High-Performance Poly(3-hexyl thiophene)-Based Organic Photovoltaics with Side-Chain Engineering of Core Units of Small Molecule Acceptors.

In this study, we synthesized a series of four large-band gap small molecule acceptors with side-chain engineering of the dithieno-pyrrolo-fused pentacyclic benzotriazole (BZTTP or Y1 core) or the fused-ring dithienothiophene-pyrrolobenzothiadiazole (TPBT or Y6 core) with difluoro-indene-dione (IO2F) or dichloro-indene-dione (IO2Cl) end groups to form Y1-IO2F, Y1-IO2Cl, Y6-IO2F, and Y6-IO2Cl acceptors, respectively, for blending with poly(3-hexyl thiophene) (P3HT) for bulk heterojunction organic photovoltaics. The complementary UV-vis absorption spectra of these small molecules and P3HT along with their offset energy bands allow broad absorption and effective electron transfer. Through synchrotron wide-angle X-ray scattering (WAXS) analyses and contact angle measurements, we found that the blend of the small molecule Y6-IO2F (having a TPBT core) and P3HT achieves an optimum morphology that balances their crystallinity and miscibility, among those of these four blends, leading to a substantial enhancement in the short-circuit current density and thus power conversion efficiency (PCE) in their devices. For example, the P3HT:Y6-IO2F (w/w: 1/1.2) device exhibited a champion PCE of 10.5% with a short current density (Jsc) value of 15.9 mA/cm2 as compared to the P3HT:Y1-IO2F device having a PCE of 2.2% with a Jsc value of 5.7 mA/cm2 because of the higher Y6-IO2F (with TPBT core) molecular packing that facilitated carrier transport in the devices. The enhanced thermal stability exhibited by the devices incorporating Y6-IO2F and Y6-IO2Cl, as compared to that of Y1-IO2F and Y1-IO2Cl devices, is also due to the more planar TPBT core structure, while the photostability of devices incorporating Y6-IO2Cl and Y1-IO2Cl is better than that of devices incorporating Y6-IO2F and Y1-IO2F, owing to more photostable chemical structures. These results present an outstanding performance for P3HT-based organic solar cells. Moreover, these small molecule blends are processed with an environmentally friendly solvent tetrahydrofuran, demonstrating both the sustainability and commercial viability of these types of organic photovoltaics.

Chiral Silica with Preferred-Handed Helical Structure via Chiral Transfer.

A strategy to obtain chiral silica using an achiral stereoregular polymer with polyhedral oligomeric silsesquioxane (POSS) side chains is described herein. The preferred helical conformation of the POSS-containing polymer could be achieved by mixing isotactic polymethacrylate-functionalized POSS (it-PMAPOSS) and a chiral dopant. The array structure of POSS molecules, which are placed along the helical conformation, is memorized even after removing the chiral dopant at high temperatures, leading to a chiral silica compound with exclusive optical activity after calcination.

Mitochondrial oxidative stress by Lon-PYCR1 maintains an immunosuppressive tumor microenvironment that promotes cancer progression and metastasis.

Mitochondrial Lon is a chaperone protein whose upregulation increases the production of mitochondrial reactive oxygen species (ROS). However, there is a lack of information in detail on how mitochondrial Lon regulates cancer metastasis through ROS production in the tumor microenvironment (TME). Our results show that elevated Lon promotes epithelial-mesenchymal transition (EMT) via ROS-dependent p38 and NF-κB-signaling. We further identified pyrroline-5-carboxylate reductase 1 (PYCR1) as a client of chaperone Lon, which induces mitochondrial ROS and EMT by Lon. Mitochondrial Lon induces ROS-dependent production of inflammatory cytokines, such as TGF-ß, IL-6, IL-13, and VEGF-A, which consequently activates EMT, angiogenesis, and M2 macrophage polarization. In addition, Lon expression is induced upon the activation and M2 polarization of macrophages, which further promotes M2 macrophages to enhance the immunosuppressive microenvironment and metastatic behaviors in the TME. This raises the possibility that manipulation of the mitochondrial redox balance in the TME may serve as a therapeutic strategy to improve T cell function in cancer immunotherapy.

