WorldWideScience

Sample records for target basic mechanisms

  1. Posttraumatic Headache: Basic Mechanisms and Therapeutic Targets.

    Science.gov (United States)

    Kamins, Joshua; Charles, Andrew

    2018-06-01

    Frequent or continuous headache, often refractory to medical therapy, is a common occurrence after head trauma. In addition to being the most common acute symptom after traumatic brain injury (TBI), headache is also one of the most persistent and disabling symptoms. Different studies indicate that 18-58% of those suffering a TBI will have significant headache at 1 year following the trauma. In addition to being disabling on its own, posttraumatic headache (PTH) is a predictor of overall outcome after concussion. Despite its remarkable prevalence and associated social and economic costs, many fundamental and important questions about PTH remain unanswered. The purpose of this review is to identify key questions regarding the clinical characteristics of posttraumatic headache, its basic mechanisms, and its optimal management. We discuss phenotypic features of PTH, pathophysiological mechanisms of TBI including potential overlaps with those of migraine and other primary headache disorders, and potential novel targets for treatment. We suggest different strategies to finding answers to the questions regarding PTH in order to advance the understanding of the disorder and develop more effective therapies. © 2018 American Headache Society.

  2. Basic Mechanics with Engineering Applications

    CERN Document Server

    Jones, J; Fawcett, J N

    2012-01-01

    This book gives a sufficient grounding in mechanics for engineers to tackle a significant range of problems encountered in the design and specification of simple structures and machines. It also provides an excellent background for students wishing to progress to more advanced studies in three-dimensional mechanics.

  3. Basic Automotive Mechanics. Florida Vocational Program Guide.

    Science.gov (United States)

    University of South Florida, Tampa. Dept. of Adult and Vocational Education.

    This program guide identifies primary concerns in the organization, operation, and evaluation of a basic automotive mechanics program. It is designed for local school district and community college administrators, instructors, program advisory committees, and regional coordinating councils. The guide begins with the Dictionary of Occupational…

  4. Basic mechanisms for the new millennium

    International Nuclear Information System (INIS)

    Dressendorfer, P.V.

    1998-01-01

    This part of the Short Course will review the basic mechanisms for radiation effects in semiconductor devices. All three areas of radiation damage will be considered -- total dose, displacement effects, and single event effects. Each of these areas will be discussed in turn. First an overview and background will be provided on the historical understanding of the damage mechanism. Then there will be a discussion of recent enhancements to the understanding of those mechanisms and an up-to-date picture provided of the current state of knowledge. Next the potential impact of each of these damage mechanisms on devices in emerging technologies and how the mechanisms may be used to understand device performance will be described, with an emphasis on those likely to be of importance in the new millennium. Finally some additional thoughts will be presented on how device scaling expected into the next century may impact radiation hardness

  5. Theoretical physics 6 quantum mechanics : basics

    CERN Document Server

    Nolting, Wolfgang

    2017-01-01

    This textbook offers a clear and comprehensive introduction to the basics of quantum mechanics, one of the core components of undergraduate physics courses. It follows on naturally from the previous volumes in this series, thus developing the physical understanding further on to quantized states. The first part of the book introduces wave equations while exploring the Schrödinger equation and the hydrogen atom. More complex themes are covered in the second part of the book, which describes the Dirac formulism of quantum mechanics. Ideally suited to undergraduate students with some grounding in classical mechanics and electrodynamics, the book is enhanced throughout with learning features such as boxed inserts and chapter summaries, with key mathematical derivations highlighted to aid understanding. The text is supported by numerous worked examples and end of chapter problem sets. About the Theoretical Physics series Translated from the renowned and highly successful German editions, the eight volumes of this...

  6. The sleep-wake-cycle: basic mechanisms.

    Science.gov (United States)

    Jones, B E

    1989-11-01

    The physiologic characteristics of the sleep-wake states have been well defined and some of the chemical and neuron systems that participate in the cyclic generation and maintenance of these states have been identified. The actual dynamic process by which these systems interact to generate the basic sleep-wake cycle, however, remains a mystery.

  7. Basic mechanisms of MCD in animal models.

    Science.gov (United States)

    Battaglia, Giorgio; Becker, Albert J; LoTurco, Joseph; Represa, Alfonso; Baraban, Scott C; Roper, Steven N; Vezzani, Annamaria

    2009-09-01

    Epilepsy-associated glioneuronal malformations (malformations of cortical development [MCD]) include focal cortical dysplasias (FCD) and highly differentiated glioneuronal tumors, most frequently gangliogliomas. The neuropathological findings are variable but suggest aberrant proliferation, migration, and differentiation of neural precursor cells as essential pathogenetic elements. Recent advances in animal models for MCDs allow new insights in the molecular pathogenesis of these epilepsy-associated lesions. Novel approaches, presented here, comprise RNA interference strategies to generate and study experimental models of subcortical band heterotopia and study functional aspects of aberrantly shaped and positioned neurons. Exciting analyses address impaired NMDA receptor expression in FCD animal models compared to human FCDs and excitatory imbalances in MCD animal models such as lissencephaly gene ablated mice as well as in utero irradiated rats. An improved understanding of relevant pathomechanisms will advance the development of targeted treatment strategies for epilepsy-associated malformations.

  8. Basic Gasoline Engine Mechanics. Florida Vocational Program Guide.

    Science.gov (United States)

    University of South Florida, Tampa. Dept. of Adult and Vocational Education.

    This packet contains a program guide and Career Merit Achievement Plan (Career MAP) for the implementation of a basic gasoline engine mechanics program in Florida secondary and postsecondary schools. The program guide describes the program content and structure, provides a program description, lists job titles under the program, and includes a…

  9. Orientation, Sketching, Mechanical Drawing, Drafting--Basic: 9253.01.

    Science.gov (United States)

    Dade County Public Schools, Miami, FL.

    The course introduces the student to the drafting trade, freehand sketching, and basic mechanical drawing. The course has no prerequisites and will guide the student into drafting concepts and serve as a foundation for further study in vocational drafting. Requiring a total of 45 class hours, eight hours are utilized in orientation, 15 hours are…

  10. Automotive Chassis; Automotive Mechanics-Basic: 9043.02.

    Science.gov (United States)

    Dade County Public Schools, Miami, FL.

    This automotive chassis course is designed to familiarize the beginning student of the history and development of the automobile with basic concepts common to the automobile industry, and general information that is required for successful advancement in the automotive mechanics field. It is one quinmester in a series of quinmester outlines…

  11. Monolithic Controlled Delivery Systems: Part I. Basic Characteristics and Mechanisms

    Directory of Open Access Journals (Sweden)

    Rumiana Blagoeva

    2006-04-01

    Full Text Available The article considers contemporary systems for controlled delivery of active agents, such as drugs, agricultural chemicals, pollutants and additives in the environment. A useful classification of the available controlled release systems (CRS is proposed according to the type of control (passive, active or self-preprogrammed and according to the main controlling mechanism (diffusion, swelling, dissolution or erosion. Special attention is given to some of the most used CRS - polymer monoliths. The structural and physical-chemical characteristics of CRS as well as the basic approaches to their production are examined. The basic mechanisms of controlled agent release are reviewed in detail and factors influencing the release kinetics are classified according to their importance. The present study can be helpful for understanding and applying the available mathematical models and for developing more comprehensive ones intended for design of new controlled delivery systems.

  12. Basic mechanisms of rTMS: Implications in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Arias-Carrión Oscar

    2008-04-01

    Full Text Available Abstract Background Basic and clinical research suggests a potential role for repetitive transcranial magnetic stimulation (rTMS in the treatment of Parkinson's disease. However, compared to the growing number of clinical studies on its putative therapeutic properties, the studies on the basic mechanisms of rTMS are surprisingly scarce. Results Animal studies have broadened our understanding of how rTMS affects brain circuits and the causal chain in brain-behavior relationships. The observed changes are thought to be to neurotransmitter release, transsynaptic efficiency, signaling pathways and gene transcription. Furthermore, recent studies suggest that rTMS induces neurogenesis, neuronal viability and secretion of neuroprotective molecules. Conclusion The mechanisms underlying the disease-modifying effects of these and related rTMS in animals are the principle subject of the current review. The possible applications for treatment of Parkinson's disease are discussed.

  13. Basic description of tailings from Aitik focusing on mechanical behavior

    OpenAIRE

    Bhanbhro, Riaz; Knutsson, Roger; Rodriguez, Juan; Edeskär, Tommy; Knutsson, Sven

    2013-01-01

    Tailings are artificial granular materials that behave different as compared to natural soil of equal grain sizes. Tailings particle sizes, shapes, gradation and mechanical behavior may influence the performance of tailings dams. Hence it is essential to understand the tailings materials in depth. This article describes present studies being carried out on Aitik tailings. Basic tailings characteristics including specific gravity, phase relationships, particle sizes, particle shapes and direct...

  14. Basic Mechanisms of Action of the Antiepileptic Drugs

    Directory of Open Access Journals (Sweden)

    Kuzmanova R.

    2017-10-01

    Full Text Available Available antiepileptic drugs interact with a variety of different molecular targets. The mechanism of action of most anticonvulsants is most often complex with a number of affected regions. The combination of mechanisms of action of drugs in particular proportions can possibly determine the showcase of its antiepileptic activity. The common factor between the different supposed mechanisms for a number of drugs includes the possibility for modulating the excitatory and inhibitory neurotransmission through effects upon the voltage-gated ion channels, synaptic plasticity, heterogeneous receptors, and metabolism of neurotransmitters. There are controversial data on the extent to which a specific action can be the reason for the wholesome anticonvulsive characteristics of various medications, as well as the relation with the presence of undesired drug effects. The complexity of the action of some antiepileptic drugs creates conditions for optimal choice during therapy. In many cases, the insufficient familiarity with individual genetic differences and the disease related receptor damages can hinder defining a particular drug action. Characterizing the mechanisms of action of the present antiepileptic medications would increase the understanding for the pathophysiological mechanisms of epileptic seizures, as well as the development of new therapeutic strategies. The development of novel antiepileptic drugs and the ongoing research regarding the mechanism of action of established antiepileptic drugs, are continuously increasing the level of complexity in the spectrum of molecular targets relevant for epilepsy therapy. The current state of knowledge as well as the limitations in our understanding should guide future research aiming for a more detailed elucidation of the impact of genetics and pathophysiological mechanisms on interindividual differences in expression and function of antiepileptic drug targets.

  15. Fluid mechanics aspects of magnetic drug targeting.

    Science.gov (United States)

    Odenbach, Stefan

    2015-10-01

    Experiments and numerical simulations using a flow phantom for magnetic drug targeting have been undertaken. The flow phantom is a half y-branched tube configuration where the main tube represents an artery from which a tumour-supplying artery, which is simulated by the side branch of the flow phantom, branches off. In the experiments a quantification of the amount of magnetic particles targeted towards the branch by a magnetic field applied via a permanent magnet is achieved by impedance measurement using sensor coils. Measuring the targeting efficiency, i.e. the relative amount of particles targeted to the side branch, for different field configurations one obtains targeting maps which combine the targeting efficiency with the magnetic force densities in characteristic points in the flow phantom. It could be shown that targeting efficiency depends strongly on the magnetic field configuration. A corresponding numerical model has been set up, which allows the simulation of targeting efficiency for variable field configuration. With this simulation good agreement of targeting efficiency with experimental data has been found. Thus, the basis has been laid for future calculations of optimal field configurations in clinical applications of magnetic drug targeting. Moreover, the numerical model allows the variation of additional parameters of the drug targeting process and thus an estimation of the influence, e.g. of the fluid properties on the targeting efficiency. Corresponding calculations have shown that the non-Newtonian behaviour of the fluid will significantly influence the targeting process, an aspect which has to be taken into account, especially recalling the fact that the viscosity of magnetic suspensions depends strongly on the magnetic field strength and the mechanical load.

  16. Basic Coandă MAV Fluid Dynamics and Flight Mechanics

    Science.gov (United States)

    Djojodihardjo, H.; Ahmed, RI

    2017-04-01

    Capitalizing on the basic fundamental principles, the Fluid Dynamics and Flight Mechanics of a semi-spherical Coandă MAV configurations are revisited and analyzed as a baseline. A mathematical model for a spherical Coandă MAV in hover and translatory motion is developed and analyzed from first physical principles. To gain further insight into the prevailing flow field around a Coandă MAV, as well as to verify the theoretical prediction presented in the work, a computational fluid dynamic CFD simulations for a Coandă MAV generic model are elaborated. The mathematical model and derived performance measures are shown to be capable in describing the physical phenomena of the flow field of the semi-spherical Coandă MAV. The relationships between the relevant parameters of the mathematical model of the Coandă MAV to the forces acting on it are elaborated subsequently.

  17. Basic mechanisms of radiation effects on electronic materials and devices

    International Nuclear Information System (INIS)

    Winokur, P.S.

