Hodge numbers of nodal double octics

Let B be a surface of even degree d in P³ with nodes as the only singular points. In [1] Clemens proved that the topology of the small resolution of the double covering of P³ branched along B depends not only on the number of nodes but also on the so-called defect, a non-negative integer describing their configuration.

The aim of this note is to give an elementary proof of the Clemens. result and to present some geometric interpretation of defect.     

Synthesis of Active Metabolites of Carvedilol,an Antihypertensive Drug

A simple synthetic route for active metabolites of carvedilol is reported. The metabolites 4′-hydroxycarvedilol and 5′-hydroxycarvedilol have exhibited high activity for β-blockade. We have disclosed syntheses of 4′-hydroxycarvedilol and 5′-hydroxycarvedilol from commercially available vanillin and isovanillin, respectively.     

Exploring the Reactivity of a Frustrated Sn/P Lewis Pair: The Highly Selective Complexation of the cis-Azobenzene Photoisomer

The reactivity of the geminal frustrated Lewis pair (FLP) (F₅C₂)₃SnCH₂P(tBu)₂ ( 1 ) was explored by reacting it with a variety of small molecules (PhOCN, PhNCS, PhCCH, tBuCCH, H₃CC(O)CH=CH₂, Ph[C(O)]₂Ph, PhN=NPh and Me₃SiCHN₂), featuring polar or non-polar multiple bonds and/or represent α,β-unsaturated systems. While most adducts are formed readily, the binding of azobenzene requires UV-induced photoisomerization, which results in the highly selective complexation of cis-azobenzene. In the case of benzil, the reaction does not lead to the expected 1,2- or 1,4-addition products, but to the non-stereoselective (tBu)₂PCH₂-transfer to a prochiral keto function of benzil. All adducts of 1 were characterised by means of multinuclear NMR spectroscopy, elemental analyses and X-ray diffraction experiments.     

Design,synthesis and biological evaluation of pyridyl substituted benzoxazepinones as potent and selective inhibitors of aldosterone synthase

Exorbitant aldosterone is closely associated with various severe diseases, including congestive heart failure and chronic kidney disease. As aldosterone synthase is the pivotal enzyme in aldosterone biosynthesis, its inhibition constitutes a promising treatment for these diseases. Via a structure-based approach, a series of pyridyl substituted 3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-ones were designed as inhibitors of aldosterone synthase. Six compounds (5j, 5l, 5m 5w, 5x and 5y) distinguished themselves with potent inhibition (IC₅₀ <100 nmol/L) and high selectivity over homogenous 11β-hydroxylase. As the most promising compound, 5x exhibited an IC₅₀ of 12 nmol/L and an excellent selectivity factor (SF) of 157, which are both superior to those of the reference fadrazole (IC₅₀ = 21 nmol/L, SF = 7). Importantly, 5x showed no inhibition against steroidogenic CYP17, CYP19 and a panel of hepatic CYP enzymes indicating an outstanding safety profile. As it manifested satisfactory pharmacokinetic properties in rats, compound 5x was considered as a drug candidate for further development.     

A modular attachment mechanism for software network evolution

A modular attachment mechanism of software network evolution is presented in this paper. Compared with the previous models, our treatment of object-oriented software system as a network of modularity is inherently more realistic. To acquire incoming and outgoing links in directed networks when new nodes attach to the existing network, a new definition of asymmetric probabilities is given. Based on this, modular attachment instead of single node attachment in the previous models is then adopted. The proposed mechanism is demonstrated to be able to generate networks with features of power-law, small-world, and modularity, which represents more realistic properties of actual software networks. This work therefore contributes to a more accurate understanding of the evolutionary mechanism of software systems. What is more, explorations of the effects of various software development principles on the structure of software systems have been carried out, which are expected to be beneficial to the software engineering practices.     

Ladderane Natural Products: From the Ground Up

The ladderane family of natural products are well known for their linearly concatenated cyclobutane skeletal structure. Owing to their unique carbocyclic framework, several chemical syntheses have been reported since their discovery in 2002. The focus of this review is to showcase the novel tactics that have been used to generate the ladderane core and the challenges that are associated with the synthesis of these unusual and complex natural products.     

抗肿瘤缺氧诱导因子-1的小分子抑制剂

肿瘤的缺氧微环境与其增殖、分化、血管生成、能量代谢、耐药性的发生以及患者预后状况密切相关。缺氧诱导因子1(Hypoxia-inducible factor 1, HIF-1)是细胞适应缺氧环境的重要转录因子和调控蛋白,通过调控下游靶基因如EPO、VEGF、GLUT等的表达,促进血管新生及有氧糖酵解以适应缺氧的环境,进而影响肿瘤细胞代谢、血管生成和肿瘤转移等。因此,开发以HIF-1为靶标的小分子抑制剂药物有望成为一种有效的肿瘤治疗方法。本文就HIF-1小分子抑制剂在肿瘤学研究中的进展进行综述,旨在为靶向HIF-1抗肿瘤药物的研发提供新思路。     

Strongly enhanced quadrupole deformation in a class of N≈Z nuclei driven by large-scale clustering?

The formation of large size clusters,and/or their relative motion as a possible excitation mode,are sugge sted to be closely related to the origin of deformation in specific cases,namely the case of two doubly-magic clusters or two clusters with nearby characterization.New lifetime data in N=Z ~(76)Sr and ~(80)Zr leading to large B(E2) values are reproduced consistently and well within this approach,along with data for a few neighboring N≈Z nuclei.These results are compared to previous studies of ~(32)S and ~(20)Ne and all of them support the ideas of the large-scale cluster approach.     

Collection of NMR Scalar and Residual Dipolar Couplings Using a Single Experiment

A new DMSO‐compatible aligning gel based on cross‐linked poly(2‐hydroxylethyl methacrylate) (poly‐HEMA) has been developed. Due to a significant difference in bulk magnetic susceptibility between the DMSO inside and outside the gel, it is possible to simultaneously collect isotropic and anisotropic NMR data, such as residual dipolar couplings (RDC), in the same NMR tube. RDC‐assisted structural analysis of menthol and the alkaloid retrorsine is reported as proof of concept.     

Small molecule‐mediated glass transition of acrylic copolymers: Effect of hydrogen bonding strength on glass transition temperature

Poly(styrene‐co‐ethyl acrylate) [P(St‐co‐EA)] with different ratios of St/EA was mixed with the small molecule 4,4′‐thio‐bis(6‐tert‐butyl‐m‐methyl phenol) (AO300) to investigate the influence of hydrogen bonding strength on the glass transition behavior. The glass transition temperature (T_g) linearly increased after adding AO300, and the slope value decreased with increased St/EA ratio. All lines could be extended to 62 °C, demonstrating that T_g of the small molecule in situ detected by the polymer chain was much higher than that by small molecule itself (29 °C). Fourier transform infrared spectroscopy analysis showed that the small molecules began to be self‐associated at a concentration where the hydrogen bonded carbonyl ratio of the bulk polymer was approximately 0.5 and irrespective of the St/EA ratio. Above the critical loading, the mixture's T_g negatively deviated from the linearly extended lines because of self‐association of the small molecules. The apparent T_g of AO300 was found to strongly depend on intermolecular hydrogen bonding number and strength. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 400–408