Ortho-Fluorination of azophenols increases the mesophase stability of photoresponsive hydrogen-bonded liquid crystals

Photoresponsive liquid crystals (LCs) whose alignment can be controlled with UV-Visible light are appealing for a range of photonic applications. From the perspective of exploring the interplay between the light response and the self-assembly of the molecular components, supramolecular liquid crystals are of particular interest. They allow elaborating the structure-property relationships that govern the optical performance of LC materials by subtle variation of the chemical structures of the building blocks. Herein we present a supramolecular system comprising azophenols and stilbazoles as hydrogen-bond donors and acceptors, respectively, and show that ortho-fluorination of the azophenol dramatically increases the thermal stability of the LC phases, an important characteristics in their further utilization in photonics. The systems exhibit fast photoinduced order-disorder transitions, and rapid recovery of the liquid-crystalline state once the light irradiation is ceased, due to the photochemical properties of azophenols

Public Perceptions of the Midwest\u27s Pavements - Iowa - Executive Summary

This report summarizes Iowa results of a five year, Pooled Fund study involving the Wisconsin, Iowa, and Minnesota DOTs designed to 1) assess the public\u27s perceptions of the departments’ pavement improvement strategies and 2) to develop customer-based thresholds of satisfaction with pavements on rural two lane highways in each state as related to the Departments’ physical indices, such as pavement ride and condition. The primary objective was to seek systematic customer input to improve the Departments’ pavement improvement policies by 1) determining how drivers perceive the departments’ pavements in terms of comfort and convenience but also in terms of other tradeoffs departments had not previously considered, 2) determining relationships between perceptions and measured pavement condition thresholds (including a general level of tolerance of winter ride conditions in two of the states), and 3) identifying important attributes and issues that may not have been considered in the past. Secondary objectives were 1) to provide a tool for systematic customer input in the future and 2) provide information which can help structure public information programs. A University of Wisconsin-Extension survey lab conducted the surveys under the direction of a multi-disciplinary team from Marquette University. Approximately 4500 drivers in the three states participated in the three phases of the project. Researchers conducted six focus groups in each state, approximately 400 statewide telephone interviews in each state and 700-800 targeted telephone interviews in each state. Approximately 400 winter ride interviews were conducted in Wisconsin and Minnesota. A summary of the method for each survey is included. In Phase I, focus groups were conducted with drivers to get an initial indication of what the driving public believes in regards to pavements and to frame issues for inclusion in the more representative state-wide surveys of drivers conducted in Phase II of the project. Phase II interviews gathered information about improvement policy trade-off issues and about preliminary thresholds of improvement in terms of physical pavement indices. In Phase III, a two step recruitment and post-drive interview procedure yielded thresholds of ride and condition index summarized for each state. Results show that, in general, the driving public wants longer lasting pavements and are willing to pay for them. They want to minimize construction delay, improve entire sections of highway at one time but they dislike detours, and prefer construction under traffic even if it stretches out construction time. Satisfaction with pavements does not correlate directly to a high degree with physical pavement indices, but was found instead to be a complex, multi-faceted phenomenon. A psychological model (after Fishbein/Ajzen) was applied to explain satisfaction to a respectable degree (R2 of .7) for the social sciences. Results also indicate a high degree of trust in the three DOTs which is enhanced when the public is asked for input on specific highway segments. Conclusions and recommendations include a three-step methodology for other state studies. Physical data thresholds based on both public satisfaction and the agreement to improve are presented for each state\u27s physical pavement indices (ride and condition). Recommendations for changes to the quality ranges of the physical indices where appropriate are also made

Functional Characterisation of Alpha-Galactosidase A Mutations as a Basis for a New Classification System in Fabry Disease

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The study has been supported partially by an unrestricted scientific grant from Shire Human Genetic Therapies (Germany

Cooling dynamics of a dilute gas of inelastic rods: a many particle simulation

We present results of simulations for a dilute gas of inelastically colliding particles. Collisions are modelled as a stochastic process, which on average decreases the translational energy (cooling), but allows for fluctuations in the transfer of energy to internal vibrations. We show that these fluctuations are strong enough to suppress inelastic collapse. This allows us to study large systems for long times in the truely inelastic regime. During the cooling stage we observe complex cluster dynamics, as large clusters of particles form, collide and merge or dissolve. Typical clusters are found to survive long enough to establish local equilibrium within a cluster, but not among different clusters. We extend the model to include net dissipation of energy by damping of the internal vibrations. Inelatic collapse is avoided also in this case but in contrast to the conservative system the translational energy decays according to the mean field scaling law, E(t)\propto t^{-2}, for asymptotically long times.Comment: 10 pages, 12 figures, Latex; extended discussion, accepted for publication in Phys. Rev.

