Synthesis and Conformational Analysis of Cyclotetrapeptide Mimetic β‐Turn Templates and Validation as 3D Scaffolds

The conformations of all stereoisomers of PMRI cyclotetrapeptide mimetics 1 – 8 are essentially determined by the predisposition of the diamine to stabilize β‐turns. The peptide mimetics can be regarded as 3D scaffolds for designing molecules with a predictable display of the pharmacophores. We used the models for testing novel RGD analogues as α_vβ₃‐integrin receptor antagonists.

     

Characterization of New PPARγ Agonists: Benzimidazole Derivatives – the Importance of Position 2

Probing SAR : The 1‐(biphenyl‐4‐ylmethyl)‐1H‐benzo[d]imidazole moiety is known to be an essential structural component of telmisartan for PPARγ activation. This study focused on the substituents at position 2 of the benzimidazole in an attempt to optimize PPARγ activation. In particular, the elongation of the alkyl chain and the introduction of an aromatic ring system were studied (shown).

     

Structure and photocatalytic performance of magnetically separable titania photocatalysts for the degradation of propachlor

A magnetic photocatalyst was prepared by modification of TiO₂ nanoparticles (Degussa P25) with nanocrystalline γ-Fe₂O₃ nanoparticles through a protective lining made up of two oppositely charged polyelectrolytes. As-prepared magnetically separable photocatalysts differing in γ-Fe₂O₃ loading (3, 8, 13, 20 and 30 wt.%) were characterized by XRD, TEM, thermal analysis, Mössbauer and magnetic measurements. The photocatalytic efficiency of the nanocomposite catalysts was evaluated using a chloroacetanilide herbicide (propachlor) in water as model compound. The primary degradation of propachlor followed pseudo-first-order kinetics according to the Langmuir–Hinshelwood model. Generally, all magnetic photocatalysts exhibit good catalytic activity towards organic pollutants, do not suffer from photodissolution and can be reused several times without any decrease in their photocatalytic activity.     

Optimisation and Evaluation of La0.6Sr0.4CoO3 – δ Cathode for Intermediate Temperature Solid Oxide Fuel Cells

In this work, La_0.6Sr_0.4CoO_{3 – δ}/Ce_{1 – x}Gd_xO_{2 – δ} (LSC/GDC) composite cathodes are investigated for SOFC application at intermediate temperatures, especially below 700 °C. The symmetrical cells are prepared by spraying LSC/GDC composite cathodes on a GDC tape, and the lowest polarisation resistance (R_p) of 0.11 Ω cm² at 700 °C is obtained for the cathode containing 30 wt.‐% GDC. For the application on YSZ electrolyte, symmetrical LSC cathodes are fabricated on a YSZ tape coated on a GDC interlayer. The impact of the sintering temperature on the microstructure and electrochemical properties is investigated. The optimum temperature is determined to be 950 °C; the corresponding R_p of 0.24 Ω cm² at 600 °C and 0.06 Ω cm² at 700 °C are achieved, respectively. An YSZ‐based anode‐supported solid oxide fuel cell is fabricated by employing LSC/GDC composite cathode sintered at 950 °C. The cell with an active electrode area of 4 × 4 cm² exhibits the maximum power density of 0.42 W cm^–2 at 650 °C and 0.54 W cm^–2 at 700 °C. More than 300 h operating at 650 °C is carried out for an estimate of performance and degradation of a single cell. Despite a decline at the beginning, the stable performance during the later term suggests a potential application.     

气藏钻井井控难易程度确定方法与装置研究

溢流发生后的井控难易程度的有效评价是气藏钻井中井控成功的关键所在。提出了利用关井压力恢复曲线来判断钻井井控难易程度的方法,研制了天然气井钻井安全井控装置,并开发了配套软件系统。系统能够根据地层特征建立关井压力恢复图版,根据装置采集的关井压力恢复曲线的评价点位置来判断井控难易程度,评价点在图版中位置越靠上则欠平衡程度越大,评价点与起始点连线斜率越大则地层系数越大,都造成井控难度增加。该项研究为天然气井钻井现场井控操作提供了依据。     

