells expressing wild-type connexin43, connexin40 or connexin45 and connexins fused with a V5/6-His tag to the carboxyl terminus (CT) domain (Cx43-tag, Cx40-tag, Cx45-tag) were used to study connexin expression and the electrical properties of gap junction channels. Immunoblots and immunolabeling indicated that tagged connexins are synthesized and targeted to gap junctions in a similar manner to their wild-type counterparts. Voltage-clamp experiments on cell pairs revealed that tagged connexins form functional channels. Comparison of multichannel and single-channel conductances indicates that tagging reduces the number of operational channels, implying interference with hemichannel trafficking, docking and/or channel opening. Tagging provoked connexin-specific effects on multichannel and single-channel properties. The Cx43-tag was most affected and the Cx45-tag, least. The modifications included (1) V(j)-sensitive gating of I(j) (V(j), gap junction voltage; I(j), gap junction current), (2) contribution and (3) kinetics of I(j) deactivation and (4) single-channel conductance. The first three reflect alterations of fast V(j) gating. Hence, they may be caused by structural and/or electrical changes on the CT that interact with domains of the amino terminus and cytoplasmic loop. The fourth reflects alterations of the ion-conducting pathway. Conceivably, mutations at sites remote from the channel pore, e.g., 6-His-tagged CT, affect protein conformation and thus modify channel properties indirectly. Hence, V5/6-His tagging of connexins is a useful tool for expression studies in vivo. However, it should not be ignored that it introduces connexin-dependent changes in both expression level and electrophysiological properties. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

Aims: Remodelling of gap junctions, involving reduction of total gap junction quantity and down-regulation of connexin43 (Cx43), contributes to the arrhythmic substrate in congestive heart failure. However, little is known of the underlying mechanisms. Recent studies from in vitro systems suggest that the connexin-interacting protein zonula occludens-1 (ZO-1) is a potential mediator of gap junction remodelling. We therefore examined the hypothesis that ZO-1 contributes to reduced expression of Cx43 gap junctions in congestive heart failure. [ABSTRACT FROM PUBLISHER]

HeLa cells expressing rat connexin43 (Cx43) and/or mouse Cx45 were studied with the dual voltage-clamp technique. Different types of cell pairs were established and their gap junction properties determined, i.show $132#e. the dependence of the instantaneous and steady-state conductances (gj,inst, gj,ss) on the transjunctional voltage (Vj) and the kinetics of inactivation of the gap junction current (Ij). Pairs of singly transfected cells showed homogeneous behaviour at both Vj polarities. Homotypic Cx43-Cx43 and Cx45-Cx45 cell pairs yielded distinct symmetrical functions gj,inst=f(Vj) and gj,ss=f(Vj). Heterotypic Cx43-Cx45 preparations exhibited asymmetric functions gj,inst=f(Vj) and gj,ss=f(Vj) suggesting that connexons Cx43 and Cx45 gate with positive and negative Vj, respectively. Preparations containing a singly (Cx43 or Cx45) or doubly (Cx43/45) transfected cell showed quasi-homogeneous behaviour at one Vj polarity and heterogeneous behaviour at the other polarity. The former yielded Boltzmann parameters intermediate between those of Cx43-Cx43, Cx45-Cx45 and Cx43-Cx45 preparations; the latter could not be explained by homotypic and heterotypic combinations of homomeric connexons. Each pair of doubly transfected cells (Cx43/Cx45) yielded unique functions gj,inst=f(Vj) and gj,ss=f(Vj). This can not be explained by combinations of homomeric connexons. We conclude that Cx43 and Cx45 form homomeric-homotypic, homomeric-heterotypic channels as well as heteromeric-homotypic and heteromeric-heterotypic channels. This has implications for the impulse propagation in specific areas of the heart. [ABSTRACT FROM AUTHOR]

Gap junctions, assembled from connexins, 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, connexin40 and connexin45 are found in distinctive combinations and relative quantities in different, functionally specialized subsets of cardiomyocyte. Alterations of gap junction organization and connexin expression are now well established as a consistent feature of human heart disease in which there is an arrhythmic tendency. These alterations may take the form of structural remodelling, involving disturbances in the distribution of gap junctions and/or alteration of the amount or type of connexin(s) expressed. In the diseased ventricles, the most consistent quantitative alteration involves heterogeneous reduction in connexin43 expression. In the atria, features of gap organization and connexin expression have been implicated in the initiation of atrial fibrillation and, once the condition becomes chronic, gap junction alterations associated with remodelling may contribute to persistence of the condition. By correlating data from studies on the human patient with those from animal and cell models, alterations in gap junctions and connexins have emerged as important factors to be considered in understanding the pro-arrhythmic substrate found in a variety of forms of heart disease. [Copyright &y& Elsevier]

