Extracellular Iron is a Modulator of the Differentiation of Osteoclast Lineage Cells.

Osteoclasts originate from the hematopoietic stem cell and share a differentiation pathway with the cells of the monocyte/macrophage lineages. Development and activation of osteoclasts, and as a consequence regulation of bone resorption, depend on two growth factors: macrophage colony-stimulating factor and receptor activator of NF-κB ligand. Furthermore, cell development and activity are modulated by a microenvironment composed of cytokines and growth factors and of the extracellular matrix. Membrane transporters are a means for cells to interact with their environment. Within this study, the expression of proteins regulating cellular iron homeostasis in osteoclast-like cells grown from bone marrow-derived progenitors was compared to the expression of this set of proteins by monocyte/macrophage lineage cells. In differentiating osteoclasts, levels of transcripts encoding transferrin receptor 1 and divalent metal transporter 1 (Slc11A2) were increased, while levels of transcripts encoding ferroportin (Slc40A1) and natural resistance-associated macrophage protein 1 (Slc11A1) were decreased. Supplementation of the culture media with exogenous iron led to an increase in the proliferation of osteoclast progenitor cells and to the expression of a macrophage-like phenotype, while the development of osteoclasts was reduced. Upon transfer of mature OC onto a CaP substrate, iron depletion of the medium with the Fe(3+)-chelator Deferoxamine Mesylate decreased CaP dissolution by ~30 %, which could be restored by addition of exogenous iron. During the 24 h of the assay, no effects were observed on total TRAP activity. The data demonstrate transcriptional regulation of the components of cellular iron transporters during OC development and suggests that iron homeostasis may contribute to fine-tuning of the RANKL-induced OC development.

Thermodynamics of zinc insertion in CuGaS2:Ti, used as a modulator agent in an intermediate-band photovoltaic material

An intermediate-bandphotovoltaicmaterial, which has an isolated metallic band located between the top of the valence band and bottom of the conduction band of some semiconductors, has been proposed as third generation solar cell to be used in photovoltaic applications. Density functional theory calculations of Zn in CuGaS2:Ti have previously shown that, the intermediate-band position can be modulated in proportion of Zn insertion in such a way that increasing Zn concentration can lead to aband-gap reduction, and an adjustment of the intermediate-band position. This could be interesting in the formation of an intermediate-bandmaterial, that has the maximum efficiency theoretically predicted for the intermediate-band solar cell. In this work, the energetics of several reaction schemes that could lead to the decomposition of the modulated intermediate-bandphotovoltaicmaterial, CuGaS2:Ti:Zn, is studied in order to assess the thermodynamic stability of this material. Calculations of the total free energy and disorder entropy have been taken into account, to get the reaction energy and free energy of the compound decomposition, which is found to be thermodynamically favorable

New Considerations in the Input Filter Design of a Three-Phase Buck-Type PWM Rectifier for Aircraft Applications

An EMI filter for a three-phase buck-type medium power pulse-width modulation rectifier is designed. This filter considers differential mode noise and complies with MIL-STD-461E for the frequency range of 10kHz to 10MHz. In industrial applications, the frequency range of the standard starts at 150kHz and the designer typically uses a switching frequency of 28kHz because the fifth harmonic is out of the range. This approach is not valid for aircraft applications. In order to design the switching frequency in aircraft applications, the power losses in the semiconductors and the weight of the reactive components should be considered. The proposed design is based on a harmonic analysis of the rectifier input current and an analytical study of the input filter. The classical industrial design does not consider the inductive effect in the filter design because the grid frequency is 50/60Hz. However, in the aircraft applications, the grid frequency is 400Hz and the inductance cannot be neglected. The proposed design considers the inductance and the capacitance effect of the filter in order to obtain unitary power factor at full power. In the optimization process, several filters are designed for different switching frequencies of the converter. In addition, designs from single to five stages are considered. The power losses of the converter plus the EMI filter are estimated at these switching frequencies. Considering overall losses and minimal filter volume, the optimal switching frequency is selected.

