Total Synthesis and Biological Assessment of Mandelalide A

A new convergent total synthesis of the marine macrolide mandelalide A ( 1 ) has been developed that is based on macrocyclic ring closure by a Shiina‐type macrolactonization and the construction of the requisite precursor seco acid by a highly efficient Sonogashira cross‐coupling reaction between two fragments of comparable complexity. Key steps in the elaboration of the acid building block were the enantioselective, catalytic addition of a protected acetylene to crotonaldehyde and the construction of the tetrahydropyran unit that is embedded in the macrocycle by means of an acid‐catalyzed Prins reaction. The synthesis of the alcohol fragment features the formation of the trisubstituted tetrahydrofuran ring through an acetal cleavage/epoxide opening cascade reaction and a rarely used radical alkynylation of a primary alkyl iodide. Intriguingly, the dihydroxylation of a terminal double bond as part of the synthesis of this building block gave the same major product for both the α‐ and β‐AD‐mix reagents, albeit with moderate or low selectivity. Synthetic mandelalide A ( 1 ) was a potent proliferation inhibitor of A549, HT460, and H1299 human lung cancer cells in vitro, but not of SK‐N‐SH neuroblastoma cells. However, in no case did we observe complete cell kill even at the highest compound concentration tested (5 μm ).     

Stress analysis by combination of holographic interferometry and boundary-integral method

The paper describes a hybrid experimental and numerical method analysis of bodies. It consists of the experimental method of double-aperture speckle interferometry and the boundary-integral method. The interference patterns allowing evaluation of the displacement vector are obtained by the speckle interferometry. The boundary displacements obtained experimentally are conveniently used for the calculation of stresses in the body by the boundary-integral method. Some examples bear witness of the effectiveness and accuracy of the hybrid technique.     

Viscoelastic crack analysis by the boundary integral equation method

Summary The linear viscoelastic three-dimensional crack problem is analyzed by combining the correspondence principle and the boundary integral equation method. In a general crack analysis the usual boundary integral equations lead to a nonunique formulation of the problem, because they do not involve information about the loading on the crack surface. Here, the boundary integro-differential equations are applied to the numerical calculation of the crack opening displacement of a penny-shaped crack in an infinite linear viscoelastic body. Moreover, the influence of several parameters of the three-parameter viscoelastic model on the crack opening displacement and the incubation time is shown.

---

Viskoelastische Rißanalyse durch Randintegralgleichungen

Übersicht Das linear viskoelastisch räumliche Rißproblem wird mit Hilfe einer Kombination von Korrespondenzprinzip und Randintegralgleichungsverfahren gelöst. In einer allgemeinen Rißanalyse führen die üblichen Randintegrale zu einer nicht eindeutigen Formulierung dieses Problems, weil die Angaben über Belastung und Rißoberfläche fehlen. Das Randintegralgleichungsverfahren wird für die numerische Berechnung der Rißerweiterung eines münzförmigen Risses in einem unendlich linear viskoelastischen Körper angewendet. Weiterhin wird der Einfluß von verschiedenen Parametern des räumlich viskoelastischen Modells auf die Rißerweiterung und die Inkubationszeit gezeigt.

     

Emergency Optically Stimulated Luminescence Dosimetry Using Different Materials

Several materials were tested as possible individual emergency dosimeters using Optically Stimulated Luminescence (OSL) as means to assess the exposure. Materials investigated included human nails, business cards and plastic buttons. The OSL properties of these materials were studied in comparison with those of teeth. Most samples revealed OSL signals only after exposure to ionizing radiation; some samples of business cards, however, displayed a strong initial "native" signal (i.e. existing in the samples prior to irradiation). The sensitivity (minimum measurable dose) of the samples was found to vary significantly from sample to sample of the same material and was in the range from several tens of mGy to a few dozens of Gy. The dose response curves were linear for doses below 10 Gy. Fading of the OSL signals was estimated for different lenghts of times and found to be ~95%, 45%, 30% and 15% for samples of teeth, business cards, buttons and nails, respectively, following storage at room temperature in the dark for a period of 3 weeks after exposure. For samples stored under routine laboratory light, fading was much faster and the radiation-induced signals almost disappeared after a few hours of such illumination. It was concluded that the tested materials could be used in triage situations to detect and estimate the possible overexposure of individuals if the measurements can be performed soon enough after exposure.     

Magneto-crystalline properties of BaFe12−2x M x Sn x O19 (M = Sn, Ni, Zn) ferrite powders

BaFe_12?2x M _x Sn _x O₁₉ compounds, where M?=?Sn²⁺, Ni²⁺ or Zn²⁺ ions, were synthesized by mechanical milling and partially by citrate precursor methods. Analysis of magneto-crystalline structure has been carried out by Mössbauer spectroscopy. The Sn⁴⁺ ions replace Fe³⁺ ions on 2b and slightly on 2a?+?4f₁ sites, Zn²⁺ ions strongly prefer 4f₁ sites, Sn²⁺ ions prefer 4f₁ sites too and Ni²⁺ ions occupy 4f₂ and 12k or 2a sites. The magnetic properties were evaluated by the vibrating sample magnetometry and the thermomagnetic analysis. A large variation of the intrinsic coercivity H _c (330 to 78 kA/m) and of temperature coefficient of coercivity of ΔH _c /Δ? (0.39 to 0.22 kA/m°C) were achieved as a function of the (Zn–Sn) and (Sn–Sn) substitutions, respectively. The Curie temperature T _c decreased with the (Ni–Sn) substitution from 447 to 399°C.     

