A review on iron chelators as potential therapeutic agents for the treatment of Alzheimer’s and Parkinson’s diseases

Iron plays a vital role in several cellular functions due to its unique physiochemical properties. Iron concentration increases in the brain with age due to multiple factors. Excessive amount of iron can lead to formation of reactive oxygen species. Neurodegenerative disorders are characterized by iron supplemented increase in oxidative stress and cellular damage. There is an urgent need of novel therapies which should not only provide symptomatic relief but also be able to modulate iron accumulation in the brain. Therefore, the development of novel iron chelators as neuroprotective agents for the treatment of neurodegeneration is an emerging trend. Several iron chelators including 8-hydroxyquinoline derivatives, dopaminergic agonists and natural products are under preclinical and clinical investigations for the treatment of neurodegenerative disorders.

     

On the use of information theory for detecting upper limb motor dysfunction: An application to Parkinson’s disease

Parkinson’s disease (PD) is a chronic neurodegenerative disorder characterized by a selective loss of dopaminergic neurons in the substantia nigra, decreased striatal dopamine levels, and consequent extrapyramidal motor dysfunctions. Several potential early diagnostic markers of PD have been proposed. Since they have not been validated in presymptomatic PD, the diagnosis and monitoring of the disease is based on subjective clinical assessment of cognitive and motor symptoms. In this study, we investigated interjoint coordination synergies in the upper limb of healthy and parkinsonian subjects during the performance of unconstrained linear-periodic movements in a horizontal plane using the mutual information (MI). We found that the MI is a sensitive metric in detecting upper limb motor dysfunction, thus suggesting that this method might be applicable to quantitatively evaluating the effects of the antiparkinsonian medication and to monitor the disease progression.     

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.     

Structure-based design and analysis of MAO-B inhibitors for Parkinson’s disease: using in silico approaches

Parkinson’s disease (PD) is a degenerative disorder of the CNS, characterized by cerebral depletion of dopamine (DA), hence one of the approaches to delay the depletion of DA is to inhibit its oxidative deamination. Monoamine oxidases (MAO) carry out the oxidative deamination of monoamines like DA. These are intracellular enzymes, located on the outer mitochondrial membrane. MAO-A and MAO-B are the two subtypes of which MAO-B is the most predominant enzyme and is commonly found in the brain. Inhibition of the MAO-B enzyme boosts the effect of both endogenous and exogenous DA. In this study, we have carried out crystal structure analysis and structure-based design of MAO-B inhibitors. We also performed molecular dynamics, flexible docking, induced-fit docking and ADME prediction of the newly designed compounds.     

Experimental determination of the conditions for the transition of Jupiter’s atmosphere to the conducting state

The intensity of optical radiation and resistance of a hydrogen-helium layer with He mass fraction Y=m_He/(m_He+m_H)?0.24, which corresponds to the composition of the outer layers of Jupiter’s atmosphere [2], were simultaneously measured under multiple shock compression up to 164 GPa in plane geometry. The initial pressure and temperature of the mixture were equal to 8 MPa and 77.4 K, respectively, and the velocity of steel strikers was equal to 6.2 km/s. These conditions allowed the generation of the final compressed curve close to the adiabatic states of Jupiter’s atmosphere according to the models proposed in [2, 3]. The conditions for the appearance of the conducting phase in the compression process and the achieved level of electrical conductivity were determined. The experimental data were compared with the one-dimensional fluid-dynamic simulation of the compression process using the equation of state for the mixture in a model similar to the one proposed in [3, 8]. The experimental data were also compared with the behavior of pure components having the same initial density as in the mixture and compressed to the same final pressure.     

A novel technique of laser measurement for the surface roughness

This paper describes a non-contact system for the surface roughness measurement without damage. It is suitable for various materials.     

Design and in vitro analysis of SIRT2 inhibitor targeting Parkinson’s disease

Molecular Diversity - Inhibition of Sirtuin2 (SIRT2) protein rescues the α-synuclein toxicity in vitro and in vivo models of Parkinson’s disease (PD). Thioacetyl group can structurally...     

