Investigations of Pyrrole-Imidazole Polyamide Effects on DNA Replication

Pyrrole–Imidazole polyamides are programmable, cell-permeable small molecules that bind in the minor groove of double-stranded DNA sequence-specifically. Polyamide binding has been shown to alter the local helical structure of DNA, disrupt protein-DNA interactions, and modulate endogenous gene expression. Py–Im polyamides targeted to the androgen receptor-DNA interface have been observed to decrease expression of androgen-regulated genes, upregulate p53, and induce apoptosis in a hormone-sensitive prostate cancer cell line. Here we report that androgen response element (ARE)-targeted polyamides induced DNA replication stress in a hormone-insensitive prostate cancer cell line. The ATR checkpoint kinase was activated in response to this stress, causing phosphorylation of MCM2, and FANCD2 was monoubiquitinated. Surprisingly, little single-stranded DNA was exhibited, and the ATR targets RPA2 and Chk1 were not phosphorylated. We conclude that polyamide induces relatively low level replication stress, and suggest inhibition of the replicative helicase as a putative mechanism based on in vitro assays. We also demonstrate polyamide-induced inhibition of DNA replication in cell free extracts from X. laevis oocytes. In this system, inhibition of chromatin decondensation is observed, preventing DNA replication initiation. Finally, we show that Py-Im polyamides targeted to the ARE and ETS binding sequence downregulate AR- and ERG-driven signaling in a prostate cancer cell line harboring the TMPRSS2-ERG fusion. In a mouse xenograft model, ARE-targeted polyamide treatment reduced growth of the tumor.

Marco-reloj-despertador basado en FPGA

Gordon E. Moore, cofundador de Intel, predijo en una publicación del año 1965 que aproximadamente cada dos años se duplicaría el número de transistores presentes en un circuito integrado, debido a las cada vez mejores tecnologías presentes en el proceso de elaboración [1]. A esta ley se la conoce como Ley de Moore y su cumplimiento se ha podido constatar hasta hoy en día. Gracias a ello, con el paso del tiempo cada vez se presentan en el mercado circuitos integrados más potentes, con mayores prestaciones para realizar tareas cada vez más complejas. Un tipo de circuitos integrados que han podido evolucionar de forma importante son los dispositivos de lógica programable, circuitos integrados que permiten implementar sobre ellos las funciones lógicas deseadas. Hasta hace no muchos años, dichos dispositivos eran capaces de incorporar circuitos compuestos por unas pocas funciones lógicas, pero gracias al proceso de miniaturización predicho por la Ley de Moore, hoy en día son capaces de implementar circuitos tan complejos como puede ser un microprocesador; dichos dispositivos reciben el nombre de FPGA, siglas de Field Programmable Gate Array. El presente proyecto tiene como objetivo construir un marco de fotos digital con reloj y despertador programable, valiéndose para ello de la FPGA Cyclone II de Altera y una pantalla táctil de la casa Terasic. Con este fin, se documentará en primera instancia los dispositivos a utilizar con sus características y posibilidades que plantean, para pasar posteriormente al diseño de la aplicación y su implementación e integración en la placa para comprobar su correcto funcionamiento.

Generación automática de VHDL mediante Simulink HDL coder y aplicación al procesado de señales

