The amyloid precursor protein (APP) binds the PIKfyve complex and modulates its function

Phosphoinositides are important components of eukaryotic membranes that are required for multiple forms of membrane dynamics. Phosphoinositides are involved in defining membrane identity, mediate cell signalling and control membrane trafficking events. Due to their pivotal role in membrane dynamics, phosphoinositide de-regulation contributes to various human diseases. In this review, we will focus on the newly emerging regulation of the PIKfyve complex, a phosphoinositide kinase that converts the endosomal phosphatidylinositol-3-phosphate [PI(3)P] to phosphatidylinositol-3,5-bisphosphate [PI(3,5)P2)], a low abundance phosphoinositide of outstanding importance for neuronal integrity and function. Loss of PIKfyve function is well known to result in neurodegeneration in both mousemodels and human patients. Our recent work has surprisingly identified the amyloid precursor protein (APP), the central molecule in Alzheimer s disease aetiology, as a novel interaction partner of a subunit of the PIKfyve complex, Vac14. Furthermore, it has been shown that APP modulates PIKfyve function and PI(3,5)P2 dynamics, suggesting that the APP gene family functions as regulator of PI(3,5)P2 metabolism. The recent advances discussed in this review suggest a novel, unexpected, â-amyloid-independent mechanism for neurodegeneration in Alzheimer s disease.

Uniquely Identifiable Tamper-Evident Device Using Coupling between Subwavelength Gratings

Reliability and sensitive information protection are critical aspects of integrated circuits. A novel technique using near-field evanescent wave coupling from two subwavelength gratings (SWGs), with the input laser source delivered through an optical fiber is presented for tamper evidence of electronic components. The first grating of the pair of coupled subwavelength gratings (CSWGs) was milled directly on the output facet of the silica fiber using focused ion beam (FIB) etching. The second grating was patterned using e-beam lithography and etched into a glass substrate using reactive ion etching (RIE). The slightest intrusion attempt would separate the CSWGs and eliminate near-field coupling between the gratings. Tampering, therefore, would become evident. Computer simulations guided the design for optimal operation of the security solution. The physical dimensions of the SWGs, i.e. period and thickness, were optimized, for a 650 nm illuminating wavelength. The optimal dimensions resulted in a 560 nm grating period for the first grating etched in the silica optical fiber and 420 nm for the second grating etched in borosilicate glass. The incident light beam had a half-width at half-maximum (HWHM) of at least 7 µm to allow discernible higher transmission orders, and a HWHM of 28 µm for minimum noise. The minimum number of individual grating lines present on the optical fiber facet was identified as 15 lines. Grating rotation due to the cylindrical geometry of the fiber resulted in a rotation of the far-field pattern, corresponding to the rotation angle of moiré fringes. With the goal of later adding authentication to tamper evidence, the concept of CSWGs signature was also modeled by introducing random and planned variations in the glass grating. The fiber was placed on a stage supported by a nanomanipulator, which permitted three-dimensional displacement while maintaining the fiber tip normal to the surface of the glass substrate. A 650 nm diode laser was fixed to a translation mount that transmitted the light source through the optical fiber, and the output intensity was measured using a silicon photodiode. The evanescent wave coupling output results for the CSWGs were measured and compared to the simulation results.

Amplificador integrador com ganho programável por largura de pulso

This work deals with the research and development of a Pulse Width Programmable Gain Integrating Amplifier. Two Pulse Width Programmable Gain Amplifier architectures are proposed, one based on discrete components and another based on switched capacitors. From the operating requirements defined for the study, parameters are defined and simulations are carried out to validate the architecture. Subsequently, the circuit and the software are developed and tested. It is performed the evaluation of the circuits regarding the two proposed architectures, and from that, an architecture is selected to be improved, aiming the development of an integrated circuit in a future work.

Uma leitura atual do bairro da Ribeira em Natal/RN a partir dos dois circuitos da economia urbana

The present study aims to analyze the spatial organization of the Ribeira district in Natal/ RN from the two circuits of the urban economy. For its realization, was used the bibliographical, documentary and field research. From the information collected in the field research and of secondary data was elaborated the maps, tables, graphics, frames and photographic collections. In the analysis of the results identified the presence of two circuits of the urban economy in the said neighborhood, thus as the predominance of the upper circuit compared to the lower circuit between the surveyed establishments, well as the role that each of the circuits represents to their spatial organization. Some variables such as technology, organization, information, publicity and consumption were important to establish the main differences between the circuits.