    1989-01-01

    Many defense and nuclear reactor systems require complementary metal-oxide semiconductor integrated circuits that are tolerant to high levels of radiation. This radiation can result from space, hostile environments or nuclear reactor and accelerator beam environments. In addition, many techniques used to fabricate today's complex very-large-scale integration circuits expose the circuits to ionizing radiation during the process sequence. Whatever its origin, radiation can cause significant damage to integrated-circuit materials. This damage can lead to circuit performance degradation, logic upset, and even catastrophic circuit failure. This paper provides a brief overview of the basic mechanisms for radiation damage to silicon-based integrated circuits. Primary emphasis is on the effects of total-dose ionizing radiation on metal-oxide-semiconductor (MOS) structures

  18. Pharmacologic pre- and postconditioning for stroke: Basic mechanisms and translational opportunity

    Directory of Open Access Journals (Sweden)

    Elga Esposito

    2015-01-01

    Full Text Available Beyond reperfusion therapies, there are still no widely effective therapies for ischemic stroke. Although much progress has been made to define the molecular pathways involved, targeted neuroprotective strategies have often failed in clinical trials. An emerging hypothesis suggests that focusing on single targets and mechanisms may not work since ischemic stroke triggers multiple pathways in multiple cell types. In this review, we briefly survey and assess the opportunities that may be afforded by pre- and postconditioning therapies, with particular attention to pharmacologic pre- and postconditioning. Pharmacologic conditioning may be defined as the use of chemical agents either before or shortly after stroke onset to trigger mechanisms of endogenous tolerance that are thought to involve evolutionarily conserved signals that offer broad protection against ischemia. Importantly, many of the pharmacologic agents may also have been previously used in humans, thus providing hope for translating basic mechanisms into clinical applications.

  19. Cooperation Mechanisms To Achieve Eu Renewable Targets

    DEFF Research Database (Denmark)

    Klinge Jacobsen, Henrik; Pade, Lise-Lotte; Schröder, Sascha Thorsten

    2014-01-01

    targets. Furthermore, countries might find themselves competing for investment in a market with limited capital available. In both cases, the cost-efficiency of the renewable support policies is reduced compared to a coordinated solution. Barriers for joint support such as network regulation regarding......There are considerable benefits from cooperating among member states on meeting the 2020 renewable energy sources (RES) targets. Today countries are supporting investments in renewable energy by many different types of support schemes and with different levels of support. The EU has opened...... for cooperation mechanisms such as joint support schemes for promoting renewable energy to meet the 2020 targets. The potential coordination benefits, with more efficient localisation and composition of renewable investment, can be achieved by creating new areas/sub-segments of renewable technologies where...

  20. Pharmaceutical Approaches to Target Antibiotic Resistance Mechanisms.

    Science.gov (United States)

    Schillaci, Domenico; Spanò, Virginia; Parrino, Barbara; Carbone, Anna; Montalbano, Alessandra; Barraja, Paola; Diana, Patrizia; Cirrincione, Girolamo; Cascioferro, Stella

    2017-10-26

    There is urgent need for new therapeutic strategies to fight the global threat of antibiotic resistance. The focus of this Perspective is on chemical agents that target the most common mechanisms of antibiotic resistance such as enzymatic inactivation of antibiotics, changes in cell permeability, and induction/activation of efflux pumps. Here we assess the current landscape and challenges in the treatment of antibiotic resistance mechanisms at both bacterial cell and community levels. We also discuss the potential clinical application of chemical inhibitors of antibiotic resistance mechanisms as add-on treatments for serious drug-resistant infections. Enzymatic inhibitors, such as the derivatives of the β-lactamase inhibitor avibactam, are closer to the clinic than other molecules. For example, MK-7655, in combination with imipenem, is in clinical development for the treatment of infections caused by carbapenem-resistant Enterobacteriaceae and Pseudomonas aeruginosa, which are difficult to treat. In addition, other molecules targeting multidrug-resistance mechanisms, such as efflux pumps, are under development and hold promise for the treatment of multidrug resistant infections.

  1. BASIC

    DEFF Research Database (Denmark)

    Hansen, Pelle Guldborg; Schmidt, Karsten

    2017-01-01

    De sidste 10 år har vi været vidner til opkomsten af et nyt evidensbaseret policy paradigme, Behavioural Public Policy (BPP), der søger at integrere teoretiske og metodiske indsigter fra adfærdsvidenskaberne i offentlig politikudvikling. Arbejdet med BPP har dog båret præg af, at være usystematisk...... BPP. Tilgangen består dels af den overordnede proces-model BASIC og dels af et iboende framework, ABCD, der er en model for systematisk adfærdsanalyse, udvikling, test og implementering af adfærdsrettede løsningskoncepter. Den samlede model gør det muligt for forskere såvel som offentligt ansatte...

  2. Vectors, tensors and the basic equations of fluid mechanics

    CERN Document Server

    Aris, Rutherford

    1962-01-01

    Introductory text, geared toward advanced undergraduate and graduate students, applies mathematics of Cartesian and general tensors to physical field theories and demonstrates them in terms of the theory of fluid mechanics. 1962 edition.

  3. Basic flight mechanics a simple approach without equations

    CERN Document Server

    Tewari, Ashish

    2016-01-01

    This book presents flight mechanics of aircraft, spacecraft, and rockets to technical and non-technical readers in simple terms and based purely on physical principles. Adapting an accessible and lucid writing style, the book retains the scientific authority and conceptual substance of an engineering textbook without requiring a background in physics or engineering mathematics. Professor Tewari explains relevant physical principles of flight by straightforward examples and meticulous diagrams and figures. Important aspects of both atmospheric and space flight mechanics are covered, including performance, stability and control, aeroelasticity, orbital mechanics, and altitude control. The book describes airplanes, gliders, rotary wing and flapping wing flight vehicles, rockets, and spacecraft and visualizes the essential principles using detailed illustration. It is an ideal resource for managers and technicians in the aerospace industry without engineering degrees, pilots, and anyone interested in the mechanic...

  4. Basic Mechanisms Leading to Fatigue Failure of Structural Materials

    Czech Academy of Sciences Publication Activity Database

    Polák, Jaroslav; Petráš, Roman; Mazánová, Veronika

    2016-01-01

    Roč. 69, č. 2 (2016), s. 289-294 ISSN 0972-2815. [International Conference on CREEP , FATIGUE and CREEP -FATIGUE INTERACTION /7./. Kalpakkam, 19.01.2016-22.01.2016] R&D Projects: GA ČR(CZ) GA13-23652S Institutional support: RVO:68081723 Keywords : Damage mechanism * Fatigue crack initiation * Austenitic steel * Oxide cracking Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 0.533, year: 2016

  5. Basic mechanisms of urgency: roles and benefits of pharmacotherapy.

    Science.gov (United States)

    Michel, Martin Christian; Chapple, Christopher R

    2009-12-01

    Since urgency is key to the overactive bladder syndrome, we have reviewed the mechanisms underlying how bladder filling and urgency are sensed, what causes urgency and how this relates to medical therapy. Review of published literature. As urgency can only be assessed in cognitively intact humans, mechanistic studies of urgency often rely on proxy or surrogate parameters, such as detrusor overactivity, but these may not necessarily be reliable. There is an increasing evidence base to suggest that the sensation of ‘urgency’ differs from the normal physiological urge to void upon bladder filling. While the relative roles of alterations in afferent processes, central nervous processing, efferent mechanisms and in intrinsic bladder smooth muscle function remain unclear, and not necessarily mutually exclusive, several lines of evidence support an important role for the latter. A better understanding of urgency and its causes may help to develop more effective treatments for voiding dysfunction.

  6. Grid-Connected Distributed Generation: Compensation Mechanism Basics

    Energy Technology Data Exchange (ETDEWEB)

    Aznar, Alexandra Y [National Renewable Energy Laboratory (NREL), Golden, CO (United States); ; ; ; Zinaman, Owen R [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-10-02

    This short report defines compensation mechanisms for grid-connected, behind-the-meter distributed generation (DG) systems as instruments that comprise three core elements: (1) metering and billing arrangements, (2) sell rate design, and (3) retail rate design. This report describes metering and billing arrangements, with some limited discussion of sell rate design. We detail the three possible arrangements for metering and billing of DG: net energy metering (NEM); buy all, sell all; and net billing.

  7. Basic considerations for the mechanical design of heating reactors

    International Nuclear Information System (INIS)

    Rau, P.

    1997-01-01

    The paper discusses the principal aspects of the mechanical design of the reactor unit for a nuclear district heating plant. It is reasoned that the design must be specifically tailored to the characteristics of the applications, and that the experience gained with the design practice of big nuclear power stations must also be incorporated. Some examples of the design solutions for the SIEMENS NRH-200 are presented for illustration. (author). 7 refs, 10 figs

  8. Basic considerations for the mechanical design of heating reactors

    Energy Technology Data Exchange (ETDEWEB)

    Rau, P [Siemens AG, Unternehmensbereich KWU, Erlangen (Germany)

    1997-09-01

    The paper discusses the principal aspects of the mechanical design of the reactor unit for a nuclear district heating plant. It is reasoned that the design must be specifically tailored to the characteristics of the applications, and that the experience gained with the design practice of big nuclear power stations must also be incorporated. Some examples of the design solutions for the SIEMENS NRH-200 are presented for illustration. (author). 7 refs, 10 figs.

  9. Epigenetics and allergy: from basic mechanisms to clinical applications.

    Science.gov (United States)

    Potaczek, Daniel P; Harb, Hani; Michel, Sven; Alhamwe, Bilal Alashkar; Renz, Harald; Tost, Jörg

    2017-04-01

    Allergic diseases are on the rise in the Western world and well-known allergy-protecting and -driving factors such as microbial and dietary exposure, pollution and smoking mediate their influence through alterations of the epigenetic landscape. Here, we review key facts on the involvement of epigenetic modifications in allergic diseases and summarize and critically evaluate the lessons learned from epigenome-wide association studies. We show the potential of epigenetic changes for various clinical applications: as diagnostic tools, to assess tolerance following immunotherapy or possibly predict the success of therapy at an early time point. Furthermore, new technological advances such as epigenome editing and DNAzymes will allow targeted alterations of the epigenome in the future and provide novel therapeutic tools.

  10. Basic mechanisms of urgency: preclinical and clinical evidence.

    Science.gov (United States)

    Michel, Martin C; Chapple, Christopher R

    2009-08-01

    Urgency is the core symptom of the overactive bladder symptom complex, but the underlying mechanisms are not fully understood. To review clinical and experimental studies related to how bladder filling and urgency are sensed and what causes urgency and to discuss how this process affects potential therapeutic strategies. Review of published reports. The definition of urgency as a desire implies that it can only be assessed in cognitively intact patients and that animal studies have to rely on surrogate markers thereof, such as detrusor overactivity (DO); however, DO and urgency are not always associated. While the precise mechanisms of how urgency is sensed remain unclear, accumulating evidence suggests that they may differ from the physiologic sensation of bladder filling. Studies on the neurophysiology of urgency sensing are hampered by reliance on the surrogate marker DO. Functional brain imaging may help to understand the central neurophysiology, but, until now, it has not specifically focused on urgency. With regard to causes of urgency, multiple theories have been forwarded. While none of them has been proven, it should be noted that they are not mutually exclusive, and, in specific patients, different causes may be present. The development of improved therapeutic strategies against urgency will be helped by a better understanding of how urgency is perceived and the underlying causes. Rigorous use of existing definitions and the search for reliable surrogate markers will aid such attempts.

  11. On the basic mechanism of Pixelized Photon Detectors

    Energy Technology Data Exchange (ETDEWEB)

    Otono, H. [Department of Physics, School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)], E-mail: otono@icepp.s.u-tokyo.ac.jp; Oide, H. [Department of Physics, School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Yamashita, S. [International Center for Elementary Particle Physics, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Yoshioka, T. [Neutron Science Laboratory, High Energy Accelerator Research Organization (KEK), 1-1 Oho, Tsukuba, Ibaraki 305-0801 (Japan)

    2009-10-21

    A Pixelized Photon Detector (PPD) is a generic name for the semiconductor devices operated in the Geiger-mode, such as Silicon PhotoMultiplier and Multi-Pixel Photon Counter, which has high photon counting capability. While the internal mechanisms of the PPD have been intensively studied in recent years, the existing models do not include the avalanche process. We have simulated the multiplication and quenching of the avalanche process and have succeeded in reproducing the output waveform of the PPD. Furthermore our model predicts the existence of dead-time in the PPD which has never been numerically predicted. For searching the dead-time, we also have developed waveform analysis method using deconvolution which has the potential to distinguish neighboring pulses precisely. In this paper, we discuss our improved model and waveform analysis method.

  12. Inclusive mechanisms of governance and justice targeting youth to ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Inclusive mechanisms of governance and justice targeting youth to counter violent extremism in the IGAD region ... and generate evidence to influence the existing and emerging processes and mechanisms related to CVE to ... Innovation.

