Highly Conducting pi-Conjugated Molecular Junctions Covalently Bonded to Gold Electrodes

We measure electronic conductance through single conjugated molecules bonded to Au metal electrodes with direct Au-C covalent bonds using the scanning tunneling microscope based break-junction technique. We start with molecules terminated with trimethyltin end groups that cleave off in situ resulting in formation of a direct covalent sigma bond between the carbon backbone and the gold metal electrodes. The molecular carbon backbone used in this study consist of a conjugated pi-system that has one terminal methylene group on each end, which bonds to the electrodes, achieving large electronic coupling of the electrodes to the pi-system. The junctions formed with the prototypical example of 1,4-dimethylenebenzene show a conductance approaching one conductance quantum (G0 = 2e2/h). Junctions formed with methylene terminated oligophenyls with two to four phenyl units show a hundred-fold increase in conductance compared with junctions formed with amine-linked oligophenyls. The conduction mechanism for these longer oligophenyls is tunneling as they exhibit an exponential dependence of conductance with oligomer length. In addition, density functional theory based calculations for the Au-xylylene-Au junction show near-resonant transmission with a cross-over to tunneling for the longer oligomers.Comment: Accepted to the Journal of the American Chemical Society as a Communication

Reversal of TGF-β1 stimulation of α-smooth muscle actin and extracellular matrix components by cyclic AMP in Dupuytren's - derived fibroblasts

<p>Abstract</p> <p>Background</p> <p>Myofibroblasts, a derived subset of fibroblasts especially important in scar formation and wound contraction, have been found at elevated levels in affected Dupuytren's tissues. Transformation of fibroblasts to myofibroblasts is characterized by expression of alpha- smooth muscle actin (α-SMA) and increased production of extracellular matrix (ECM) components, both events of relevance to connective tissue remodeling. We propose that increasing the activation of the cyclic AMP (cAMP)/protein kinase A signaling pathway will inhibit transforming growth factor-beta1 (TGF-β₁)-induced ECM synthesis and myofibroblast formation and may provide a means to blunt fibrosis.</p> <p>Methods</p> <p>Fibroblasts derived from areas of Dupuytren's contracture cord (DC), from adjacent and phenotypically normal palmar fascia (PF), and from palmar fascia from patients undergoing carpal tunnel release (CTR; CT) were treated with TGF-β₁(2 ng/ml) and/or forskolin (10 μM) (a known stimulator of cAMP). Total RNA and protein extracted was subjected to real time RT-PCR and Western blot analysis.</p> <p>Results</p> <p>The basal mRNA expression levels of fibronectin- extra domain A (FN1-EDA), type I (COL1A2) and type III collagen (COL3A1), and connective tissue growth factor (CTGF) were all significantly increased in DC- and in PF-derived cells compared to CT-derived fibroblasts. The TGF-β₁stimulation of α-SMA, CTGF, COL1A2 and COL3A1 was greatly inhibited by concomitant treatment with forskolin, especially in DC-derived cells. In contrast, TGF-β₁stimulation of FN1-EDA showed similar levels of reduction with the addition of forskolin in all three cell types.</p> <p>Conclusion</p> <p>In sum, increasing cAMP levels show potential to inhibit the formation of myofibroblasts and accumulation of ECM components. Molecular agents that increase cAMP may therefore prove useful in mitigating DC progression or recurrence.</p

Effect of Surfactants on the Structure and Morphology of Magnesium Borate Hydroxide Nanowhiskers Synthesized by Hydrothermal Route

Magnesium borate hydroxide (MBH) nanowhiskers were synthesized using a one step hydrothermal process with different surfactants. The effect surfactants have on the structure and morphology of the MBH nanowhiskers has been investigated. The X-ray diffraction profile confirms that the as-synthesized material is of single phase, monoclinic MgBO2(OH). The variations in the size and shape of the different MBH nanowhiskers have been discussed based on the surface morphology analysis. The annealing of MBH nanowhiskers at 500 °C for 4 h has significant effect on the crystal structure and surface morphology. The UV–vis absorption spectra of the MBH nanowhiskers synthesized with and without surfactants show enhanced absorption in the low-wavelength region, and their optical band gaps were estimated from the optical band edge plots. The photoluminescence spectra of the MBH nanowhiskers produced with and without surfactants show broad emission band with the peak maximum at around 400 nm, which confirms the dominant contribution from the surface defect states