Mo2C/SAPO-11催化剂上正己烷异构化反应研究

利用程序升温还原法制备了SAPO-11负载碳化钼催化剂。XRD分析表明,利用正己烷作为碳源得到了对异构化具有活性的β-Mo2C。通过连续流动固定床反应装置,以正己烷为模型反应物,考察了反应温度、压力、空速和氢烃体积比对β-Mo2C/SAPO-11催化剂临氢异构化反应性能的影响。结果显示,SAPO-11负载碳化钼催化剂上的正己烷异构化的最适宜反应条件为温度380℃, 压力1.5MPa,体积空速1.0h-1,氢烃体积比200:1。在适宜条件下反应物转化率为82.19%,异构物选择性和收率分别达到73.57%和60.47%。     

All Night Long: The Architectural Jazz of the Texas Rangers

In the mid-1950s, a group of young faculty at the University of Texas School of Architecture in Austin - aka the Texas Rangers - entertained themselves with weekly sessions of a sophisticated, collective drawing game, ‘Dot-the-Dot’, in which there was an emphasis on inventive fluency in hand drawing as well as an innate knowledge of historic European city plans. What happened when Mark Morris , Visiting Associate Professor at Cornell University, decided in a design studio to ask present-day students to revive the game?     

Discovery of a Novel Triazolopyridine Derivative as a Tankyrase Inhibitor

More than 80% of colorectal cancer patients have adenomatous polyposis coli (APC) mutations, which induce abnormal WNT/β-catenin activation. Tankyrase (TNKS) mediates the release of active β-catenin, which occurs regardless of the ligand that translocates into the nucleus by AXIN degradation via the ubiquitin-proteasome pathway. Therefore, TNKS inhibition has emerged as an attractive strategy for cancer therapy. In this study, we identified pyridine derivatives by evaluating in vitro TNKS enzyme activity and investigated N-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-1-(2-cyanophenyl)piperidine-4-carboxamide (TI-12403) as a novel TNKS inhibitor. TI-12403 stabilized AXIN2, reduced active β-catenin, and downregulated β-catenin target genes in COLO320DM and DLD-1 cells. The antitumor activities of TI-12403 were confirmed by the viability of the colorectal cancer cells and its lack of visible toxicity in DLD-1 xenograft mouse model. In addition, combined 5-FU and TI-12403 treatment synergistically inhibited proliferation to a greater extent than that in a single drug treatment. Our observations suggest that TI-12403, a novel selective TNKS1 inhibitor, may be a suitable compound for anticancer drug development.     

Expression of DDX11 and DNM1L at the 12p11 Locus Modulates Systemic Lupus Erythematosus Susceptibility

Objectives: This study employed genetic and functional analyses using OASIS meta-analysis of multiple existing GWAS and gene-expression datasets to identify novel SLE genes. Methods: Four hundred and ten genes were mapped using SNIPPER to 30 SLE GWAS loci and investigated for expression in three SLE GEO-datasets and the Cordoba {"type":"entrez-geo","attrs":{"text":"GSE50395","term_id":"50395"}}GSE50395-dataset. Blood eQTL for significant SNPs in SLE loci and STRING for functional pathways of differentially expressed genes were used. Confirmatory qPCR on SLE monocytes was performed. The entire 12p11 locus was investigated for genetic association using two additional GWAS. Expression of 150 genes at this locus was assessed. Based on this significance, qPCRs for DNM1L and KRAS were performed. Results: Fifty genes were differentially expressed in at least two SLE GEO-datasets, with all probes directionally aligned. DDX11, an RNA helicase involved in genome stability, was downregulated in both GEO and Cordoba datasets. The most significant SNP, rs3741869 in OASIS locus 12p11.21, containing DDX11, was a cis-eQTL regulating DDX11 expression. DDX11 was found repressed. The entire 12p11 locus showed three association peaks. Gene expression in GEO datasets identified DNM1L and KRAS, besides DDX11. Confirmatory qPCR validated DNM1L as an SLE susceptibility gene. DDX11, DNM1L and KRAS interact with each other and multiple known SLE genes including STAT1/STAT4 and major components of IFN-dependent gene expression, and are responsible for signal transduction of cytokines, hormones, and growth-factors, deregulation of which is involved in SLE-development. Conclusion: A genomic convergence approach with OASIS analysis of multiple GWAS and expression datasets identified DDX11 and DNM1L as novel SLE-genes, the expression of which is altered in monocytes from SLE patients. This study lays the foundation for understanding the pathogenic involvement of DDX11 and DNM1L in SLE by identifying them using a systems-biology approach, while the 12p11 locus harboring these genes was previously missed by four independent GWAS.