Plasticidade dependente da experiência induzida por manipulação da matriz extracelular

The primary somatosensory cortex (S1) receives inputs from peripheral tactile receptors and plays a crucial role on many important behaviors. However, the plastic potential of this region is greatly reduced during adulthood, limiting functional recovery after injuries. This fact is due to the presence, in the brain parenchima, of structures and substances that have an inhibitory effect on plasticity, such as chondroitin sulfate proteoglicans (CSP) present in the perineuronal.nets (PNNs) surrounding a subset of neurons. Maturation of PNNs coincide with the closure of critical periods of plasticity in cortical areas, since CSP act to stabilize synaptic contacts. Removal of CSP is proven to be an effective therapeutic approach to restore plasticity and increase the odds of functional recovery after cortical lesion. In the present work, we removed CSP from the sensorimotor cortex of rats to restore plasticity and promote the compensatory morphofunctional regeneration of cortical circuits modified by removal of mystacial vibrissae during the critical period. Treatment with the CSP-digesting enzyme chondroitinase ABC proved efficient to restore plasticity in S1 circuits, as evidenced by morphological rearrangements and functional recovery.

Plasticidade dependente da experiência induzida por manipulação da matriz extracelular

The primary somatosensory cortex (S1) receives inputs from peripheral tactile receptors and plays a crucial role on many important behaviors. However, the plastic potential of this region is greatly reduced during adulthood, limiting functional recovery after injuries. This fact is due to the presence, in the brain parenchima, of structures and substances that have an inhibitory effect on plasticity, such as chondroitin sulfate proteoglicans (CSP) present in the perineuronal.nets (PNNs) surrounding a subset of neurons. Maturation of PNNs coincide with the closure of critical periods of plasticity in cortical areas, since CSP act to stabilize synaptic contacts. Removal of CSP is proven to be an effective therapeutic approach to restore plasticity and increase the odds of functional recovery after cortical lesion. In the present work, we removed CSP from the sensorimotor cortex of rats to restore plasticity and promote the compensatory morphofunctional regeneration of cortical circuits modified by removal of mystacial vibrissae during the critical period. Treatment with the CSP-digesting enzyme chondroitinase ABC proved efficient to restore plasticity in S1 circuits, as evidenced by morphological rearrangements and functional recovery.

Método híbrido para projeto de superfícies seletivas em frequência

This thesis presents a hybrid technique of frequency selective surfaces project (FSS) on a isotropic dielectric layer, considering various geometries for the elements of the unit cell. Specifically, the hybrid technique uses the equivalent circuit method in conjunction with genetic algorithm, aiming at the synthesis of structures with response single-band and dual-band. The equivalent circuit method allows you to model the structure by using an equivalent circuit and also obtaining circuits for different geometries. From the obtaining of the parameters of these circuits, you can get the transmission and reflection characteristics of patterned structures. For the optimization of patterned structures, according to the desired frequency response, Matlab™ optimization tool named optimtool proved to be easy to use, allowing you to explore important results on the optimization analysis. In this thesis, numeric and experimental results are presented for the different characteristics of the analyzed geometries. For this, it was determined a technique to obtain the parameter N, which is based on genetic algorithms and differential geometry, to obtain the algebraic rational models that determine values of N more accurate, facilitating new projects of FSS with these geometries. The optimal results of N are grouped according to the occupancy factor of the cell and the thickness of the dielectric, for modeling of the structures by means of rational algebraic equations. Furthermore, for the proposed hybrid model was developed a fitness function for the purpose of calculating the error occurred in the definitions of FSS bandwidths with transmission features single band and dual band. This thesis deals with the construction of prototypes of FSS with frequency settings and band widths obtained with the use of this function. The FSS were initially reviewed through simulations performed with the commercial software Ansoft Designer ™, followed by simulation with the equivalent circuit method for obtaining a value of N in order to converge the resonance frequency and the bandwidth of the FSS analyzed, then the results obtained were compared. The methodology applied is validated with the construction and measurement of prototypes with different geometries of the cells of the arrays of FSS.

Método híbrido para projeto de superfícies seletivas em frequência

This thesis presents a hybrid technique of frequency selective surfaces project (FSS) on a isotropic dielectric layer, considering various geometries for the elements of the unit cell. Specifically, the hybrid technique uses the equivalent circuit method in conjunction with genetic algorithm, aiming at the synthesis of structures with response single-band and dual-band. The equivalent circuit method allows you to model the structure by using an equivalent circuit and also obtaining circuits for different geometries. From the obtaining of the parameters of these circuits, you can get the transmission and reflection characteristics of patterned structures. For the optimization of patterned structures, according to the desired frequency response, Matlab™ optimization tool named optimtool proved to be easy to use, allowing you to explore important results on the optimization analysis. In this thesis, numeric and experimental results are presented for the different characteristics of the analyzed geometries. For this, it was determined a technique to obtain the parameter N, which is based on genetic algorithms and differential geometry, to obtain the algebraic rational models that determine values of N more accurate, facilitating new projects of FSS with these geometries. The optimal results of N are grouped according to the occupancy factor of the cell and the thickness of the dielectric, for modeling of the structures by means of rational algebraic equations. Furthermore, for the proposed hybrid model was developed a fitness function for the purpose of calculating the error occurred in the definitions of FSS bandwidths with transmission features single band and dual band. This thesis deals with the construction of prototypes of FSS with frequency settings and band widths obtained with the use of this function. The FSS were initially reviewed through simulations performed with the commercial software Ansoft Designer ™, followed by simulation with the equivalent circuit method for obtaining a value of N in order to converge the resonance frequency and the bandwidth of the FSS analyzed, then the results obtained were compared. The methodology applied is validated with the construction and measurement of prototypes with different geometries of the cells of the arrays of FSS.