Gordon E. Moore, co-fundador de Intel, predijo en una publicación del año 1965 que aproximadamente cada dos años se duplicaría el número de transistores presentes en un circuito integrado, debido a las cada vez mejores tecnologías presentes en el proceso de elaboración. A esta ley se la conoce como Ley de Moore y su cumplimiento se ha podido constatar hasta hoy en día. Gracias a ello, con el paso del tiempo cada vez se presentan en el mercado circuitos integrados más potentes, con mayores prestaciones para realizar tareas cada vez más complejas. Un tipo de circuitos integrados que han podido evolucionar de forma importante por dicho motivo, son los dispositivos de lógica programable, circuitos integrados que permiten implementar sobre ellos las funciones lógicas que desee implementar el usuario. Hasta hace no muchos años, dichos dispositivos eran capaces de implementar circuitos compuestos por unas pocas funciones lógicas, pero gracias al proceso de miniaturización predicho por la Ley de Moore, hoy en día son capaces de implementar circuitos tan complejos como puede ser un microprocesador; dichos dispositivos reciben el nombre de FPGA, siglas de Field Programmable Gate Array. Debido a la mayor capacidad y por lo tanto a diseños más complejos implementados sobre las FPGA, en los últimos años han aparecido herramientas cuyo objetivo es hacer más fácil el proceso de ingeniería dentro de un desarrollo en este tipo de dispositivos, como es la herramienta HDL Coder de la compañía MathWorks, creadores también Matlab y Simulink, unas potentes herramientas usadas ampliamente en diferentes ramas de la ingeniería. El presente proyecto tiene como objetivo evaluar el uso de dicha herramienta para el procesado digital de señales, usando para ello una FPGA Cyclone II de la casa Altera. Para ello, se empezará analizando la herramienta escogida comparándola con herramientas de la misma índole, para a continuación seleccionar una aplicación de procesado digital de señal a implementar. Tras diseñar e implementar la aplicación escogida, se deberá simular en PC para finalmente integrarla en la placa de evaluación seleccionada y comprobar su correcto funcionamiento. Tras analizar los resultados de la aplicación de implementada, concretamente un analizador de la frecuencia fundamental de una señal de audio, se ha comprobado que la herramienta HDL Coder, es adecuada para este tipo de desarrollos, facilitando enormemente los procesos tanto de implementación como de validación gracias al mayor nivel de abstracción que aporta.

星载激光测距仪的高精度时间间隔测量单元

高精度时间间隔测量单元(TIU)是星载激光测距仪的关键部件。基于现场可编程门阵列(FPGA)研制出了满足星载要求的高精度、高集成度时间间隔测量单元。该单元采用数字计数法结合数字延迟线插入法的技术,在0.5～10 km的测量距离范围内,时间分辨率为500 ps。通过地面检测,在全程范围内保持了良好的线性度,标准偏差小于270 ps。该单元同时具备测量脉冲回波宽度的能力,可以获取目标的脉冲展宽信息。由于单元选用的元器件都具有航天产品性能,因此其设计和技术指标可满足星载激光测距仪的应用。

Implementación de un sistema de adquisición de datos analógico para la medida experimental de la posición y aceleración.

[ES]El objetivo de este proyecto es el desarrollo de un sistema de adquisición y tratamiento de señales analógicas para la medida experimental de la posición y aceleración. Por un lado, la adquisición de señales se llevará a cabo mediante una placa electrónica programable llamada “Arduino”. Por otro lado, haciendo uso de la plataforma LabVIEW, se creará un programa para analizar dichas señales. Se medirán señales analógicas provenientes de diferentes sensores (inclinómetros y acelerómetros).

Diseño de la lógica programable de un sistema de monitorización de estructuras.

[ES]El objeto de este trabajo es desarrollar la lógica programable de una FPGA para un sistema de monitorización de estructuras. El diseño se compone de un generador de señales arbitrarias y un sistema de adquisición. El sistema de monitorización está dirigido al campo aeronáutico, pero se puede emplear en otras áreas.

Del diseño a la programación de sistemas de control para la automatización de procesos industriales basados en PLC`s

Actualmente las mayoría de sistemas de automatización industrial utilizan los Autómatas Programables (PLC - Programmable Logic Controller) como sistemas de control y el diseño de dicho sistema se realiza mediante el lenguaje de modelado Grafcet. SFCEdit es un editor de Grafcet que permite el diseño de estos sistemas de control y la exportación de los mismos en un formato XML. Resumen Por otra parte tenemos la norma IEC 61131-3 que busca estandarizar los lenguajes de programación de los PLC de esta manera no se tendría que usar un lenguaje distinto por cada fabricante, y la organización PLCOpen rigiéndose por la norma ha creado un formato XML para cada lenguaje, en los cuales se basa el traductor. Resumen Habitualmente el paso del diseño a la programación se realiza de forma manual. La automatización de este proceso es el objetivo general del proyecto realizado. En esté se ha desarrollado una herramienta que permite realizar la traducción del diseño gráfico al estándar IEC 61131-3 considerando las particularidades de algunos fabricantes de PLCs como Beckhoff (TwinCAT) y TSX Micro (PL7Pro). Además la herramienta realiza la traducción al formato XML de PLCOpen. Resumen El traductor funciona recibiendo un fichero XML (exportado de SFCEdit) procesa su información y genera los ficheros en función de la compatibilidad que el usuario seleccione.

