Ultrasonic stimulation of the brain to enhance the release of dopamine – A potential novel treatment for Parkinson’s disease

Parkinson’s disease (PD) is characterized by the decrease of dopamine (DA) production and release in the substantia nigra and striatum regions of the brain. Transcranial ultrasound has been exploited recently for neuromodulation of the brain in a number of fields. We have stimulated DA release in PC12 cells using low-intensity continuous ultrasound (0.1 W/cm² − 0.3 W/cm², 1 MHz), 12 h after exposure at 0.2 W/cm², 40 s, the amount of DA content eventually increased 78.5% (p = 0.004). After 10-day ultrasonic treatment (0.3 W/cm², 5 min/d), the DA content in the striatum of PD mice model restored to 81.07% of the control (vs 43.42% in the untreated PD mice model). In addition to this the locomotion activity was restored to the normal level after treatment. We suggest that the low intensity ultrasound-induced DA release can be attributed to a combination of neuron regeneration and improved membrane permeability produced by the mechanical force of ultrasound. Our study indicates that the application of transcranial ultrasound applied below FDA limits, could provide a candidate for relatively safe and noninvasive PD therapy through an amplification of DA levels and the stimulation of dopaminergic neuron regeneration without contrast agents.     

A comparison of the effect of the ellipticity on the small and large solid-core PCF’s characteristics

In this paper we study small and large solid-core PCFs with elliptical shaped air-holes for the hexagonal lattice, which were constructed by omitting one air-hole (small core) and seven air-holes (large core), respectively, and we compare their characteristics with those with circular holes. We use two types of ellipticity: vertical and horizontal. Birefringence, dispersion, and the numerical apertures of the fundamental modes are analyzed using commercial simulation software. Also, the confinement loss is obtained. The effect of ellipticity on these characteristics is investigated in detail. It is found that the type of ellipticity of the air holes affects the numerical aperture and hence confinement loss significantly, but it has no crucial effect on either the dispersion or the birefringence for the small and large core PCFs.     

Effects of an anisotropic parabolic potential and Coulomb’s impurity potential on the energy characteristics of asymmetrical semi-exponential CsI quantum wells

Because of its unique optoelectronic properties,people have studied the characteristics of polarons in various quantum well(QW)models.Among them,the asymmetrical semiexponential QW(ASEQW)is a new model for studying the structure of QWs in recent years.It is of great significance to study the influences of the impurity and anisotropic parabolic confinement potential(APCP)on the crystal’s properties,because some of the impurities,usually regarded as Coulomb’s impurity potential(CIP),will exist in the crystal more or less,and the APCP has flexible adjustment parameters.However,the energy characteristics of the ASEQW under the combined actions of impurities and APCP have not been studied,which is the motivation of this paper.Using the linear combination operation and Lee-Low-Pines unitary transformation methods,we investigate the vibrational frequency and the ground state energy of the strong coupling polaron in an ASEQW with the influences of the CIP at the origin of coordinates and APCP,and make a comparison between our results and previous literature’s.Our numerical results about the energy properties in the ASEQW influenced by the CIP and APCP may have important significances for experimental design and device preparation.     

A remark on the energy conditions for Hawking’s area theorem

Hawking’s area theorem is a fundamental result in black hole theory that is universally associated with the null energy condition. That this condition can be weakened is illustrated by the formulation of a strengthened version of the theorem based on an energy condition that allows for violations of the null energy condition. With the semi-classical context in mind, some brief remarks pertaining to the suitability of the area theorem and its energy condition are made.     

A Lower Bound on the Lyapunov Exponent for the Generalized Harper’s Model

We obtain a lower bound for the Lyapunov exponent of a family of discrete Schrödinger operators \((Hu)_n=u_{n+1}+u_{n-1}+2a_1\cos 2\pi (\theta +n\alpha )u_n+2a_2\cos 4\pi (\theta +n\alpha )u_n\), that incorporates both \(a_1\) and \(a_2,\) thus going beyond the Herman’s bound.     

