Targeting the Progression of Parkinson’s Disease

By the time a patient first presents with symptoms of Parkinson’s disease at the clinic, a significant proportion (50-70%) of the cells in the substantia nigra (SN) has already been destroyed. This degeneration progresses until, within a few years, most of the cells have died. Except for rare cases of familial PD, the initial trigger for cell loss is unknown. However, we do have some clues as to why the damage, once initiated, progresses unabated. It would represent a major advance in therapy to arrest cell loss at the stage when the patient first presents at the clinic. Current therapies for Parkinson’s disease focus on relieving the motor symptoms of the disease, these unfortunately lose their effectiveness as the neurodegeneration and symptoms progress. Many experimental approaches are currently being investigated attempting to alter the progression of the disease. These range from replacement of the lost neurons to neuroprotective therapies; each of these will be briefly discussed in this review. The main thrust of this review is to explore the interactions between dopamine, alpha synuclein and redox-active metals. There is abundant evidence suggesting that destruction of SN cells occurs as a result of a self-propagating series of reactions involving dopamine, alpha synuclein and redox-active metals. A potent reducing agent, the neurotransmitter dopamine has a central role in this scheme, acting through redox metallo-chemistry to catalyze the formation of toxic oligomers of alpha-synuclein and neurotoxic metabolites including 6-hydroxydopamine. It has been hypothesized that these feed the cycle of neurodegeneration by generating further oxidative stress. The goal of dissecting and understanding the observed pathological changes is to identify therapeutic targets to mitigate the progression of this debilitating disease

Superconducting fluctuation corrections to ultrasound attenuation in layered superconductors

We consider the temperature dependence of the sound attenuation and sound velocity in layered impure metals due to superconducting fluctuations of the order parameter above the critical temperature. We obtain the dependence on material properties of these fluctuation corrections in the hydrodynamic limit, where the electron mean free path is much smaller than the wavelength of sound and where the electron collision rate is much larger than the sound frequency. For longitudinal sound propagating perpendicular to the layers, the open Fermi surface condition leads to a suppression of the divergent contributions to leading order, in contrast with the case of paraconductivity. The leading temperature dependent corrections, given by the Aslamazov-Larkin, Maki-Thompson and density of states terms, remain finite as T->Tc. Nevertheless, the sensitivity of new ultrasonic experiments on layered organic conductors should make these fluctuations effects measurable.Comment: 13 pages, 6 figures. Accepted for PRB. Added discussion on incoherent interlayer tunneling and other small modifications suggested by referee

The dependence of the EIT wave velocity on the magnetic field strength

"EIT waves" are a wavelike phenomenon propagating in the corona, which were initially observed in the extreme ultraviolet (EUV) wavelength by the EUV Imaging Telescope (EIT). Their nature is still elusive, with the debate between fast-mode wave model and non-wave model. In order to distinguish between these models, we investigate the relation between the EIT wave velocity and the local magnetic field in the corona. It is found that the two parameters show significant negative correlation in most of the EIT wave fronts, {\it i.e.}, EIT wave propagates more slowly in the regions of stronger magnetic field. Such a result poses a big challenge to the fast-mode wave model, which would predict a strong positive correlation between the two parameters. However, it is demonstrated that such a result can be explained by the fieldline stretching model, \emph{i.e.,} that "EIT waves" are apparently-propagating brightenings, which are generated by successive stretching of closed magnetic field lines pushed by the erupting flux rope during coronal mass ejections (CMEs).Comment: 11 pages, 8 figures, accepted for publication in Solar Phy