Enhanced Reactivity of Aluminum Complexes Containing P-Bridged Biphenolate Ligands in Ring-Opening Polymerization Catalysis.

Aluminum complexes containing [RP(O)(2-O-3,5-tBu2C6H2)2]2- [R = tBu (3a), Ph (3b)] have been synthesized, structurally characterized, and their reactivity studied in comparison with those of their [RP(2-O-3,5-tBu2C6H2)2]2- [R = tBu (2a), Ph (2b)] analogs. Treating AlMe3 with one equiv of H2[3a-b] in THF at 0°C affords quantitatively [3a-b]AlMe, subsequent reactions of which with benzyl alcohol in THF at 25°C generate {[3a-b]Al(µ2-OCH2Ph)}2. The methyl [3a-b]AlMe and the benzyloxide {[3a-b]Al(µ2-OCH2Ph)}2 are all active for catalytic ring-opening polymerization (ROP) of ε-caprolactone and rac-lactide (rac-LA). Controlled experiments reveal that {[3a]Al(µ2-OCH2Ph)}2 is competent in living polymerization. Kinetic studies indicate that [3a]AlMe, in the presence of benzyl alcohol, catalyzes ROP of rac-LA at a rate faster than [3b]AlMe and [2a]AlMe(THF) by a factor of 1.8 and 23.6, respectively, highlighting the profound reactivity enhancement in ROP catalysis by varying the P-substituents of these biphenolate complexes of aluminum.

CUDA-based acceleration and BPN-assisted automation of bilateral filtering for brain MR image restoration.

PURPOSE: Bilateral filters have been substantially exploited in numerous magnetic resonance (MR) image restoration applications for decades. Due to the deficiency of theoretical basis on the filter parameter setting, empirical manipulation with fixed values and noise variance-related adjustments has generally been employed. The outcome of these strategies is usually sensitive to the variation of the brain structures and not all the three parameter values are optimal. This article is in an attempt to investigate the optimal setting of the bilateral filter, from which an accelerated and automated restoration framework is developed. METHODS: To reduce the computational burden of the bilateral filter, parallel computing with the graphics processing unit (GPU) architecture is first introduced. The NVIDIA Tesla K40c GPU with the compute unified device architecture (CUDA) functionality is specifically utilized to emphasize thread usages and memory resources. To correlate the filter parameters with image characteristics for automation, optimal image texture features are subsequently acquired based on the sequential forward floating selection (SFFS) scheme. Subsequently, the selected features are introduced into the back propagation network (BPN) model for filter parameter estimation. Finally, the k-fold cross validation method is adopted to evaluate the accuracy of the proposed filter parameter prediction framework. RESULTS: A wide variety of T1-weighted brain MR images with various scenarios of noise levels and anatomic structures were utilized to train and validate this new parameter decision system with CUDA-based bilateral filtering. For a common brain MR image volume of 256 × 256 × 256 pixels, the speed-up gain reached 284. Six optimal texture features were acquired and associated with the BPN to establish a "high accuracy" parameter prediction system, which achieved a mean absolute percentage error (MAPE) of 5.6%. Automatic restoration results on 2460 brain MR images received an average relative error in terms of peak signal-to-noise ratio (PSNR) less than 0.1%. In comparison with many state-of-the-art filters, the proposed automation framework with CUDA-based bilateral filtering provided more favorable results both quantitatively and qualitatively. CONCLUSIONS: Possessing unique characteristics and demonstrating exceptional performances, the proposed CUDA-based bilateral filter adequately removed random noise in multifarious brain MR images for further study in neurosciences and radiological sciences. It requires no prior knowledge of the noise variance and automatically restores MR images while preserving fine details. The strategy of exploiting the CUDA to accelerate the computation and incorporating texture features into the BPN to completely automate the bilateral filtering process is achievable and validated, from which the best performance is reached.

Aluminum complexes containing biphenolate phosphine ligands: synthesis and living ring-opening polymerization catalysis.