Análise computacional do desempenho de estratégia para o religamento controlado de linhas de transmissão

The search for mitigation solutions, with respect to the effects of overvoltages linked to the energization and reclosing maneuvers of transmission lines include a challenging subject with strong impact on the insulation coordination of electrical systems. Although the recognition of classical and commercial proposals to mitigate these phenomena, other possibilities are certainly still worthwhile highlighting and investigations. In this context, the present work is grounded in the exposure of the physical and mathematical foundations of a strategy based on controlled switchings, whose moments to the line reclosing are pre-programmed. The computational evaluation of the effectiveness of the methodology is made using the ATP simulator, which are studies in a typical electrical system subjected to the action of short-circuits fallowed by shutdowns and subsequent reclosing, under the action of technology here focused and lack thereof.

Atividade antiangiogênica da forma recombinante da proteína 21 de Trypanosoma cruzi

Chagas disease, caused by the parasite Trypanosoma cruzi, is the cause of Chronic chagasic cardiomyopathy (CCC). The prospection of innovative therapeutic agents against CCC is a major task. The recombinant form of 21 (rP21), a secreted T. cruzi protein involved in host cell invasion and on progression of chronic inflammatory processes have been studied as a potential novel therapeutic target. Our present work aimed to verify and investigate the impact of rP21 in the formation of blood vessels in vitro and in vivo. First, tEnd cells were treated with different concentrations of rP21 or bacterial extract and viability and cellular adhesion were evaluated by MTT and angiogenesis inhibition by Matrigel tube formation assay and murine model. To verify the proteolytic activity of rP21 on extracellular matrix (ECM) components, fibrinogen, matrigel and fibronectin was incubated with rP21 or not. In addition, we performed proliferation assays and cell cycle analysis. Furthermore, the accumulation and distribution of F-actin was determined by Phalloidin staining using ImageJ software. Finally, tEnd cells were incubated with rP21 and the mRNA levels were analyzed by real-time PCR. Our results showed that rP21 did not alter cell viability and adhesion, but strongly inhibited vessel formation in vitro and in vivo. Tube formation assay showed that angiogenesis inhibition was dependent of the CXCR4-rP21 binding. In addition to these results, we observed that the rP21 was able to inhibit cell proliferation and promoted a significant reduction in the number of 4n cells (G2/M phase). Moreover, we found that rP21 significantly increased F-actin levels and this protein was able to modulate expression of genes related to angiogenesis and actin cytoskeleton. However, rP21 showed no significant activity on the matrix components. In this sense, we conclude that the rP21-endothelial cells (ECs) interaction via CXCR4 promotes inhibition of vessel formation through a cascade of intracellular events, such as inhibition of ECs proliferation and modulation of the expression of molecules associated with angiogenic processes and actin cytoskeleton.

Estudo comparativo de dois conversores Boost quadrático com comutação suave monochaveados para aplicação de rastreamento de máxima potência em sistemas fotovoltaicos

This paper makes a comparative study of two Soft Single Switched Quadratic Boost Converters (SSS1 and SSS2) focused on Maximum Power Point Tracking (MPPT) of a PV array using Perturb and Observe (P&O) algorithm. The proposed converters maintain the static gain characteristics and dynamics of the original converter with the advantage of considerably reducing the switching losses and Electromagnetic Interference (EMI). It is displayed the input voltage Quadratic Boost converter modeling; qualitative and quantitative analysis of soft switching converters, defining the operation principles, main waveforms, time intervals and the state variables in each operation steps, phase planes of resonant elements, static voltage gain expressions, analysis of voltage and current efforts in semiconductors and the operational curves at 200 W to 800 W. There are presented project of PI, PID and PID + Notch compensators for MPPT closed-loop system and resonant elements design. In order to analyze the operation of a complete photovoltaic system connected to the grid, it was chosen to simulate a three-phase inverter using the P-Q control theory of three-phase instantaneous power. Finally, the simulation results and experimental with the necessary comparative analysis of the proposed converters will be presented.