  13. Synchronizing the tracking eye movements with the motion of a visual target: Basic neural processes.

    Science.gov (United States)

    Goffart, Laurent; Bourrelly, Clara; Quinet, Julie

    2017-01-01

    In primates, the appearance of an object moving in the peripheral visual field elicits an interceptive saccade that brings the target image onto the foveae. This foveation is then maintained more or less efficiently by slow pursuit eye movements and subsequent catch-up saccades. Sometimes, the tracking is such that the gaze direction looks spatiotemporally locked onto the moving object. Such a spatial synchronism is quite spectacular when one considers that the target-related signals are transmitted to the motor neurons through multiple parallel channels connecting separate neural populations with different conduction speeds and delays. Because of the delays between the changes of retinal activity and the changes of extraocular muscle tension, the maintenance of the target image onto the fovea cannot be driven by the current retinal signals as they correspond to past positions of the target. Yet, the spatiotemporal coincidence observed during pursuit suggests that the oculomotor system is driven by a command estimating continuously the current location of the target, i.e., where it is here and now. This inference is also supported by experimental perturbation studies: when the trajectory of an interceptive saccade is experimentally perturbed, a correction saccade is produced in flight or after a short delay, and brings the gaze next to the location where unperturbed saccades would have landed at about the same time, in the absence of visual feedback. In this chapter, we explain how such correction can be supported by previous visual signals without assuming "predictive" signals encoding future target locations. We also describe the basic neural processes which gradually yield the synchronization of eye movements with the target motion. When the process fails, the gaze is driven by signals related to past locations of the target, not by estimates to its upcoming locations, and a catch-up is made to reinitiate the synchronization. © 2017 Elsevier B.V. All rights

  14. Basic MR relaxation mechanisms and contrast agent design.

    Science.gov (United States)

    De León-Rodríguez, Luis M; Martins, André F; Pinho, Marco C; Rofsky, Neil M; Sherry, A Dean

    2015-09-01

    The diagnostic capabilities of magnetic resonance imaging (MRI) have undergone continuous and substantial evolution by virtue of hardware and software innovations and the development and implementation of exogenous contrast media. Thirty years since the first MRI contrast agent was approved for clinical use, a reliance on MR contrast media persists, largely to improve image quality with higher contrast resolution and to provide additional functional characterization of normal and abnormal tissues. Further development of MR contrast media is an important component in the quest for continued augmentation of diagnostic capabilities. In this review we detail the many important considerations when pursuing the design and use of MR contrast media. We offer a perspective on the importance of chemical stability, particularly kinetic stability, and how this influences one's thinking about the safety of metal-ligand-based contrast agents. We discuss the mechanisms involved in MR relaxation in the context of probe design strategies. A brief description of currently available contrast agents is accompanied by an in-depth discussion that highlights promising MRI contrast agents in the development of future clinical and research applications. Our intention is to give a diverse audience an improved understanding of the factors involved in developing new types of safe and highly efficient MR contrast agents and, at the same time, provide an appreciation of the insights into physiology and disease that newer types of responsive agents can provide. © 2015 Wiley Periodicals, Inc.

  15. Experimental Study on Basic Mechanical Properties of BFRP Bars

    Science.gov (United States)

    Fan, Xiaochun; Xu, Ting; Zhou, Zhengrong; Zhou, Xun

    2017-10-01

    Basalt Fiber Reinforced Polymer (BFRP) bars have the advantages of corrosion resistance, high strength, light weight, good dielectric properties, and they are new type of green reinforced alternative material. In order to determine the mechanical properties of BFRP bars, the tensile strength of basalt fiber bars was necessary to be studied. The diameters of the basalt fiber bars were compared by means of uniaxial tensile test in this article. Then the stress-strain curve can be drawn out. The results show that the stress - strain curve of BFRP bars present straight line relation, and there is no sign before failure; there is no yield platform on the stress-strain curve of BFRP bars, which are typical brittle material;the tensile strength of BFRP bars is about 3 times higher than that of ordinary steel bars. and the elastic modulus is about 1/5 of that of ordinary steel; the ultimate tensile strength of BFRP bars varies little with the increase of diameter, but there exist some differences in modulus values.

  16. Triple vacuum glazing: Heat transfer and basic mechanical design constraints

    Energy Technology Data Exchange (ETDEWEB)

    Manz, H.; Brunner, S.; Wullschleger, L. [Swiss Federal Laboratories for Materials Testing and Research (EMPA), Laboratory for Applied Physics in Building, Ueberlandstrasse 129, CH-8600 Duebendorf (Switzerland)

    2006-12-15

    Given the major role played by windows with regard to energy losses from buildings in cold climates, low thermal transmittance is an indispensable property of glazing in low-energy buildings. Evacuation offers the only means of achieving negligible gaseous conduction in glazing cavities. Application of low-emittance coatings to glass sheet surfaces inside the cavity reduces the radiative heat transfer. The feasibility of double vacuum glazing using arrays of support pillars between the glass sheets has been shown by other authors. This type of glazing is commercially manufactured today. Based on these achievements, our study set out to investigate heat transfer in triple vacuum glazing by means of (i) an analytical thermal network model and (ii) a numerical finite difference model. The study focused on the impact of the following parameters on thermal transmittance: emittances of glass sheet surfaces inside the cavity, support pillar radius, support pillar separation and thermal conductivity of support pillar material. The design procedure for triple vacuum glazing taking into account not only thermal but also mechanical stresses due to atmospheric pressure, i.e., to enable identification of favourable parameter sets, is presented. Our findings suggest that use of the triple vacuum glazing concept can significantly reduce the thermal transmittances achieved by the best insulation glazing units currently on the market. E.g., a centre-of-glazing thermal transmittance of less than 0.2Wm{sup -2}K{sup -1} is achievable using stainless steel support pillars, 6mm/4mm/6mm sheets of untempered soda-lime glass and four low-emittance coatings ({epsilon}=0.03). (author)

  17. Differences between application of some basic principles of quantum mechanics on atomic and mesoscopic levels

    OpenAIRE

    Nikulov, Alexey

    2005-01-01

    Formalism of the quantum mechanics developed for microscopic (atomic) level comes into collision with some logical difficulties on mesoscopic level. Some fundamental differences between application of its basic principles on microscopic and mesoscopic levels are accentuated.

  18. Why Basic Calcium Phosphate Crystals Should Be Targeted In the Treatment of Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Claire-Louise Murphy

    2014-07-01

    Full Text Available Osteoarthritis (OA is the most common form of arthritis and results in significant social, psychological, and economic costs. It is characterised by progressive cartilage loss, bone remodelling, osteophyte formation, and synovial inflammation with resultant joint pain and disability. Since OA affects the entire joint, it is not surprising that there has been difficulty developing an effective targeted treatment. Treatments available for structural disease modification are limited. Current options appear to mostly reduce symptoms. Basic calcium phosphate (BCP crystals represent a potential therapeutic target in OA; they have been found in 100% of knee and hip cartilages removed at joint replacement. Intra-articular BCP crystals are associated with large joint effusions and dissolution of intra-articular structures, synovial proliferation, and marked degeneration as assessed by diagnostic imaging. While BCP deposition has been considered by many to be simply a consequence of advanced OA, there is substantial evidence to support BCP crystal deposition as an active pathogenic mediator of OA. BCP crystals exhibit a multiplicity of biologic effects in vitro including the ability to stimulate mitogenesis and prostaglandin, cytokine, and matrix metalloproteinase (MMP synthesis in a number of cell types including macrophages, synovial fibroblasts, and chondrocytes. BCP crystals also contribute to inflammation in OA through direct interaction with the innate immune system. Intra-articular BCP crystals can elicit synovial inflammation and cartilage degradation in mice in vivo . Although intra-articular BCP crystals are difficult to detect at the bedside, advances in modern technology should allow improved identification and quantitation of BCP crystals. Our article focuses on why basic calcium crystals are important in the pathogenesis of OA. There is ample evidence that BCP crystals should be explored as a therapeutic target in OA.

  19. Hepatocarcinoma: from pathogenic mechanisms to target therapy

    Directory of Open Access Journals (Sweden)

    Luigi Manzione

    2011-12-01

    Full Text Available Hepatocellular carcinoma (HCC is among the most prevalent and lethal cancers worldwide. It is currently estimated that there are 14,000–18,000 new cases of hepatocellular carcinoma in the United States each year. It is often difficult to identify individuals at risk for HCC. The main associated diseases are chronic hepatitis B and chronic hepatitis C viral infections. While a significant number of potential mutations have been generated including p53 and Insulin-like Growth Factor, our understanding of the molecular mechanisms driving the genesis and progression of HCC remain limited. HCC screening is recommended in high-risk patients. High-risk patients include virtually all patients with cirrhosis and some HBV-infected patients irrespective of cirrhosis (>40 years in men and >50 years in women. A diagnostic approach to HCC has been developed incorporating serology, cytohistology, and radiological characteristics. A precise staging of the disease may help decide on prognosis as well as choice of therapy with the greatest survival potential. Liver transplantation, in theory, is the optimal therapeutic option for HCC; it simultaneously removes the tumor and underlying cirrhosis thus minimizing the risk of HCC recurrence. When it is impossible for this to be performed, percutaneous ablation, chemoembolization, chemotherapy and the newer molecular therapies can be used. Sorafenib is the only drug registered today for the treatment of advanced HCC.

  20. Basic requirements of mechanical properties for nuclear pressure vessel materials in ASME-BPV code

    International Nuclear Information System (INIS)

    Ning Dong; Yao Weida

    2011-01-01

    The four basic aspects of strengths, ductility, toughness and fatigue strengths can be summarized for overall mechanical properties requirements of materials for nuclear pressure-retaining vessels in ASME-BPV code. These mechanical property indexes involve in the factors of melting, manufacture, delivery conditions, check or recheck for mechanical properties and chemical compositions, etc. and relate to degradation and damage accumulation during the use of materials. This paper specifically accounts for the basic requirements and theoretic basis of mechanical properties for nuclear pressure vessel materials in ASME-BPV code and states the internal mutual relationships among the four aspects of mechanical properties. This paper focuses on putting forward at several problems on mechanical properties of materials that shall be concerned about during design and manufacture for nuclear pressure vessels according to ASME-BPV code. (author)

  1. Optical and mechanical design of beam-target coupling sensor

    International Nuclear Information System (INIS)

    Wang Liquan; Li Tian'en; Feng Bin; Xiang Yong; Li Keyu; Zhong Wei; Liu Guodong

    2012-01-01

    A sensor based on conjugate principle has been designed for matching the light beams and the target in inertial confinement fusion. It can avoid the direct illumination of the simulation collimating light on the target under test in targeting processes. This paper introduces the optical and mechanical design of the sensor, according to its design functions and working principle. The resolution of the optical images obtained in experiments reaches 6 μm and the beam-target matching accuracy is 8.8 μm. The sensor has been successfully applied to the Shenguang-Ⅲ facility. Statistical analyses of the four-hole CH target images derived with pinhole camera shows that the targeting accuracy of the facility is better than 25 μm, satisfying the design requirements. (authors)

  2. Teaching Basic Quantum Mechanics in Secondary School Using Concepts of Feynman Path Integrals Method

    Science.gov (United States)

    Fanaro, Maria de los Angeles; Otero, Maria Rita; Arlego, Marcelo

    2012-01-01

    This paper discusses the teaching of basic quantum mechanics in high school. Rather than following the usual formalism, our approach is based on Feynman's path integral method. Our presentation makes use of simulation software and avoids sophisticated mathematical formalism. (Contains 3 figures.)

  3. The mechanism of gene targeting in human somatic cells.

    Directory of Open Access Journals (Sweden)

    Yinan Kan

    2014-04-01

    Full Text Available Gene targeting in human somatic cells is of importance because it can be used to either delineate the loss-of-function phenotype of a gene or correct a mutated gene back to wild-type. Both of these outcomes require a form of DNA double-strand break (DSB repair known as homologous recombination (HR. The mechanism of HR leading to gene targeting, however, is not well understood in human cells. Here, we demonstrate that a two-end, ends-out HR intermediate is valid for human gene targeting. Furthermore, the resolution step of this intermediate occurs via the classic DSB repair model of HR while synthesis-dependent strand annealing and Holliday Junction dissolution are, at best, minor pathways. Moreover, and in contrast to other systems, the positions of Holliday Junction resolution are evenly distributed along the homology arms of the targeting vector. Most unexpectedly, we demonstrate that when a meganuclease is used to introduce a chromosomal DSB to augment gene targeting, the mechanism of gene targeting is inverted to an ends-in process. Finally, we demonstrate that the anti-recombination activity of mismatch repair is a significant impediment to gene targeting. These observations significantly advance our understanding of HR and gene targeting in human cells.

  4. Basic targeting strategies for rendezvous and flyby missions to the near-Earth asteroids

    Science.gov (United States)

    Perozzi, Ettore; Rossi, Alessandro; Valsecchi, Giovanni B.