Rapid and Efficient Clearance of Blood-borne Virus by Liver Sinusoidal Endothelium

The liver removes quickly the great bulk of virus circulating in blood, leaving only a small fraction to infect the host, in a manner characteristic of each virus. The scavenger cells of the liver sinusoids are implicated, but the mechanism is entirely unknown. Here we show, borrowing a mouse model of adenovirus clearance, that nearly all infused adenovirus is cleared by the liver sinusoidal endothelial cell (LSEC). Using refined immunofluorescence microscopy techniques for distinguishing macrophages and endothelial cells in fixed liver, and identifying virus by two distinct physicochemical methods, we localized adenovirus 1 minute after infusion mainly to the LSEC (∼90%), finding ∼10% with Kupffer cells (KC) and none with hepatocytes. Electron microscopy confirmed our results. In contrast with much prior work claiming the main scavenger to be the KC, our results locate the clearance mechanism to the LSEC and identify this cell as a key site of antiviral activity

The marine soundscape of the Perth Canyon

The Perth Canyon is a submarine canyon off Rottnest Island in Western Australia. It is rich in biodiversity in general, and important as a feeding and resting ground for great whales on migration. Australia's Integrated Marine Observing System (IMOS) has moorings in the Perth Canyon monitoring its acoustical, physical and biological oceanography. Data from these moorings, as well as weather data from a near-by Bureau of Meteorology weather station on Rottnest Island and ship traffic data from the Australian Maritime Safety Authority were correlated to characterise and quantify the marine soundscape between 5 and 3000. Hz, consisting of its geophony, biophony and anthrophony. Overall, biological sources are a strong contributor to the soundscape at the IMOS site, with whales dominating seasonally at low (15-100. Hz) and mid frequencies (200-400. Hz), and fish or invertebrate choruses dominating at high frequencies (1800-2500. Hz) at night time throughout the year. Ships contribute significantly to the 8-100. Hz band at all times of the day, all year round, albeit for a few hours at a time only. Wind-dependent noise is significant at 200-3000. Hz; winter rains are audible underwater at 2000-3000. Hz. We discuss how passive acoustic data can be used as a proxy for ocean weather. Passive acoustics is an efficient way of monitoring animal visitation times and relative densities, and potential anthropogenic influences

The nosological significance of Folie à Deux: a review of the literature

BACKGROUND: Folie à Deux is a rare syndrome that has attracted much clinical attention. There is increasing doubt over the essence of the condition and the validity of the original description, such that it remains an elusive entity difficult to define. METHOD: We conducted a systematic review of the literature of all cases reporting the phenomenon of Folie à Deux, from the years 1993–2005. RESULTS: 64 cases were identified of which 42 met the inclusion criteria. The diagnoses in the primary and secondary were more heterogeneous than current diagnostic criteria suggest. There exists a high degree of similarity between the primary and secondary in terms of susceptibility to psychiatric illness, family and past psychiatric history, than previously thought. CONCLUSION: Folie à Deux can occur in many situations outside the confines of the current classification systems and is not as rare as believed, and should alert the clinician to unrecognized psychiatric problems in the secondary

Modelling of redox flow battery electrode processes at a range of length scales : a review

In this article, the different approaches reported in the literature for modelling electrode processes in redox flow batteries (RFBs) are reviewed. RFB models vary widely in terms of computational complexity, research scalability and accuracy of predictions. Development of RFB models have been quite slow in the past, but in recent years researchers have reported on a range of modelling approaches for RFB system optimisation. Flow and transport processes, and their influence on electron transfer kinetics, play an important role in the performance of RFBs. Macro-scale modelling, typically based on a continuum approach for porous electrode modelling, have been used to investigate current distribution, to optimise cell design and to support techno-economic analyses. Microscale models have also been developed to investigate the transport properties within porous electrode materials. These microscale models exploit experimental tomographic techniques to characterise three-dimensional structures of different electrode materials. New insights into the effect of the electrode structure on transport processes are being provided from these new approaches. Modelling flow, transport, electrical and electrochemical processes within the electrode structure is a developing area of research, and there are significant variations in the model requirements for different redox systems, in particular for multiphase chemistries (gas–liquid, solid–liquid, etc.) and for aqueous and non-aqueous solvents. Further development is essential to better understand the kinetic and mass transport phenomena in the porous electrodes, and multiscale approaches are also needed to enable optimisation across the relevent length scales

