Measurement of atmospheric neutrino flux consistent with tau neutrino appearance

A search for the appearance of tau neutrinos from nu(mu) <--> nu(tau) oscillations in the atmospheric neutrinos has been performed using 1489.2 days of atmospheric neutrino data from the Super-Kamiokande-I experiment. A best fit tau neutrino appearance signal of 138+/-48(stat)-32(+15)(syst) events is obtained with an expectation of 78+/-26(syst). The hypothesis of no tau neutrino appearance is disfavored by 2.4 sigma.     

Multireference configuration interaction calculation of the B(2)a"-X(2)a" transition of halogen- and methyl-substituted vinoxy radicals

Ground and second excited electronic states of halogen and monomethyl substituted vinoxy radicals were studied by multireference configuration interaction (MRCI) calculation. Optimized geometries, rotational constants and vibrational frequencies of vinoxy and 1-fluorovinoxy showed good agreement with experimental values. Differences in calculated and observed B-X electronic transition energies were less than 0.1 eV and observed trends of blue shift upon increasing the number of substituted halogen atoms were reproduced by MRCI calculation. Observed fluorescence lifetimes of the vibrationless level in B state were in good agreement with calculated values. Rotational profiles of the 0-0 vibronic bands were successfully simulated with calculated rotational constants and transition dipole moments. Energy differences between planar and nonplanar optimized geometries in B state showed good correlation with the onset of fast nonradiative decay in B state, supporting the proposed mechanism of nonradiative decay via avoided crossings from B to A state which is followed by the decay to the ground state via conical intersections.     

Recent advances in fluorescent probes for the detection of reactive oxygen species

Reactive oxygen species (ROS) have captured the interest of many researchers in the chemical, biological, and medical fields since they are thought to be associated with various pathological conditions. Fluorescent probes for the detection of ROS are promising tools with which to enhance our understanding of the physiological roles of ROS, because they provide spatial and temporal information about target biomolecules in in vivo cellular systems. ROS probes, designed to detect specific ROS with a high selectivity, would be desirable, since it is now becoming clear that each ROS has its own unique physiological activity. However, dihydro-compounds such as 2′,7′-dichlorodihydrofluorescein (DCFH), which have traditionally been used for detecting ROS, tend to react with a wide variety of ROS and are not completely photostable. Some attractive fluorescent probes that exhibit a high degree of selectivity toward specific ROS have recently been reported, and these selective probes are expected to have great potential for elucidating unknown physiological mechanisms associated with their target ROS. This review focuses on the design, detection mechanism, and performance of fluorescent probes for the detection of singlet oxygen (¹O₂), hydrogen peroxide (H₂O₂), hydroxyl radicals (^.OH), or superoxide anion (O₂ ^−.), a field in which remarkable progress has been achieved in the last few years.     

Large molecular assembly of amphotericin B formed in ergosterol-containing membrane evidenced by solid-state NMR of intramolecular bridged derivative

Amphotericin B (AmB 1) is known to assemble and form an ion channel across biomembranes. We have recently reported that conformation-restricted derivatives of AmB 2-4 show different ergosterol preferences in ion-channel assays, which suggested that the orientation of the mycosamine strongly affects the sterol selectivity of AmB. The data allowed us to assume that compound 3 showing the highest selectivity would reflect the active conformation of AmB in the channel assembly. In this study, to gain further insight into the active conformation of AmB, we prepared a new intramolecular-bridged derivative 5, where the linker encompassed a hydrophilic glycine moiety. The derivative has almost equivalent ion-channel activity to those of AmB and 3. The antifungal activity of 5 compared with 3 improves significantly, possibly because the increasing hydrophilicity in the linker enhances the penetrability through the fungal cell wall. Conformation of 5 was well converged and very similar to that of 3, thus further supporting the notion that the conformations of these derivatives reproduce the active structure of AmB in the channel complex. Then we used the derivative to probe the mobility of AmB in the membrane by solid-state NMR. To measure dipolar couplings and chemical shift anisotropies, we incorporated [1-(13)C,(15)N]glycine into the linker. The results indicate that 5 is mostly immobilized in ergosterol-containing DMPC bilayers, implying formation of large aggregates of 5. Meanwhile some fraction of 5 remains mobile in sterol-free DMPC bilayers, suggesting promotion of AmB aggregation by ergosterol.     

Generation of carbamoyl- and thiocarbamoyllithium synthons having a hydrogen(s) or an aryl group on the nitrogen and their trapping with carbonyl electrophiles

Dimetalated amides 1 (Y = O) were generated as the synthons of carbamoyllithiums 2 (Y = O) by the reaction of isocyanates with iBu2AlTenBu and a subsequent tellurium-lithium exchange reaction. A series of amide derivatives 3 (Y = O) were obtained by the trapping of dianion 1 with electrophiles. This transformation can be successfully applied to the generation and trapping of thiocarbamoyllithium synthons 1 (Y = S) as well as to the nucleophilic introduction of the parent carbamoyl moiety H2NC(O).     

