To investigate the effects of the phase state (ordered or disordered) of self-assembled monolayers (SAMs) on the growth mode of pentacene films and the performance of organic thin-film transistors (OTFTs), we deposited pentacene molecules on SAMs of octadecyltrichlorosilane (ODTS) with different alkyl-chain orientations at various substrate temperatures (30, 60, and 90 degrees C). We found that the SAM phase state played an important role in both cases. Pentacene films grown on relatively highly ordered SAMs were found to have a higher crystallinity and a better interconnectivity between the pentacene domains, which directly serves to enhance the field-effect mobility, than those grown on disordered SAMs. Furthermore, the differences in crystallinity and field-effect mobility between pentacene films grown on ordered and disordered substrates increased with increasing substrate temperature. These results can be possibly explained by (1) a quasi-epitaxy growth of the pentacene film on the ordered ODTS monolayer and (2) the temperature-dependent alkyl chain mobility of the ODTS monolayers.

Obtaining control over the supramolecular organization of electronically active p-conjugated polymers [1] would make it possible to fine-tune and optimize their electrical properties for applications in organic field-effect transistors (OFETs) [2][3][4][5] and sensors. [6,7] Typically, it is far more challenging to obtain high-quality single crystals of conjugated polymers by facile solution processing than oligomers [8] and small molecules, [9] which are prepared by vacuum processes. However, 1D, highquality, single-crystal semiconductors comparable to inorganic single crystals, such as silicon nanowires, have not hitherto been observed for conjugated polymers. Self-organized poly(3-hexylthiophene) (P3HT), [10][11][12][13][14][15][16][17][18] with its supramolecular 2D structure, is of special interest because the 1D electronic properties of the p-conjugated polymer chains are modified by the increased interchain stacking that results from p-p interactions. Therefore, the possibility of achieving good electrical performance as a result of 2D transport (i.e., band-like transport) in self-organized single-crystal P3HT has spurred its use in enhanced polymer electronic devices (PEDs). By better control of structural anisotropy, and by developing P3HT structures with strongly p-p interacting building blocks coinciding with the direction of current flow in PEDs, optimized electrical performance and, possibly, a truly delocalized transport regime may be attained. We report here the preparation and properties of high-quality, 1D single-crystal P3HT microwires grown by a facile self-assembly process in dilute solution. Figure 1 outlines the fabrication steps for the preparation of low-voltage, gate-modulated PEDs based on well-faceted, 1D single-crystal P3HT microwires. Dense octadecyltrichlorosilane (ODTS) self-assembled monolayers (SAMs) (structure shown in Fig. 1A) possessing sufficient robustness are used as the molecular dielectrics to reduce the operating voltage of COMMUNICATIONS

Recently, the use of solution-processable conjugated polymer semiconductors in thin-film transistors (TFTs) has been extensively studied because of their suitability for fabricating large-area devices using established solution-deposition techniques (e.g., spin-coating, screen printing, or inkjet printing). [1][2][3][4][5][6][7][8] An attractive feature of the solution process is that different materials can be easily blended to optimize the electronic and optoelectronic properties for device applications. [9][10][11] Blends of semiconducting and dielectric polymers can combine the optical and electrical properties of semiconductors with the characteristics of dielectric polymers. However, the use of these blends as active layers in TFTs always causes a decrease in the device performance because the dielectric polymer ''dilutes'' the current density. [12,13] Controlling the phase separation in the direction perpendicular to the substrate to form bilayer structures should be an effective way to diminish this effect because it allows retention of the connectivity of the semiconducting layer in the channel region. To this end, organic-semiconductor/dielectric-polymer blends with vertical phase separation have been used to fabricate high-performance TFTs with low operating voltage [14] or with improved environmental stability [15] at high semiconductor concentration (!40%). In a recent publication, [16] Goffri et al. reported that the concentration of semiconductor in crystalline/crystalline bicomponent semiconductor/dielectricpolymer systems can be reduced to a value as low as 3 wt % without any degradation in device performance. However, all structures reported in previous studies are dielectric-top and semiconductor-bottom structures. It would be very interesting to investigate a semiconductor-top and dielectric-bottom bilayer structure, because this structure is identical to the configuration of the semiconductor and dielectric layers in the bottom-gate TFT device. For this reason formation of a semiconductor-top and dielectric-bottom bilayer in a one-step process may provide a simple route for the fabrication of TFT devices.In the present Communication, we report for the first time the fabrication of a semiconductor-top and dielectric-bottom bilayer structure by means of surface-induced vertical phase separation of poly(3-hexylthiophene) (P3HT) and poly(methyl methacrylate) (PMMA) blends. Because the ultrathin and defect-free PMMA dielectric layer can act as blind material, a modifier at the semiconductor/dielectric interface, or a dielectric layer, these bilayer blends have versatile uses in TFTs.Films composed of P3HT/PMMA blends were fabricated by spin-casting chlorobenzene solutions of the polymers onto bare silicon substrates (see Fig. 1a, inset). Since the hydrophilicities of P3HT and PMMA are very different, water contact-angle measurements were carried out to determine qualitatively the changes in composition taking place on the surface of the blended films. The variation of the water contact angle as a ...

