DC Circuits Containing Resistors and Capacitors

Expression of the Drosophila melanogaster ATP synthase a subunit gene is regulated by a transcriptional element containing GAF and Adf-1 binding sites Ana Talamillo 1, *, Miguel Angel Ferna ´ ndez-Moreno 1 , Francisco Martı ´ nez-Azorı ´ n 1 ,Bele ´ n Bornstein 1,2 , Pilar Ochoa 1 and Rafael Garesse 1 1 Departamento de Bioquı ´ mica, Instituto de Investigaciones Biome ´ dicas ‘Alberto Sols’, CSIC-UAM, Facultad de Medicina, Universidad Auto ´ noma de Madrid, Spain; 2 Servicio de Bioquı ´ mica, Hospital Severo Ochoa, Legane ´ s, Madrid, Spain Mitochondrial biogenesis is a complex and highly regulated process that requires the controlled expression of hundreds of genes encoded in two separated genomes, namely the nuclear and mitochondrial genomes. To identify regulatory proteins involved in the transcriptional control of key nuc- lear-encoded mitochondrial genes, we have performed a detailed analysis of t he promoter region of the a subunit of the Drosophila melanogaster F 1 F 0 ATP synthase complex. Using transient transfection assays, we have identified a 56 bp cis-acting proximal r egulatory r egion t hat c ontains binding sites for the GAGA factor and the alcohol dehy- drogenase distal factor 1. In vitro mutagenesis revealed that both sites are f unctional, and phylogenetic footprinting showed that they are conserved in other Drosophila species and in Anopheles gambiae. The 56 bp region has regulatory enhancer properties and strongly activates heterologous promoters i n an o rientation-independent manner. In addi- tion, Northern blot and RT-PCR analysis identified two a-F1-ATPase mRNAs that differ in the length of the 3¢ untranslated region due to the selection of alternative polyadenylation sites. Keywords: mitochondria; a-F 1 -ATPase; GAGA; Adf-1; transcription regulation. The bulk of cellular ATP is synthesized through oxidative phosphorylation (OXPHOS) that takes place in the mito- chondria. The OXPHOS system is composed of five multisubunit complexes embedded in the inner mitochond- rial membrane and two small electron carriers, ubiquinone and cytochrome c [1]. The O XPHOS system is generated in a unique manner. The majority of the more than 80 OXPHOS subunits are encoded by genes in the nuclear DNA (n-DNA), while 13 essential subunits are encoded i n the mitochondrial DNA (mtDNA), contributing to four out of the five OXPHOS complexes. The mtDNA consists of a small, double-stranded, circular DNA molecule that is transcribed and translated within this organelle. However, all of the components involved in the replication, maintenance and expression of the mtDNA, as well as the factors that participate in t he assembly of the respiratory complexes, are encoded in the nucleus. Therefore, correct OXPHOS func- tion relies on the co ordinated expression of numerous genes encoded in two physically separated genetic systems [2,3]. The multisubunit enzyme ATP synthase (complex V of the OXPHOS system) is p resent in the membranes of eubacteria, mitochondria and chloroplasts. It synthesizes ATP by means of a rotary mechanism coupled to the electrochemical gradient generated by the electron transport chain [4]. The mitochondrial ATP synthase of animals contains 16 subunits and i s responsible for the synthesis of t he majority of cellular ATP, th ereby DC Circuits Containing Resistors and Capacitors DC Circuits Containing Resistors and Capacitors Bởi: OpenStaxCollege When you use a flash camera, it takes a few seconds to charge the capacitor that powers the flash The light flash discharges the capacitor in a tiny fraction of a second Why does charging take longer than discharging? This question and a number of other phenomena that involve charging and discharging capacitors are discussed in this module RC Circuits An RC circuit is one containing a resistor R and a capacitor C The capacitor is an electrical component that stores electric charge [link] shows a simple RC circuit that employs a DC (direct current) voltage source The capacitor is initially uncharged As soon as the switch is closed, current flows to and from the initially uncharged capacitor As charge increases on the capacitor plates, there is increasing opposition to the flow of charge by the repulsion of like charges on each plate In terms of voltage, this is because voltage across the capacitor is given by Vc = Q / C , where