PWM Control of a Buck Converter with an Amorphous Core Coil

Pulse-width modulation is widely used to control electronic converters. One of the most topologies used for high DC voltage/low DC voltage conversion is the Buck converter. It is obtained as a second order system with a LC filter between the switching subsystem and the load. The use of a coil with an amorphous magnetic material core instead of air core lets design converters with smaller size. If high switching frequencies are used for obtaining high quality voltage output, the value of the auto inductance L is reduced throughout the time. Then, robust controllers are needed if the accuracy of the converter response must not be affected by auto inductance and load variations. This paper presents a robust controller for a Buck converter based on a state space feedback control system combined with an additional virtual space variable which minimizes the effects of the inductance and load variations when a not-toohigh switching frequency is applied. The system exhibits a null steady-state average error response for the entire range of parameter variations. Simulation results are presented.

Physical data acquisition and PWM signal generation using a microcontroller allowing control for DC motor rotation speed

El objetivo de este proyecto es diseñar un sistema capaz de controlar la velocidad de rotación de un motor DC en función del valor de temperatura obtenido de un sensor. Para ello se generará con un microcontrolador una señal PWM, cuyo ciclo de trabajo estará en función de la temperatura medida. En lo que respecta a la fase de diseño, hay dos partes claramente diferenciadas, relativas al hardware y al software. En cuanto al diseño del hardware puede hacerse a su vez una división en dos partes. En primer lugar, hubo que diseñar la circuitería necesaria para adaptar los niveles de tensión entregados por el sensor de temperatura a los niveles requeridos por ADC, requerido para digitalizar la información para su posterior procesamiento por parte del microcontrolador. Por tanto hubo que diseñar capaz de corregir el offset y la pendiente de la función tensión-temperatura del sensor, a fin de adaptarlo al rango de tensión requerido por el ADC. Por otro lado, hubo que diseñar el circuito encargado de controlar la velocidad de rotación del motor. Este circuito estará basado en un transistor MOSFET en conmutación, controlado mediante una señal PWM como se mencionó anteriormente. De esta manera, al variar el ciclo de trabajo de la señal PWM, variará de manera proporcional la tensión que cae en el motor, y por tanto su velocidad de rotación. En cuanto al diseño del software, se programó el microcontrolador para que generase una señal PWM en uno de sus pines en función del valor entregado por el ADC, a cuya entrada está conectada la tensión obtenida del circuito creado para adaptar la tensión generada por el sensor. Así mismo, se utiliza el microcontrolador para representar el valor de temperatura obtenido en una pantalla LCD. Para este proyecto se eligió una placa de desarrollo mbed, que incluye el microcontrolador integrado, debido a que facilita la tarea del prototipado. Posteriormente se procedió a la integración de ambas partes, y testeado del sistema para comprobar su correcto funcionamiento. Puesto que el resultado depende de la temperatura medida, fue necesario simular variaciones en ésta, para así comprobar los resultados obtenidos a distintas temperaturas. Para este propósito se empleó una bomba de aire caliente. Una vez comprobado el funcionamiento, como último paso se diseñó la placa de circuito impreso. Como conclusión, se consiguió desarrollar un sistema con un nivel de exactitud y precisión aceptable, en base a las limitaciones del sistema. SUMMARY: It is obvious that day by day people’s daily life depends more on technology and science. Tasks tend to be done automatically, making them simpler and as a result, user life is more comfortable. Every single task that can be controlled has an electronic system behind. In this project, a control system based on a microcontroller was designed for a fan, allowing it to go faster when temperature rises or slowing down as the environment gets colder. For this purpose, a microcontroller was programmed to generate a signal, to control the rotation speed of the fan depending on the data acquired from a temperature sensor. After testing the whole design developed in the laboratory, the next step taken was to build a prototype, which allows future improvements in the system that are discussed in the corresponding section of the thesis.

Analysis and optimized design of a distributed multi-stage EMC filter for an interleaved three-phase PWM-rectifier system for aircraft applications

Different possible input filter configurations for a modular three-phase PWM rectifier system consisting of three interleaved converter cells are studied. The system is designed for an aircraft application where MIL-STD-461E conducted EMI standards have to be met and system weight is a critical design issue. The importance of a LISN model on the simulated noise levels and the effect of interleaving and power unbalance between the different converter modules is discussed. The effect of the number of filter stages and the degree of distribution of the filter stages among the individual converter modules on the weight and losses of the input filter is studied and optimal filter structures are proposed.