Perfil dos HPA prioritários na exaustão de veículo a diesel, no combustível diesel utilizado durante os ensaios de emissão veicular e no óleo lubrificante do motor

As concentrações na exaustão e os fatores de emissão dos hidrocarbonetos policíclicos aromáticos (HPA) prioritários de um veículo a diesel e as suas respectivas concentrações no diesel usado durante os ensaios de emissão veicular foram determinados com a finalidade de estimar a contribuição dos HPA provenientes do combustível nas emissões. Os produtos da combustão foram coletados diretamente nas emissões brutas do escapamento, utilizando um sistema de amostragem a volume constante sem diluição dos gases da exaustão. Os HPA associados ao MP foram amostrados de forma estratificada, utilizando um impactador em cascata MOUDI e filtros de fibra de vidro como substratos, e os HPA em fase gasosa foram amostrados usando cartuchos de amberlite XAD-2. A concentração dos HPA no óleo lubrificante do motor também foi monitorada ao longo do tempo até a sua troca após 12.000 km de uso. Após a extração e tratamento das amostras, a identificação e quantificação dos HPA foram realizadas, utilizando cromatografia de fase gasosa acoplada à espectrometria de massas (CG-EM) com injetor de grande volume de vaporização com a temperatura programável (PTV-LVI). Cinco variáveis do PTV-LVI foram otimizadas, utilizando planejamento de experimentos, o que permitiu obter limites de detecção menores do que 2,0 g L-1. Somente 7 dos 16 HPA prioritários foram identificados na exaustão: NAP, ACY, ACE, FLU, FEN, FLT e PYR. Os ensaios de emissão veicular foram realizados com o veículo em modo estacionário, sem aplicação de carga e com baixa velocidade de rotação do motor (1500 rpm), utilizando um diesel com menor teor de enxofre (10 mg kg-1) e com 5% v/v de biodiesel. Esses fatores possivelmente contribuíram para reduzir as emissões dos outros 9 HPA a valores abaixo dos limites de detecção do método desenvolvido. Aproximadamente 80% da massa dos HPA totais associados ao MP estavam presentes em partículas com tamanho entre 1,0 m e 56 nm, e aproximadamente 4,5% estavam presentes em partículas menores do que 56 nm. Partículas menores que 2,5 m são facilmente inaladas e depositadas no trato respiratório e na região alveolar, justificando a preocupação com relação às emissões de HPA associados a partículas provenientes da exaustão veicular de motores a diesel. Somente 5 dos 7 HPA identificados na exaustão foram detectados no diesel: NAP, ACY, FLU, FEN e PYR. A razão entre os fatores de emissão (g L-1diesel) dos HPA na exaustão e suas respectivas concentrações do diesel (g L-1) variaram de 0,01 0,02 a 0,05 0,029, dependendo do HPA. Esses valores indicam que pelo menos 95 a 99% dos HPA identificados no diesel foram destruídos e/ou transformados em outros compostos durante a combustão, e/ou foram retidos no reservatório do óleo lubrificante. Por outro lado, os HPA que tiveram maiores concentrações no diesel também apresentaram maiores fatores de emissão, o que sugere que os HPA provenientes do diesel possuem uma contribuição significativa para as emissões dos HPA totais. O perfil dos HPA prioritários no óleo lubrificante mostrou-se semelhante ao perfil dos HPA no diesel e nas emissões totais, onde o NAP, FEN e PYR foram os HPA majoritários