Q is the amount of charge stored on each plate and C is the capacitance This voltage opposes the battery, growing from zero to the maximum emf when fully emf charged The current thus decreases from its initial value of I0 = R to zero as the voltage on the capacitor reaches the same value as the emf When there is no current, there is no IR drop, and so the voltage on the capacitor must then equal the emf of the voltage source This can also be explained with Kirchhoff’s second rule (the loop rule), discussed in Kirchhoff’s Rules, which says that the algebraic sum of changes in potential around any closed loop must be zero emf The initial current is I0 = R , because all of the IR drop is in the resistance Therefore, the smaller the resistance, the faster a given capacitor will be charged Note that the internal resistance of the voltage source is included in R, as are the resistances of 1/13 ⋅ DC Circuits Containing Resistors and Capacitors the capacitor and the connecting wires In the flash camera scenario above, when the batteries powering the camera begin to wear out, their internal resistance rises, reducing the current and lengthening the time it takes to get ready for the next flash (a) An RC circuit with an initially uncharged capacitor Current flows in the direction shown (opposite of electron flow) as soon as the switch is closed Mutual repulsion of like charges in the capacitor progressively slows the flow as the capacitor is charged, stopping the current when the capacitor is fully charged and Q = C emf (b) A graph of voltage across the capacitor versus time, with the switch closing at time t = (Note that in the two parts of the figure, the capital script E stands for emf, q stands for the charge stored on the capacitor, and τ is the RC time constant.) Voltage on the capacitor is initially zero and rises rapidly at first, since the initial current is a maximum [link](b) shows a graph of capacitor voltage versus time (t) starting when the switch is closed at t = The voltage approaches emf asymptotically, since the closer it gets to emf the less current flows The equation for voltage versus time when charging a capacitor C through a resistor R, derived using calculus, is V = emf(1 − e − t / RC ) (charging), where V is the voltage across the capacitor, emf is equal to the emf of the DC voltage source, and the exponential e = 2.718 … is the base of the natural logarithm Note that the units of RC are seconds We define τ = RC, where τ (the Greek letter tau) is called the time constant for an RC circuit As noted before, a small resistance R allows the capacitor to charge faster This is reasonable, since a larger current flows through a smaller resistance It is also reasonable that the smaller the capacitor C, the less time needed to charge it Both factors are contained in τ = RC More quantitatively, consider what happens when t = τ = RC Then the voltage on the capacitor is V = emf(1 − e − 1) = emf(1 − 0.368) = 632⋅emf 2/13 DC Circuits Containing Resistors and Capacitors This means that in the time τ = RC, the voltage rises to 0.632 of its final value The voltage will rise 0.632 of the remainder in the next time τ It is a characteristic of the exponential function that the final value is never reached, but 0.632 of the remainder to that value is achieved in every time, τ In just a few multiples of the time constant τ, then, the final value is very nearly achieved, as the graph in [link](b) illustrates Discharging a Capacitor Discharging a capacitor through a resistor proceeds in a similar fashion, as [link] V illustrates Initially, the current is I0 = R0 , driven by the initial voltage V0 on the capacitor As the voltage decreases, the current and hence the rate of discharge decreases, implying another exponential formula for V Using calculus, the voltage V on a capacitor C being discharged through a resistor R is found to be V = V e − t / RC(discharging) (a) Closing the ...[...]