A modified greedy algorithm for dispersively weighted 3-set cover

The set cover problem is that of computing a minimum weight subfamily F^′, given a family F of weighted subsets of a base set U, such that every element of U is covered by some subset in F^′. The k-set cover problem is a variant in which every subset is of size at most k. It has been long known that the problem can be approximated within a factor of by the greedy heuristic, but no better bound has been shown except for the case of unweighted subsets. In this paper we consider approximation of a restricted version of the weighted 3-set cover problem, as a first step towards better approximation of general k-set cover problem, where any two distinct subset costs differ by a multiplicative factor of at least 2. It will be shown, via LP duality, that an improved approximation bound of H(3)-1/6 can be attained, when the greedy heuristic is suitably modified for this case. A key to our algorithm design and analysis is the Gallai-Edmonds structure theorem for maximum matchings.     

Growth and characterization of pyrene crystals on carbon nanofibers

Pyrene crystals were grown on carbon nanofibers (CNFs) by dispersing pyrene polycrystals and CNFs in water during ultrasonic irradiation, and they were characterized by scanning electron microscopy, X-ray diffractometry (XRD) and spectroscopy. The XRD measurements indicated that the orientation and size of the pyrene crystals on the CNF aggregates were different from that of the added pyrene polycrystals. Based on the spectroscopic properties of the pyrene crystals on the CNFs, the pyrene crystals on the CNF aggregates and on the individual CNFs were determined to be polycrystals and single crystals, respectively. These results indicate that pyrene crystals are produced on the CNFs by recrystallization of the added pyrene polycrystals and their crystal states depend on the aggregation state of the CNFs.     

Targeted sonodynamic therapy using protein-modified TiO2 nanoparticles

Our previous study suggested new sonodynamic therapy for cancer cells based on the delivery of titanium dioxide (TiO₂) nanoparticles (NPs) modified with a protein specifically recognizing target cells and subsequent generation of hydroxyl radicals from TiO₂ NPs activated by external ultrasound irradiation (called TiO₂/US treatment). The present study first examined the uptake behavior of TiO₂ NPs modified with pre-S1/S2 (model protein-recognizing hepatocytes) by HepG2 cells for 24 h. It took 6 h for sufficient uptake of the TiO₂ NPs by the cells. Next, the effect of the TiO₂/US treatment on HepG2 cell growth was examined for 96 h after the 1 MHz ultrasound was irradiated (0.1 W/cm², 30 s) to the cells which incorporated the TiO₂ NPs. Apoptosis was observed at 6 h after the TiO₂/US treatment. Although no apparent cell-injury was observed until 24 h after the treatment, the viable cell concentration had deteriorated to 46% of the control at 96 h. Finally, the TiO₂/US treatment was applied to a mouse xenograft model. The pre-S1/S2-immobilized TiO₂ (0.1 mg) was directly injected into tumors, followed by 1 MHz ultrasound irradiation at 1.0 W/cm² for 60 s. As a result of the treatment repeated five times within 13 days, tumor growth could be hampered up to 28 days compared with the control conditions.     

Molecular Dynamics Simulation Studies on the Aggregation of Amyloid-β Peptides and Their Disaggregation by Ultrasonic Wave and Infrared Laser Irradiation

Alzheimer’s disease is understood to be caused by amyloid fibrils and oligomers formed by aggregated amyloid-β (Aβ) peptides. This review article presents molecular dynamics (MD) simulation studies of Aβ peptides and Aβ fragments on their aggregation, aggregation inhibition, amyloid fibril conformations in equilibrium, and disruption of the amyloid fibril by ultrasonic wave and infrared laser irradiation. In the aggregation of Aβ, a β-hairpin structure promotes the formation of intermolecular β-sheet structures. Aβ peptides tend to exist at hydrophilic/hydrophobic interfaces and form more β-hairpin structures than in bulk water. These facts are the reasons why the aggregation is accelerated at the interface. We also explain how polyphenols, which are attracting attention as aggregation inhibitors of Aβ peptides, interact with Aβ. An MD simulation study of the Aβ amyloid fibrils in equilibrium is also presented: the Aβ amyloid fibril has a different structure at one end from that at the other end. The amyloid fibrils can be destroyed by ultrasonic wave and infrared laser irradiation. The molecular mechanisms of these amyloid fibril disruptions are also explained, particularly focusing on the function of water molecules. Finally, we discuss the prospects for developing treatments for Alzheimer’s disease using MD simulations.