The Biochemical Mechanisms of Antimicrobial Photodynamic Therapy†

The unbridled dissemination of multidrug-resistant pathogens is a major threat to global health and urgently demands novel therapeutic alternatives. Antimicrobial photodynamic therapy (aPDT) has been developed as a promising approach to treat localized infections regardless of drug resistance profile or taxonomy. Even though this technique has been known for more than a century, discussions and speculations regarding the biochemical mechanisms of microbial inactivation have never reached a consensus on what is the primary cause of cell death. Since photochemically generated oxidants promote ubiquitous reactions with various biomolecules, researchers simply assumed that all cellular structures are equally damaged. In this study, biochemical, molecular, biological and advanced microscopy techniques were employed to investigate whether protein, membrane or DNA damage correlates better with dose-dependent microbial inactivation kinetics. We showed that although mild membrane permeabilization and late DNA damage occur, no correlation with inactivation kinetics was found. On the other hand, protein degradation was analyzed by three different methods and showed a dose-dependent trend that matches microbial inactivation kinetics. Our results provide a deeper mechanistic understanding of aPDT that can guide the scientific community toward the development of optimized photosensitizing drugs and also rationally propose synergistic combinations with antimicrobial chemotherapy.     

Frustration driven stock market dynamics: Leverage effect and asymmetry

By applying inverse statistics to financial data it has recently been found from empirical studies that indices exhibit a pronounced gain-loss asymmetry [M.H. Jensen, Phys. Rev. Lett. 83 (1999) 76; I. Simonsen, M.H. Jensen, A. Johansen, Eur. Phys. J. B 27 (2002) 583; M.H. Jensen, A. Johansen, I. Simonsen, Physica A 324 (2003) 338]. This gain-loss asymmetry appears to have some similarities with the stylized fact leverage effect and we investigate if they could be of same origin. For this purpose we introduce the Frustration Governed Market model which includes correlations in time between a model index and its individual stocks. It is shown that the model reproduces very well the empirical findings with respect to gain-loss asymmetry and leverage. In special cases, however, the model may produce leverage without a pronounced gain-loss asymmetry.     

Kinetic study of the reaction between hydroxylated polybutadienes and isocyanates. 1. Reaction with tolylene diisocyanate (TDI)

A comparative kinetic study of the reaction of three different hydroxylated liquid polybutadienes (M _n ? 3000) — R - 45M, R-45HT, and H-034—and tolylene diisocyanate (TDI), was carried out in toluene solution. An analytical method was used to follow the kinetics of the reactions at four different temperatures. The reactions presented an apparent second-order rate law. In the second-order plots, a discontinuity was observed. The R-45M polybutadiene was about twice more reactive than R-45HT and H-034; these latter two polybutadienes presented similar reactivities.     

Structure and conformational equilibrium of thiacalix[4]arene by density functional theory

Density functional theory calculations for the structure and conformational equilibrium of thiacalix[4]arene are reported. The conformational equilibrium of thiacalix[4]arene, a heterocalixarene in which the phenol groups are bridged by sulphur atoms is compared to the conformational equilibrium of calix[4]arene. Thiacalix[4]arene conformational energies relative to the cone conformer (ΔE's) are reduced in comparison with calix[4]arene. This conformational change is in qualitative agreement with recent NMR spectroscopy measurements of the conformational equilibrium for a tetraethylether of thiacalix[4]arene in a CDCl₃ solution which indicates an enhanced chemical exchange of thiacalixarene conformers in comparison with similar methylene bridged structures. Density functional theory results for the structure of thiacalix[4]arene are in good agreement with recent X-ray diffraction measurements. The electrostatic potentials in the cone conformers of thiacalix[4]arene and calix[4]arene suggest that their complexation or recognition abilities can be significantly different. Dipole moments of the four thiacalix[4]arene conformers are in the order: cone>1,2-alternate>partial-cone>1,3-alternate.     

Application of a Palladium‐Catalyzed C−H Functionalization/Indolization Method to Syntheses of cis‐Trikentrin A and Herbindole B

We describe herein formal syntheses of the indole alkaloids cis‐trikentrin A and herbindole B from a common meso‐hydroquinone intermediate prepared by a ruthenium‐catalyzed [2+2+1+1] cycloaddition that has not been used previously in natural product synthesis. Key steps include a sterically demanding Buchwald–Hartwig amination as well as a unique C(sp³)?H amination/indole formation. Studies toward a selective desymmetrization of the meso‐hydroquinone are also reported.     

A PASE-based approach towards 12-(1H-1,2,3-triazol-1-yl)-indolo[2,1-a]isoquinolines via the reaction of 3-(isoquinolin-1-yl)-1,2,4-triazines with benzyne

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Is it me or not me? Modulation of perceptual-motor awareness and visuomotor performance by mindfulness meditation

ABSTRACT: BACKGROUND: Attribution of agency involves the ability to distinguish our own actions and their sensory consequences which are self-generated from those generated by external agents. There are several pathological cases in which motor awareness is dramatically impaired. On the other hand, awareness-enhancement practices like tai-chi and yoga are shown to improve perceptual-motor awareness. Meditation is known to have positive impacts on perception, attention and consciousness itself, but it is still unclear how meditation changes sensorimotor integration processes and awareness of action. The aim of this study was to investigate how visuomotor performance and self-agency is modulated by mindfulness meditation. This was done by studying meditators' performance during a conflicting reaching task, where the congruency between actions and their consequences is gradually altered. This task was presented to novices in meditation before and after an intensive 8 weeks mindfulness meditation training (MBSR). The data of this sample was compared to a group of long-term meditators and a group of healthy non-meditators. RESULTS: Mindfulness resulted in a significant improvement in motor control during perceptual-motor conflict in both groups. Novices in mindfulness demonstrated a strongly increased sensitivity to detect external perturbation after the MBSR intervention. Both mindfulness groups demonstrated a speed/accuracy trade-off in comparison to their respective controls. This resulted in slower and more accurate movements. CONCLUSIONS: Our results suggest that mindfulness meditation practice is associated with slower body movements which in turn may lead to an increase in monitoring of body states and optimized re-adjustment of movement trajectory, and consequently to better motor performance. This extended conscious monitoring of perceptual and motor cues may explain how, while dealing with perceptual-motor conflict, improvement in motor control goes beyond the mere increase of movement time. The reduction of detection threshold in the MBSR group is also likely due to the enhanced monitoring of these processes. Our findings confirmed our assumptions about the positive effect of mindfulness on perceptual-motor integration processes.     

Disintegration-of-measure techniques for commuting multivariable weighted shifts

We employ techniques from the theory of disintegration of measuresto study the Lifting Problem for commuting n-tuples of subnormalweighted shifts. We obtain a new necessary condition for theexistence of a lifting, and generate new pathology associatedwith bringing together the Berger measures associated to eachindividual weighted shift. For subnormal 2-variable weightedshifts, we then find the precise relation between the Bergermeasure of the pair and the Berger measures of the shifts associatedto horizontal rows and vertical columns of weights. 2000 MathematicsSubject Classification 47B20, 47B37, 47A13, 28A50 (primary),44A60, 47-04, 47A20 (secondary).