Liquid-crystal electro-optic modulator based on electrohydrodynamic effects

A new method of light modulation is reported. This method is based on the electro-optical properties of nematic materials and on the use of a new wedge structure. The advantages of this structure are the possibility of modulating nonpolarized light and the improved signal-to-noise ratio. The highest modulating frequency obtained is 25 kHz.

Interleaved multi-cell isolated three-phase PWM rectifier system for aircraft applications

Recently there has been an important increase in electric equipment, as well as, electric power demand in aircrafts applications. This prompts to the necessity of efficient, reliable, and low-weight converters, especially rectifiers from 115VAC to 270VDC because these voltages are used in power distribution. In order to obtain a high efficiency, in aircraft application where the derating in semiconductors is high, normally several semiconductors are used in parallel to decrease the conduction losses. However, this is in conflict with high reliability. To match both goals of high efficiency and reliability, this work proposes an interleaved multi-cell rectifier system, employing several converter cells in parallel instead of parallel-connected semiconductors. In this work a 10kW multi-cell isolated rectifier system has been designed where each cell is composed of a buck type rectifier and a full bridge DC-DC converter. The implemented system exhibits 91% of efficiency, high power density (10kW/10kg), low THD (2.5%), and n−1 fault tolerance which complies, with military aircraft standards.

A Cannabinoid CB1 Receptor Positive Allosteric Modulator Reduces Neuropathic Pain in the Mouse with no Psychoactive Effects

Peer reviewed

Pituitary adenylyl cyclase-activating peptide: A pivotal modulator of glutamatergic regulation of the suprachiasmatic circadian clock

The circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus organizes behavioral rhythms, such as the sleep–wake cycle, on a near 24-h time base and synchronizes them to environmental day and night. Light information is transmitted to the SCN by direct retinal projections via the retinohypothalamic tract (RHT). Both glutamate (Glu) and pituitary adenylyl cyclase-activating peptide (PACAP) are localized within the RHT. Whereas Glu is an established mediator of light entrainment, the role of PACAP is unknown. To understand the functional significance of this colocalization, we assessed the effects of nocturnal Glu and PACAP on phasing of the circadian rhythm of neuronal firing in slices of rat SCN. When coadministered, PACAP blocked the phase advance normally induced by Glu during late night. Surprisingly, blocking PACAP neurotransmission, with either PACAP6–38, a specific PACAP receptor antagonist, or anti-PACAP antibodies, augmented the Glu-induced phase advance. Blocking PACAP in vivo also potentiated the light-induced phase advance of the rhythm of hamster wheel-running activity. Conversely, PACAP enhanced the Glu-induced delay in the early night, whereas PACAP6–38 inhibited it. These results reveal that PACAP is a significant component of the Glu-mediated light-entrainment pathway. When Glu activates the system, PACAP receptor-mediated processes can provide gain control that generates graded phase shifts. The relative strengths of the Glu and PACAP signals together may encode the amplitude of adaptive circadian behavioral responses to the natural range of intensities of nocturnal light.

Mapmodulin: A possible modulator of the interaction of microtubule-associated proteins with microtubules

We have purified and characterized a 31-kDa protein named mapmodulin that binds to the microtubule-associated proteins (MAPs) MAP2, MAP4, and tau. Mapmodulin binds free MAPs in strong preference to microtubule-associated MAPs, and appears to do so via the MAP’s tubulin-binding domain. Mapmodulin inhibits the initial rate of MAP2 binding to microtubules, a property that may allow mapmodulin to displace MAPs from the path of organelles translocating along microtubules. In support of this possibility, mapmodulin stimulates the microtubule- and dynein-dependent localization of Golgi complexes in semi-intact CHO cells. To our knowledge, mapmodulin represents the first example of a protein that can bind and potentially regulate multiple MAP proteins.

Loperamide: A positive modulator for store-operated calcium channels?

