Concentration-dependent mobility in organic field-effect transistors probed by infrared spectromicroscopy of the charge density profile

We show that infrared imaging of the charge density profile in organic field-effect transistors (FETs) can probe transport characteristics which are difficult to access by conventional contact-based measurements. Specifically, we carry out experiments and modeling of infrared spectromicroscopy of poly(3-hexylthiophene) (P3HT) FETs in which charge injection is affected by a relatively low resistance of the gate insulators. We conclude that the mobility of P3HT has a power-law density dependence, which is consistent with the activated transport in disorder-induced tails of the density of states.Comment: 3+ pages, 2 figure

Multi-tasking Sulf1/Sulf2 enzymes do not only facilitate extracellular cell signalling but also participate in cell cycle related nuclear events

This study demonstrates highly dynamic spatial and temporal pattern of SULF1/SULF2 expression in a number of neuronal cell types growing in normal culture medium that included their transient nuclear mobilisation. Their nuclear translocation became particularly apparent during cell proliferation as both SULF1/SULF2 demonstrated not only cell membrane associated expression, their known site of function but also transient nuclear mobilisation during nuclear cell division. Nuclear localisation was apparent not only by immunocytochemical staining but also confirmed by immunoblotting staining of isolated nuclear fractions of C6, U87 and N2A cells. Immunocytochemical analysis demonstrated rapid nuclear exit of both SULF1/SULF2 following cell division that was slightly delayed but not blocked in a fraction of the polyploid cells observed in C6 cells. The overexpression of both Sulf1 and Sulf2 genes in C6 and U87 cells markedly promoted in vitro growth of these cells accompanied by nuclear mobilisation while inhibition of both these genes inhibited cell proliferation with little or no nuclear SULF1/SULF2 mobilisation. SULF1/SULF2 activity in these cells thus demonstrated a clear co-ordination of extracellular cell signalling with nuclear events related to cell proliferation

Effect of Baseline Subretinal Fluid on Treatment Outcomes in VIVID-DME and VISTA-DME Studies

Purpose To evaluate the effect of baseline subretinal fluid (SRF) on treatment outcomes with intravitreal aflibercept injection (IAI) versus laser treatment in patients with diabetic macular edema (DME) in the VIVID and VISTA studies. Design Post hoc analysis of 2 randomized controlled trials. Participants Eight hundred seventy-two patients with DME. Methods We randomized patients to receive IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 monthly doses (2q8), or laser. Main Outcome Measures Effect of presence or absence of baseline SRF on visual outcomes in the integrated dataset at weeks 52 and 100. Results Mean best-corrected visual acuity (BCVA) gains in the 2q4, 2q8, and laser arms at week 52 were +14.5, +11.0, and –2.3 letters, respectively, (those with baseline SRF) and +10.3, +10.6, and +2.5 letters, respectively, (those without). At week 100, mean gains were +13.5, +10.9, and −2.3 letters (those with baseline SRF) and +10.6, +10.0, and +2.7 letters (those without). The treatment effect for IAI versus laser from baseline to week 52 of 100 was greater for patients with baseline SRF versus those without (nominal P Conclusions This post hoc analysis demonstrated the visual outcome benefits of IAI over laser, regardless of baseline SRF status. A greater treatment effect of IAI was observed in patients with baseline SRF versus those without; however, no meaningful impact of baseline SRF status on treatment outcomes with IAI was demonstrated, indicating that the differential effects of laser might have been the driving force behind the different treatment outcomes in both groups

Infrared signatures of high carrier densities induced in semiconducting poly(3-hexylthiophene) by fluorinated organosilane molecules

We report on infrared (IR) absorption and dc electrical measurements of thin films of poly(3-hexylthiophene) (P3HT) that have been modified by a fluoroalkyl trichlorosilane (FTS). Spectra for FTS-treated films were compared to data for electrostatically-doped P3HT in an organic field-effect transistor (OFET). The appearance of a prominent polaron band in mid-IR absorption data for FTS-treated P3HT supports the assertion of hole doping via a charge-transfer process between FTS molecules and P3HT. In highly-doped films with a significantly enhanced polaron band, we find a monotonic Drude-like absorption in the far-IR, signifying delocalized states. Utilizing a simple capacitor model of an OFET, we extracted a carrier density for FTS-treated P3HT from the spectroscopic data. With carrier densities reaching 10$^{14}$ holes/cm$^2$, our results demonstrate that FTS doping provides a unique way to study the metal-insulator transition in polythiophenes

Reversible and Irreversible Interactions of Poly(3-hexylthiophene) with Oxygen Studied by Spin-Sensitive Methods

