Polymeric Squaraine Dyes as Electron Donors in Bulk Heterojunction Solar Cells

A polysquaraine low band gap polymer was synthesized by Yamamoto coupling of a monomeric dibromo indolenine squaraine dye. The resulting polymer has a weight average molar mass in the order of Mw ~30.000-50.000 and a polydispersity of ca. 1.7 as determined by gel-permeation chromatography (GPC). The electronic properties of monomer and polymer were investigated by cyclic voltammetry, absorption and emission spectroscopy. Owing to exciton coupling the absorption bands of the polymer are red-shifted and strongly broadened compared to the monomer squaraine dye. Bulk heterojunction solar cells were prepared from blends of the polysquaraine with the fullerene derivative [6,6]-phenyl C61-butyric acid methyl ester (PCBM) in different weight ratios (1:3 to 1:1). The power conversion efficiencies under simulated AM 1.5 conditions yielded 0.45 % for these non-optimized systems. The external quantum efficiency (EQE) shows that the photoresponse spans the range from 300 to 850 nm, which illustrates the promising properties of this novel organic semiconductor as a low band gap donor material in organic photovoltaics.Comment: 10 pages, 7 figure

Location-Specific Epigenetic Regulation of the Metallothionein 3 Gene in Esophageal Adenocarcinomas

Metallothionein 3 (MT3) maintains intracellular metal homeostasis and protects against reactive oxygen species (ROS)-induced DNA damage. In this study, we investigated the epigenetic alterations and gene expression of the MT3 gene in esophageal adenocarcinomas (EACs).Using quantitative bisulfite pyrosequencing, we detected unique DNA methylation profiles in the MT3 promoter region. The CpG nucleotides from -372 to -306 from the transcription start site (TSS) were highly methylated in tumor (n = 64) and normal samples (n = 51), whereas CpG nucleotides closest to the TSS (-4 and +3) remained unmethylated in all normal and most tumor samples. Conversely, CpG nucleotides in two regions (from -139 to -49 and +296 to +344) were significantly hypermethylated in EACs as compared to normal samples [FDR<0.001, -log10(FDR)>3.0]. The DNA methylation levels from -127 to -8 CpG sites showed the strongest correlation with MT3 gene expression (r = -0.4, P<0.0001). Moreover, the DNA hypermethylation from -127 to -8 CpG sites significantly correlated with advanced tumor stages and lymph node metastasis (P = 0.005 and P = 0.0313, respectively). The ChIP analysis demonstrated a more repressive histone modification (H3K9me2) and less active histone modifications (H3K4me2, H3K9ace) in OE33 cells than in FLO-1 cells; concordant with the presence of higher DNA methylation levels and silencing of MT3 expression in OE33 as compared to FLO-1 cells. Treatment of OE33 cells with 5-Aza-deoxycitidine restored MT3 expression with demethylation of its promoter region and reversal of the histone modifications towards active histone marks.In summary, EACs are characterized by frequent epigenetic silencing of MT3. The choice of specific regions in the CpG island is a critical step in determining the functional role and prognostic value of DNA methylation in cancer cells

Lepton Flavor Non-Conservation

In the present work we review the most prominent lepton flavor violating processes (\mu \ra e\gamma, \mu \ra 3e, $(\mu , e)$ conversion, $M-\bar M$ oscillations etc), in the context of unified gauge theories. Many currently fashionable extensions of the standard model are considered, such as: {\it i)} extensions of the fermion sector (right-handed neutrino); {\it ii)} minimal extensions involving additional Higgs scalars (more than one isodoublets, singly and doubly charged isosinglets, isotriplets with doubly charged members etc.); {\it iii)} supersymmetric or superstring inspired unified models emphasizing the implications of the renormalization group equations in the leptonic sector. Special attention is given to the experimentaly most interesting $(\mu - e)$ conversion in the presence of nuclei. The relevant nuclear aspects of the amplitudes are discussed in a number of fashionable nuclear models. The main features of the relevant experiments are also discussed, and detailed predictions of the above models are compared to the present experimental limits.Comment: (IOA-300/93, review article, 83p, 6 epsf figures , available upon request from [email protected])

Anatomy of the high-frequency ambient seismic wave field at the TCDP borehole.