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     

A novel approach to a Brillouin–LIDAR for remote sensing of the ocean temperature

Ocean temperature profiles are of great importance in oceanography. For instance, an efficient remote sensing measurement technique of these profiles will facilitate climate studies and improvements in weather forecast. In this paper we describe developments towards a practical implementation of a Brillouin–LIDAR system capable of measuring temperature profiles in the ocean. In particular, we focus on our recent work on fiber amplifiers and a receiver unit based on a Faraday anomalous dispersion optical filter. PACS 42.79.Qx; 42.60.By; 42.62.Fi; 42.68.Xy; 42.50.Nn     

Relativistic treatment of the spin-zero particles subject to the second Pschl Teller-like potential

The three-dimensional Klein–Gordon equation is solved for the case of equal vector and scalar second Pschl–Teller potential by proper approximation of the centrifugal term within the framework of the asymptotic iteration method.Energy eigenvalues and the corresponding wave function are obtained analytically.Eigenvalues are computed numerically for some values of n and ?.It is found that the results are in good agreement with the findings of other methods for short-range potential.     

Exploring the Transition of Human α-Synuclein from Native to the Fibrillar State: Insights into the Pathogenesis of Parkinson’s Disease

The etiology of Parkinson’s disease involves the interplay between the environmental and genetic factors. Here in this study human α-synuclein upon exposure to 100 μM pendimethalin for 12 h in vitro passes through a partially folded state which proceeds to the aggregated state and terminally ends in the fibrillar phase. Variations in the ANS fluorescence intensities led to the detection of intermediate and aggregated states at 6 and 10 h respectively. Far-UV CD analysis depicted significant α-helical content for intermediate state at 6 h in presence of 100 μM pendimethalin. Further increasing the incubation time to 12 h resulted in a predominant β-sheet content which was confirmed to be fibrillar by TEM. Turbidity, Rayleigh scattering analysis, Congo red assay and ThT measurements supported the TEM data i.e. the formation of fibrillar structure of human α-synuclein upon 12 h incubation. Thus, our observation could suggest a possible underlying molecular basis for Parkinson’s disease.

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Graphical Abstract Schematic elucidation of the factors involved in the fibrillation of α-Synuclein during Parkinson’s pathogenesis.

     

A Gribov equation for the photon Green’s function

We present a derivation of the Gribov equation for the gluon/photon Green’s function D(q). Our derivation is based on the second derivative of the gauge-invariant quantity Trln?D(q), which we interpret as the gauge-boson ‘self-loop’. By considering the higher-order corrections to this quantity, we are able to obtain a Gribov equation which sums the logarithmically enhanced corrections. By solving this equation, we obtain the non-perturbative running coupling in both QCD and QED. In the case of QCD, α _S has a singularity in the space-like region corresponding to super-criticality, which is argued to be resolved in Gribov’s light-quark confinement scenario. For the QED coupling in the UV limit, we obtain a ∝ Q ² behavior for space-like Q ²=?q ². This implies the decoupling of the photon and an NJLVL-type effective theory in the UV limit.     

A Generalization of the Bargmann’s Theory of Ray Representations

The paper contains a complete theory of factors for ray representations acting in a Hilbert bundle, which is a generalization of the known Bargmanns theory. With its help, we have reformulated the standard quantum theory so that the gauge freedom emerges naturally from the very nature of quantum laws. The theory is of primary importance in the investigations of covariance (in contradistinction to symmetry) of a quantum theory which possesses a nontrivial gauge freedom. In that case the group in question is not any symmetry group but a covariance group only – the case not yet investigated in depth. It is shown that the factor of a covariance group representation depends on space and time when the system in question possesses gauge freedom. In nonrelativistic theories, the factor depends on time only. In relativistic theory, the Hilbert bundle is built over spacetime while in the nonrelativistic case-over time. We explain two applications of this generalization: in the theory of a quantum particle in gravitational field in the nonrelativistic limit, and in quantum electrodynamics.     