Optical wave turbulence and wave condensation in a nonlinear optical experiment

We present theory, numerical simulations and experimental observations of a 1D optical wave system. We show that this system is of a dual cascade type, namely, the energy cascading directly to small scales, and the photons or wave action cascading to large scales. In the optical context the inverse cascade is particularly interesting because it means the condensation of photons. We show that the cascades are induced by a six-wave resonant interaction process described by weak turbulence theory. We show that by starting with weakly nonlinear randomized waves as an initial condition, there exists an inverse cascade of photons towards the lowest wavenumbers. During the cascade nonlinearity becomes strong at low wavenumbers and, due to the focusing nature of the nonlinearity, it leads to modulational instability resulting in the formation of solitons. Further interaction of the solitons among themselves and with incoherent waves leads to the final condensate state dominated by a single strong soliton. In addition, we show the existence of the direct energy cascade numerically and that it agrees with the wave turbulence prediction.

Physical Insights, Steady Aerodynamic Effects, and a Design Tool for Low-Pressure Turbine Flutter

The successful, efficient, and safe turbine design requires a thorough understanding of the underlying physical phenomena. This research investigates the physical understanding and parameters highly correlated to flutter, an aeroelastic instability prevalent among low pressure turbine (LPT) blades in both aircraft engines and power turbines. The modern way of determining whether a certain cascade of LPT blades is susceptible to flutter is through time-expensive computational fluid dynamics (CFD) codes. These codes converge to solution satisfying the Eulerian conservation equations subject to the boundary conditions of a nodal domain consisting fluid and solid wall particles. Most detailed CFD codes are accompanied by cryptic turbulence models, meticulous grid constructions, and elegant boundary condition enforcements all with one goal in mind: determine the sign (and therefore stability) of the aerodynamic damping. The main question being asked by the aeroelastician, ``is it positive or negative?'' This type of thought-process eventually gives rise to a black-box effect, leaving physical understanding behind. Therefore, the first part of this research aims to understand and reveal the physics behind LPT flutter in addition to several related topics including acoustic resonance effects. A percentage of this initial numerical investigation is completed using an influence coefficient approach to study the variation the work-per-cycle contributions of neighboring cascade blades to a reference airfoil. The second part of this research introduces new discoveries regarding the relationship between steady aerodynamic loading and negative aerodynamic damping. Using validated CFD codes as computational wind tunnels, a multitude of low-pressure turbine flutter parameters, such as reduced frequency, mode shape, and interblade phase angle, will be scrutinized across various airfoil geometries and steady operating conditions to reach new design guidelines regarding the influence of steady aerodynamic loading and LPT flutter. Many pressing topics influencing LPT flutter including shocks, their nonlinearity, and three-dimensionality are also addressed along the way. The work is concluded by introducing a useful preliminary design tool that can estimate within seconds the entire aerodynamic damping versus nodal diameter curve for a given three-dimensional cascade.

El nuevo carácter de la dependencia intelectual

La cuestión de la "dependencia intelectual" es una de las preocupaciones más antiguas y sistemáticas del pensamiento latinoamericano. En este trabajo observamos cuáles han sido los cambios recientes en las formas de producción intelectual y su circulación que atraviesan los espacios nacionales, segmentando los procesos de consagración. Argumentamos que la colonialidad intelectual no describe la actual situación de nuestros campos académicos, más bien caracterizados por la convivencia conflictiva de la autonomía y la heteronomía. La dependencia académica, sin embargo, existe, pero es necesario observarla y analizarla como "situación concreta" llevando a fondo el enfoque relacional de la tradición histórico-estructural latinoamericana. En esta línea, primero analizamos el itinerario latinoamericano del debate sobre la dependencia intelectual, para luego proponer una definición operativa de dependencia académica. Finalmente, desarrollamos nuestra propuesta analítica para observar la producción de conocimientos en la periferia a partir de la articulación del concepto de "campo" y de "circuito".

Anclaje, dinámicas e impactos territoriales de la cadena global de cítricos dulces en el nordeste argentino

El artículo analiza firmas insertas en circuitos globalizados de exportación de frutas frescas, así como la interfase empresas-territorios. Se focaliza en la producción argentina de cítricos dulces y particularmente en un espacio productivo, y se interesa por cómo se traduce la construcción de los circuitos globales en los espacios y actores locales. Para ello, desarrolla una tipología de empresas e indicadores de anclaje y recurre a una combinación de fuentes cuantitativas y cualitativas, con vistas a desentrañar la “caja negra” del comportamiento empresarial. Se concluye que existen diferentes grados de anclaje territorial y combinaciones variables de fijación y movilidad por parte de las empresas. La adopción de una modalidad de agricultura empresarial multilocalizada, orientada al aprovechamiento de las peculiaridades de los diferentes ambientes locales, conduce a la desarticulación de espacios en función de sus características productivas y de sus diversos contextos sociales e institucionales. De esta forma se promueve la conformación de agentes de características flexibles, transformando su reproducción en contingente.