First synthesis of a steroid containing an unstable 19-nor-androsta-1,5-dien-3-one system

Mechanisms involved in the maintenance of human pregnancy and initiation of labour are poorly defined. A novel steroid hormone named estradienolone (ED), and having an unusual 19-nor-androsta-1,5-dien-3-one system, was previously reported. However, ED is scarcely available from urine, placenta and blood of pregnant women. For this reason, we have synthesized ED in order to verify its proposed structure. Although a 1,5-dien-3-one system had already been described for a C19-steroid (androstane) nucleus (no possible aromatization), the synthesis of the 19-nor-analogue is a major challenge because this system is very sensitive to aromatization. We now describe the successful construction and characterization of this unstable system. Starting from nortestosterone, the synthesis of 17β-hydroxy-19-nor-androsta-1,5-dien-3-one (1) is based on a protection of the 5,6-double bond, the introduction of the second 1,2-double bond, the careful recovery of the exo double bond and a final regioselective oxidation or reduction.     

Interlaboratory study to improve the quality of trace element determinations in rainwater

This is the first publication which describes the development of a reference material (RM) for the determination of 11 trace elements (Cu, Pb, Mn, Ni, Zn, Fe, Cd, Co, V, As and Al) in rainwater at microgram per liter concentrations. An interlaboratory comparison study for the determination of trace elements in rainwater was carried out for material performance studies to establish analyte concentrations with a stated uncertainty. Fifteen reputed laboratories from Asia, Europe and North America participated in the study. These laboratories used their regular in-house methods to analyze the rainwater samples. The aim of this study is to establish concentration levels of trace elements in rainwater based on interlaboratory study results. Details of the production, homogeneity and stability of the reference sample are given in this article. The organization of the study and the quality assurance measures undertaken at the organizer's laboratory are described. The analytical results obtained from individual laboratories and the analytical methods used for the determination of trace elements in rainwater are discussed. Based on the results obtained from the intercomparison study, certified values as well as informative values are assigned to the 11 trace elements in rainwater.     

Maps of several variables of finite total variation. II. E. Helly-type pointwise selection principles

Given a=(a₁,…,an), b=(b₁,…,bn)∈Rn with a<b componentwise and a map f from the rectangle into a metric semigroup M=(M,d,+), denote by the Hildebrandt-Leonov total variation of f on , which has been recently studied in [V.V. Chistyakov, Yu.V. Tretyachenko, Maps of several variables of finite total variation. I, J. Math. Anal. Appl. (2010), submitted for publication]. The following Helly-type pointwise selection principle is proved: If a sequence{fj}_j∈Nof maps frominto M is such that the closure in M of the set{fj(x)}_j∈Nis compact for eachandis finite, then there exists a subsequence of{fj}_j∈N, which converges pointwise onto a map f such that. A variant of this result is established concerning the weak pointwise convergence when values of maps lie in a reflexive Banach space (M,‖⋅‖) with separable dual M^∗.     

Distant total irregularity strength of graphs via random vertex ordering

Let $c:V\cup E\to \{1,2,\dots ,k\}$ be a (not necessarily proper) total colouring of a graph $G=(V,E)$ with maximum degree $\Delta$. Two vertices $u,v\in V$ are sum distinguished if they differ with respect to sums of their incident colours, i.e. $c\left(u\right)+{\sum }_{e?u}c\left(e\right)\ne c\left(v\right)+{\sum }_{e?v}c\left(e\right)$. The least integer $k$ admitting such colouring $c$ under which every $u,v\in V$ at distance $1\le d(u,v)\le r$ in $G$ are sum distinguished is denoted by ${\mathrm{ts}}_r\left(G\right)$. Such graph invariants link the concept of the total vertex irregularity strength of graphs with so-called 1-2-Conjecture, whose concern is the case of $r=1$. Within this paper we combine probabilistic approach with purely combinatorial one in order to prove that ${\mathrm{ts}}_r\left(G\right)\le (2+o\left(1\right)){\Delta }^{r?1}$ for every integer $r\ge 2$ and each graph $G$, thus improving the previously best result: ${\mathrm{ts}}_r\left(G\right)\le 3{\Delta }^{r?1}$.     