On the effect of electric potential on resistance of metals’ surface to microindentation

The effect of electric potential on the microindentation resistance is investigated experimentally for aluminum and zirconium samples. The effects of the electric potential proper applied to a sample and of the potential arising due to contact potential difference between metals with different electron work functions are compared. A qualitative equivalence of these two types of electrical action is revealed. A possibility of a significant (over 10%) change in the metal microhardness due to the above nentioned actions is established.     

Alternative Proof for the Localization of Sinai’s Walk

We give an alternative proof of the localization of Sinais random walk in random environment under weaker hypothesis than the ones used by Sinai. Moreover, we give estimates that are stronger than the one of Sinai on the localization neighborhood and on the probability for the random walk to stay inside this neighborhood.     

Green’s tensor for crystals of the hexagonal system

Expressions for components of the Green’s tensor of the basic equation of the elasticity theory for hexagonal system crystals have been obtained using the Lifshitz-Rozentsveig method. A problem is in principle reduced to finding the roots of a sixth-order algebraic equation. They are either complex or purely imaginary for all known hcp metals. In both cases, the desired components of the Green’s tensor are calculated exactly in contrast to metals of the cubic system. A limiting transition to the isotropic approximation is shown.     

Comparison of different experimental methods for the assessment of the room’s acoustics

The paper presents the acoustics analysis of three different enclosed spaces. These spaces (rooms) have different geometrical shapes and sizes and serve for different purposes. The early decay time, reverberation time, clarity and center time are evaluated with Dirac, WinMLS, Aurora and Caracad software using simple, low-cost equipment. The listed acoustic parameters were determined using linear sine sweep and impulsive sources. Comparisons between experimental measurements, simulations and analytic results were done. The room impulse response measurement proved to be the most reliable method to evaluate the properties of different rooms even if the measurements are perturbed by non-idealities of the low-cost equipment.     

A novel approach to identifying the ultrasonic echoes for inspecting well cementing quality

I.IlltroductionUltrasoulceyaluatingtechniqueshavebeenaPpliedtoinspectoil-wellcemelltingqualityformanyyears-Aconventionalapproachisbasedonwaveformfeaturesoftheultrasonicechoesfromtheexploredstructuresinwell.Bytheapproach,theechoesarewindowed,andthebondingqualitiesbetweenthecementandboththesteelpipeandtheformationareevaluatedaccordingtowavenergiesinthewindows.GenerallywecantheillterfacebetweenthepipeandthecementSurfaceOne,theinterfacebetweenthecementandtheformationSurfaceTwol1],Thisapproachis…     

A study of non-extensivity in the Earth’s magnetosphere

Magnetic storms are undoubtedly among the most important phenomena in space physics and also a central subject of space weather. The non-extensive Tsallis entropy has been recently introduced, as an effective complexity measure for the analysis of the geomagnetic activity D _st index. Tsallis entropy has been shown to sensitively detect the complexity dissimilarity between pre-storm activity and intense magnetic storms in the Earth’s magnetosphere. Here, we show that the D _st time series obey a modified form of the Gutenberg-Richter law for the case of non-extensive statistics, thus providing evidence for universality in magnetic storm and earthquake occurrence.     

Multiple scattering polarization – Application of Chandrasekhar’s formalisms to the atmosphere of brown dwarfs and extrasolar planets

Chandrasekhar’s formalisms for the transfer of polarized radiation are used to explain the observed dust scattering polarization of brown dwarfs in the optical band. Model polarization profiles for hot and young directly imaged extrasolar planets are presented with specific prediction of the degree of polarization in the infrared. The model invokes Chandrasekhar’s formalism for the rotation-induced oblateness of the objects that gives rise to the necessary asymmetry for yielding net non-zero disk integrated linear polarization. The observed optical polarization constrains the surface gravity and could be a tool to estimate the mass of extrasolar planets.