On-line topographic analysis in the SEM

A novel method for on-line topographic analysis of rough surfaces in the SEM has been investigated. It utilises a digital minicomputer configured to act as a programmable scan generator and automatic focusing unit. The computer is coupled to the microscope through digital-to-analogue converters which enable it to generate ramp waveforms allowing the beam to be scanned over a small sub-region of the field under program control. A further digital-to-analogue converter regulates the current supply to the objective lens of the microscope. The video signal is sampled by means of an analogue-to-digital converter and the resultant binary code stored in the computer's memory as an array of numbers describing relative image intensity. Computations based on the intensity gradient of the image allow the objective lens current to be found for the in-focus condition, which may be related to the working distance through a previous calibration experiment. The sensitivity of the method for detecting small height changes is theoretically of the order of 1 μm. In practice the operator specifies features of interest by means of a mobile spot cursor injected into the SEM display screen, or he may scan the specimen at sub-regions corresponding to pre-determined points on a regular grid defined by him. The operation then proceeds under program control. | A novel method for on-line topographic analysis of rough surfaces in the SEM has been investigated. It utilizes a digital minicomputer configured to act as a programmable scan generator and automatic focusing unit. A further digital-to-analog converter regulates the current supply to the objective lens of the microscope. The video signal is sampled by means of an analog-to-digital converter and the resultant binary code stored in the computer's memory as an array of numbers describing relative image intensity. The sensitivity of the method for detecting small height changes is theroretically of the order of 1 mu m.

Topographical analysis in the SEM using an automatic focusing technique

A novel technique for automated topographical analysis in the SEM has been investigated. It utilizes a 16-bit minicomputer arranged to act as an automatic focusing unit. The computer is coupled to the objective lens of the microscope, by means of a digital to analogue converter, and may regulate the excitation of the lens under program control. Further digital-to-analogue converters allow the computer to act as a programmable scan generator by applying ramp waveforms to the scan amplifiers, permitting the beam to be swept over a small sub-region of the field of interest. The video signal is sampled and applied to an analogue-to-digital converter; the resultant binary numbers are stored in computer memory as an array of values representing relative image intensities within a subregion. A differencing algorithm applied to the collected data allows the level of objective lens excitation to be found at which the sharpness of the image is optimized, and the excitation may be related to the working distance for that subregion through a previous calibration experiment. The sensitivity of the method for detecting small height changes is theoretically of the order of 1 μm.

Sperm cryopreservation of Indian major carp, Labeo rohita: cryodiluents, sperm: cryodiluent dilution ratio and cryoprotectan t concentration

Cryogenic preservation trials of spermatozoa of Labeo rohita were carried out. Twenty four cryodiluents (extender + cryoprotectant), with the combination of six extenders such as egg-yolk citrate, urea-egg-yolk, 0.9% NaCl, Kurokura-2, Ma and Mb and four cryoprotectants viz. DMSO, glycerol, methanol and ethanol, were used to screen out the suitable cryodiluents. Sperm was preserved in 0.25ml plastic straw in programmable freezer. Two step freezing method was followed. Sperm preserved with egg-yolk citrate and urea-egg-yolk containing 10% DMSO showed best post-thaw motility (80%) followed by 0.9% NaCl (60%) and Kurokura-2(30%) solutions. Sperm with the extenders M" and Mb clotted at the time of equilibration and also after few days of preservation. Egg-yolk citrate mixed with ethanol and methanol also showed good percentage of motility (80%) but egg-yolk citrate with glycerol showed less sperm motility (>60%). To determine suitable dilution ratio of milt and cryodiluent two best extender eggyolk citrate and urea-egg-yolk with four cryoprotectants such as DMSO, glycerol, methanol and ethanol at different ratio viz 1:2,1:4,1:7,1:10,1:15 and 1:20 were used. Highest post-thaw motility (>80%) was observed when milt was preserved with egg-yolk citrate containing 10% DMSO at 1:2, 1:4, 1:7 and 1:10 dilutions. Meanwhile using glycerol as cryoprotectants provided less post thaw motility at lower dilution ratio but with the increase of its dilution showed good sperm motility compared with other cryoprotectants. Finally, evaluation on the effect of cryoprotectant concentration on post-thaw sperm motility was conducted. Egg-yolk citrate and four cryoprotectant i.e. DMSO, glycerol, methanol and ethanol with six different concentrations namely 5%,7%, 10%, 15%, 20% and 30%.were evaluated. Among the cryoprotectants DMSO, methanol and ethanol showed highest post-thaw motility (about 80%) at 7% and 10% concentrations. Although glycerol was not suitable at low concentration but its 20% and 30% concentration levels provided best post-thaw motility. No post-thaw motility was obtained with DMSO at 30% concentration. The overall analysis on cryoprotectant concentration indicated that below 5% and above 20% cryoprotectant concentrations could not be suitable for effective cryopreservation of spermatozoa.