Nanoimprint Lithography with UV-Curable Hyperbranched Polymer Nanocomposites

Nano-scale patterns were produced with UV-curable acrylated hyperbranched polymer nanocomposites using nanoimprint lithography with a glass master in a rapid, low-pressure process. The pattern of the glass master was replicated with composites containing up to 25 vol% SiO₂ with a shape fidelity better than 98%. Photo-rheology, interferometry and atomic force microscopy were used to analyze the material behavior. Attention was paid to the relationship between composition, nanoparticle dispersion, kinetics of photo-polymerisation, shrinkage, pressure and shape fidelity of nano-gratings. It was shown that the gel-point of the nanocomposite was an important factor that determined the stability as well as the dimensions of the imprinted structure. Dimensional accuracy also strongly depended on the level of internal stress, which in fact increased with the amount of silica. A resin rich layer on the surface of the composite accounted for the good surface quality of the nano-pattern.     

Strongly nonlinear internal soliton load on a small vertical circular cylinder in two-layer fluids

The solutions of MCC theory are used to investigate larger-amplitude strongly nonlinear internal soliton load on a small surface-piercing circular cylinder in two-layer fluids. By comparing the wave profiles and instantaneous horizontal velocities calculated by MCC theory with those of KdV theory and experimental data, we verify the validity of MCC theory for larger-amplitude strongly nonlinear internal soliton. The accelerations are computed, and then force and torque on a small cylinder are estimated based on Morison’s formula for both MCC and KdV theories. Computed results show that the internal soliton force and torque become more and more large and wide with the increase of amplitude for MCC theory. The location of torque crest calculated by MCC theory departs from origin (moving to the right) as the amplitude grows and whenever the inertial term is included or not, the wave forces computed based on the two theories both have small discrepancies for the same amplitude, but when the inertial term is included, the torque obtained by MCC theory will be much larger and the torque obtained by KdV still have a small discrepancy. The reasons are presented in detail. The internal wave force will be underestimated if the traditional KdV theory is used. Therefore, ocean engineers should consider the large-amplitude strongly nonlinear internal soliton load on marine construct carefully.     

Neighborhood search approaches to non-coplanar beam orientation optimization for total marrow irradiation using IMRT

We consider the beam orientation optimization (BOO) problem for total marrow irradiation (TMI) treatment planning using intensity modulated radiation therapy (IMRT). Currently, IMRT is not widely used in TMI treatment delivery; furthermore, the effect of using non-coplanar beam orientations is not known. We propose and implement several variations of a single neighborhood search algorithm that solves the BOO problem effectively when gantry angles and couch translations are considered. Our work shows that the BOO problem for TMI cases can be solved in a clinically acceptable amount of time and leads to treatment plans that are more effective than the conventional approach to TMI.     

Spirastrellolide studies. Synthesis of the C(1)-C(25) southern hemispheres of spirastrellolides A and B, exploiting anion relay chemistry

Construction of the C(1)-C(25) southern fragments of both spirastrellolide A and B are described. Highlights of the syntheses include effective use of the three component anion relay chemistry (ARC) tactic recently introduced by our laboratory, a stereoselective spirocyclization via concomitant Ferrier reaction to elaborate the BC spiroketal and use of two dithiane unions to install the A ring as well as C(22)-C(25) fragment. The synthesis proceeded with longest linear sequences of 33 and 32 steps, respectively for spirastrellolide A and spirastrellolide B.     

An Enantioselective Approach to the Securinega Alkaloids: The Total Synthesis of (+)-Norsecurinine and (+)-Allonorsecurinine

Total syntheses of (+)-norsecurinine and (+)-allonorsecurinine are described that utilize a rhodium carbenoid-initiated O-H insertion/Claisen rearrangement/1,2-allyl migration domino process for the stereoselective introduction of the tertiary alcohol moiety. Overall the employed strategy is flexible and will allow access to other members of the Securinega family of alkaloids.     

Total synthesis of neomethymycin and novamethymycin

Total synthesis of neomethymycin and novamethymycin has been achieved. These two macrolides contains 12-membered macrolactones as aglycones and belong to the methymycin family of antibiotics, which appears in the pikromycin biosynthetic pathway. The segments in the 12-membered macrolactone that are responsible for causing structural difference in neomethymycin and novamethymycin were synthesized by starting with methyl d-(+)-lactate and d-glucose, for neomethynolide, and for novamethynolide, respectively. The key steps in synthesis of neomethynolide and novamethynolide, which are aglycones for neomethymycin and novamethymycin, respectively, were asymmetric aldol reactions, Yamaguchi esterification, and ring-closing metathesis using Grubbs’ second generation catalyst. Finally, the coupling of agylcones with the corresponding trichloroacetimidates, followed by deprotection, completed the total synthesis of these two macrolide antibiotics.