International audienceThe Taiwan Chelungpu-fault Drilling Project (TCDP) installed a vertical seismic array between 950 and 1270 m depth in an active thrust fault environment. In this paper we analyze continuous noise records of the TCDP array between 1 and 16 Hz. We apply multiple array processing and noise correlation techniques to study the noise source process, properties of the propagation medium, and the ambient seismic wave field. Diurnal amplitude and slowness patterns suggest that noise is generated by cultural activity. The vicinity of the recording site to the excitation region, indicated by a narrow azimuthal distribution of propagation directions, leads to a predominant ballistic propagation regime. This is evident from the compatibility of the data with an incident plane wave model, polarized direct arrivals of noise correlation functions, and the asymmetric arrival shape. Evidence for contributions from scattering comes from equilibrated earthquake coda energy ratios, the frequency dependent randomization of propagation directions, and the existence of correlation coda waves. We conclude that the ballistic and scattered propagation regime coexist, where the first regime dominates the records, but the second is weaker yet not negligible. Consequently, the wave field is not equipartitioned. Correlation signal-to-noise ratios indicate a frequency dependent noise intensity. Iterations of the correlation procedure enhance the signature of the scattered regime. Discrepancies between phase velocities estimated from correlation functions and in-situ measurements are associated with the array geometry and its relative orientation to the predominant energy flux. The stability of correlation functions suggests their applicability in future monitoring efforts

Metallothionein in human oesophagus, Barrett's epithelium and adenocarcinoma

The potential of the metal-binding protein, metallothionein, in assessing the progression of normal oesophagus through Barrett's to adenocarcinoma was investigated. Metallothionein was quantitatively determined in resected tissues from patients undergoing oesophagectomy for high grade dysplasia/adenocarcinoma and in biopsies from patients with Barrett's syndrome. In 10 cancer patients, metallothionein concentrations in adenocarcinoma were not significantly different from normal oesophagus, although six had elevated metallothionein concentrations in the metaplastic tissue bordering the adenocarcinoma. In 17 out of 20 non-cancer patients with Barrett's epithelium, metallothionein was significantly increased by 108% (P<0.004). There was no association between the metallothionein levels in Barrett's epithelium and the presence of inflammatory cells, metaplasia or dysplasia. Metallothionein is a marker of progression from normal to Barrett's epithelium but is not increased in oesophageal adenocarcinoma

Propagating Cell-Membrane Waves Driven by Curved Activators of Actin Polymerization

Cells exhibit propagating membrane waves which involve the actin cytoskeleton. One type of such membranal waves are Circular Dorsal Ruffles (CDR) which are related to endocytosis and receptor internalization. Experimentally, CDRs have been associated with membrane bound activators of actin polymerization of concave shape. We present experimental evidence for the localization of convex membrane proteins in these structures, and their insensitivity to inhibition of myosin II contractility in immortalized mouse embryo fibroblasts cell cultures. These observations lead us to propose a theoretical model which explains the formation of these waves due to the interplay between complexes that contain activators of actin polymerization and membrane-bound curved proteins of both types of curvature (concave and convex). Our model predicts that the activity of both types of curved proteins is essential for sustaining propagating waves, which are abolished when one type of curved activator is removed. Within this model waves are initiated when the level of actin polymerization induced by the curved activators is higher than some threshold value, which allows the cell to control CDR formation. We demonstrate that the model can explain many features of CDRs, and give several testable predictions. This work demonstrates the importance of curved membrane proteins in organizing the actin cytoskeleton and cell shape

Direct multiplex imaging and optogenetics of Rho GTPases enabled by near-infrared FRET

Direct visualization and light control of several cellular processes is a challenge, owing to the spectral overlap of available genetically encoded probes. Here we report the most red-shifted monomeric near-infrared (NIR) fluorescent protein, miRFP720, and the fully NIR Forster resonance energy transfer (FRET) pair miRFP670-miRFP720, which together enabled design of biosensors compatible with CFP-YFP imaging and blue-green optogenetic tools. We developed a NIR biosensor for Rac1 GTPase and demonstrated its use in multiplexed imaging and light control of Rho GTPase signaling pathways. Specifically, we combined the Rac1 biosensor with CFP-YFP FRET biosensors for RhoA and for Rac1-GDI binding, and concurrently used the LOV-TRAP tool for upstream Rac1 activation. We directly observed and quantified antagonism between RhoA and Rac1 dependent on the RhoA-downstream effector ROCK; showed that Rac1 activity and GDI binding closely depend on the spatiotemporal coordination between these two molecules; and simultaneously observed Rac1 activity during optogenetic manipulation of Rac1.Peer reviewe

