Morphology control via dual solvent crystallization for high-mobility functionalized pentacene-blend thin film transistors

We present an approach to improving the performance of solution processed organic semiconductor transistors based on a dual solvent system. We here apply this to a blend containing the ?-conjugated small molecule 6,13 bis(triisopropylsilylethynyl) pentacene (TIPS-pentacene) and polystyrene, which acts as an inert binder. Using a semiconductor-binder solution of two solvents, where the main solvent is a better solvent of the small molecule and second solvent is a better solvent of the polymer, crystal morphologies can be altered and transistor mobilities increased by almost an order of magnitude. In this way, air-ambient and solution-processed transistors with linear and saturation mobilities higher than 1 cm2 V?1 s?1 have been fabricated. We discuss how the solubility properties of the formulation components can be used to identify solvent candidates that promote an efficient self-assembly of the small molecule

Potential therapeutic application of gold nanoparticles in B-chronic lymphocytic leukemia (BCLL): enhancing apoptosis

B-Chronic Lymphocytic Leukemia (CLL) is an incurable disease predominantly characterized by apoptosis resistance. We have previously described a VEGF signaling pathway that generates apoptosis resistance in CLL B cells. We found induction of significantly more apoptosis in CLL B cells by co-culture with an anti-VEGF antibody. To increase the efficacy of these agents in CLL therapy we have focused on the use of gold nanoparticles (GNP). Gold nanoparticles were chosen based on their biocompatibility, very high surface area, ease of characterization and surface functionalization. We attached VEGF antibody (AbVF) to the gold nanoparticles and determined their ability to kill CLL B cells. Gold nanoparticles and their nanoconjugates were characterized using UV-Visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS). All the patient samples studied (N = 7) responded to the gold-AbVF treatment with a dose dependent apoptosis of CLL B cells. The induction of apoptosis with gold-AbVF was significantly higher than the CLL cells exposed to only AbVF or GNP. The gold-AbVF treated cells showed significant down regulation of anti-apoptotic proteins and exhibited PARP cleavage. Gold-AbVF treated and GNP treated cells showed internalization of the nanoparticles in early and late endosomes and in multivesicular bodies. Non-coated gold nanoparticles alone were able to induce some levels of apoptosis in CLL B cells. This paper opens up new opportunities in the treatment of CLL-B using gold nanoparticles and integrates nanoscience with therapy in CLL. In future, potential opportunities exist to harness the optoelectronic properties of gold nanoparticles in the treatment of CLL

Fabrication and Characterization of Poly(Propylene Fumarate) Scaffolds with Controlled Pore Structures Using 3-Dimensional Printing and Injection Molding

Poly(propylene fumarate) (PPF) is an injectable, biodegradable polymer that has been used for fabricating preformed scaffolds in tissue engineering applications because of in situ crosslinking characteristics. Aiming for understanding the effects of pore structure parameters on bone tissue ingrowth, 3-dimensional (3D) PPF scaffolds with controlled pore architecture have been produced in this study from computer-aided design (CAD) models. We have created original scaffold models with 3 pore sizes (300, 600, and 900 µm) and randomly closed 0%, 10%, 20%, or 30% of total pores from the original models in 3 planes. PPF scaffolds were fabricated by a series steps involving 3D printing of support/build constructs, dissolving build materials, injecting PPF, and dissolving support materials. To investigate the effects of controlled pore size and interconnectivity on scaffolds, we compared the porosities between the models and PPF scaffolds fabricated thereby, examined pore morphologies in surface and cross-section using scanning electron microscopy, and measured permeability using the falling head conductivity test. The thermal properties of the resulting scaffolds as well as uncrosslinked PPF were determined by differential scanning calorimetry and thermogravimetric analysis. Average pore sizes and pore shapes of PPF scaffolds with 600- and 900-µm pores were similar to those of CAD models, but they depended on directions in those with 300-µm pores. Porosity and permeability of PPF scaffolds decreased as the number of closed pores in original models increased, particularly when the pore size was 300 µm as the result of low porosity and pore occlusion. These results show that 3D printing and injection molding technique can be applied to crosslinkable polymers to fabricate 3D porous scaffolds with controlled pore structures, porosity, and permeability using their CAD models