    2001-01-01

    Missions to asteroids and comets are becoming increasingly feasible both from a technical and a financial point of view. In particular, those directed towards the Near-Earth Asteroids have proven suitable for a low-cost approach, thus attracting the major space agencies as well as private companies. The choice of a suitable target involves both scientific relevance and mission design considerations, being often a difficult task to accomplish due to the limited energy budget at disposal. The aim of this paper is to provide an approach to basic trajectory design which allows to account for both aspects of the problem, taking into account scientific and technical information. A global characterization of the Near-Earth Asteroids population carried out on the basis of their dynamics, physical properties and flight dynamics considerations, allows to identify a group of candidates which satisfy both, the scientific and engineering requirements. The feasibility of rendezvous and flyby missions towards them is then discussed and the possibility of repeated encounters with the same object is investigated, as an intermediate scenario. Within this framework, the capability of present and near future launch and propulsion systems for interplanetary missions is also addressed.

  5. Small target pre-detection with an attention mechanism

    Science.gov (United States)

    Wang, Yuehuan; Zhang, Tianxu; Wang, Guoyou

    2002-04-01

    We introduce the concept of predetection based on an attention mechanism to improve the efficiency of small-target detection by limiting the image region of detection. According to the characteristics of small-target detection, local contrast is taken as the only feature in predetection and a nonlinear sampling model is adopted to make the predetection adaptive to detect small targets with different area sizes. To simplify the predetection itself and decrease the false alarm probability, neighboring nodes in the sampling grid are used to generate a saliency map, and a short-term memory is adopted to accelerate the `pop-out' of targets. We discuss the fact that the proposed approach is simple enough in computational complexity. In addition, even in a cluttered background, attention can be led to targets in a satisfying few iterations, which ensures that the detection efficiency will not be decreased due to false alarms. Experimental results are presented to demonstrate the applicability of the approach.

  6. Targeting Specific HATs for Neurodegenerative Disease Treatment: Translating Basic Biology to Therapeutic Possibilities

    Directory of Open Access Journals (Sweden)

    Sheila K. Pirooznia

    2013-03-01

    Full Text Available Dynamic epigenetic regulation of neurons is emerging as a fundamental mechanism by which neurons adapt their transcriptional responses to specific developmental and environmental cues. While defects within the neural epigenome have traditionally been studied in the context of early developmental and heritable cognitive disorders, recent studies point to aberrant histone acetylation status as a key mechanism underlying acquired inappropriate alterations of genome structure and function in post-mitotic neurons during the aging process. Indeed, it is becoming increasingly evident that chromatin acetylation status can be impaired during the lifetime of neurons through mechanisms related to loss of function of histone acetyltransferase (HATs activity. Several HATs have been shown to participate in vital neuronal functions such as regulation of neuronal plasticity and memory formation. As such, dysregulation of such HATs has been implicated in the pathogenesis associated with age-associated neurodegenerative diseases and cognitive decline. In order to counteract the loss of HAT function in neurodegenerative diseases, the current therapeutic strategies involve the use of small molecules called histone deacetylase (HDAC inhibitors that antagonize HDAC activity and thus enhance acetylation levels. Although this strategy has displayed promising therapeutic effects, currently used HDAC inhibitors lack target specificity, raising concerns about their applicability. With rapidly evolving literature on HATs and their respective functions in mediating neuronal survival and higher order brain function such as learning and memory, modulating the function of specific HATs holds new promises as a therapeutic tool in neurodegenerative diseases. In this review, we focus on the recent progress in research regarding epigenetic histone acetylation mechanisms underlying neuronal activity and cognitive function. We discuss the current understanding of specific HDACs and

  7. Mechanical design and development of a high power target system for the SLC Positron Source

    International Nuclear Information System (INIS)

    Reuter, E.; Mansour, D.; Porter, T.; Sax, W.; Szumillo, A.

    1991-12-01

    In order to bring the SLC Positron Source luminosity up to design specifications, the previous (stationary) positron target had to be replaced with a version which could reliably dissipate the higher power levels and cyclic pulsed thermal stresses of the high intensity 33GeV electron beam. In addition to this basic requirement, the new target system had to meet SLAC's specifications for Ultra High Vacuum, be remotely controllable, ''radiation hard,'' and designed in such a way that it could be removed and replaced quickly and easily with minimum personnel exposure to radiation. It was also desirable to integrate the target and collection components into a compact, easily manufacturable, and easily maintainable module. This paper briefly summarize the mechanical design and development of the new modular target system, its associated controls and software, alignment, and the quick removal system. Operational experience gained with the new system over the first running cycle is also summarized

  8. Amino Acid Metabolism and Transport Mechanisms as Potential Antifungal Targets

    Directory of Open Access Journals (Sweden)

    Matthew W. McCarthy

    2018-03-01

    Full Text Available Discovering new drugs for treatment of invasive fungal infections is an enduring challenge. There are only three major classes of antifungal agents, and no new class has been introduced into clinical practice in more than a decade. However, recent advances in our understanding of the fungal life cycle, functional genomics, proteomics, and gene mapping have enabled the identification of new drug targets to treat these potentially deadly infections. In this paper, we examine amino acid transport mechanisms and metabolism as potential drug targets to treat invasive fungal infections, including pathogenic yeasts, such as species of Candida and Cryptococcus, as well as molds, such as Aspergillus fumigatus. We also explore the mechanisms by which amino acids may be exploited to identify novel drug targets and review potential hurdles to bringing this approach into clinical practice.

  9. Basic course theoretical physics. Vol. 5/1. Quantum mechanics - foundations. 7. upd. ed.

    International Nuclear Information System (INIS)

    Nolting, Wolfgang

    2009-01-01

    The favoured basic course theoretical physics covers in seven volumes all fields relevant for the diploma. Each volume mediates well thought the in each semester necessary theoretically-physical tools. Numerous exercise problem with extensive solutions serve for the deepening of the matter. The first part of the fifth volume begins with an inductive foundation of quantum mechanics in order to illustrate after a study and summary of the formal foundations of quantum mechanics on simple model systems the concepts and term formations. The present new edition was fundamentally worked out and supplemented. The meanwhile proved two-color presentation allows a very understandable and fast approach to the matter [de

  10. The analysis on the basic technology and radiation induced voltaic mechanism for nuclear battery

    International Nuclear Information System (INIS)

    Hwang, Woan; Lee, B. O.; Min, B. T.; Kang, H. Y.; Kim, B. H.; Park, J. H.; Seo, H. S.

    2000-12-01

    Present study is for nuclear battery technology directly converting radiation energy to electricity among various nuclear energy, and it is anticipated that an interest in direct conversion of nuclear energy into electricity shall be increased as the conversion efficiency enhances. The battery should promise cheap, reliable power from a package small and light enough to be mobile, and with energy density great enough for use as a space based power supply. Various radiation-electricity conversion mechanism so far have been reported since G.J. Moseley reported the operation of a high-voltage nuclear battery using radium. The most important conversion mechanisms are RTG (Radioisotope Thermoelectric Generator) converting the heat produced from radioisotope to electricity using the temperature difference, and NRG (Nuclear Resonance Generator) using free electrons from the collision between α, βrays and copper coil. It is well known that RTG and NRG mechanisms are most practical way because their efficiencies high. The basic technology on radiation-electricity conversion mechanism, interaction mechanism between β ray and material, shielding for β ray, and technical backgrounds and a state of the art for RTG and NRG technologies, are analyzed in this report. Basic data on the conceptual design for the prototype of nuclear battery are prepared

  11. The analysis on the basic technology and radiation induced voltaic mechanism for nuclear battery

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Woan; Lee, B. O.; Min, B. T.; Kang, H. Y.; Kim, B. H.; Park, J. H.; Seo, H. S

    2000-12-01

    Present study is for nuclear battery technology directly converting radiation energy to electricity among various nuclear energy, and it is anticipated that an interest in direct conversion of nuclear energy into electricity shall be increased as the conversion efficiency enhances. The battery should promise cheap, reliable power from a package small and light enough to be mobile, and with energy density great enough for use as a space based power supply. Various radiation-electricity conversion mechanism so far have been reported since G.J. Moseley reported the operation of a high-voltage nuclear battery using radium. The most important conversion mechanisms are RTG (Radioisotope Thermoelectric Generator) converting the heat produced from radioisotope to electricity using the temperature difference, and NRG (Nuclear Resonance Generator) using free electrons from the collision between {alpha}, {beta}rays and copper coil. It is well known that RTG and NRG mechanisms are most practical way because their efficiencies high. The basic technology on radiation-electricity conversion mechanism, interaction mechanism between {beta} ray and material, shielding for {beta} ray, and technical backgrounds and a state of the art for RTG and NRG technologies, are analyzed in this report. Basic data on the conceptual design for the prototype of nuclear battery are prepared.

  12. [Basic and clinical studies of the gene product-targeting therapy based on leukemogenesis--editorial].

    Science.gov (United States)

    Chen, Sai-Juan; Chen, Li-Juan; Zhou, Guang-Biao

    2005-02-01

    In the last twenty years, using all-trans retinoic acid (ATRA) as a differentiation inducer, Shanghai Institute of Hematology has achieved an important breakthrough in the treatment of acute promyelocytic leukemia (APL), which realized the theory of reversing phenotype of cells and provided a successful model of differentiation therapy in cancers. Our group first discovered in the world the variant chromosome translocation t(11;17)(q23;q21) of APL, and cloned the PML-RAR alpha, PLZF-RAR alpha and NPM-RAR alpha fusion genes corresponding to the characterized chromosome translocations t(15;17); t(11;17) and t(5;17) in APL. Moreover, establishment of transgenic mice model of APL proved their effects on leukemogenesis. The ability of ATRA to modify the recruitment of nuclear receptor co-repressor with PML-RAR alpha but not PLZF-RAR alpha caused by the variant chromosome translocation elucidated the therapeutic mechanism of ATRA from the molecular level and provides new insight into transcription-modulating therapy. Since 1994, our group has successfully applied arsenic trioxide (As(2)O(3)) in treating relapsed APL patients, with the complete remission rate of 70% - 80%. The molecular mechanism study revealed that As(2)O(3) exerts a dose-dependent dual effect on APL. Low-dose As(2)O(3) induced partial differentiation of APL cells, while the higher dose induced apoptosis. As(2)O(3) binds ubiquitin like SUMO-1 through the lysine 160 of PML, resulting in the degradation of PML-RAR alpha. Taken together, ATRA and As(2)O(3) target the transcription factor PML-RAR alpha, the former by retinoic acid receptor and the latter by PML sumolization, both induce PML-RAR alpha degradation and APL cells differentiation and apoptosis. Because of the different acting pathways, ATRA and As(2)O(3) have no cross-resistance and can be used as combination therapy. Clinical trial in newly diagnosed APL patients showed that ATRA/As(2)O(3) in combination yields a longer disease-free survival

  13. The targeting of immunosuppressive mechanisms in hematological malignancies

    DEFF Research Database (Denmark)

    Andersen, M H

    2014-01-01

    enzymes such as indoeamine-2,3-dioxygenase (IDO). The possible therapeutic targeting of these pathways is also discussed. Exciting new strategies that might affect future antileukemia immunotherapy include monoclonal antibodies that block inhibitory T-cell pathways (PD-1/PD-L1) and the prevention...... of tryptophan depletion by IDO inhibitors. Furthermore, the clinical effect of several chemotherapeutic drugs may arise from the targeting of immunosuppressive cells. Evidence for a new feedback mechanism to suppress the function of regulatory immune cells was recently provided by the identification...... and characterization of spontaneous cytotoxic T lymphocyte (CTL) responses against regulatory immune cells. Such specific CTLs may be immensely useful in anticancer immunotherapy (for example, by anticancer vaccination). The targeting of one or more immunosuppressive pathways may be especially interesting...

  14. Emerging targets for addiction neuropharmacology: From mechanisms to therapeutics.

    Science.gov (United States)

    Ubaldi, Massimo; Cannella, Nazzareno; Ciccocioppo, Roberto

    2016-01-01

    Drug abuse represents a considerable burden of disease and has enormous economic impacts on societies. Over the years, few medications have been developed for clinical use. Their utilization is endowed with several limitations, including partial efficacy or significant side effects. On the other hand, the successful advancement of these compounds provides an important proof of concept for the feasibility of drug development programs in addiction. In recent years, a wealth of information has been generated on the psychological mechanisms, genetic or epigenetic predisposing factors, and neurobiological adaptations induced by drug consumption that interact with each other to contribute to disease progression. It is now clear that addiction develops through phases, from initial recreational use to excessive consumption and compulsive drug seeking, with a shift from positive to negative reinforcement driving motivated behaviors. A greater understanding of these mechanisms has opened new vistas in drug development programs. Researchers' attention has been shifted from investigation of classical targets associated with reward to biological substrates responsible for negative reinforcement, impulse loss of control, and maladaptive mechanisms resulting from protracted drug use. From this research, several new biological targets for the development of innovative therapies have started to emerge. This chapter offers an overview of targets currently under scrutiny for the development of new medications for addiction. This work is not exhaustive but rather it provides a few examples of how this research has advanced in recent years by virtue of studies carried out in our laboratory. © 2016 Elsevier B.V. All rights reserved.