Effective treatment for glioblastoma (GBM) is limited by the presence of the blood–brain barrier (BBB) and rapid resistance to single agent therapies. To address these issues, we developed a transferrin-functionalized nanoparticle (Tf-NP) that can deliver dual combination therapies. Using intravital imaging, we show the ability of Tf-NPs to traverse intact BBB in mice as well as achieve direct tumor binding in two intracranial orthotopic models of GBM. Treatment of tumor-bearing mice with Tf-NPs loaded with temozolomide and the bromodomain inhibitor JQ1 leads to increased DNA damage and apoptosis that correlates with a 1.5- to 2-fold decrease in tumor burden and corresponding increase in survival compared to equivalent free-drug dosing. Immunocompetent mice treated with Tf-NP-loaded drugs also show protection from the effects of systemic drug toxicity, demonstrating the preclinical potential of this nanoscale platform to deliver novel combination therapies to gliomas and other central nervous system tumors.

New limits are presented on the cross section for weakly interacting massive particle (WIMP) nucleon scattering in the KIMS CsI(Tℓ) detector array at the Yangyang Underground Laboratory. The exposure used for these results is 24 524.3  kg·days. Nuclei recoiling from WIMP interactions are identified by a pulse shape discrimination method. A low energy background due to alpha emitters on the crystal surfaces is identified and taken into account in the analysis. The detected numbers of nuclear recoils are consistent with zero and 90% confidence level upper limits on the WIMP interaction rates are set for electron equivalent energies from 3 to 11 keV. The 90% upper limit of the nuclear recoil event rate for 3.6-5.8 keV corresponding to 2-4 keV in NaI(Tℓ) is 0.0098 counts/kg/keV/day, which is below the annual modulation amplitude reported by DAMA. This is incompatible with interpretations that enhance the modulation amplitude such as inelastic dark matter models. We establish the most stringent cross section limits on spin-dependent WIMP-proton elastic scattering for the WIMP masses greater than 20  GeV/c2.

Considerable attention has focused on the health-promoting effects of red wine and its nonflavonoid polyphenol compound resveratrol. However, the underlying molecular mechanisms and molecular target(s) of red wine or other potentially active ingredients in red wine remain unknown. Here, we report that red wine extract (RWE) or the red wine flavonoid quercetin inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced transformation of JB6 promotion-sensitive mouse skin epidermal (JB6 P+) cells. The activation of activator protein-1 and nuclear factor-KB induced by TPA was dose dependently inhibited by RWE or quercetin treatment. Western blot and kinase assay data revealed that RWE or quercetin inhibited mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) 1 and Raf1 kinase activities and subsequently attenuated TPAinduced phosphorylation of ERK/p90 ribosomal S6 kinase. Although either RWE or quercetin suppressed Raf1 kinase activity, they were more effective in inhibiting MEK1 activity. Importantly, quercetin exerted stronger inhibitory effects than PD098059, a well-known pharmacologic inhibitor of MEK. Resveratrol did not affect either MEK1 or Raf1 kinase activity. Pull-down assays revealed that RWE or quercetin (but not resveratrol) bound with either MEK1 or Raf1. RWE or quercetin also dose dependently suppressed JB6 P+ cell transformation induced by epidermal growth factor or H-Ras, both of which are involved in the activation of MEK/ ERK signaling. Docking data suggested that quercetin, but not resveratrol, formed a hydrogen bond with the backbone amide group of Ser 212 , which is the key interaction for stabilizing the inactive conformation of the activation loop of MEK1. [Cancer Res 2008;68(3):946-55]