... interests include ASIC and FPGA design, digital arithmetic, and development of embedded systems He is the author of about 30 international papers and communications xix 1 INTRODUCTION The design of embedded systems, that is, circuits designed for specific applications, is based on a series of decisions as well as on the use of several types of development techniques For example: Selection of the data... Generation or selection of algorithms Selection of hardware platforms Hardware – software partitioning Program generation New hardware synthesis Cosimulation, coemulation, and prototyping Some of these activities have a close relationship with the study of arithmetic algorithms and circuits, especially in the case of systems including a great amount of data processing (e.g., ciphering and deciphering, image... language of the chosen microprocessor 1.6 SYNTHESIS Once the hardware– software partition has been defined, all the tasks assigned to the specific hardware (FPGA, ASIC) must be translated into circuit descriptions Some important synthesis principles and methods are described in Chapter 10 The synthesis of arithmetic circuits, based on the algorithms of Chapters 4 –8, is the topic of Chapters 11– 15, and an... reading of the new_character and sign input signals, reading of the character input and updating of the summary, writing of the summary and of the start command within the interface registers: 10 INTRODUCTION summary:=(0, 0, 0, 0); start:=0; loop wait for command=0 while command>0 loop null; end loop; wait for command=1 (new_character) or 2 (sign) while command=0 loop null; end loop; if command=1 then... possible choices concerning the internal representation of data He must conform to some fixed Synthesis of Arithmetic Circuits: FPGA, ASIC, and Embedded Systems ´ By Jean-Pierre Deschamps, Gery J A Bioul, and Gustavo D Sutter Copyright # 2006 John Wiley & Sons, Inc 1 2 INTRODUCTION and predefined data types such as integer, floating-point, double NANO EXPRESS Open Access Nanofluid bioconvection in water-based suspensions containing nanoparticles and oxytactic microorganisms: oscillatory instability Andrey V Kuznetsov Abstract The aim of this article is to prop ose a novel type of a nanofluid that contains both nanoparticles and motile (oxytactic) microorganisms. The benefits of adding motile microorganisms to the suspension include enhanced mass transfer, microscale mixing, and anticipated improved stability of the nanofluid. In order to understand the behavior of such a suspension at the fundamental level, this article investigates its stability when it occupies a shallow horizontal layer. The oscillatory mode of nanofluid biocon vection may be induced by the interaction of three competing agencies: oxytactic microorganisms, heating or cooling from the bottom, and top or bottom- heavy nanoparticle distribution. The model includes equations expressing conservation of total mass, momentum, thermal energy, nanoparticles, microorganisms, and oxygen. Physical mechanisms responsible for the slip velocity between the nanoparticles and the base fluid, such as Brownian motion and thermophoresis, are accounted for in the model. An approximate analytical solution of the eigenvalue problem is obtained using the Galerkin method. The obtained solution provides important physical insights into the behavior of this system; it also explains when the oscillatory mode of instability is possible in such system. Introduction The term “nanofluid” was coined by Choi in his seminal paper presented in 1995 at the ASME Winter Annual Meeting [1]. It refers to a liquid containing a dispersion of submicronic solid particles (nanoparticles) with typi- cal length on the order of 1-50 nm [2]. The unique properties of nanofluids include the impressive enhance- ment of thermal conductivity as well as overall heat transfer [3-7]. Various mechanisms leading t o heat transfer enhancement in nanofluids are discussed in numerous publications; see, for example [8-12]. Wang [13-15] pioneered in develo ping the constructal approach, created by Bejan [16-19], for designing nano- fluids. Nanofluids enhance the thermal performance of the base fluid; the utilization of the constructal theory makes it possible to design a nanofluid with the best microstructure and performance within a specified type of microstructures. Recent publications show significant interest in appli- cations of nanofluids in various types of microsystems. These include microchannels [20], microheat pipes [21], microchannel heat sinks [22], and microreactors [23]. There is also significant potential in using nanomaterials in different bio -microsystems, such as enzyme biosen- sors [24]. In [25], the performance of a bioseparation system for cap turing nanoparticles was simulated. There is also strong interest i n developing chip-size microde- vices