Understanding of degradation mechanisms in polymer:fullerene bulk-heterojunctions on the microscopic level aimed at improving their intrinsic stability is crucial for the breakthrough of organic photovoltaics. These materials are vulnerable to exposure to light and/or oxygen, hence they involve electronic excitations. To unambiguously probe the excited states of various multiplicities and their reactions with oxygen, we applied combined magneto-optical methods based on multifrequency (9 and 275 GHz) electron paramagnetic resonance (EPR), photoluminescence (PL), and PL-detected magnetic resonance (PLDMR) to the conjugated polymer poly(3-hexylthiophene) (P3HT) and polymer:fullerene bulk heterojunctions (P3HT:PCBM; PCBM = [6,6]-phenyl-C61-butyric acid methyl ester). We identified two distinct photochemical reaction routes, one being fully reversible and related to the formation of polymer:oxygen charge transfer complexes, the other one, irreversible, being related to the formation of singlet oxygen under participation of bound triplet excitons on the polymer chain. With respect to the blends, we discuss the protective effect of the methanofullerenes on the conjugated polymer bypassing the triplet exciton generation

Mitochondria form cholesterol-rich contact sites with the nucleus during retrograde response

Cholesterol metabolism is pivotal to cellular homeostasis, hormones production, and membranes composition. Its dysregulation associates with malignant reprogramming and therapy resistance. Cholesterol is trafficked into the mitochondria for steroidogenesis by the transduceome protein complex, which assembles on the outer mitochondrial membrane (OMM). The highly conserved, cholesterol-binding, stress-reactive, 18kDa translocator protein (TSPO), is a key component of this complex. Here, we modulate TSPO to study the process of mitochondrial retrograde signalling with the nucleus, by dissecting the role played by cholesterol and its oxidized forms. Using confocal and ultrastructural imaging, we describe that TSPO enriched mitochondria, remodel around the nucleus, gathering in cholesterol-enriched domains (or contact sites). This communication is controlled by HMG-CoA reductase inhibitors (statins), molecular and pharmacological regulation of TSPO. The described Nucleus-Associated Mitochondria (NAM) seem to be implementing survival signalling in aggressive forms of breast cancer. This work therefore provides the first evidence for a functional and bio-mechanical tethering between mitochondria and nucleus, as being the basis of pro-survival mechanisms, thus establishing a new paradigm in cross-organelle communication via cholesterol re-distribution

Electrochemically Top Gated Graphene: Monitoring Dopants by Raman Scattering

We demonstrate electrochemical top gating of graphene by using a solid polymer electrolyte. This allows to reach much higher electron and hole doping than standard back gating. In-situ Raman measurements monitor the doping. The G peak stiffens and sharpens for both electron and hole doping, while the 2D peak shows a different response to holes and electrons. Its position increases for hole doping, while it softens for high electron doping. The variation of G peak position is a signature of the non-adiabatic Kohn anomaly at $\Gamma$. On the other hand, for visible excitation, the variation of the 2D peak position is ruled by charge transfer. The intensity ratio of G and 2D peaks shows a strong dependence on doping, making it a sensitive parameter to monitor charges.Comment: 7 pages, 8 figure

Extracellular Sulfatases, Elements of the Wnt Signaling Pathway, Positively Regulate Growth and Tumorigenicity of Human Pancreatic Cancer Cells

BACKGROUND: Heparan sulfate proteoglycans (HSPGs) are control elements in Wnt signaling, which bind extracellularly to Wnt ligands and regulate their ability to interact with signal transduction receptors on the cell surface. Sulf-1 and Sulf-2 are novel extracellular sulfatases that act on internal glucosamine-6-sulfate (6S) modifications within HSPGs and thereby modulate HSPG interactions with various signaling molecules, including Wnt ligands. Emerging evidence indicates the importance of reactivated Wnt signaling in a number of cancers, including pancreatic adenocarcinoma. PRINCIPLE FINDINGS: Both Sulf proteins were upregulated in human pancreatic adenocarcinoma tumors and were broadly expressed in human pancreatic adenocarcinoma cell lines. Expression of human extracellular sulfatases Sulf-1 and Sulf-2 enhanced Wnt signaling in a reconstituted system. Three of four pancreatic adenocarcinoma cell lines tested exhibited autocrine Wnt signaling, in that extracellular Wnt ligands were required to initiate downstream Wnt signaling. Exposure of these pancreatic adenocarcinoma cells to a catalytically inactive form of Sulf-2 or siRNA-mediated silencing of endogenous Sulf-2 inhibited both Wnt signaling and cell growth. Sulf-2 silencing in two of these lines resulted in markedly reduced tumorigenesis in immunocompromised mice. CONCLUSIONS/SIGNIFICANCE: We have identified the Sulfs as potentiators of autocrine Wnt signaling in pancreatic cancer cells and have demonstrated their contribution to the growth and tumorigenicity of these cells. Since the Sulfs are extracellular enzymes, they would be attractive targets for therapy of pancreatic cancer. Our results run counter to the prevailing view in the literature that the Sulfs are negative regulators of tumorigenesis