Effect of magnetic pulse treatment on the magnetic characteristics of yttrium–iron garnets

The effect weak (10–100 kA m^–1) low-frequency (10–20 Hz) pulsed magnetic fields have on the surface structure and magnetic characteristics of yttrium–iron garnet Y₃Fe₅O₁₂ is studied by means of electron and Mössbauer spectroscopy. A mechanism is proposed for the variation of saturation magnetization in Y₃Fe₅O₁₂ after magnetic pulse treatment. The mechanism is associated with the change in the spin state of iron ions localized in the tetrahedral sublattice.     

Metabolism of amyloid β peptide and pathogenesis of Alzheimer’s disease

The conversion of what has been interpreted as “normal brain aging” to Alzheimer’s disease (AD) via transition states, i.e., preclinical AD and mild cognitive impairment, appears to be a continuous process caused primarily by aging-dependent accumulation of amyloid β peptide (Aβ) in the brain. This notion however gives us a hope that, by manipulating the Aβ levels in the brain, we may be able not only to prevent and cure the disease but also to partially control some very significant aspects of brain aging. Aβ is constantly produced from its precursor and immediately catabolized under normal conditions, whereas dysmetabolism of Aβ seems to lead to pathological deposition upon aging. We have focused our attention on elucidation of the unresolved mechanism of Aβ catabolism in the brain. In this review, I describe a new approach to prevent AD development by reducing Aβ burdens in aging brains through up-regulation of the catabolic mechanism involving neprilysin that can degrade both monomeric and oligomeric forms of Aβ. The strategy of combining presymptomatic diagnosis with preventive medicine seems to be the most pragmatic in both medical and socioeconomical terms.     

Molecular dynamics and structure-based virtual screening and identification of natural compounds as Wnt signaling modulators: possible therapeutics for Alzheimer’s disease

Molecular Diversity - Wnt signaling pathway is an evolutionarily conserved pathway responsible for neurogenesis, axon outgrowth, neuronal polarity, synapse formation, and maintenance....     

Combined ligand-based and structure-based design of PDE 9A inhibitors against Alzheimer’s disease

Molecular Diversity - PDE9 enzyme hydrolyzes cGMP, which is involved in the regulation of synaptic plasticity through the NMDA pathway (a well-known excitotoxic target for AD) via activation of...     

Solution of A. Einstein’s Problem on the Density of Matter in the Universe

Russian Physics Journal - On the basis of the special theory of relativity and a solution of the Schwarzschild equations of general relativity, a generalized equation of...     

The effect of vacuum annealing on the remediation abilities of iron and iron−nickel nanoparticles

Zero-valent iron nanoparticles are effective remediators of uranium from solution. It is postulated that the improved core crystallinity and the migration of impurity phases to the nanoparticle surfaces induced by annealing may improve their corrosion resistance and reactive lifespan. The ability of annealed and non-annealed Fe and FeNi nanoparticles to remediate a U-contaminated effluent from AWE, Aldermaston was investigated. Nanoparticles (of diameter typically between 0 and 100 nm) were introduced to the effluent and allowed to react for 7 days during which the liquid and nanoparticulate solids were periodically sampled. In all the systems, the maximum U-uptake occurred within 1 h of introduction, with variable efficiency. The Fe nanoparticles removed 98% of the total U from solution, resulting in a final U-concentration of <4 μg/L. A rapid release of Fe into solution was recorded early in the reaction period: attributed to limited partial dissolution of the nanoparticles. Annealing the Fe nanoparticles did not affect their efficiency but the dissolution of Fe was significantly reduced and X-ray Photoelectron Spectroscopy indicated slower progressive oxidation. The performance of the FeNi nanoparticles was significantly improved by annealing, with U-uptake increasing from 50 to 94%. Although the dissolution of Ni was completely inhibited by annealing, the Fe dissolution increased compared to that observed for the non-annealed FeNi nanoparticles, in contrast to behaviour exhibited by Fe-annealed nanoparticles. In all the systems, U was reduced to U(IV) and retained on the surfaces of the nanoparticulate solids for up to 48 h; the U-stability was not affected by annealing the Fe or the FeNi nanoparticles before use.     