  15. Membrane Fluidity Changes, A Basic Mechanism of Interaction of Gravity with Cells?

    Science.gov (United States)

    Kohn, Florian; Hauslage, Jens; Hanke, Wolfgang

    2017-10-01

    All life on earth has been established under conditions of stable gravity of 1g. Nevertheless, in numerous experiments the direct gravity dependence of biological processes has been shown on all levels of organization, from single molecules to humans. According to the underlying mechanisms a variety of questions, especially about gravity sensation of single cells without specialized organelles or structures for gravity sensing is being still open. Biological cell membranes are complex structures containing mainly lipids and proteins. Functional aspects of such membranes are usually attributed to membrane integral proteins. This is also correct for the gravity dependence of cells and organisms which is well accepted since long for a wide range of biological systems. However, it is as well established that parameters of the lipid matrix are directly modifying the function of proteins. Thus, the question must be asked, whether, and how far plain lipid membranes are affected by gravity directly. In principle it can be said that up to recently no real basic mechanism for gravity perception in single cells has been presented or verified. However, it now has been shown that as a basic membrane parameter, membrane fluidity, is significantly dependent on gravity. This finding might deliver a real basic mechanism for gravity perception of living organisms on all scales. In this review we summarize older and more recent results to demonstrate that the finding of membrane fluidity being gravity dependent is consistent with a variety of published laboratory experiments. We additionally point out to the consequences of these recent results for research in the field life science under space condition.

  16. Design considerations in mechanical face seals for improved performance. I - Basic configurations

    Science.gov (United States)

    Ludwig, L. P.; Greiner, H. F.

    1977-01-01

    Basic assembly configurations of the mechanical face seal are described and some advantages associated with each are listed. The various forms of seal components (the primary seal, secondary seal, etc.) are illustrated, and functions pointed out. The technique of seal pressure balancing and its application is described; and the concept of the PV factor, its different forms and limitations are discussed. Brief attention is given to seal lubrication since it is covered in detail in a companion paper. Finally, the operating conditions for various applications of low pressure seals (aircraft transmissions) are listed, and the seal failure mode of a particular application is discussed.

  17. Design considerations in mechanical face seals for improved performance. 1: Basic configurations

    Science.gov (United States)

    Ludwig, L. P.; Greiner, H. F.

    1977-01-01

    Basic assembly configurations of the mechanical face seal are described and some advantages associated with each are listed. The various forms of seal components are illustrated, and functions pointed out. The technique of seal pressure balancing and its application are described; and the concept of the PV factor, its different forms and limitations are discussed. Brief attention is given to seal lubrication since it is covered in detail in a companion paper. Finally, the operating conditions for various applications of low pressure seals (aircraft transmissions) are listed, and the seal failure mode of a particular application is discussed.

  18. Impact of Aggregates Size and Fibers on basic Mechanical Properties of Asphalt Emulsion—Cement Concrete

    Science.gov (United States)

    Fu, Jun; Liu, Zhihong; Liu, Jie

    2018-01-01

    Asphalt Emulsion—Cement Concrete (AECC) is currently considered as a typical semi-flexibility material. One of the disadvantages of this material is brittle fracture and lacking ductility. This study aims at accelerating the basic mechanical properties of AECC using fibers and different aggregates size. The mix of AECC was introduced and the different content of fibers and aggregates size were studied. The results showed that the smaller aggregates size could improve the young’s modulus and compressive strength as well as fiber. The modulus-compressive strength ratio of fiber reinforced AECC is always below 500.

  19. The cancer cell adhesion resistome: mechanisms, targeting and translational approaches.

    Science.gov (United States)

    Dickreuter, Ellen; Cordes, Nils

    2017-06-27

    Cell adhesion-mediated resistance limits the success of cancer therapies and is a great obstacle to overcome in the clinic. Since the 1990s, where it became clear that adhesion of tumor cells to the extracellular matrix is an important mediator of therapy resistance, a lot of work has been conducted to understand the fundamental underlying mechanisms and two paradigms were deduced: cell adhesion-mediated radioresistance (CAM-RR) and cell adhesion-mediated drug resistance (CAM-DR). Preclinical work has evidently demonstrated that targeting of integrins, adapter proteins and associated kinases comprising the cell adhesion resistome is a promising strategy to sensitize cancer cells to both radiotherapy and chemotherapy. Moreover, the cell adhesion resistome fundamentally contributes to adaptation mechanisms induced by radiochemotherapy as well as molecular drugs to secure a balanced homeostasis of cancer cells for survival and growth. Intriguingly, this phenomenon provides a basis for synthetic lethal targeted therapies simultaneously administered to standard radiochemotherapy. In this review, we summarize current knowledge about the cell adhesion resistome and highlight targeting strategies to override CAM-RR and CAM-DR.

  20. Neural Conflict–Control Mechanisms Improve Memory for Target Stimuli

    Science.gov (United States)

    Krebs, Ruth M.; Boehler, Carsten N.; De Belder, Maya; Egner, Tobias

    2015-01-01

    According to conflict-monitoring models, conflict serves as an internal signal for reinforcing top-down attention to task-relevant information. While evidence based on measures of ongoing task performance supports this idea, implications for long-term consequences, that is, memory, have not been tested yet. Here, we evaluated the prediction that conflict-triggered attentional enhancement of target-stimulus processing should be associated with superior subsequent memory for those stimuli. By combining functional magnetic resonance imaging (fMRI) with a novel variant of a face-word Stroop task that employed trial-unique face stimuli as targets, we were able to assess subsequent (incidental) memory for target faces as a function of whether a given face had previously been accompanied by congruent, neutral, or incongruent (conflicting) distracters. In line with our predictions, incongruent distracters not only induced behavioral conflict, but also gave rise to enhanced memory for target faces. Moreover, conflict-triggered neural activity in prefrontal and parietal regions was predictive of subsequent retrieval success, and displayed conflict-enhanced functional coupling with medial-temporal lobe regions. These data provide support for the proposal that conflict evokes enhanced top-down attention to task-relevant stimuli, thereby promoting their encoding into long-term memory. Our findings thus delineate the neural mechanisms of a novel link between cognitive control and memory. PMID:24108799

  1. Neural conflict-control mechanisms improve memory for target stimuli.

    Science.gov (United States)

    Krebs, Ruth M; Boehler, Carsten N; De Belder, Maya; Egner, Tobias

    2015-03-01

    According to conflict-monitoring models, conflict serves as an internal signal for reinforcing top-down attention to task-relevant information. While evidence based on measures of ongoing task performance supports this idea, implications for long-term consequences, that is, memory, have not been tested yet. Here, we evaluated the prediction that conflict-triggered attentional enhancement of target-stimulus processing should be associated with superior subsequent memory for those stimuli. By combining functional magnetic resonance imaging (fMRI) with a novel variant of a face-word Stroop task that employed trial-unique face stimuli as targets, we were able to assess subsequent (incidental) memory for target faces as a function of whether a given face had previously been accompanied by congruent, neutral, or incongruent (conflicting) distracters. In line with our predictions, incongruent distracters not only induced behavioral conflict, but also gave rise to enhanced memory for target faces. Moreover, conflict-triggered neural activity in prefrontal and parietal regions was predictive of subsequent retrieval success, and displayed conflict-enhanced functional coupling with medial-temporal lobe regions. These data provide support for the proposal that conflict evokes enhanced top-down attention to task-relevant stimuli, thereby promoting their encoding into long-term memory. Our findings thus delineate the neural mechanisms of a novel link between cognitive control and memory. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Evaluation of the basic mechanical and thermal properties of deep crystalline rocks

    International Nuclear Information System (INIS)

    Park, Byoung Yoon; Bae, Dae Seok; Kim, Chun Soo; Kim, Kyung Su; Koh, Young Kwon; Jeon, Seok Won

    2001-04-01

    This report provides the mechanical and thermal properties of granitic intact rocks obtained from Deep Core Drilling Program which is carried out as part of the assessment of deep geological environmental condition. These data are the basic material properties of the core samples from the boreholes drilled up to 500 m depth at the Yusung and Kosung sites. These sites were selected based on the result of preliminary site evaluation study. In this study, the mechanical properties include density, porosity, P-wave velocity, S-wave velocity, uniaxial compressive strength, Young's modulus, Poisson's ratio, tensile strength, and shear strength of fractures, and the thermal properties are heat conductivity, thermal expansion coefficient, specific heat and so on. Those properties were measured through laboratory tests and these data are compared with the existing test results of several domestic rocks

  3. Evaluation of the basic mechanical and thermal properties of deep crystalline rocks

    Energy Technology Data Exchange (ETDEWEB)

    Park, Byoung Yoon; Bae, Dae Seok; Kim, Chun Soo; Kim, Kyung Su; Koh, Young Kwon; Jeon, Seok Won

    2001-04-01

    This report provides the mechanical and thermal properties of granitic intact rocks obtained from Deep Core Drilling Program which is carried out as part of the assessment of deep geological environmental condition. These data are the basic material properties of the core samples from the boreholes drilled up to 500 m depth at the Yusung and Kosung sites. These sites were selected based on the result of preliminary site evaluation study. In this study, the mechanical properties include density, porosity, P-wave velocity, S-wave velocity, uniaxial compressive strength, Young's modulus, Poisson's ratio, tensile strength, and shear strength of fractures, and the thermal properties are heat conductivity, thermal expansion coefficient, specific heat and so on. Those properties were measured through laboratory tests and these data are compared with the existing test results of several domestic rocks.

  4. The role of auditory abilities in basic mechanisms of cognition in older adults

    Directory of Open Access Journals (Sweden)

    Massimo eGrassi

    2013-10-01

    Full Text Available The aim of this study was to assess age-related differences between young and older adults in auditory abilities and to investigate the relationship between auditory abilities and basic mechanisms of cognition in older adults. Although there is a certain consensus that the participant’s sensitivity to the absolute intensity of sounds (such as that measured via pure tone audiometry explains his/her cognitive performance, there is not yet much evidence that the participant’s auditory ability (i.e., the whole supra-threshold processing of sounds explains his/her cognitive performance. Twenty-eight young adults (age < 35, 26 young-old adults (65 ≤ age ≤75 and 28 old-old adults (age > 75 were presented with a set of tasks estimating several auditory abilities (i.e., frequency discrimination, intensity discrimination, duration discrimination, timbre discrimination, gap detection, amplitude modulation detection, and the absolute threshold for a 1 kHz pure tone and the participant’s working memory, cognitive inhibition, and processing speed. Results showed an age-related decline in both auditory and cognitive performance. Moreover, regression analyses showed that a subset of the auditory abilities (i.e., the ability to discriminate frequency, duration, timbre, and the ability to detect amplitude modulation explained a significant part of the variance observed in processing speed in older adults. Overall, the present results highlight the relationship between auditory abilities and basic mechanisms of cognition.

  5. Multidimensional Generalized Functions in Aeroacoustics and Fluid Mechanics. Part 1; Basic Concepts and Operations

    Science.gov (United States)

    Farassat, Fereidoun; Myers, Michael K.

    2011-01-01

    This paper is the first part of a three part tutorial on multidimensional generalized functions (GFs) and their applications in aeroacoustics and fluid mechanics. The subject is highly fascinating and essential in many areas of science and, in particular, wave propagation problems. In this tutorial, we strive to present rigorously and clearly the basic concepts and the tools that are needed to use GFs in applications effectively and with ease. We give many examples to help the readers in understanding the mathematical ideas presented here. The first part of the tutorial is on the basic concepts of GFs. Here we define GFs, their properties and some common operations on them. We define the important concept of generalized differentiation and then give some interesting elementary and advanced examples on Green's functions and wave propagation problems. Here, the analytic power of GFs in applications is demonstrated with ease and elegance. Part 2 of this tutorial is on the diverse applications of generalized derivatives (GDs). Part 3 is on generalized Fourier transformations and some more advanced topics. One goal of writing this tutorial is to convince readers that, because of their powerful operational properties, GFs are absolutely essential and useful in engineering and physics, particularly in aeroacoustics and fluid mechanics.

  6. Mechanisms of Acupuncture Therapy in Ischemic Stroke Rehabilitation: A Literature Review of Basic Studies.

    Science.gov (United States)

    Chavez, Lina M; Huang, Shiang-Suo; MacDonald, Iona; Lin, Jaung-Geng; Lee, Yu-Chen; Chen, Yi-Hung

    2017-10-28

    Acupuncture is recommended by the World Health Organization (WHO) as an alternative and complementary strategy for stroke treatment and for improving stroke care. Clinical trial and meta-analysis findings have demonstrated the efficacy of acupuncture in improving balance function, reducing spasticity, and increasing muscle strength and general well-being post-stroke. The mechanisms underlying the beneficial effects of acupuncture in stroke rehabilitation remain unclear. The aim of this study was to conduct a literature review, summarize the current known mechanisms in ischemic stroke rehabilitation through acupuncture and electroacupuncture (EA) therapy, and to detail the frequently used acupoints implicated in these effects. The evidence in this review indicates that five major different mechanisms are involved in the beneficial effects of acupuncture/EA on ischemic stroke rehabilitation: (1) Promotion of neurogenesis and cell proliferation in the central nervous system (CNS); (2) Regulation of cerebral blood flow in the ischemic area; (3) Anti-apoptosis in the ischemic area; (4) Regulation of neurochemicals; and, (5) Improvement of impaired long-term potentiation (LTP) and memory after stroke. The most frequently used acupoints in basic studies include Baihui (GV20), Zusanli (ST36), Quchi (LI11), Shuigou (GV26), Dazhui (GV14), and Hegu (LI4). Our findings show that acupuncture exerts a beneficial effect on ischemic stroke through modulation of different mechanisms originating in the CNS.