Ex vivo quantification of mTHPC concentration in tissue: influence of chemical extraction on the optical properties

A method for the quantification of the concentration of the photosensitizer meso-tetra(hydroxyphenyl) chlorin (mTHPC) in tissue samples is presented. The technique is an extension of a previously published method based on alkaline hydrolysis of tissue, using Solvable as a tissue solubilizer. mTHPC quantification was achieved by subsequent fluorescence spectroscopy. Since the original extraction method involved multiple steps in which water dilution of the sample was implemented, we studied the spectral characteristics of mTHPC in different Solvable/water mixtures. Using UV-VIS absorption and fluorescence spectroscopy, it was demonstrated that the spectral characteristics of mTHPC vary for different Solvable concentrations. In the range of 20-100% Solvable, the fluorescence intensity of mTHPC did not change, while dramatic changes in the mTHPC fluorescence intensity were observed for lower Solvable concentrations (< 20%) due to increasing hydrophilicity of the environment, combined with pH alterations. We also demonstrated that the absorption and fluorescence spectra of the dissolved tissue were time-dependent. Longer incubation of the samples resulted in a significant increase of the native tissue chromophore fluorescence. This implies that for the correct quantification of photosensitizer concentrations, the fluorescence of native tissue chromophores must be accounted for.     

Electrophoretic methods for analysis of urinary polypeptides in IgA-associated renal diseases

We evaluated the utility of SDS-PAGE/Western blot and CE coupled with MS (CE-MS) for detection of urinary polypeptide biomarkers of renal disease in patients with IgA-associated glomerulonephritides. In a reference cohort of 402 patients with various renal disorders and 207 healthy controls, we defined CE-MS patterns of renal damage and IgA nephropathy (IgAN). In a blinded analysis of a separate cohort of patients with IgAN (n = 10), Henoch-Schoenlein purpura (HSP) with nephritis (n = 10), and IgA-associated glomerulonephritis due to hepatitis C virus (HCV)-induced cirrhosis (n = 9), and healthy controls (n = 12), we compared SDS-PAGE/Western blot and CE-MS against clinical urinalysis for detection of urinary proteins/polypeptides. Urinalysis indicated proteinuria for 50, 90, and 33% of patients, respectively, and for none of the healthy controls. SDS-PAGE/Western blot showed urinary polypeptides abnormality for 90, 80, and 67% of patients, respectively, and for none of the healthy controls. CE-MS indicated a Renal Damage Pattern in 80, 80, and 100 of patients, respectively, and in 17% of healthy controls, with the more specific IgAN Pattern in 90, 90, and 1%, respectively, and in none of the healthy controls. Based on differences in CE-MS patterns, the disease mechanisms may differ among various IgA-associated glomerulonephritides. These exploratory findings should be evaluated in a prospective study with contemporaneous renal biopsy and urinary testing. If validated, it may be feasible to adapt the CE-MS methodology to develop novel tests to detect renal injury at earlier stages, assess clinical manifestations, and monitor responses to therapy in patients with IgA-associated renal diseases.     

Operator differential-algebraic equations with noise arising in fluid dynamics

We study linear semi-explicit stochastic operator differential algebraic equations (DAEs) for which the constraint equation is given in an explicit form. In particular, this includes the Stokes equations arising in fluid dynamics. We combine a white noise polynomial chaos expansion approach to include stochastic perturbations with deterministic regularization techniques. With this, we are able to include Gaussian noise and stochastic convolution terms as perturbations in the differential as well as in the constraint equation. By the application of the polynomial chaos expansion method, we reduce the stochastic operator DAE to an infinite system of deterministic operator DAEs for the stochastic coefficients. Since the obtained system is very sensitive to perturbations in the constraint equation, we analyze a regularized version of the system. This then allows to prove the existence and uniqueness of the solution of the initial stochastic operator DAE in a certain weighted space of stochastic processes.     

Directed Hydrogenations and an Ireland–Claisen Rearrangement Linked to Evans–Tishchenko Chemistry: The Highly Efficient Total Synthesis of the Marine Cyclodepsipeptide Doliculide

Two new convergent total syntheses have been developed for the cytotoxic, actin microfilament‐stabilizing marine cyclodepsipeptide doliculide ( 1 ). A key strategic element of both routes is the establishment of the central stereogenic center of the characteristic polydeoxypropionate stereotriad by means of a hydroxyl‐directed catalytic hydrogenation of a trisubstituted double bond. The requisite olefin substrates were obtained through a modified Suzuki–Miyaura coupling or through Ireland–Claisen rearrangement of a propionate ester, respectively; the latter was the direct result of a highly selective Evans–Tishchenko reduction of a hydroxy ketone that had been obtained in a stereoselective Paterson aldol reaction. Doliculide ( 1 ) was finally obtained in a total number of 17 or 15 (14) linear steps, respectively, which represents a substantial improvement over previous syntheses of this highly bioactive natural product.