for evaluating nanoparticle toxicity; Huh et al. [26] suggested a biomimetic microsystem that reconstitutes the critical functional alveolar-capillary interface of the human lung to evaluate toxic and inflammatory responses of the lung to silica nanoparticles. The aim of this article is to propose a novel type of a nanoflui d that contains both nan oparticles and oxytactic microorganisms, such as a soil bacterium Bacillus subti- lis. These particular microorganisms are oxygen consu- mers that swim up the oxygen concentration gradient. There are important similarities and differences between nanoparticles and motile microorganisms. In their impressive review of nanofluids research, Wang and Fan [27] pointed out that nanofluids involve four scales: the BioMed Central Page 1 of 9 (page number not for citation purposes) Genetic Vaccines and Therapy Open Access Research Prevention of airway inflammation with topical cream containing imiquimod and small interfering RNA for natriuretic peptide receptor Xiaoqin Wang 1,2 , Weidong Xu 2 , Subhra Mohapatra 3,4 , Xiaoyuan Kong 2 , Xu Li 1 , Richard F Lockey 2,4 and Shyam S Mohapatra* 2,4 Address: 1 Clinical Laboratory Center of First Affiliated Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, China, 2 Division of Allergy and Immunology, Culverhouse Airway Disease and Nanomedicine Research Center, University of South Florida College of Medicine, Tampa, Florida, USA, 3 Endocrinology Division, Internal Medicine, University of South Florida College of Medicine, Tampa, Florida, USA and 4 James A. Haley VA Medical Center, Tampa, Florida, USA Email: Xiaoqin Wang - xwang1@health.usf.edu; Weidong Xu - wxu@health.usf.edu; Subhra Mohapatra - smohapa2@health.usf.edu; Xiaoyuan Kong - xkong@health.usf.edu; Xu Li - lixu@tom.com; Richard F Lockey - rlockey@health.usf.edu; Shyam S Mohapatra* - smohapat@health.usf.edu * Corresponding author Abstract Background: Asthma is a complex disease, characterized by reversible airway obstruction, hyperresponsiveness and chronic inflammation. Principle pharmacologic treatments for asthma include bronchodilating beta2-agonists and anti-inflammatory glucocorticosteroids; but these agents do not target the main cause of the disease, the generation of pathogenic Th2 cells. We previously reported reduction in allergic inflammation in mice deficient in the ANP receptor NPRA. Here we determined whether siRNA for natriuretic peptide receptor A (siNPRA) protected against asthma when administered transdermally. Methods: Imiquimod cream mixed with chitosan nanoparticles containing either siRNA green indicator (siGLO) or siNPRA was applied to the skin of mice. Delivery of siGLO was confirmed by fluorescence microscopy. The anti-inflammatory activity of transdermal siNPRA was tested in OVA-sensitized mice by measuring airway hyperresponsiveness, eosinophilia, lung histopathology and pro-inflammatory cytokines. Results: SiGLO appearing in the lung proved the feasibility of transdermal delivery. In a mouse asthma model, BALB/c mice treated with imiquimod cream containing siNPRA chitosan nanoparticles showed significantly reduced airway hyperresponsiveness, eosinophilia, lung histopathology and pro-inflammatory cytokines IL-4 and IL-5 in lung homogenates compared to controls. Conclusion: These results demonstrate that topical cream containing imiquimod and siNPRA nanoparticles exerts an anti-inflammatory effect and may provide a new and simple therapy for asthma. Published: 15 February 2008 Genetic Vaccines and Therapy 2008, 6:7 doi:10.1186/1479-0556-6-7 Received: 9 October 2007 Accepted: 15 February 2008 This article is available from: http://www.gvt-journal.com/content/6/1/7 © 2008 Wang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Genetic Vaccines and Therapy 2008, 6:7 http://www.gvt-journal.com/content/6/1/7 Page 2 of 9 (page number not for citation purposes) Introduction Chitosan is a natural cationic polysaccharide extracted from crustacean shells. It is a good candidate for the deliv- ery of genes and drugs because of its biodegradability, bio- compatibility, mucoadhesiveness, low immunogenicity, and strong immunostimulatory properties [1-3]. It has been found to have beneficial properties including antico- agulant, wound-healing and anti-microbial activities. Chitosan has also been widely used in controlled drug delivery [4-7] because it is nontoxic, nonhemolytic, slowly