  7. LORETA Neurofeedback in the Precuneus: Operant Conditioning in Basic Mechanisms of Self-Regulation.

    Science.gov (United States)

    Cannon, Rex L; Baldwin, Debora R; Diloreto, Dominic J; Phillips, Sherman T; Shaw, Tiffany L; Levy, Jacob J

    2014-10-01

    Low-resolution brain electomagnetic tomography (LORETA) neurofeedback provides a mechanism to influence the electrical activity of the brain in intracranial space. The aim of this study was to determine the effects of LORETA neurofeedback (LNFB) in the precuneus as a mechanism for improving self-regulation in controls and a heterogeneous diagnostic group (DX). Thirteen participants completed between 10 and 20 sessions of LNFB training in a 3-voxel cluster in the left precuneus. The participants included 5 nonclinical university students, and 8 adults with heterogeneous psychiatric diagnoses. We assessed the effects of LNFB with neurophysiological measures as well as pre- and post-Personality Assessment Inventory (PAI) subscales and selected subtests from the Delis-Kaplan Executive Function System (DKEFS). There was a significant total relative power increase at the precuneus for baseline contrasts for the control group. The DX group did not reach significant levels. All participants showed improvements in executive functions and tended to report significantly less psychopathology. The basic neural mechanisms of self-regulation are poorly understood. The data obtained in this study demonstrate that LNFB in a heterogeneous population enhances executive functions while concordantly decreasing endorsement of psychological symptoms. The alpha frequency in the brain may represent integrative functioning relative to operant efficiency and self-regulatory mechanisms. © EEG and Clinical Neuroscience Society (ECNS) 2014.

  8. Molecular mechanism and potential targets for bone metastasis

    International Nuclear Information System (INIS)

    Iguchi, Haruo

    2007-01-01

    The incidence of bone metastasis has been increasing in all cancers in recent years. Bone metastasis is associated with substantial morbidity, including bone pain, pathological fracture, neurological deficit and/or hypercalcemia. Thus, the management of bone metastasis in patients is a clinically significant issue. In the process of bone metastasis, the primary mechanism responsible for bone destruction is cancer cell-mediated stimulation of osteoclastic bone resorption, which results in osteolysis and release of various growth factors from the bone matrix. These growth factors are prerequisites for successful colonization and subsequent invasive growth of cancer cells in bone, which is called a 'vicious cycle.' Thus, it is important to elucidate what molecules are involved in this step of bone destruction, and the understanding of these molecular mechanisms could lead to develop molecular-target therapies for bone metastasis. Bisphosphonates introduced in the treatment for bone metastasis have been shown to reduce skeletal morbidity. In Japan, the most potent bisphosphonate, zoledronate (ZOMETA), was introduced in this past April, and a phase III clinical trial of humanized anti-receptor activator of NF-κB ligand (RANKL) monoclonal antibody (Denosumab) against bone metastasis is under way as a global study. These new agents, which are targeted to osteoclasts, are considered to be standard management in the care of bone metastasis patients in combination with chemotherapy and/or hormone therapy. (author)

  9. Nature's amazing biopolymer: basic mechanical and hydrological properties of soil affected by plant exudates

    Science.gov (United States)

    Naveed, Muhammad; Roose, Tiina; Raffan, Annette; George, Timothy; Bengough, Glyn; Brown, Lawrie; Keyes, Sam; Daly, Keith; Hallett, Paul

    2016-04-01

    Plant exudates are known to have a very large impact on soil physical properties through changes in mechanical and hydrological processes driven by long-chain polysaccharides and surface active compounds. Whilst these impacts are well known, the basic physical properties of these exudates have only been reported in a small number of studies. We present data for exudates obtained from barley roots and chia seeds, incorporating treatments examining biological decomposition of the exudates. When these exudates were added to a sandy loam soil, contact angle and drop penetration time increased exponentially with increasing exudate concentration. These wetting properties were strongly correlated with both exudate density and zero-shear viscosity, but not with exudate surface tension. Water holding capacity and water repellency of exudate mixed soil tremendously increased with exudate concentration, however they were significantly reduced on decomposition when measured after 14 days of incubation at 16C. Mechanical stability greatly increased with increasing exudate amendment to soils, which was assessed using a rheological amplitude sweep test near saturation, at -50 cm matric potential (field capacity) using indentation test, and at air-dry condition using the Brazilian test. This reflects that exudates not only attenuate plant water stress but also impart mechanical stability to the rhizosphere. These data are highly relevant to the understanding and modelling of rhizosphere development, which is the next phase of our research.

  10. Vitamin D for the Treatment of Epilepsy: Basic Mechanisms, Animal Models and Clinical Trials

    Directory of Open Access Journals (Sweden)

    Kevin Pendo

    2016-12-01

    Full Text Available There is increasing evidence supporting dietary and alternative therapies for epilepsy, including the ketogenic diet, modified Atkins diet, and omega-3 fatty acids. Vitamin D is actively under investigation as a potential intervention for epilepsy. Vitamin D is fat soluble steroid which shows promise in animal models of epilepsy. Basic research has shed light on the possible mechanisms by which Vitamin D may reduce seizures, and animal data support the efficacy of Vitamin D in rat and mouse models of epilepsy. Very little clinical data exists to support the treatment of human epilepsy with Vitamin D, but positive findings from preliminary clinical trials warrant larger Phase I and II clinical trials in order to more rigorously determine the potential therapeutic value of Vitamin D as a treatment for human epilepsy.

  11. Basic mechanisms in the laser control of non-Markovian dynamics

    Science.gov (United States)

    Puthumpally-Joseph, R.; Mangaud, E.; Chevet, V.; Desouter-Lecomte, M.; Sugny, D.; Atabek, O.

    2018-03-01

    Referring to a Fano-type model qualitative analogy we develop a comprehensive basic mechanism for the laser control of the non-Markovian bath response and fully implement it in a realistic control scheme, in strongly coupled open quantum systems. Converged hierarchical equations of motion are worked out to numerically solve the master equation of a spin-boson Hamiltonian to reach the reduced electronic density matrix of a heterojunction in the presence of strong terahertz laser pulses. Robust and efficient control is achieved increasing by a factor of 2 the non-Markovianity measured by the time evolution of the volume of accessible states. The consequences of such fields on the central system populations and coherence are examined, putting the emphasis on the relation between the increase of non-Markovianity and the slowing down of decoherence processes.

  12. From Discrete Space-Time to Minkowski Space: Basic Mechanisms, Methods and Perspectives

    Science.gov (United States)

    Finster, Felix

    This survey article reviews recent results on fermion systems in discrete space-time and corresponding systems in Minkowski space. After a basic introduction to the discrete setting, we explain a mechanism of spontaneous symmetry breaking which leads to the emergence of a discrete causal structure. As methods to study the transition between discrete space-time and Minkowski space, we describe a lattice model for a static and isotropic space-time, outline the analysis of regularization tails of vacuum Dirac sea configurations, and introduce a Lorentz invariant action for the masses of the Dirac seas. We mention the method of the continuum limit, which allows to analyze interacting systems. Open problems are discussed.

  13. Revisiting the Basic Symptom Concept: Towards Translating Risk Symptoms for Psychosis into Neurobiological Targets

    Directory of Open Access Journals (Sweden)

    Frauke eSchultze-Lutter

    2016-01-01

    Full Text Available In its initial formulation, the concept of basic symptoms (BSs integrated findings on the early symptomatic course of schizophrenia and first in vivo evidence of accompanying brain aberrations. It argued that the subtle subclinical disturbances in mental processes described as BSs were the most direct self-experienced expression of the underlying neurobiological aberrations of the disease. Other characteristic symptoms of psychosis (e.g., delusions, hallucinations were conceptualized as secondary phenomena, resulting from dysfunctional beliefs and suboptimal coping styles with emerging BSs and/or concomitant stressors. While BSs can occur in many mental disorders, in particular affective disorders, a subset of perceptive and cognitive BSs appear to be specific to psychosis and are currently employed in two alternative risk criteria. However, despite their clinical recognition in the early detection of psychosis, neurobiological research on the aetiopathology of psychosis with neuroimaging methods has only just begun to consider the neural correlate of BSs. This perspective paper reviews the emerging evidence of an association between BSs and aberrant brain activation, connectivity patterns, and metabolism, and outlines promising routes for the use of BSs in aetiopathological research on psychosis.

  14. Basic quantum mechanics for three Dirac equations in a curved spacetime

    International Nuclear Information System (INIS)

    Arminjon, Mayeul

    2010-01-01

    We study the basic quantum mechanics for a fully general set of Dirac matrices in a curved spacetime by extending Pauli's method. We further extend this study to three versions of the Dirac equation: the standard (Dirac-Fock-Weyl or DFW) equation, and two alternative versions, both of which are based on the recently proposed linear tensor representations of the Dirac field (TRD). We begin with the current conservation: we show that the latter applies to any solution of the Dirac equation, if the field of Dirac matrices γμ satisfies a specific PDE. This equation is always satisfied for DFW with its restricted choice for the γμ matrices. It similarly restricts the choice of the γμ matrices for TRD. However, this restriction can be achieved. The frame dependence of a general Hamiltonian operator is studied. We show that in any given reference frame with minor restrictions on the spacetime metric, the axioms of quantum mechanics impose a unique form for the Hilbert space scalar product. Finally, the condition for the general Dirac Hamiltonian operator to be Hermitian is derived in a general curved spacetime. For DFW, the validity of this hermeticity condition depends on the choice of the γμ matrices. (author)

  15. Cannabinoid-Induced Hyperemesis: A Conundrum—From Clinical Recognition to Basic Science Mechanisms

    Directory of Open Access Journals (Sweden)

    Nissar A. Darmani

    2010-07-01

    Full Text Available Cannabinoids are used clinically on a subacute basis as prophylactic agonist antiemetics for the prevention of nausea and vomiting caused by chemotherapeutics. Cannabinoids prevent vomiting by inhibition of release of emetic neurotransmitters via stimulation of presynaptic cannabinoid CB1 receptors. Cannabis-induced hyperemesis is a recently recognized syndrome associated with chronic cannabis use. It is characterized by repeated cyclical vomiting and learned compulsive hot water bathing behavior. Although considered rare, recent international publications of numerous case reports suggest the contrary. The syndrome appears to be a paradox and the pathophysiological mechanism(s underlying the induced vomiting remains unknown. Although some traditional hypotheses have already been proposed, the present review critically explores the basic science of these explanations in the clinical setting and provides more current mechanisms for the induced hyperemesis. These encompass: (1 pharmacokinetic factors such as long half-life, chronic exposure, lipid solubility, individual variation in metabolism/excretion leading to accumulation of emetogenic cannabinoid metabolites, and/or cannabinoid withdrawal; and (2 pharmacodynamic factors including switching of the efficacy of Δ9-THC from partial agonist to antagonist, differential interaction of Δ9-THC with Gs and Gi signal transduction proteins, CB1 receptor desensitization or downregulation, alterations in tissue concentrations of endocannabinoid agonists/inverse agonists, Δ9-THC-induced mobilization of emetogenic metabolites of the arachidonic acid cascade, brainstem versus enteric actions of Δ9-THC, and/or hypothermic versus hyperthermic actions of Δ9-THC. In addition, human and animal findings suggest that chronic exposure to cannabis may not be a prerequisite for the induction of vomiting but is required for the intensity of emesis.

  16. Targeted genomic biomarkers for diagnosis and therapy: from basic research to clinical perspective

    International Nuclear Information System (INIS)

    Thakur, Mathew L.

    2014-01-01

    In 2010, more than 30,000 men succumbed to prostate cancer (PC) and more than 240,000 new PC cases were identified in the USA. Digital rectal examination, MRI, and a blood test for prostate specific antigen (PSA) determination play a significant role in detecting advanced PC. However, they are not considered reliable tools for early warning of PC, to detect recurrent cancer or to determine metastatic status of the disease. Unreliable diagnosis results in undertreatment or overtreatment of patients with minimal benefit, enormous morbidity, incontinence, and/or impotence. Histology remains the mainstay of PC confirmation. However, out of >750,000 biopsies performed each year in the USA, >65% show benign pathology, causing patient morbidity and costing hundreds of millions of healthcare dollars. Biological fluids, including urine, represent a promising source of biomarkers for detection and prediction of PC prognosis. Because urine is available non-invasively and readily, numerous studies targeting DNA, RNA, protein and metabolite based biomarkers have been performed. However, none have yet reached the clinic. Even FDA approved PCA3 test has low sensitivity and limitations in predicting aggressive PC

  17. Electron loss mechanisms in collisions of He+ ions with various targets

    International Nuclear Information System (INIS)

    Sant'Anna, M.M.; Melo, W.S.; Santos, A.C.F.; Sigaud, G.M.; Montenegro, E.C.