Fibrillation is the most common arrhythmia observed in clinical practice. Understanding of the mechanisms underlying its initiation and maintenance remains incomplete. Functional re-entries are potential drivers of the arrhythmia. Two main concepts are still debated, the “leading circle” and the “spiral wave or rotor” theories. The homogeneous subclone of the HL1 atrial-derived cardiomyocyte cell line, HL1-6, spontaneously exhibits re-entry on a microscopic scale due to its slow conduction velocity and the presence of triggers, making it possible to examine re-entry at the cellular level. We therefore investigated the re-entry cores in cell monolayers through the use of fluorescence optical mapping at high spatiotemporal resolution in order to obtain insights into the mechanisms of re-entry. Re-entries in HL1-6 myocytes required at least two triggers and a minimum colony area to initiate (3.5 to 6.4 mm 2 ). After electrical activity was completely stopped and re-started by varying the extracellular K + concentration, re-entries never returned to the same location while 35% of triggers re-appeared at the same position. A conduction delay algorithm also allows visualisation of the core of the re-entries. This work has revealed that the core of re-entries is conduction blocks constituted by lines and/or groups of cells rather than the round area assumed by the other concepts of functional re-entry. This highlights the importance of experimentation at the microscopic level in the study of re-entry mechanisms. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article presents an obituary for physicist Hui-Chun Liu, known for his research on semiconductor quantum devices.

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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]

The relation between free-carrier absorption and intersubband transitions in semiconductor heterostructures is resolved by comparing a sequence of structures. Our numerical and analytical results show how free-carrier absorption evolves from the intersubband transitions in the limit of infinite number of wells with vanishing barrier width. It is explicitly shown that the integral of the absorption over frequency matches the value obtained by the f-sum rule. This shows that a proper treatment of intersubband transitions is fully sufficient to simulate the entire electronic absorption in heterostructure THz devices. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

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 μm thick to 140 μm 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. [ABSTRACT FROM AUTHOR]

In the human heart, ventricular myocytes express connexin43 (Cx43) and traces of Cx45. In congestive heart failure, Cx43 levels decrease, Cx45 levels increase and gap junction size decreases. To determine whether alterations of connexin coexpression ratio influence gap junction size, we engineered a rat liver epithelial cell line that endogenously expresses Cx43 to coexpress inducible levels of Cx45 under stimulation of the insect hormone, ponasterone A. In cells induced to express Cx45, gap junction sizes are significantly reduced (by 15% to 20%; p < 0.001), an effect that occurs despite increased levels of junctional connexons made from both connexins. In contrast, coexpression of Cx40 with Cx43 does not lead to any change in gap junction size. These results are consistent with the idea that increased Cx45 expression in the failing ventricle contributes to decreased gap junction size. [ABSTRACT FROM AUTHOR]

Abstract: Transition of arterial smooth muscle cells from the contractile to the synthetic phenotype in vivo is associated with up-regulation of the gap-junctional protein, connexin43 (Cx43). However, the role of increased Cx43 expression in relation to the characteristic features of the synthetic phenotype – altered growth, differentiation or synthetic activity – has not previously been defined. In the present study, growth was induced in cultured human aortic smooth muscle cells by treatment with thrombin and with PDGF-bb; growth arrest was induced by serum deprivation and contact inhibition. Alterations in Cx43 expression and gap-junctional communication were analyzed in relation to expression of markers for contractile differentiation and extracellular matrix synthesis. Treatment with thrombin, but not PDGF-bb, led to up-regulation of Cx43 gap junctions, increased synthetic activity yet also enhanced contractile differentiation. Inhibition of growth by deprivation of serum growth factors in sub-confluent cultures had no effect on Cx43 expression or contractile differentiation. Growth arrest by contact inhibition led to progressive reduction in Cx43 expression, in parallel with progressive increase in expression of differentiation markers but no alteration in synthetic activity. Of a range of stimuli examined, only thrombin had the combined effect of increasing Cx43 gap-junction communication, growth and synthesis, yet it also enhanced contractile differentiation. Down-regulation of Cx43 and improved contractile differentiation occurred only when growth arrest was induced through the contact–inhibition pathway, though, in this instance, synthesis remained undiminished. We conclude that Cx43 levels, though having common correlates, are not exclusively linked to the cell phenotype or the state of growth. [Copyright &y& Elsevier]

Abstract: 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-β1 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-β1 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-β1 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 α-1(I) and α1(III) procollagen transcripts, contractile differentiation was assessed by immunoconfocal microscopy and Western blotting of the markers smooth muscle α-actin, calponin and smooth muscle heavy chain isoform 1 (SM1), and growth was measured by BrdU incorporation. Our results demonstrate that TGF-β1 significantly up-regulates Cx43 expression and intercellular communication, in concert with increased expression of α-actin, calponin and SM1. Concomitant with contractile protein expression, ECM synthesis was increased rather than decreased, TGF-β1 inducing a significant up-regulation of both procollagen transcripts. These effects were independent of growth. We conclude that in human aortic SMCs, TGF-β1 treatment leads to up-regulation of Cx43-mediated gap-junctional communication and increased synthetic activity yet, somewhat paradoxically, also enhanced contractile differentiation. [Copyright &y& Elsevier]