Identification of tetrahydrocarbazoles as novel multifactorial drug candidates for treatment of Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder and the most frequent cause of dementia. To date, there are only a few approved drugs for AD, which show little or no effect on disease progression. Impaired intracellular calcium homeostasis is believed to occur early in the cascade of events leading to AD. Here, we examined the possibility of normalizing the disrupted calcium homeostasis in the endoplasmic reticulum (ER) store as an innovative approach for AD drug discovery. High-throughput screening of a small-molecule compound library led to the identification of tetrahydrocarbazoles, a novel multifactorial class of compounds that can normalize the impaired ER calcium homeostasis. We found that the tetrahydrocarbazole lead structure, first, dampens the enhanced calcium release from ER in HEK293 cells expressing familial Alzheimer's disease (FAD)-linked presenilin 1 mutations. Second, the lead structure also improves mitochondrial function, measured by increased mitochondrial membrane potential. Third, the same lead structure also attenuates the production of amyloid-beta (A beta) peptides by decreasing the cleavage of amyloid precursor protein (APP) by beta-secretase, without notably affecting alpha- and gamma-secretase cleavage activities. Considering the beneficial effects of tetrahydrocarbazoles addressing three key pathological aspects of AD, these compounds hold promise for the development of potentially effective AD drug candidates

View-Based Encoding of Actions in Mirror Neurons of Area F5 in Macaque Premotor Cortex

SummaryConverging experimental evidence indicates that mirror neurons in the monkey premotor area F5 encode the goals of observed motor acts [1–3]. However, it is unknown whether they also contribute to encoding the perspective from which the motor acts of others are seen. In order to address this issue, we recorded the visual responses of mirror neurons of monkey area F5 by using a novel experimental paradigm based on the presentation of movies showing grasping motor acts from different visual perspectives. We found that the majority of the tested mirror neurons (74%) exhibited view-dependent activity with responses tuned to specific points of view. A minority of the tested mirror neurons (26%) exhibited view-independent responses. We conclude that view-independent mirror neurons encode action goals irrespective of the details of the observed motor acts, whereas the view-dependent ones might either form an intermediate step in the formation of view independence or contribute to a modulation of view-dependent representations in higher-level visual areas, potentially linking the goals of observed motor acts with their pictorial aspects

Mirror neurons in monkey area F5 do not adapt to the observation of repeated actions

Repetitive presentation of the same visual stimulus entails a response decrease in the action potential discharge of neurons in various areas of the monkey visual cortex. It is still unclear whether this repetition suppression effect is also present in single neurons in cortical premotor areas responding to visual stimuli, as suggested by the human functional magnetic resonance imaging literature. Here we report the responses of 'mirror neurons' in monkey area F5 to the repeated presentation of action movies. We find that most single neurons and the population at large do not show a significant decrease of the firing rate. On the other hand, simultaneously recorded local field potentials exhibit repetition suppression. As local field potentials are believed to be better linked to the blood-oxygen-level-dependent (BOLD) signal exploited by functional magnetic resonance imaging, these findings suggest caution when trying to derive conclusions on the spiking activity of neurons in a given area based on the observation of BOLD repetition suppression

Melanoma Inhibitory Activity (MIA) increases the invasiveness of pancreatic cancer cells

BACKGROUND: Melanoma inhibitory activity (MIA) is a small secreted protein that interacts with extracellular matrix proteins. Its over-expression promotes the metastatic behavior of malignant melanoma, thus making it a potential prognostic marker in this disease. In the present study, the expression and functional role of MIA was analyzed in pancreatic cancer by quantitative real-time PCR (QRT-PCR), immunohistochemistry, immunoblot analysis and ELISA. To determine the effects of MIA on tumor cell growth and invasion, MTT cell growth assays and modified Boyden chamber invasion assays were used. RESULTS: The mRNA expression of MIA was 42-fold increased in pancreatic cancers in comparison to normal pancreatic tissues (p < 0.01). In contrast, MIA serum levels were not significantly different between healthy donors and pancreatic cancer patients. In pancreatic tissues, MIA was predominantly localized in malignant cells and in tubular complexes of cancer specimens, whereas normal ductal cells, acinar cells and islets were devoid of MIA immunoreactivity. MIA significantly promoted the invasiveness of cultured pancreatic cancer cells without influencing cell proliferation. CONCLUSION: MIA is over-expressed in pancreatic cancer and has the potential of promoting the invasiveness of pancreatic cancer cells

Diffraction in low-energy electron scattering from DNA: bridging gas phase and solid state theory

Using high-quality gas phase electron scattering calculations and multiple scattering theory, we attempt to gain insights on the radiation damage to DNA induced by secondary low-energy electrons in the condensed phase, and to bridge the existing gap with the gas phase theory and experiments. The origin of different resonant features (arising from single molecules or diffraction) is discussed and the calculations are compared to existing experiments in thin films.Comment: 40 pages preprint, 12 figures, submitted to J. Chem. Phy