    1995-01-01

    The electron loss of high-velocity ions by neutral atoms is due to two different and competing mechanisms. In the screening mode, the electron loss is basically due to the nucleus-electron interaction, with the target electrons assuming the passive role of decreasing the Coulomb field of the target nucleus in the vicinity of the projectile active electron. For a fixed projectile velocity, this contribution is expected to give a non-linear dependence with the target atomic number Z 2 due to the incomplete screening at the impact parameter region where the projectile ionization is more likely to occur. Within first-order theories, if the screening is completely absent, the expected dependence would be Z 2 2 ; with screening, it should scale between Z 2 and Z 2 2 . On the other hand, in the antiscreening mode, where the loss is due to the action of the target electrons and the target nucleus plays no active role, the expected dependence would be approximately linear with Z 2 . Thus, for first-order theories, the expected overall dependence with Z 2 would be dominated by the screening mode as Z 2 increases. We have measured total electron-loss cross sections of He + ions impinging upon He, Ne, Ar, Kr and Xe targets in the energy range from 1.0 to 4.0 MeV to complement previous measurements and the results point towards a much smaller contribution from the screening mode than expected from first-order theories, possibly due to a saturation effect manifested only in the screening channel. (orig.)

  18. Targeted basic research to highlight the role of estrogen and estrogen receptors in the cardiovascular system.

    Science.gov (United States)

    Dworatzek, Elke; Mahmoodzadeh, Shokoufeh

    2017-05-01

    Epidemiological, clinical and animal studies revealed that sex differences exist in the manifestation and outcome of cardiovascular disease (CVD). The underlying molecular mechanisms implicated in these sex differences are not fully understood. The reasons for sex differences in CVD are definitely multifactorial, but major evidence points to the contribution of sex steroid hormone, 17β-estradiol (E2), and its receptors, estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). In this review, we summarize past and present studies that implicate E2 and ER as important determinants of sexual dimorphism in the physiology and pathophysiology of the heart. In particular, we give an overview of studies aimed to reveal the role of E2 and ER in the physiology of the observed sex differences in CVD using ER knock-out mice. Finally, we discuss recent findings from novel transgenic mouse models, which have provided new information on the sexual dimorphic roles of ER specifically in cardiomyocytes under pathological conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Development of a mobile manipulator for nuclear plant disaster, HELIOS X. Mechanical design and basic experiments

    International Nuclear Information System (INIS)

    Noda, Satsuya; Hirose, Shigeo; Ueda, Koji; Nakano, Hisami; Horigome, Atsushi; Endo, Gen

    2016-01-01

    In places such as nuclear power plant disaster area, which it is difficult for human workers to enter, robots are required to scout those places instead of human workers. In this paper, we present a mobile manipulator HELIOS X for a nuclear plant decommissioning task. Firstly, we address demands and specifications for the robot, considering the mission of reconnaissance. Then we outline the system of the robot, mainly focusing on the following mechanism: 'Crank Wheel', 'Main Arm', 'Sphere Link Wrist', 'Camera Arm', 'Control System' and 'System architecture'. Especially, we installed 3 degree of freedom 'Camera Arm' on the 'Main Arm', in order to improve functionality of remote control system. This enables the operator to monitor both the gripper and its overall view of the robot. 'Camera Arm' helps the operator to recognize the distance from an object to the gripper, because the operator can interactively move the viewpoint of the camera, and monitor from another camera angle without changing the gripper's position. We confirmed the basic functionality of mobile base, 'Main Arm' and 'Camera Arm' through hardware experiments. We also demonstrated that HELIOS X could pass through the pull-to-open door with a substantial closing force when the operator watched camera view only. (author)

  20. Ketosis and diabetic ketoacidosis in response to SGLT2 inhibitors: Basic mechanisms and therapeutic perspectives.

    Science.gov (United States)

    Qiu, Hongyu; Novikov, Aleksandra; Vallon, Volker

    2017-07-01

    Inhibitors of the sodium-glucose cotransporter SGLT2 are a new class of antihyperglycemic drugs that have been approved for the treatment of type 2 diabetes mellitus (T2DM). These drugs inhibit glucose reabsorption in the proximal tubules of the kidney thereby enhancing glucosuria and lowering blood glucose levels. Additional consequences and benefits include a reduction in body weight, uric acid levels, and blood pressure. Moreover, SGLT2 inhibition can have protective effects on the kidney and cardiovascular system in patients with T2DM and high cardiovascular risk. However, a potential side effect that has been reported with SGLT2 inhibitors in patients with T2DM and particularly during off-label use in patients with type 1 diabetes is diabetic ketoacidosis. The US Food and Drug Administration recently warned that SGLT2 inhibitors may result in euglycemic ketoacidosis. Here, we review the basic metabolism of ketone bodies, the triggers of diabetic ketoacidosis, and potential mechanisms by which SGLT2 inhibitors may facilitate the development of ketosis or ketoacidosis. This provides the rationale for measures to lower the risk. We discuss the role of the kidney and potential links to renal gluconeogenesis and uric acid handling. Moreover, we outline potential beneficial effects of modestly elevated ketone body levels on organ function that may have therapeutic relevance for the observed beneficial effects of SGLT2 inhibitors on the kidney and cardiovascular system. Copyright © 2017 John Wiley & Sons, Ltd.

  1. Analysis of trophic responses in lesioned brain: focus on basic fibroblast growth factor mechanisms

    Directory of Open Access Journals (Sweden)

    Chadi G.

    1998-01-01

    Full Text Available The actions of fibroblast growth factors (FGFs, particularly the basic form (bFGF, have been described in a large number of cells and include mitogenicity, angiogenicity and wound repair. The present review discusses the presence of the bFGF protein and messenger RNA as well as the presence of the FGF receptor messenger RNA in the rodent brain by means of semiquantitative radioactive in situ hybridization in combination with immunohistochemistry. Chemical and mechanical injuries to the brain trigger a reduction in neurotransmitter synthesis and neuronal death which are accompanied by astroglial reaction. The altered synthesis of bFGF following brain lesions or stimulation was analyzed. Lesions of the central nervous system trigger bFGF gene expression by neurons and/or activated astrocytes, depending on the type of lesion and time post-manipulation. The changes in bFGF messenger RNA are frequently accompanied by a subsequent increase of bFGF immunoreactivity in astrocytes in the lesioned pathway. The reactive astrocytes and injured neurons synthesize increased amount of bFGF, which may act as a paracrine/autocrine factor, protecting neurons from death and also stimulating neuronal plasticity and tissue repair

  2. Mechanisms of resistance to HER family targeting antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Kruser, Tim J. [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI (United States); Wheeler, Deric L., E-mail: dlwheeler@wisc.edu [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI (United States)

    2010-04-15

    The epidermal growth factor (EGF) family of receptor tyrosine kinases consists of four members: EGFR (HER1/ErbB1), HER2/neu (ErbB2), HER3 (ErbB3) and HER4 (ErbB4). Receptor activation via ligand binding leads to downstream signaling that influence cell proliferation, angiogenesis, invasion and metastasis. Aberrant expression or activity of EGFR and HER2 have been strongly linked to the etiology of several human epithelial cancers including but not limited to head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and breast cancer. With this, intense efforts have been made to inhibit the activity of the EGFR and HER2 by designing antibodies against the ligand binding domains (cetuximab, panitumumab and trastuzumab) or small molecules against the tyrosine kinase domains (erlotinib, gefitinib, and lapatinib). Both approaches have shown considerable clinical promise. However, increasing evidence suggests that the majority of patients do not respond to these therapies, and those who show initial response ultimately become refractory to treatment. While mechanisms of resistance to tyrosine kinase inhibitors have been extensively studied, resistance to monoclonal antibodies is less well understood, both in the laboratory and in the clinical setting. In this review, we discuss resistance to antibody-based therapies against the EGFR and HER2, similarities between these resistance profiles, and strategies to overcome resistance to HER family targeting monoclonal antibody therapy.

  3. Liquid metal embrittlement. From basic concepts to recent results related to structural materials for liquid metal spallation targets

    International Nuclear Information System (INIS)

    Gorse, D.; Goryachev, S.; Auger, T.

    2003-01-01

    At first, the basic features of LME are recalled (definition, characteristics, embrittling couples), together with classical experimental features and open questions. Then, a review of a few very recent results obtained on classical embrittling couples but using new powerful investigation techniques developed in France is proposed. Second we define LMC. The 'LME-LMC' correlation is postulated. Then we concentrate on the LME-LMC problem related to the build-up of the Liquid Metal Spallation target in the frame of the MEGAPIE project. The Russian expertise on LME is briefly mentioned. Then we present some results obtained in the frame of the Groupement de Recherche' GEDEON, focusing on steel grade T91 in contact with lead and lead-bismuth eutectic, in agreement with Russian literature. (author)

  4. The value of basic research insights into atrial fibrillation mechanisms as a guide to therapeutic innovation: a critical analysis.

    Science.gov (United States)

    Heijman, Jordi; Algalarrondo, Vincent; Voigt, Niels; Melka, Jonathan; Wehrens, Xander H T; Dobrev, Dobromir; Nattel, Stanley

    2016-04-01

    Atrial fibrillation (AF) is an extremely common clinical problem associated with increased morbidity and mortality. Current antiarrhythmic options include pharmacological, ablation, and surgical therapies, and have significantly improved clinical outcomes. However, their efficacy remains suboptimal, and their use is limited by a variety of potentially serious adverse effects. There is a clear need for improved therapeutic options. Several decades of research have substantially expanded our understanding of the basic mechanisms of AF. Ectopic firing and re-entrant activity have been identified as the predominant mechanisms for arrhythmia initiation and maintenance. However, it has become clear that the clinical factors predisposing to AF and the cellular and molecular mechanisms involved are extremely complex. Moreover, all AF-promoting and maintaining mechanisms are dynamically regulated and subject to remodelling caused by both AF and cardiovascular disease. Accordingly, the initial presentation and clinical progression of AF patients are enormously heterogeneous. An understanding of arrhythmia mechanisms is widely assumed to be the basis of therapeutic innovation, but while this assumption seems self-evident, we are not aware of any papers that have critically examined the practical contributions of basic research into AF mechanisms to arrhythmia management. Here, we review recent insights into the basic mechanisms of AF, critically analyse the role of basic research insights in the development of presently used anti-AF therapeutic options and assess the potential value of contemporary experimental discoveries for future therapeutic innovation. Finally, we highlight some of the important challenges to the translation of basic science findings to clinical application. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  5. New mechanisms and targets in the treatment of bone fragility.

    Science.gov (United States)

    Martin, T John; Seeman, Ego

    2007-01-01

    Bone modelling and remodelling are cell-mediated processes responsible for the construction and reconstruction of the skeleton throughout life. These processes are chiefly mediated by locally generated cytokines and growth factors that regulate the differentiation, activation, work and life span of osteoblasts and osteoclasts, the cells that co-ordinate the volumes of bone resorbed and formed. In this way, the material composition and structural design of bone is regulated in accordance with its loading requirements. Abnormalities in this regulatory system compromise the material and structural determinants of bone strength producing bone fragility. Understanding the intercellular control processes that regulate bone modelling and remodelling is essential in planning therapeutic approaches to prevention and treatment of bone fragility. A great deal has been learnt in the last decade. Clinical trials carried out exclusively with drugs that inhibit bone resorption have identified the importance of reducing the rate of bone remodelling and so the progression of bone fragility to achieved fracture reductions of approx. 50%. These trials have also identified limitations that should be placed upon interpretation of bone mineral density changes in relation to treatment. New resorption inhibitors are being developed, based on mechanisms of action that are different from existing drugs. Some of these might offer resorption inhibition without reducing bone formation. More recent research has provided the first effective anabolic therapy for bone reconstruction. Daily injections of PTH (parathyroid hormone)-(1-34) have been shown in preclinical studies and in a large clinical trial to increase bone tissue mass and reduce the risk of fractures. The action of PTH differs from that of the resorption inhibitors, but whether it is more effective in fracture reduction is not known. Understanding the cellular and molecular mechanisms of PTH action, particularly its interactions with

  6. Target-to-Target Repetition Cost and Location Negative Priming Are Dissociable: Evidence for Different Mechanisms

    Science.gov (United States)

    Chao, Hsuan-Fu

    2011-01-01

    In a location-selection task, the repetition of a prior distractor location as the target location would slow down the response. This effect is termed the location negative priming (NP) effect. Recently, it has been demonstrated that repetition of a prior target location as the current target location would also slow down response. Because such…

  7. Obesity and kidney disease: from population to basic science and the search for new therapeutic targets.

    Science.gov (United States)

    Whaley-Connell, Adam; Sowers, James R

    2017-08-01

    The global burden of kidney disease is increasing strikingly in parallel with increases in obesity and diabetes. Indeed, chronic kidney disease (CKD) and end-stage renal disease (ESRD) coupled with comorbidities such as obesity, diabetes, and hypertension cost the health care system hundreds of billions of dollars in the US alone. The progression to ESRD in patients with obesity and diabetes continues despite widespread use of inhibitors of the renin-angiotensin-aldosterone system (RAAS) along with aggressive blood pressure and glycemic control in these high-risk populations. Thereby, it is increasingly important to better understand the underlying mechanisms involved in obesity-related CKD in order to develop new strategies that prevent or interrupt the progression of this costly disease. In this context, a key mechanism that drives development and progression of kidney disease in obesity is endothelial dysfunction and associated tubulointerstitial fibrosis. However, the precise interactive mechanisms in the development of aortic and kidney endothelial dysfunction and tubulointerstitial fibrosis remain unclear. Further, strategies specifically targeting kidney fibrosis have yielded inconclusive benefits in human studies. While clinical data support the benefits derived from inhibition of the RAAS, there is a tremendous amount of residual risk for the progression of kidney disease in individuals with obesity and diabetes. There is promising experimental data to suggest that exercise, targeting inflammation and oxidative stress, lowering uric acid, and targeting the mineralocorticoid receptor signaling and/or sodium channel inhibition could improve tubulointerstitial fibrosis and mitigate progression of kidney disease in persons with obesity and diabetes. Published by Elsevier Inc.