biodegradable and capable of encapsulating a drug UMI Number: 3195285 3195285 2006 UMI Microform Copyright All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. ProQuest Information and Learning Company 300 North Zeeb Road P.O. Box 1346 Ann Arbor, MI 48106-1346 by ProQuest Information and Learning Company. Copyright © 2005 by Rogelio Siles All rights reserved ABSTRACT Design, Synthesis, and Biological Evaluation of New Anti-cancer Nitrogen-Containing Combretastatins and Novel Cysteine Protease Inhibitors for the Treatment of Chagas Rogelio Siles Mentor: Kevin G. Pinney, Ph.D. In an effort to combat cancer, the development of a relatively new type of anti- cancer drugs known as vascular disrupting agents (VDAs) seems to be a promising clinical approach. VDAs selectively interfere with blood flow in the microvessels that carry nutrients and oxygen to the tumor. Blockage of these vessels will stop tumor growth, produce necrosis, and hence prevent proliferation of cancer cells through the body. The discovery of a group of VDAs known as combretastatins (CA) has sparked an exciting area of anti-cancer drug discovery due to their robust biological activity as evidenced through clinical success, particularly for combretastatin A-4 phosphate (CA- 4P) and one nitrogen-based combretastatin CA-4 analogue, AVE8062 which are currently in clinical development. Herein, a small library of seventeen new synthetic oxygen and nitrogen-bearing CA-1 and CA-4 analogues is described. Three of these analogues showed significant inhibition of tubulin assembly (IC 50 = 2-3 µM) as well as in vitro cytotoxicity against selected human cancer cell lines and in vivo blood flow reduction in SCID mice (23-25% at 10 mg/Kg) suggesting that they have potential for further prodrug modification and development as vascular disrupting agents for the treatment of solid tumor cancers. A separate research project has concentrated on the development of cysteine protease inhibitors, primarily focused toward the inhibition of cruzain, the major cysteine protease of Trypanosoma cruzi which is the agent of the parasitic disease called Chagas’ disease. Currently there is no satisfactory treatment for this disease, and the two accepted drugs, nifurtimox and benznidazole, are associated with significant clinical toxicity. A library of fourteen small non-peptidic thiosemicarbazones has been successfully designed, synthesized and tested against cruzain and cathepsin L from which five compounds showed significant cruzain inhibition in the low namolar range. Although the most active compound synthesized, which is a bromotetrahydronaphthalene thiosemicarbazone, exhibited an IC 50 =12 nM against cruzain, it also showed activity against cathepsin L (IC 50 =134 nM). This new pharmacophore introduced may prove useful as a lead compound for further optimization. In addition, this research revealed further insights into the complex structure-activity relationship parameters which may lead to the further development of more selective cruzain inhibitors. TABLE OF CONTENTS List of Figures vii List of Tables x List of Schemes xi List of Abbreviations xiii Acknowledgments xvii Dedication xix Chapter One: Introduction 1 Chapter Two: Synthesis and Biological Evaluation of Novel Combretastatin Vascular Disrupting Agents 4 Introduction 4 Background 8 Carcinogenesis and the Cell Cycle 8 Targets for Cancer Chemotherapy 10 Vascular-Targeting Therapies 13 Antiangiogenic Therapy 16 Vascular Disrupting Agents 19 Small Molecule Vascular Disrupting Agents 22 Tubulin Binding Agents 23 Colchicine-Binding Site Agents 31 iii Chapter Three: Materials and Methods 38 General Section 38 Synthesis of Nitrogen-Based Combretastatin A-4 39 Synthesis of Nitrogen-Based Combretastatin A-1 49 Synthesis of a ... fundamental and it is an emf 7/13 DC Circuits Containing Resistors and Capacitors PhET Explorations: Circuit Construction Kit (DC only) An electronics kit in your computer! Build circuits with resistors, ... Solution for (a) 6/13 DC Circuits Containing Resistors and Capacitors The time constant τ is given by the equation τ = RC Entering the given values for resistance and capacitance (and remembering that... causes the muscles to contract and pump blood Sometimes the heart rhythm is abnormal and the heartbeat is too high or too low 5/13 DC Circuits Containing Resistors and Capacitors The artificial pacemaker