This report describes the synthesis, structure, and reactivity of aluminum complexes containing tridentate biphenolate phosphine ligands of the type [RP(2-O-3,5-C6H2tBu2)2]2- (R = tBu (2a), Ph (2b)). Alkane elimination of AlMe3 with one equiv. of H2[2a] or H2[2b] in THF at 0 °C cleanly affords colorless crystalline [2a]AlMe(THF) (3a) and [2b]AlMe(THF) (3b), respectively. An X-ray diffraction study of 3a showed it to be a five-coordinate THF-bound species, whose coordination geometry is best described as trigonal bipyramidal, having the phosphorus donor and THF at axial positions. Treatment of either in situ prepared or isolated methyl complexes 3a,b with one equiv. of benzyl alcohol in toluene or THF generated their corresponding benzyloxides {[2a,b]Al(µ2-OCH2Ph)}2 (4a,b). An X-ray diffraction study of 4a revealed a dimeric structure, in which the coordination geometry of aluminum is also distorted trigonal bipyramidal with the tridentate 2a ligand being facially bound. In the presence of one equiv. of benzyl alcohol, complex 3a is a competent catalyst precursor for the living ring-opening polymerization of ε-caprolactone (ε-CL) and rac-lactide (rac-LA), producing poly(ε-caprolactone) and poly(rac-lactide), respectively, in a controlled manner. As such, well-defined block copolymers of ε-CL with rac-LA can also be prepared by catalytic 3a. Kinetic studies revealed that 3a catalyzes the polymerization of rac-lactide at a rate 2-fold faster than that of 3b, indicating the significance of the P-substituent effect on this catalysis. Interestingly, the polymerization rate of rac-lactide by 3a is 16.5 times faster than that of l-lactide under otherwise identical conditions.

A two-center study for the quality control of [(18)F]FDG using FASTlab phosphate cassettes.

OBJECTIVE: The GE FASTlab radiosynthesis module is routinely used for the production of [(18)F]FDG, utilizing the commercially available phosphate cassettes. Because of the observation of a white precipitate in the product vial before the product expiry time, we re-examined the quality of the produced [(18)F]FDG solution. METHODS: Phosphate buffered [(18)F]FDG solution was synthesized on the FASTlab and analyzed at both National Taiwan University Hospital (NTUH) of Taiwan and Royal Brisbane and Women's Hospital (RBWH) of Australia. In addition to the standard product quality control (QC), the concentration of aluminum (Al(3+)) as probable cause of the precipitations in the [(18)F]FDG solution was analyzed by inductively coupled plasma mass spectrometry (ICP-MS at RBWH) and inductively coupled plasma optical emission spectrometry (ICP-OES at NTUH), and using three semi-quantitative methods at NTUH, Advantec(®) Alumi Check Test Strip, Quantofix(®) Aluminum Test Strip and MColortest™ Aluminum Test kit. RESULTS: The precipitates were observed in the [(18)F]FDG solution within 24 (NTUH) and 6 (RBWH) hours after the end of synthesis in 38-100 % of the batches, dependent on the batch of the FASTlab cassettes. Addition of metal-free HCl(aq) to aliquots of [(18)F]FDG containing precipitate, followed by ICP-MS analysis revealed Al(3+) concentrations of 70-80 ppm. Al(3+) concentrations of 10-12 ppm were detected in [(18)F]FDG batches that did not show any precipitation. In contrast, less than 5 ppm of the residual Al(3+) was detected by semi-quantitative methods in all batches. CONCLUSION: The US (USP), British (BP), European (EP) and Japanese (JP) pharmacopeias demand that [(18)F]FDG for injection should be clear and particulate free within the given shelf-life/expiration time. To avoid Al-phosphate precipitation within the product expiry time, FASTlab citrate cassettes, rather than phosphate cassettes, should be used for [(18)F]FDG production. Although testing for Al(3+) is not listed in the [(18)F]FDG monographs of the USP, BP and EP, residual Al(3+) levels should be considered in the interests of patient safety.

Automatic brain MR image denoising based on texture feature-based artificial neural networks.