Caffeic acid (3,4-dihydroxycinnamic acid) is a well-known phenolic phytochemical present in many foods, including coffee. Recent studies suggested that caffeic acid exerts anticarcinogenic effects, but little is known about the underlying molecular mechanisms and specific target proteins. In this study, we found that Fyn, one of the members of the non-receptor protein tyrosine kinase family, was required for ultraviolet (UV) B-induced cyclooxygenase-2 (COX-2) expression, and caffeic acid suppressed UVB-induced skin carcinogenesis by directly inhibiting Fyn kinase activity. Caffeic acid more effectively suppressed UVB-induced COX-2 expression and subsequent prostaglandin E 2 production in JB6 P1 mouse skin epidermal (JB6 P1) cells compared with chlorogenic acid (5-O-caffeoylquinic acid), an ester of caffeic acid with quinic acid. Data also revealed that caffeic acid more effectively induced the downregulation of COX-2 expression at the transcriptional level mediated through the inhibition of activator protein-1 (AP-1) and nuclear factor-kB transcription activity compared with chlorogenic acid. Fyn kinase activity was suppressed more effectively by caffeic acid than by chlorogenic acid, and downstream mitogen-activated protein kinases (MAPKs) were subsequently blocked. Pharmacological Fyn kinase inhibitor (3-(4-chlorophenyl)1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine and leflunomide) data also revealed that Fyn is involved in UVBinduced COX-2 expression mediated through the phosphorylation of MAPKs in JB6 P1 cells. Pull-down assays revealed that caffeic acid directly bound with Fyn and non-competitively with adenosine triphosphate. In vivo data from mouse skin also supported the idea that caffeic acid suppressed UVB-induced COX-2 expression by blocking Fyn kinase activity. These results suggested that this compound could act as a potent chemopreventive agent against skin cancer.

Luteolin, a flavonoid present in various vegetables including onion and broccoli, has been reported to possess anticarcinogenic effects. However, its chemopreventive effect on UV-induced skin cancer and its mechanism are not fully understood. Herein, we examined the chemopreventive effect and associated mechanisms of luteolin in the JB6 P+ cell line and the SKH-1 hairless mouse model. Luteolin suppressed UVB-induced cyclooxygenase-2 expression and activator protein-1 and nuclear factor-κB activity in JB6 P+ cells. Immunoblot and kinase assay data showed that luteolin attenuated protein kinase Cε (PKCε) and Src kinase activities and subsequently inhibited UVB-induced phosphorylation of mitogen-activated protein kinases and the Akt signaling pathway. In addition, pull-down assays revealed that luteolin binds directly to PKCε and Src in an ATP-competitive manner. Importantly, luteolin suppressed tumor incidence, multiplicity, and overall size in SKH-1 hairless mice. Analysis of the skin by immunohistochemistry and immunoblotting showed that luteolintreated groups had a substantial reduction in the levels of cyclooxygenase-2, tumor necrosis factor-α, and proliferating cell nuclear antigen compared with groups treated with only UVB. Further analysis using skin lysates showed that luteolin inhibited PKCε and Src kinase activity. Together, these data suggest that luteolin exerts potent chemopreventive activity against UVB-induced skin cancer mainly by targeting PKCε and Src.