Theoretical Model for Cellular Shapes Driven by Protrusive and Adhesive Forces

The forces that arise from the actin cytoskeleton play a crucial role in determining the cell shape. These include protrusive forces due to actin polymerization and adhesion to the external matrix. We present here a theoretical model for the cellular shapes resulting from the feedback between the membrane shape and the forces acting on the membrane, mediated by curvature-sensitive membrane complexes of a convex shape. In previous theoretical studies we have investigated the regimes of linear instability where spontaneous formation of cellular protrusions is initiated. Here we calculate the evolution of a two dimensional cell contour beyond the linear regime and determine the final steady-state shapes arising within the model. We find that shapes driven by adhesion or by actin polymerization (lamellipodia) have very different morphologies, as observed in cells. Furthermore, we find that as the strength of the protrusive forces diminish, the system approaches a stabilization of a periodic pattern of protrusions. This result can provide an explanation for a number of puzzling experimental observations regarding cellular shape dependence on the properties of the extra-cellular matrix

Methods for the guideline-based development of quality indicators--a systematic review

<p>Abstract</p> <p>Background</p> <p>Quality indicators (QIs) are used in many healthcare settings to measure, compare, and improve quality of care. For the efficient development of high-quality QIs, rigorous, approved, and evidence-based development methods are needed. Clinical practice guidelines are a suitable source to derive QIs from, but no gold standard for guideline-based QI development exists. This review aims to identify, describe, and compare methodological approaches to guideline-based QI development.</p> <p>Methods</p> <p>We systematically searched medical literature databases (Medline, EMBASE, and CINAHL) and grey literature. Two researchers selected publications reporting methodological approaches to guideline-based QI development. In order to describe and compare methodological approaches used in these publications, we extracted detailed information on common steps of guideline-based QI development (topic selection, guideline selection, extraction of recommendations, QI selection, practice test, and implementation) to predesigned extraction tables.</p> <p>Results</p> <p>From 8,697 hits in the database search and several grey literature documents, we selected 48 relevant references. The studies were of heterogeneous type and quality. We found no randomized controlled trial or other studies comparing the ability of different methodological approaches to guideline-based development to generate high-quality QIs. The relevant publications featured a wide variety of methodological approaches to guideline-based QI development, especially regarding guideline selection and extraction of recommendations. Only a few studies reported patient involvement.</p> <p>Conclusions</p> <p>Further research is needed to determine which elements of the methodological approaches identified, described, and compared in this review are best suited to constitute a gold standard for guideline-based QI development. For this research, we provide a comprehensive groundwork.</p

Cell motility: the integrating role of the plasma membrane

The plasma membrane is of central importance in the motility process. It defines the boundary separating the intracellular and extracellular environments, and mediates the interactions between a motile cell and its environment. Furthermore, the membrane serves as a dynamic platform for localization of various components which actively participate in all aspects of the motility process, including force generation, adhesion, signaling, and regulation. Membrane transport between internal membranes and the plasma membrane, and in particular polarized membrane transport, facilitates continuous reorganization of the plasma membrane and is thought to be involved in maintaining polarity and recycling of essential components in some motile cell types. Beyond its biochemical composition, the mechanical characteristics of the plasma membrane and, in particular, membrane tension are of central importance in cell motility; membrane tension affects the rates of all the processes which involve membrane deformation including edge extension, endocytosis, and exocytosis. Most importantly, the mechanical characteristics of the membrane and its biochemical composition are tightly intertwined; membrane tension and local curvature are largely determined by the biochemical composition of the membrane and the biochemical reactions taking place; at the same time, curvature and tension affect the localization of components and reaction rates. This review focuses on this dynamic interplay and the feedbacks between the biochemical and biophysical characteristics of the membrane and their effects on cell movement. New insight on these will be crucial for understanding the motility process