The depletion of inositol trisphosphate-sensitive intracellular pools of calcium causes activation of store-operated calcium (SOC) channels. Loperamide at 10–30 μM has no effect on intracellular calcium levels alone, but augments calcium levels in cultured cells when SOC channels have been activated. In HL-60 leukemic cells, the apparent positive modulatory effect of loperamide on SOC channels occurs when these channels have been activated after ATP, thapsigargin, or ionomycin-elicited depletion of calcium from intracellular storage sites. Loperamide has no effect when levels of intracellular calcium are elevated through a mechanism not involving SOC channels by using sphingosine. Loperamide caused augmentation of intracellular calcium levels after activation of SOC channels in NIH 3T3 fibroblasts, astrocytoma 1321N cells, smooth muscle DDT-MF2 cells, RBL-2H3 mast cells, and pituitary GH4C1 cells. Only in astrocytoma cells did loperamide cause an elevation in intracellular calcium in the absence of activation of SOC channels. The augmentation of intracellular calcium elicited by loperamide in cultured cells was dependent on extracellular calcium and was somewhat resistant to agents (SKF 96365, miconazole, clotrimazole, nitrendipine, and trifluoperazine) that in the absence of loperamide effectively blocked SOC channels. It appears that loperamide augments influx of calcium through activated SOC channels.

Leptin as a modulator of sweet taste sensitivities in mice

Leptin acts as a potent inhibitory factor against obesity by regulating energy expenditure, food intake, and adiposity. The obese diabetic db/db mouse, which has defects in leptin receptor, displays enhanced neural responses and elevated behavioral preference to sweet stimuli. Here, we show the effects of leptin on the peripheral taste system. An administration of leptin into lean mice suppressed responses of peripheral taste nerves (chorda tympani and glossopharyngeal) to sweet substances (sucrose and saccharin) without affecting responses to sour, salty, and bitter substances. Whole-cell patch-clamp recordings of activities of taste receptor cells isolated from circumvallate papillae (innervated by the glossopharyngeal nerve) demonstrated that leptin activated outward K+ currents, which resulted in hyperpolarization of taste cells. The db/db mouse with impaired leptin receptors showed no such leptin suppression. Taste tissue (circumvallate papilla) of lean mice expressed leptin-receptor mRNA and some of the taste cells exhibited immunoreactivities to antibodies of the leptin receptor. Taken together, these observations suggest that the taste organ is a peripheral target for leptin, and that leptin may be a sweet-sensing modulator (suppressor) that may take part in regulation of food intake. Defects in this leptin suppression system in db/db mice may lead to their enhanced peripheral neural responses and enhanced behavioral preferences for sweet substances.

Redox state is a central modulator of the balance between self-renewal and differentiation in a dividing glial precursor cell

We have discovered that intracellular redox state appears to be a necessary and sufficient modulator of the balance between self-renewal and differentiation in dividing oligodendrocyte-type-2 astrocyte progenitor cells. The intracellular redox state of freshly isolated progenitors allows prospective isolation of cells with different self-renewal characteristics. Redox state is itself modulated by cell-extrinsic signaling molecules that alter the balance between self-renewal and differentiation: growth factors that promote self-renewal cause progenitors to become more reduced, while signaling molecules that promote differentiation cause progenitors to become more oxidized. Moreover, pharmacological antagonists of the redox effects of these cell-extrinsic signaling molecules antagonize their effects on self-renewal and differentiation, indicating that cell-extrinsic signaling molecules that modulate this balance converge on redox modulation as a critical component of their effector mechanism.

QscR, a modulator of quorum-sensing signal synthesis and virulence in Pseudomonas aeruginosa

The opportunistic pathogenic bacterium Pseudomonas aeruginosa uses quorum-sensing signaling systems as global regulators of virulence genes. There are two quorum-sensing signal receptor and signal generator pairs, LasR–LasI and RhlR–RhlI. The recently completed P. aeruginosa genome-sequencing project revealed a gene coding for a homolog of the signal receptors, LasR and RhlR. Here we describe a role for this gene, which we call qscR. The qscR gene product governs the timing of quorum-sensing-controlled gene expression and it dampens virulence in an insect model. We present evidence that suggests the primary role of QscR is repression of lasI. A qscR mutant produces the LasI-generated signal prematurely, and this results in premature transcription of a number of quorum-sensing-regulated genes. When fed to Drosophila melanogaster, the qscR mutant kills the animals more rapidly than the parental P. aeruginosa. The repression of lasI by QscR could serve to ensure that quorum-sensing-controlled genes are not activated in environments where they are not useful.