The low-lying excitations of polydiacetylene

The Pariser-Parr-Pople Hamiltonian is used to calculate and identify the nature of the low-lying vertical transition energies of polydiacetylene. The model is solved using the density matrix renormalisation group method for a fixed acetylenic geometry for chains of up to 102 atoms. The non-linear optical properties of polydiacetylene are considered, which are determined by the third-order susceptibility. The experimental 1Bu data of Giesa and Schultz are used as the geometric model for the calculation. For short chains, the calculated E(1Bu) agrees with the experimental value, within solvation effects (ca. 0.3 eV). The charge gap is used to characterise bound and unbound states. The nBu is above the charge gap and hence a continuum state; the 1Bu, 2Ag and mAg are not and hence are bound excitons. For large chain lengths, the nBu tends towards the charge gap as expected, strongly suggesting that the nBu is the conduction band edge. The conduction band edge for PDA is agreed in the literature to be ca. 3.0 eV. Accounting for the strong polarisation effects of the medium and polaron formation gives our calculated E(nBu) ca. 3.6 eV, with an exciton binding energy of ca. 1.0 eV. The 2Ag state is found to be above the 1Bu, which does not agree with relaxed transition experimental data. However, this could be resolved by including explicit lattice relaxation in the Pariser- Parr-Pople-Peierls model. Particle-hole separation data further suggest that the 1Bu, 2Ag and mAg are bound excitons, and that the nBu is an unbound exciton.Comment: LaTeX, 23 pages, 4 postscript tables and 8 postscript figure

Large-scale Bright Fronts in the Solar Corona: A Review of "EIT waves"

``EIT waves" are large-scale coronal bright fronts (CBFs) that were first observed in 195 \AA\ images obtained using the Extreme-ultraviolet Imaging Telescope (EIT) onboard the \emph{Solar and Heliospheric Observatory (SOHO)}. Commonly called ``EIT waves", CBFs typically appear as diffuse fronts that propagate pseudo-radially across the solar disk at velocities of 100--700 km s$^{-1}$ with front widths of 50-100 Mm. As their speed is greater than the quiet coronal sound speed ($c_s\leq$200 km s$^{-1}$) and comparable to the local Alfv\'{e}n speed ($v_A\leq$1000 km s$^{-1}$), they were initially interpreted as fast-mode magnetoacoustic waves ($v_{f}=(c_s^2 + v_A^2)^{1/2}$). Their propagation is now known to be modified by regions where the magnetosonic sound speed varies, such as active regions and coronal holes, but there is also evidence for stationary CBFs at coronal hole boundaries. The latter has led to the suggestion that they may be a manifestation of a processes such as Joule heating or magnetic reconnection, rather than a wave-related phenomena. While the general morphological and kinematic properties of CBFs and their association with coronal mass ejections have now been well described, there are many questions regarding their excitation and propagation. In particular, the theoretical interpretation of these enigmatic events as magnetohydrodynamic waves or due to changes in magnetic topology remains the topic of much debate.Comment: 34 pages, 19 figure

Small Polarons in Transition Metal Oxides

The formation of polarons is a pervasive phenomenon in transition metal oxide compounds, with a strong impact on the physical properties and functionalities of the hosting materials. In its original formulation the polaron problem considers a single charge carrier in a polar crystal interacting with its surrounding lattice. Depending on the spatial extension of the polaron quasiparticle, originating from the coupling between the excess charge and the phonon field, one speaks of small or large polarons. This chapter discusses the modeling of small polarons in real materials, with a particular focus on the archetypal polaron material TiO2. After an introductory part, surveying the fundamental theoretical and experimental aspects of the physics of polarons, the chapter examines how to model small polarons using first principles schemes in order to predict, understand and interpret a variety of polaron properties in bulk phases and surfaces. Following the spirit of this handbook, different types of computational procedures and prescriptions are presented with specific instructions on the setup required to model polaron effects.Comment: 36 pages, 12 figure

Coronal Dimmings and the Early Phase of a CME Observed with STEREO and Hinode/EIS

We investigate the early phase of the 13 February 2009 coronal mass ejection (CME). Observations with the twin STEREO spacecraft in quadrature allow us to compare for the first time in one and the same event the temporal evolution of coronal EUV dimmings, observed simultaneously on-disk and above the limb. We find that these dimmings are synchronized and appear during the impulsive acceleration phase of the CME, with the highest EUV intensity drop occurring a few minutes after the maximum CME acceleration. During the propagation phase two confined, bipolar dimming regions, appearing near the footpoints of a pre-flare sigmoid structure, show an apparent migration away from the site of the CME-associated flare. Additionally, they rotate around the 'center' of the flare site, i.e., the configuration of the dimmings exhibits the same 'sheared-to-potential' evolution as the postflare loops. We conclude that the motion pattern of the twin dimmings reflects not only the eruption of the flux rope, but also the ensuing stretching of the overlying arcade. Finally, we find that: (1) the global-scale dimmings, expanding from the source region of the eruption, propagate with a speed similar to that of the leaving CME front; (2) the mass loss occurs mainly during the period of strongest CME acceleration. Two hours after the eruption Hinode/EIS observations show no substantial plasma outflow, originating from the 'open' field twin dimming regions.Comment: accepted for publication in Solar Physic