Noise is one of the main sources of quality deterioration not only for visual inspection but also in computerized processing in brain magnetic resonance (MR) image analysis such as tissue classification, segmentation and registration. Accordingly, noise removal in brain MR images is important for a wide variety of subsequent processing applications. However, most existing denoising algorithms require laborious tuning of parameters that are often sensitive to specific image features and textures. Automation of these parameters through artificial intelligence techniques will be highly beneficial. In the present study, an artificial neural network associated with image texture feature analysis is proposed to establish a predictable parameter model and automate the denoising procedure. In the proposed approach, a total of 83 image attributes were extracted based on four categories: 1) Basic image statistics. 2) Gray-level co-occurrence matrix (GLCM). 3) Gray-level run-length matrix (GLRLM) and 4) Tamura texture features. To obtain the ranking of discrimination in these texture features, a paired-samples t-test was applied to each individual image feature computed in every image. Subsequently, the sequential forward selection (SFS) method was used to select the best texture features according to the ranking of discrimination. The selected optimal features were further incorporated into a back propagation neural network to establish a predictable parameter model. A wide variety of MR images with various scenarios were adopted to evaluate the performance of the proposed framework. Experimental results indicated that this new automation system accurately predicted the bilateral filtering parameters and effectively removed the noise in a number of MR images. Comparing to the manually tuned filtering process, our approach not only produced better denoised results but also saved significant processing time.

Tuning ligand structure in chiral bis(phosphite) and mixed phosphite-phosphinite PCP-palladium pincer complexes.

A range of chiral resorcinol bis(phosphite) and phosphite-phosphinite ligands were produced and their propensity to form palladium PCP-pincer complexes examined. The ease of base-assisted C-H palladation of the ligands falls in the order bis(phosphinite) > phosphite-phosphinite > bis(phosphite). The catalytic activity of the complexes in the asymmetric allylation of benzaldehyde with allyl tributyltin was examined and it was found that, contrary to expectations, ligands with 3,3'-disubstituted BINOL residues show poorer activity and stereoselectivity than unsubstituted BINOL analogues. In addition the order of activity of the pincer complexes was established as bis(phosphite) > phosphite-phosphinite > bis(phosphinite). Crystal structures of representative examples of a 3,3'-disubstituted BINOL, mono- and bis(phosphite) ligands based on 2,4-di-tert-butyl resorcinol and Pd complexes of two of the chiral complexes are presented.

Chiral palladacycles based on resorcinol monophosphite ligands: the role of the meta-hydroxyl in ligand C-H activation and catalysis.

The reactions of a range of chiral resorcinol monophosphite ligands with [PdCl(2)(NCMe)(2)] was investigated in order to establish whether the meta-hydroxyl function was involved in the orthometallation processes. These ligands underwent facile orthopalladation at room temperature in the presence of Et(3)N, whilst the equivalent hydroxyl-free analogues needed more forcing conditions to induce orthometallation. When the hydroxyl function was replaced by a similar sized methyl group no orthometallation occurred, even on heating. Furthermore the hydroxyl group influences both the structure and isomerism in the resultant palladacycles via hydrogen bonding to adjacent chloride ligands. Similarly, the hydroxyl function leads to higher enantiocontrol in the asymmetric allylation of benzaldehyde with allyl tributyltin. Representative examples of the ligands and the palladium complexes obtained were characterised by single crystal X-ray diffraction.

Biphenolate phosphine complexes of tin(IV).

The preparation and structural characterization of tin(IV) complexes supported by (2,2'-phenylphosphino)bis(4,6-di-tert-butylphenolate) ([OPO]2-) are described. The reaction of in-situ prepared Li2[OPO] with SnCl4 in THF at -35 degrees C produced [OPO]SnCl2(THF) as a THF adduct. Addition of SnCl4 to a THF solution of H2[OPO] in the presence of 2 equiv of NEt3 at room temperature led to the formation of the "ate" complex {[OPO]SnCl3}(HNEt3). The metathetical reactions of Li2[OPO] with R2SnCl2 (R=Me, n-Bu) in THF at -35 degrees C generated the corresponding five-coordinate dialkyl complexes [OPO]SnR2. In addition to the multinuclear NMR spectroscopic data for all new compounds, X-ray structures of [OPO]SnCl2(THF), [OPO]SnMe2, and [OPO]Sn(n-Bu)2 are presented.