Accounting for the energies and entropies of kinesin’s catalytic cycle

When the processive motor protein kinesin walks along the biopolymer microtubule it can occasionally make a backward step. Recent single molecule experiments on moving kinesin have revealed that the forward-to-backward step ratio decreases exponentially with the load force. Carter and Cross (Nature 435, 308-312, 2005) found that this ratio tightly followed 802 × exp[−0.95F], where F is the load force in piconewtons. A straightforward analysis of a Brownian step leads to L/(2k _B T) as the factor in front of the load force, where L is the 8 nm stepsize, k _B is the Boltzmann constant, and T is the temperature. The factor L/(2k _B T) does indeed equal 0.95 pN⁻¹. The same analysis shows how the 802 prefactor derives from the power stroke energy G as exp[G/(2k _B T)]. There are indications that the power stroke derives from the entropically driven coiling of the 30 amino acid neck linker that connects the two kinesin heads. This idea is examined and consequences are deduced.     

Observability of the effects of curl-free magnetic vector potential on the macroscale and the nature of the ‘transition amplitude wave’

We discuss here the prediction, based on a formalism by the author, on the observable effects of a curl-free magnetic vector potential on the macroscale as against the microscale of the Aharonov-Bohm effect. A new quantum concept — the ‘transition amplitude wave’ — postulated in the formalism has already been shown to exhibit matter wave manifestations in the form of one-dimensional interference effects on the macroscale. It was predicted by the formalism that the same entity would lead to the detection of a curl-free magnetic vector potential on the macroscale. We describe here the manner of generation of this quantum entity in an inelastic scattering episode and work out an algorithm to observe this radically new phenomenon, the detection of a curl-free magnetic vector potential on the macroscale. We determine the various characteristic features of such an observation which can then be looked for experimentally so as to verify the predicted effect, establishing thereby the physical reality of the new quantum entity, and to fully validate the formalism predicting it. It is also shown that this ‘transition amplitude wave’ can be regarded as a novel kind of ‘quasiparticle’ excited in the charged particle trajectory as a consequence of the scattering episode.     

Statistical physics of the spatial Prisoner’s Dilemma with memory-aware agents

We introduce an analytical model to study the evolution towards equilibrium in spatialgames, with ‘memory-aware’ agents, i.e., agents that accumulate their payoff over time. Inparticular, we focus our attention on the spatial Prisoner’s Dilemma, as it constitutes anemblematic example of a game whose Nash equilibrium is defection. Previous investigationsshowed that, under opportune conditions, it is possible to reach, in the evolutionaryPrisoner’s Dilemma, an equilibrium of cooperation. Notably, it seems that mechanisms likemotion may lead a population to become cooperative. In the proposed model, we map agentsto particles of a gas so that, on varying the system temperature, they randomly move. Indoing so, we are able to identify a relation between the temperature and the finalequilibrium of the population, explaining how it is possible to break the classical Nashequilibrium in the spatial Prisoner’s Dilemma when considering agents able to increasetheir payoff over time. Moreover, we introduce a formalism to study order-disorder phasetransitions in these dynamics. As result, we highlight that the proposed model allows toexplain analytically how a population, whose interactions are based on the Prisoner’sDilemma, can reach an equilibrium far from the expected one; opening also the way todefine a direct link between evolutionary game theory and statistical physics.     