On the Nature and Genesis of EUV Waves: A Synthesis of Observations from SOHO, STEREO, SDO, and Hinode

A major, albeit serendipitous, discovery of the SOlar and Heliospheric Observatory mission was the observation by the Extreme Ultraviolet Telescope (EIT) of large-scale Extreme Ultraviolet (EUV) intensity fronts propagating over a significant fraction of the Sun's surface. These so-called EIT or EUV waves are associated with eruptive phenomena and have been studied intensely. However, their wave nature has been challenged by non-wave (or pseudo-wave) interpretations and the subject remains under debate. A string of recent solar missions has provided a wealth of detailed EUV observations of these waves bringing us closer to resolving their nature. With this review, we gather the current state-of-art knowledge in the field and synthesize it into a picture of an EUV wave driven by the lateral expansion of the CME. This picture can account for both wave and pseudo-wave interpretations of the observations, thus resolving the controversy over the nature of EUV waves to a large degree but not completely. We close with a discussion of several remaining open questions in the field of EUV waves research.Comment: Solar Physics, Special Issue "The Sun in 360",2012, accepted for publicatio

Liposomes in Biology and Medicine

Drug delivery systems (DDS) have become important tools for the specific delivery of a large number of drug molecules. Since their discovery in the 1960s liposomes were recognized as models to study biological membranes and as versatile DDS of both hydrophilic and lipophilic molecules. Liposomes--nanosized unilamellar phospholipid bilayer vesicles--undoubtedly represent the most extensively studied and advanced drug delivery vehicles. After a long period of research and development efforts, liposome-formulated drugs have now entered the clinics to treat cancer and systemic or local fungal infections, mainly because they are biologically inert and biocompatible and practically do not cause unwanted toxic or antigenic reactions. A novel, up-coming and promising therapy approach for the treatment of solid tumors is the depletion of macrophages, particularly tumor associated macrophages with bisphosphonate-containing liposomes. In the advent of the use of genetic material as therapeutic molecules the development of delivery systems to target such novel drug molecules to cells or to target organs becomes increasingly important. Liposomes, in particular lipid-DNA complexes termed lipoplexes, compete successfully with viral gene transfection systems in this field of application. Future DDS will mostly be based on protein, peptide and DNA therapeutics and their next generation analogs and derivatives. Due to their versatility and vast body of known properties liposome-based formulations will continue to occupy a leading role among the large selection of emerging DDS

Spatial Navigation Based on Novelty Mediated Autobiographical Memory

Abstract. This paper presents a method for spatial navigation performed mainly on past experiences. The past experiences are remembered in their temporal context, i.e. as episodes of events. The learned episodes form an ac-tive autobiography that determines the future navigation behaviour. The epi-sodic and autobiographical memories are modelled to resemble the memory formation process that takes place in the rat hippocampus. The method im-plies naturally inferential reasoning in the robotic framework that may make it more flexible for navigation in unseen environments. The relation between novelty and life-long exploratory (latent) learning is shown to be important and therefore is incorporated into the learning process. As a result, active au-tobiography formation depends on latent learning while individual trials might be reward driven. The experimental results show that learning mediat-ed by novelty provides a flexible and efficient way to encode spatial informa-tion in its contextual relatedness and directionality. Therefore, performing a novel task is fast but solution is not optimal. In addition, learning becomes naturally a continuous process- encoding and retrieval phase have the same underlying mechanism, and thus do not need to be separated. Therefore, building a “life long ” autobiography is feasible.