Shedding light upon macromolecular behaviour: Luminescence studies of polymers

In this paper the use of two time-resolved luminescence techniques in the study of polymer behaviour is illustrated. Time-resolved anisotropy measurements, TRAMS, have been used to study macromolecular mobilities both in solution and bulk phases. The first use of TRAMS involving phosphorescent labels in the study of synthetic polymers is reported and the potential of the technique for future applications in polymer science is discussed. Time-resolved energy transfer has been used to study polymer compatibility and interdiffusion in blends of PS-PMMA. The data offer clear evidence of the fact that the local concentration of chain termini in phase-separated systems is enriched in the interphase regions compared to that in the two bulk phases of the blend.     

Magnetic resonance imaging of microvascular leakage induced by myocardial contrast echocardiography in rats

The extent and magnitude of microvascular leakage induced by myocardial contrast echocardiography (MCE) were characterized with contrast-aided magnetic resonance imaging (MRI). Evans blue dye, Definity ultrasound contrast agent and Omniscan magnetic resonance contrast agent were injected intravenously in anesthetized rats suspended in a water bath. Diagnostic ultrasound B mode scans with 1:4 end-systolic triggering were performed at 1.5 MHz using a cardiac phased array scanhead to provide a short axis view of the left ventricle. The in situ peak rarefactional pressure amplitude (PRPA) was 2.0 MPa. Microvascular leakage was characterized by extraction of the dye from tissue samples and by imaging the distribution and concentration of Omniscan within the myocardium. The extracted Evans blue was 2.3 times greater than in shams (P<.05) for heart samples perfused with heparin saline, and 1.6 times greater than shams (not significant) for unperfused samples. The MRI showed the penetration of the ultrasound-induced capillary leakage throughout much of the scan plane. The overall gadolinium content measured by MR showed the same trends as the extracted Evans blue, but was more variable. For pooled data (perfused and unperfused), the exposed samples were significantly increased (P<.05) relative to the sham samples for both Evans blue and gadolinium content. Omniscan leakage was also discernable in two of four MRIs from intact rats (after sacrifice). These results demonstrate a potential for MR mapping of capillary leakage induced by contrast-aided ultrasound, with a possible application to spatial characterization of local drug delivery.     

Conformational basis for asymmetric seeding barrier in filaments of three- and four-repeat tau

Tau pathology in Alzheimer's disease is intimately linked to the deposition of proteinacious filaments, which akin to infectious prions, have been proposed to spread via seeded conversion. Here we use double electron-electron resonance (DEER) spectroscopy in combination with extensive computational analysis to show that filaments of three- (3R) and four-repeat (4R) tau are conformationally distinct. Distance measurements between spin labels in the third repeat, reveal tau amyloid filaments as ensembles of known β-strand-turn-β-strand U-turn motifs. Whereas filaments seeded with 3R tau are structurally homogeneous, filaments seeded with 4R tau are heterogeneous, composed of at least three distinct conformers. These findings establish a molecular basis for the seeding barrier between different tau isoforms and offer a new powerful approach for investigating the composition and dynamics of amyloid fibril ensembles.     

Nitrile-Containing Fischerindoles from the Cultured Cyanobacterium Fischerella sp

Chemical investigation of the cultured cyanobacterium Fischerella sp. (SAG strain number 46.79) led to the isolation of four nitrile-containing indole alkaloids, namely 12-epi-fischerindole I nitrile (1), deschloro 12-epi-fischerindole I nitrile (2), 12-epi-fischerindole W nitrile (3), and deschloro 12-epi-fischerindole W nitrile (4) along with a known metabolite hapalosin. The structures were determined by detailed spectroscopic analyses on the basis of 1D and 2D NMR and HRESIMS data. All isolates were evaluated for cytotoxicity against human cancer cells and for 20S proteasome inhibition. Deschloro 12-epi-fischerindole I nitrile (2) was found to be weakly cytotoxic against HT-29 cells with an ED(50) value of 23 μM. Hapalosin showed weak cytotoxicity against HT-29 and MCF-7 cells with ED(50) values of 22 and 27 μM, respectively, as well as moderate 20S proteasome inhibition with an IC(50) value of 12 μM. Compounds 1-4 all contain a nitrile moiety instead of the isonitrile found in all fischerindoles reported to date. Compounds 3 and 4 also display a new carbon skeleton, in which a six-membered ring replaces the five-membered ring normally found in fischerindole-type alkaloids.     

Scheduling Classes on a College Campus

We consider the problem of scheduling a set of classes to classrooms with the objective of minimizing the number of classrooms used. The major constraint that we must obey is that no two classes can be assigned to the same classroom at the same time on the same day of the week. We present an algorithm that produces a nearly optimal schedule for an arbitrary set of classes. The algorithm's first stage produces a packing of classes using a combination of a greedy algorithm and a non-bipartite matching and the second stage consists of a bipartite matching.First we show that for one variant of the problem our algorithm produces schedules that require a number of classrooms that is always within a small additive constant of optimal. Then we show that for an interesting variant of the problem the same algorithm produces schedules that require a small constant factor more classrooms than optimal. Finally, we report on experimental results of our algorithm using actual data and also show how to create schedules with other desirable characteristics.     

A new approach to prostanoids

A new asymmetric approach to 11-deoxyprostanoids is presented.