A note on the integral formulation of Einstein’s equations induced on a braneworld

We revisit the integral formulation (or Greens function approach) of Einsteins equations in the context of braneworlds. The integral formulation has been proposed independently by several authors in the past, based on the assumption that it possible to give a reinterpretation of the local metric field in curved spacetimes as an integral expression involving sources and boundary conditions. This allows one to separate source-generated and source-free contributions to the metric field. As a consequence, an exact meaning to Machs Principle can be achieved in the sense that only source-generated (matter fields) contributions to the metric are allowed for; universes which do not obey this condition would be non-Machian. In this paper, we revisit this idea concentrating on a Randall–Sundrum-type model with a non-trivial cosmology on the brane. We argue that the role of the surface term (the source-free contribution) in the braneworld scenario may be quite subtler than in the 4D formulation. This may pose, for instance, an interesting issue to the cosmological constant problem.     

Green’s Function for the Hodge Laplacian on Some Classes of Riemannian and Lorentzian Symmetric Spaces

We compute the Green’s function for the wave equation on forms on the symmetric spaces M × Σ, where M is a simply connected n-dimensional Riemannian or Lorentzian manifold of constant curvature and Σ is a simply connected Riemannian surface of constant curvature. Our approach is based on a generalization to the case of differential forms of the method of spherical means and on the use of Riesz distributions on manifolds. The radial part of the Green’s function is governed by a fourth order analogue of the Heun equation.     

Electronic spin transition of iron in the Earth’s lower mantle

Silicate perovskite and ferropericlase are thought to be the primary constituents of the lower mantle, whereas silicate post-perovskite is more likely found in the lowermost mantle. Because these minerals contain certain amounts of iron, their properties and, consequently, those of the deep mantle, are strongly influenced by iron’s spin and valence states. A high-spin to low-spin crossover in ferropericlase has been observed to occur in the middle part of the lower-mantle conditions. Recent M?ssbauer results consistently show that Fe^2?+? predominantly exhibits extremely high quadrupole splittings in perovskite and post-perovskite, whereas a high-spin to low-spin transition of Fe^3?+? in the octahedral site occurs at high pressures. These results provide a new venue for discussion of the effects of the spin and valence states of iron on the physical and chemical properties of the lower mantle.     

A Proof of Scott’s Correction for Matter

This paper contains a strengthening of Stability of Matter, which in particular shows that Thomas-Fermi theory, which is already known to give the leading order contribution to the energy of Matter, if supplemented with the so-called Scott correction is correct uniformly in the number of nuclei. New more precise estimates of the volume of Matter also follow.Work partially supported under the research project Ref. PB98-0067     

Automated segmentation of transcranial sonographic images in the diagnostics of Parkinson’s disease

Images captured during routine clinical transcranial sonography (TCS) examination are of a low resolution, so can be confusing for diagnostic evaluations. Manual segmentation of brain structures (areas of the midbrain and substantia nigra (SN)) that are of special interest cause inter-observer and intra-observer variability, thus restricting the reliability of Parkinson disease (PD) diagnostics. This paper presents a new technique for automated segmentation applicable to low resolution sonographic images, and particularly to brain structures related to PD. The segmentation was performed by a modified shape-based active contour (AC) segmentation algorithm. In order to suppress the speckle noise and to improve the AC segmentation, a pre-processing technique based on the averaging of adjusted spatially varying TCS images is proposed. The latter technique was tested on clinical TCS images. The results of the automated segmentation were compared with the manual markings. Two experts on the 40 TCS images performed these markings. The comparison showed that an automated method is effective when segmentation of the midbrain is performed (averaged overlap between regions obtained automatically and outlined manually was 73.10 ± 7.45%). The results of the segmentation of the SN area showed that a sufficiently correct contour of this area could also be obtained, but the accuracy of the segmentation is related to the image quality. It should be emphasised that the main difficulty in evaluating the accuracy of automated segmentation of the SN was the indefinite “gold standard” (variation between the measurements of two experts with different experience was found). And, therefore, the diagnostic reliability of the proposed technique was inconclusive.