The Mesozoic along-strike tectono-metamorphic segmentation of Longmen Shan (eastern Tibetan plateau)

The Longmen Shan belt (eastern border of the Tibetan plateau) constitutes a tectonically active region as demonstrated by the occurrence of the unexpected 2008 Mw 7.9 Wenchuan and 2013 Mw 6.6 Lushan earthquakes in the central and southern parts of the belt respectively. These events revealed the necessity of a better understanding of the long‐term geological evolution of the belt and its effect on the present dynamics and crustal structure. New structural and thermobarometric data offer a comprehensive dataset of the paleo‐temperatures across the belt and P‐T estimates for low‐grade metamorphic domains. In the central Longmen Shan, two metamorphic jumps of 150‐200°C, 5‐6 kbar and ~50 °C, 3‐5 kbar acquired during the Early Mesozoic are observed across the Wenchuan and Beichuan faults respectively, attesting to their thrusting movement and unrevealing a major decollement between the allochtonous Songpan‐Garze metasedimentary cover (at T > 500°C) and the autochtonous units and the basement (T < 400°C). In the southern Longmen Shan, the only greenschist‐facies metamorphism is observed both in the basement (360 ± 30°C, 6 ± 2 kbar) and in the metasedimentary cover (350 ± 30°C, 3 ± 1 kbar). Peak conditions were reached at c. 80‐60 Ma in the basement and c. 55‐33 Ma in the cover, c. 50 Ma after the greenschist‐facies metamorphic overprint observed in the central Longmen Shan (c. 150‐120 Ma). This along‐strike metamorphic segmentation coincides well with the present fault segmentation and reveals that the central and southern Longmen Shan experienced different tectono‐metamorphic histories since the Mesozoic

Large-scale Identification of Chemically Induced Mutations in Drosophila melanogaster.

Forward genetic screens using chemical mutagens have been successful in defining the function of thousands of genes in eukaryotic model organisms. The main drawback of this strategy is the time-consuming identification of the molecular lesions causative of the phenotypes of interest. With whole-genome sequencing (WGS), it is now possible to sequence hundreds of strains, but determining which mutations are causative among thousands of polymorphisms remains challenging. We have sequenced 394 mutant strains, generated in a chemical mutagenesis screen, for essential genes on the Drosophila X chromosome and describe strategies to reduce the number of candidate mutations from an average of -3500 to 35 single-nucleotide variants per chromosome. By combining WGS with a rough mapping method based on large duplications, we were able to map 274 (-70%) mutations. We show that these mutations are causative, using small 80-kb duplications that rescue lethality. Hence, our findings demonstrate that combining rough mapping with WGS dramatically expands the toolkit necessary for assigning function to genes

2-Aminopurine Inhibits Lipid Accumulation Induced by Apolipoprotein E-Deficient Lipoprotein in Macrophages: Potential Role of Eukaryotic Initiation Factor-2␣ Phosphorylation in Foam Cell Formation