The associated expression of Maspin and Bax proteins as a potential prognostic factor in intrahepatic cholangiocarcinoma

BACKGROUND: Maspin, a member of the serpin family, is a suppressor of tumor growth, an inhibitor of angiogenesis and an inducer of apoptosis. Maspin induces apoptosis by increasing Bax, a member of the Bcl-2 family of apoptosis-regulating proteins. In this exploratory study, we investigated the associated expression of Maspin and Bax proteins as a potential prognostic factor in intrahepatic cholangiocarcinoma (IHCCA). METHODS: Twenty-two paraffin-embedded samples were analyzed by immunohistochemical methods using Maspin, Bax and CD34 antibodies. Maspin was scored semiquantitatively (HSCORE). Apoptosis was assessed using an antibody against cleaved caspase-3. RESULTS: The strong relationship observed between the expression of Maspin and Bax, indicates that Bax is likely to be the key effector of Maspin-mediated induction of apoptosis as indicated by the activation of cleaved caspase-3. We categorized Maspin HSCORE by calculating the optimal cutpoint. A Maspin HSCORE above the cutpoint was inversely related with tumor dimension, depth of tumor and vascular invasion. Uni/multivariate analysis suggests that a Maspin HSCORE below the cutpoint significantly worsens the patients' prognosis. Tumors with Maspin HSCORE below the cutpoint had a shorter survival (11+/-5 months) than did patients with Maspin HSCORE above the cutpoint (27+/-4 months), whereas Kaplan-Meier analysis and logrank test showed no significant difference in overall survival between the patients. CONCLUSION: The associated expression of Maspin and Bax might delay tumor progression in IHCCA. Maspin above the cutpoint might counteract tumor development by increasing cell apoptosis, and by decreasing tumor mass and cell invasion. The combined expression of Maspin and Bax appears to influence the susceptibility of tumor cholangiocytes to apoptosis and thus may be involved in delaying IHCCA progression

Chaperonin Containing T-Complex Polypeptide Subunit Eta (CCT-eta) Is a Specific Regulator of Fibroblast Motility and Contractility

Integumentary wounds in mammalian fetuses heal without scar; this scarless wound healing is intrinsic to fetal tissues and is notable for absence of the contraction seen in postnatal (adult) wounds. The precise molecular signals determining the scarless phenotype remain unclear. We have previously reported that the eta subunit of the chaperonin containing T-complex polypeptide (CCT-eta) is specifically reduced in healing fetal wounds in a rabbit model. In this study, we examine the role of CCT-eta in fibroblast motility and contractility, properties essential to wound healing and scar formation. We demonstrate that CCT-eta (but not CCT-beta) is underexpressed in fetal fibroblasts compared to adult fibroblasts. An in vitro wound healing assay demonstrated that adult fibroblasts showed increased cell migration in response to epidermal growth factor (EGF) and platelet derived growth factor (PDGF) stimulation, whereas fetal fibroblasts were unresponsive. Downregulation of CCT-eta in adult fibroblasts with short inhibitory RNA (siRNA) reduced cellular motility, both basal and growth factor-induced; in contrast, siRNA against CCT-beta had no such effect. Adult fibroblasts were more inherently contractile than fetal fibroblasts by cellular traction force microscopy; this contractility was increased by treatment with EGF and PDGF. CCT-eta siRNA inhibited the PDGF-induction of adult fibroblast contractility, whereas CCT-beta siRNA had no such effect. In each of these instances, the effect of downregulating CCT-eta was to modulate the behavior of adult fibroblasts so as to more closely approximate the characteristics of fetal fibroblasts. We next examined the effect of CCT-eta modulation on alpha-smooth muscle actin (α-SMA) expression, a gene product well known to play a critical role in adult wound healing. Fetal fibroblasts were found to constitutively express less α-SMA than adult cells. Reduction of CCT-eta with siRNA had minimal effect on cellular beta-actin but markedly decreased α-SMA; in contrast, reduction of CCT-beta had minimal effect on either actin isoform. Direct inhibition of α-SMA with siRNA reduced both basal and growth factor-induced fibroblast motility. These results indicate that CCT-eta is a specific regulator of fibroblast motility and contractility and may be a key determinant of the scarless wound healing phenotype by means of its specific regulation of α-SMA expression