A FEniCS-based programming framework for modeling turbulent flow by the Reynolds-averaged Navier-Stokes equations

Finding an appropriate turbulence model for a given flow case usually calls for extensive experimentation with both models and numerical solution methods. This work presents the design and implementation of a flexible, programmable software framework for assisting with numerical experiments in computational turbulence. The framework targets Reynolds-averaged Navier-Stokes models, discretized by finite element methods. The novel implementation makes use of Python and the FEniCS package, the combination of which leads to compact and reusable code, where model- and solver-specific code resemble closely the mathematical formulation of equations and algorithms. The presented ideas and programming techniques are also applicable to other fields that involve systems of nonlinear partial differential equations. We demonstrate the framework in two applications and investigate the impact of various linearizations on the convergence properties of nonlinear solvers for a Reynolds-averaged Navier-Stokes model. © 2011 Elsevier Ltd.

Embedded Model Predictive Control (MPC) using a FPGA

Model Predictive Control (MPC) is increasingly being proposed for application to miniaturized devices, fast and/or embedded systems. A major obstacle to this is its computation time requirement. Continuing our previous studies of implementing constrained MPC on Field Programmable Gate Arrays (FPGA), this paper begins to exploit the possibilities of parallel computation, with the aim of speeding up the MPC implementation. Simulation studies on a realistic example show that it is possible to implement constrained MPC on an FPGA chip with a 25MHz clock and achieve MPC implementation rates comparable to those achievable on a Pentium 3.0 GHz PC. Copyright © 2007 International Federation of Automatic Control All Rights Reserved.

Electrotactile touch surface by using transparent graphene

In this work we present a flexible Electrostatic Tactile (ET) surface/display realized by using new emerging material graphene. The graphene is transparent conductor which successfully replaces previous solution based on indium-thin oxide (ITO) and delivers more reliable solution for flexible and bendable displays. The electrostatic tactile surface is capable of delivering programmable, location specific tactile textures. The ET device has an area of 25 cm 2, and consists of 130 μm thin optically transparent (>76%) and mechanically flexible structure overlaid unobtrusively on top of a display. The ET system exploits electro vibration phenomena to enable on-demand control of the frictional force between the user's fingertip and the device surface. The ET device is integrated through a controller on a mobile display platform to generate fully programmable range of stimulating signals. The ET haptic feedback is formed in accordance with the visual information displayed underneath, with the magnitude and pattern of the frictional force correlated with both the images and the coordinates of the actual touch in real time forming virtual textures on the display surface (haptic virtual silhouette). To quantify rate of change in friction force we performed a dynamic friction coefficient measurement with a system involving an artificial finger mimicking the actual touch. During operation, the dynamic friction between the ET surface and an artificial finger stimulation increases by 26% when the load is 0.8 N and by 24% when the load is 1 N. © 2012 ACM.

Predictive control of a Boeing 747 aircraft using an FPGA

New embedded predictive control applications call for more eficient ways of solving quadratic programs (QPs) in order to meet demanding real-time, power and cost requirements. A single precision QP-on-a-chip controller is proposed, implemented in afield-programmable gate array (FPGA) with an iterative linear solver at its core. A novel offline scaling procedure is introduced to aid the convergence of the reduced precision solver. The feasibility of the proposed approach is demonstrated with a real-time hardware-in-the-loop (HIL) experimental setup where an ML605 FPGA board controls a nonlinear model of a Boeing 747 aircraft running on a desktop PC through an Ethernet link. Simulations show that the quality of the closed-loop control and accuracy of individual solutions is competitive with a conventional double precision controller solving linear systems using a Riccati recursion. © 2012 IFAC.