ABSTRACT We previously reported that apolipoprotein (Apo) E-deficient, ApoB48-containing (E Ϫ /B48) lipoproteins inhibited expression of lysosomal hydrolase and transformed mouse peritoneal macrophages (MPMs) into foam cells. The present study examined the effect of 2-aminopurine (2-AP), an inhibitor of eukaryotic initiation factor (eIF)-2␣ phosphorylation, on E Ϫ /B48 lipoprotein-induced changes in gene expression and foam cell formation. Our data demonstrated that E Ϫ /B48 lipoproteins enhanced phosphorylation of eIF-2␣ in macrophages. Incubation of MPMs with E Ϫ /B48 lipoproteins inhibited the translation efficiency of mRNAs encoding lysosomal acid lipase, cathepsin B, and cation-dependent mannose 6 phosphate receptor, with a parallel reduction in the level of these proteins. Addition of 2-AP to the culture media alleviated the suppressive effect of E Ϫ /B48 lipoproteins on lysosomal hydrolase mRNA translation, increased macrophage degradation of E Ϫ /B48 lipoproteins, and inhibited foam cell formation. Transfection of MPMs with a nonphosphorylatable eIF-2␣ mutant also attenuated the suppressive effect of E Ϫ /B48 lipoproteins on expression of lysosomal acid lipase, associated with a reduced accumulation of cellular cholesterol esters. This is the first demonstration that ApoE-deficient lipoproteins inhibit lysosomal hydrolase synthesis and transform macrophages into foam cells through induction of eIF-2␣ phosphorylation

AAV2-Mediated Combined Subretinal Delivery of IFN-α and IL-4 Reduces the Severity of Experimental Autoimmune Uveoretinitis

We previously showed that adeno-associated virus 2 (AAV2) mediated subretinal delivery of human interferon-alpha (IFN-α) could effectively inhibit experimental autoimmune uveoretinitis (EAU). In this study we investigated whether subretinal injection of both AVV2.IFN-α and AAV2.IL-4 had a stronger inhibition on EAU activity. B10RIII mice were subretinally injected with AAV2.IFN-α alone (1.5×107 vg), AAV2.IL-4 alone (3.55×107 vg), and AAV2.IFN-α combined with AAV2.IL-4. PBS, AAV2 vector encoding green fluorescent protein (AAV2.GFP) (5×107 vg) was subretinally injected as a control. IFN-α and IL-4 were effectively expressed in the eyes from three weeks to three months following subretinal injection of AAV2 vectors either alone or following combined administration and significantly attenuated EAU activity clinically and histopathologically. AAV2.IL-4 showed a better therapeutic effect as compared to AAV2.IFN-α. The combination of AAV2.IL-4 and AAV2.IFN-α was not significantly different as compared to AAV2.IL-4 alone. There was no difference concerning DTH (delayed-type hypersensitivity) reaction, lymphocyte proliferation and IL-17 production among the investigated treatment groups, suggesting that local retinal gene delivery did not affect the systemic immune response

Membrane lipid and expression responses of Saccharolobus islandicus REY15A to acid and cold stress

Archaea adjust the number of cyclopentane rings in their glycerol dibiphytanyl glycerol tetraether (GDGT) membrane lipids as a homeostatic response to environmental stressors such as temperature, pH, and energy availability shifts. However, archaeal expression patterns that correspond with changes in GDGT composition are less understood. Here we characterize the acid and cold stress responses of the thermoacidophilic crenarchaeon Saccharolobus islandicus REY15A using growth rates, core GDGT lipid profiles, transcriptomics and proteomics. We show that both stressors result in impaired growth, lower average GDGT cyclization, and differences in gene and protein expression. Transcription data revealed differential expression of the GDGT ring synthase grsB in response to both acid stress and cold stress. Although the GDGT ring synthase encoded by grsB forms highly cyclized GDGTs with ≥5 ring moieties, S. islandicus grsB upregulation under acidic pH conditions did not correspond with increased abundances of highly cyclized GDGTs. Our observations highlight the inability to predict GDGT changes from transcription data alone. Broader analysis of transcriptomic data revealed that S. islandicus differentially expresses many of the same transcripts in response to both acid and cold stress. These included upregulation of several biosynthetic pathways and downregulation of oxidative phosphorylation and motility. Transcript responses specific to either of the two stressors tested here included upregulation of genes related to proton pumping and molecular turnover in acid stress conditions and upregulation of transposases in cold stress conditions. Overall, our study provides a comprehensive understanding of the GDGT modifications and differential expression characteristic of the acid stress and cold stress responses in S. islandicus