Substituted thiazolamide coupled to a redox delivery system: a new gamma-secretase inhibitor with enhanced pharmacokinetic profile

Inhibition of gamma-secretase, one of the enzymes responsible for the cleavage of the amyloid precursor protein (APP) to produce pathogenic A beta peptides, is an attractive approach for the treatment of Alzheimer's disease. We have designed a new gamma-secretase thiazolamide inhibitor bearing a dihydronicotinoyl moiety as Redox Delivery System which allows specific delivery of the drug to the brain. Through, on the one hand, A beta peptide production measurements by specific in vitro assays (gamma-secretase Cell Free assay and Cell Based assay on HEK 293 APP transfected cells) and, on the other hand, pharmacokinetic studies on animal models, the new inhibitor shows a good pharmacokinetic profile as well as a potent gamma-secretase inhibitory activity in vitro. From the obtained results, it is expected that drug will be mainly delivered to the CNS with low diffusion in the peripheral tissues. Consequently the side effects of this gamma-secretase inhibitor on the immune cells could be reduced.     

On the homotopy type of (<Emphasis Type="Italic">n</Emphasis>-1)-connected (3<Emphasis Type="Italic">n</Emphasis>+1)-dimensional free chain Lie algebra

Let R be a subring ring of Q. We reserve the symbol p for the least prime which is not a unit in R; if R ?Q, then p=∞. Denote by DGL _n ^np , n≥1, the category of (n-1)-connected np-dimensional differential graded free Lie algebras over R. In [1] D. Anick has shown that there is a reasonable concept of homotopy in the category DGL _n ^np . In this work we intend to answer the following two questions: Given an object (L(V), ?) in DGL _n ³ⁿ⁺² and denote by S(L(V), ?) the class of objects homotopy equivalent to (L(V), ?). How we can characterize a free dgl to belong to S(L(V), ?)? Fix an object (L(V), ?) in DGL _n ³ⁿ⁺² . How many homotopy equivalence classes of objects (L(W), δ) in DGL _n ³ⁿ⁺² such that H _* (W, d′)?H _* (V, d) are there? Note that DGL _n ³ⁿ⁺² is a subcategory of DGL _n ^np when p>3. Our tool to address this problem is the exact sequence of Whitehead associated with a free dgl.     

Analysis of high-reflectivity metal-dielectric mirrors for edge-emitting lasers

A metal-dielectric mirror is shown as a simple solution for high-reflectivity coatings on cleaved-facet edge-emitting lasers, as well as a means to provide wavelength stabilization and spectral filtering. We show, through the use of a simple SiO2/Ti/Au coating, reflectivities better than 90% and a 25% reduction in the 30-dB linewidth of the output spectrum. Wavelength filtering and varying reflectivities are described as the result of multiple reflections and a coupled-cavity effect.     

A tentative approach to entanglement measures for a system of a three-level atom interacting with a quantized cavity-field

In this paper, an entanglement measure due to quasi-mutual entropy from initially entangled mixed states of a three-level atom interacting with a single cavity field is introduced. Detailed analytical and explicit expressions are given taking into account an arbitrary form of the intensity-dependent coupling. Despite its simplicity the model exhibits a very broad range of intricate physical effects and it is widely used in quantized theories of laser. We show that quantum revivals are possible for a broad continuous range of physical parameters in the case of initial coherent states. Entanglement degree effects are shown to be very sensitive to the initial state of the system. Numerical calculations under current experimental conditions are taken into account and it is found that the intensity-dependent coupling changes the general features dramatically.Received: 2 June 2003, Published online: 26 August 2003PACS: 03.65.Ud Entanglement and quantum nonlocality (e.g. EPR paradox, Bells inequalities, GHZ states, etc.) - 03.67.Hk Quantum communication - 42.65.-k Nonlinear optics - 32.80.Rm Multiphoton ionization and excitation to highly excited states (e.g., Rydberg states)     

Shock wave structure in a two-components gas mixture

Summary The nonlinear differential equations describing the problem of shock wave structure in a two-component gas mixture are reduced to a system of two coupled nonlinear differential equations. This system is solved numerically using the finite-difference method. It is found that the relative shock wave thickness of the mixture increases with the increase of the ratio between the viscosity coefficients when the ratio between the mass fractions is constant. It is also shown that the relative shock wave thickness of the mixture decreases with the increase of the ratio between the mass fractions when the ratio between the viscosity coefficients is constant.

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Riassunto Si riducono le equazioni differenziali non lineari che descrivono il problema della struttura dell’ onda d’urto in una miscela di gas a 2 componenti a un sistema di due equazioni differenziali accoppiate non lineari. Questo sistema si risolve numericamente usando il metodo delle differenze finite. Si trova che il relativo spessore dell’onda d’urto della miscela aumenta con l’aumento del rapporto tra i coefficienti di viscosità, quando il rapporto tra le frazioni di massa è costante. Si mostra anche che lo spessore relativo dell’onda d’urto della miscela diminuisce con l’aumento del rapporto tra le frazioni della massa, quando il rapporto tra i coefficienti di viscosità è costante.

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Резюме Нелинейные дифференциальные уравнения, описывающие проблему структуры ударной в двух-компоентной газовой смеси, сводятся к системе двух связанных нелинейыых дифференциальных уравнений. Получается, что относительная толщина ударной волны в смеси увеличвается с увеличением отношения между коэффиыентами вязкоти, когда отнощение между массовыми доями остается постоянным. Также показывается. что относительная толщина ударной волны уменьшается с увеличением отношения между массовыми долями. когда отношение между коэффициентами вязкости остается постоянным.