Biphenolate phosphine complexes of group 4 metals.

The preparation and structural characterization of a series of group 4 complexes supported by 2,2'-phenylphosphinobis(4,6-di-tert-butylphenolate) ([OPO]2-) are described. The reaction of either H2[OPO] with Ti(OR)4 (R = Et, iPr) or Li2[OPO] with TiCl4(THF)2 produced yellowish-orange crystals of Ti[OPO]2, regardless of the stoichiometry of the starting materials employed. Comproportionation of the bis-ligand complex Ti[OPO]2 with 1 equiv of TiCl4(THF)2 led to the formation of [OPO]TiCl2(THF) as brownish-red crystals. Surprisingly, treatment of H2[OPO] with [(Me3Si)2N]2MCl2 (M = Zr, Hf), irrespective of the molar ratio, generated colorless crystals of the corresponding bis-ligand complex [OPO]2M(OH2) as an aqua adduct. The solution and solid-state structures of these group 4 complexes were all characterized by multinuclear NMR spectroscopy and X-ray crystallography, respectively.

The central cavity from the (alpha/alpha)6 barrel structure of Anabaena sp. CH1 N-acetyl-D-glucosamine 2-epimerase contains two key histidine residues for reversible conversion.

N-acetyl-D-glucosamine 2-epimerase (GlcNAc 2-epimerase) catalyzes the reversible epimerization between N-acetyl-D-glucosamine (GlcNAc) and N-acetyl-D-mannosamine (ManNAc). We report here the 2.0 A resolution crystal structure of the GlcNAc 2-epimerase from Anabaena sp. CH1. The structure demonstrates an (alpha/alpha)(6) barrel fold, which shows structural homology with porcine GlcNAc 2-epimerase as well as a number of glycoside hydrolase enzymes and other sugar-metabolizing enzymes. One side of the barrel structure consists of short loops involved in dimer interactions. The other side of the barrel structure is comprised of long loops containing six short beta-sheets, which enclose a putative central active-site pocket. Site-directed mutagenesis of conserved residues near the N-terminal region of the inner alpha helices shows that R57, H239, E308, and H372 are strictly required for activity. E242 and R375 are also essential in catalysis. Based on the structure and kinetic analysis, H239 and H372 may serve as the key active site acid/base catalysts. These results suggest that the (alpha/alpha)(6) barrel represents a steady fold for presenting active-site residues in a cleft at the N-terminal ends of the inner alpha helices, thus forming a fine-tuned catalytic site in GlcNAc 2-epimerase.

Structural basis for shikimate-binding specificity of Helicobacter pylori shikimate kinase.

Shikimate kinase (EC 2.7.1.71) catalyzes the specific phosphorylation of the 3-hydroxyl group of shikimic acid in the presence of ATP. As the fifth key step in the shikimate pathway for aromatic amino acid biosynthesis in bacteria, fungi, and plants, but not mammals, shikimate kinase represents an attractive target for the development of new antimicrobial agents, herbicides, and antiparasitic agents. Here, we report the 1.8-Angstroms crystal structure of Helicobacter pylori shikimate kinase (HpSK). The crystal structure shows a three-layer alpha/beta fold consisting of a central sheet of five parallel beta-strands flanked by seven alpha-helices. An HpSK-shikimate-PO(4) complex was also determined and refined to 2.3 Angstroms, revealing induced-fit movement from an open to a closed form on substrate binding. Shikimate is located above a short 3(10) helix formed by a strictly conserved motif (GGGXV) after beta(3). Moreover, several highly conserved charged residues including Asp33 (in a conserved DT/SD motif), Arg57, and Arg132 (interacting with shikimate) are identified, guiding the development of novel inhibitors of shikimate kinase.