  8. A systematic review of basic life support training targeted to family members of high-risk cardiac patients.

    Science.gov (United States)

    Cartledge, Susie; Bray, Janet E; Leary, Marion; Stub, Dion; Finn, Judith

    2016-08-01

    Targeting basic life support (BLS) training to bystanders who are most likely to witness an out of hospital cardiac arrest (OHCA) is an important public health intervention. We performed a systematic review examining the evidence of the effectiveness of providing BLS training to family members of high-risk cardiac patients. A search of Ovid MEDLINE, CINAL, EMBASE, Informit, Cochrane Library, Web of Science, Scopus, ERIC and ProQuest Dissertations and Theses Global was conducted. We included all studies training adult family members of high-risk cardiac patients regardless of methods used for cardiopulmonary resuscitation (CPR) or BLS training. Two reviewers independently extracted data and evaluated the quality of evidence using GRADE (Grades of Recommendation, Assessment, Development and Evaluation). We included 26 of the 1172 studies identified. The majority of studies were non-randomised controlled trials (n=18), of very low to moderate quality. Currently, there is insufficient evidence to indicate a benefit of this intervention for patients; largely because of low numbers of OHCA events and high loss to follow-up. However, the majority of trained individuals were able to competently perform BLS skills, reported a willingness to use these skills and experienced lower anxiety. Whilst there is no current evidence for improvement in patient outcomes from targeted BLS training for family members, this group are willing and capable to learn these skills. Future research may need to examine longer periods of follow-up using alternate methods (e.g. cardiac arrest registries), and examine the effectiveness of training in the modern era. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. The basic science of dermal fillers: past and present Part I: background and mechanisms of action.

    Science.gov (United States)

    Gilbert, Erin; Hui, Andrea; Waldorf, Heidi A

    2012-09-01

    Dermal fillers have provided a safe and effective means for aesthetic soft tissue augmentation, and have experienced a dramatic increase in popularity during the past 10 years. Much focus has been placed upon filler technique and patient outcomes. However, there is a relative lack of literature reviewing the basic science of dermal fillers, which is vital to a physician's understanding of how each product behaves in vivo. Part I of this article reviews the basic science and evolution of both historical and contemporary dermal fillers; Part II examines their adverse effects. We endeavor to provide the physician with a practical approach to choosing products that maximize both aesthetic outcome and safety.

  10. Cellular and molecular mechanisms of HIV-1 integration targeting.

    Science.gov (United States)

    Engelman, Alan N; Singh, Parmit K

    2018-07-01

    Integration is central to HIV-1 replication and helps mold the reservoir of cells that persists in AIDS patients. HIV-1 interacts with specific cellular factors to target integration to interior regions of transcriptionally active genes within gene-dense regions of chromatin. The viral capsid interacts with several proteins that are additionally implicated in virus nuclear import, including cleavage and polyadenylation specificity factor 6, to suppress integration into heterochromatin. The viral integrase protein interacts with transcriptional co-activator lens epithelium-derived growth factor p75 to principally position integration within gene bodies. The integrase additionally senses target DNA distortion and nucleotide sequence to help fine-tune the specific phosphodiester bonds that are cleaved at integration sites. Research into virus-host interactions that underlie HIV-1 integration targeting has aided the development of a novel class of integrase inhibitors and may help to improve the safety of viral-based gene therapy vectors.

  11. Hyperglycemia Associated With Targeted Oncologic Treatment: Mechanisms and Management.

    Science.gov (United States)

    Goldman, Jonathan W; Mendenhall, Melody A; Rettinger, Sarah R

    2016-07-29

    : Molecularly targeted cancer therapy has rapidly changed the landscape of oncologic care, often improving patients' prognosis without causing as substantial a quality-of-life decrement as cytotoxic chemotherapy does. Nevertheless, targeted agents can cause side effects that may be less familiar to medical oncologists and that require the attention and expertise of subspecialists. In this review, we focus on hyperglycemia, which can occur with use of new anticancer agents that interact with cell proliferation pathways. Key mediators of these pathways include the tyrosine kinase receptors insulin growth factor receptor 1 (IGF-1R) and epidermal growth factor receptor (EGFR), as well as intracellular signaling molecules phosphatidylinositol 3-kinase (PI3K), AKT, and mammalian target of rapamycin (mTOR). We summarize available information on hyperglycemia associated with agents that inhibit these molecules within the larger context of adverse event profiles. The highest incidence of hyperglycemia is observed with inhibition of IGF-1R or mTOR, and although the incidence is lower with PI3K, AKT, and EGFR inhibitors, hyperglycemia is still a common adverse event. Given the interrelationships between the IGF-1R and cell proliferation pathways, it is important for oncologists to understand the etiology of hyperglycemia caused by anticancer agents that target those pathways. We also discuss monitoring and management approaches for treatment-related hyperglycemia for some of these agents, with a focus on our experience during the clinical development of the EGFR inhibitor rociletinib. Treatment-related hyperglycemia is associated with several anticancer agents. Many cancer patients may also have preexisting or undiagnosed diabetes or glucose intolerance. Screening can identify patients at risk for hyperglycemia before treatment with these agents. Proper monitoring and management of symptoms, including lifestyle changes and pharmacologic intervention, may allow patients to

  12. Positioning accuracy analysis of adjusting target mechanism of three-dimensional attitude

    International Nuclear Information System (INIS)

    Ma Li; Wang Kun; Sun Linzhi; Zhou Shasha

    2012-01-01

    A novel adjusting target mechanism of three-dimensional attitude is presented according to the characteristics of the target transport subsystem in inertial confinement fusion (ICF). The mechanism consists of a tangent mechanism adjusting rotation angle and a set of orthogonal tangent mechanism adjusting two-dimensional deflection angles. The structural parameters of the adjusting target mechanism are analyzed according to principle errors, structure errors and motion errors of following. The analysis results indicate that the system error of the adjusting target mechanism is influenced by the displacement of the linear actuators, the actuator ball radius, the working radius of the tangent mechanism, the angle error of the inclined installation hole, the centralization error of the actuators, the orthogonal error of the two tangent mechanism, and the angle errors of the inclined target rod inclined rotation shaft. The errors of the inclined target rod and inclined rotation shaft are the two greatest impact factors, the spherical contact error is the next. By means of precise assembly and control system compensation, the accuracy of the adjusting target mechanism can be less than 0.1 mrad. (authors)

  13. A dynamic systems model of basic developmental mechanisms : Piaget, Vygotsky, and beyond

    NARCIS (Netherlands)

    van Geert, P

    1998-01-01

    A dynamic systems model is proposed on the basis of a general developmental mechanism adopted from the theories of J. Piaget and L. S. Vygotsky, more particularly a mechanism based on the concepts assimilation versus accommodation and actual development versus zone of proximal development. In the

  14. Drug Targets and Mechanisms of Resistance in the Anaerobic Protozoa

    Science.gov (United States)

    Upcroft, Peter; Upcroft, Jacqueline A.

    2001-01-01

    The anaerobic protozoa Giardia duodenalis, Trichomonas vaginalis, and Entamoeba histolytica infect up to a billion people each year. G. duodenalis and E. histolytica are primarily pathogens of the intestinal tract, although E. histolytica can form abscesses and invade other organs, where it can be fatal if left untreated. T. vaginalis infection is a sexually transmitted infection causing vaginitis and acute inflammatory disease of the genital mucosa. T. vaginalis has also been reported in the urinary tract, fallopian tubes, and pelvis and can cause pneumonia, bronchitis, and oral lesions. Respiratory infections can be acquired perinatally. T. vaginalis infections have been associated with preterm delivery, low birth weight, and increased mortality as well as predisposing to human immunodeficiency virus infection, AIDS, and cervical cancer. All three organisms lack mitochondria and are susceptible to the nitroimidazole metronidazole because of similar low-redox-potential anaerobic metabolic pathways. Resistance to metronidazole and other drugs has been observed clinically and in the laboratory. Laboratory studies have identified the enzyme that activates metronidazole, pyruvate:ferredoxin oxidoreductase, to its nitroso form and distinct mechanisms of decreasing drug susceptibility that are induced in each organism. Although the nitroimidazoles have been the drug family of choice for treating the anaerobic protozoa, G. duodenalis is less susceptible to other antiparasitic drugs, such as furazolidone, albendazole, and quinacrine. Resistance has been demonstrated for each agent, and the mechanism of resistance has been investigated. Metronidazole resistance in T. vaginalis is well documented, and the principal mechanisms have been defined. Bypass metabolism, such as alternative oxidoreductases, have been discovered in both organisms. Aerobic versus anaerobic resistance in T. vaginalis is discussed. Mechanisms of metronidazole resistance in E. histolytica have recently

  15. Stress and PTSD Mechanisms as Targets for Pharmacotherapy of Alcohol Abuse, Addiction and Relapse

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-13-1-0126 TITLE: Stress and PTSD Mechanisms as Targets for Pharmacotherapy of Alcohol Abuse, Addiction and Relapse PRINCIPAL...10/27/2017 2. REPORT TYPE Annual 3. DATES COVERED 30 Sep 2016 — 29 Sep 2017 4. TITLE AND SUBTITLE Stress and PTSD Mechanisms as Targets for...insights into mechanism; (2) suppression of noradrenergic signaling decreases alcohol drinking in rats with a history of traumatic stress , but not in

  16. Basic processes and mechanisms of the water-rock system evolution

    OpenAIRE

    Shvartsev, Stepan Lvovich

    2007-01-01

    A new conception of progressive evolution and self-organizing presence in dead matter is developed; inner mechanisms and processes, realizing this development, are revealed. It is proven that the water-rock system satisfy these requirements

  17. Autogenous shrinkage in high-performance cement paste: An evaluation of basic mechanisms

    DEFF Research Database (Denmark)

    Lura, Pietro; Jensen, Ole Mejlhede; van Breugel, Klaas

    2003-01-01

    In this paper, various mechanisms Suggested to cause autogenous shrinkage are presented. The mechanisms are evaluated from the point of view of their soundness and applicability to quantitative modeling of autogenous shrinkage. The capillary tension approach is advantageous, because it has a sound...... mechanical and thermodynamical basis. Furthermore, this mechanism is easily applicable in a numerical model when dealing with a continuously changing microstructure. In order to test the numerical model, autogenous deformation and internal relative humidity (RH) of a Portland cement paste were measured...... on the capillary tension approach. Because a part of the RH drop in the cement paste is due to dissolved salts in the pore solution, a method is suggested to separate this effect from self-desiccation and to calculate the actual stress in the pore fluid associated with menisci formation....

  18. Translation-rotation plasticity as basic mechanism of plastic deformation in macro-, micro- and nanoindentation processes

    International Nuclear Information System (INIS)

    Grabco, D; Shikimaka, O; Harea, E

    2008-01-01

    This paper presents a brief review of multilateral examinations for the purpose of detection of interrelation between processes occuring in solids at different levels of action of exterior loading, namely, at macro-, micro- and nanoindentation. Convincing arguments supporting the rotation deformation mechanism alongside the recognized dislocation one are adduced. It has been shown that the decrease in dislocation mobility leads at all scales to the intensification of rotation plasticity and to the involvement of other plastic deformation mechanisms, such as appearance and interaction of disclinations, twinning, phase transition and compression of material. The conversion from translation plasticity to the rotation-translation one means transition to the higher level of plastic deformation, the mesolevel, when the possibilities of the previous microscopic level are exhausted. It was established that the plastic deformation zone in the vicinity of indentations could be separated into two main specific regions: (i) peripheral region predominantly with the dislocation deformation mechanism; otherwise, translation mechanism: microlevel, and (ii) quasidestructured region mainly with the disclination or the intergranular sliding mechanism: rotation mechanism, mesolevel

  19. Phase Transitions in Combinatorial Optimization Problems: Basics, Algorithms and Statistical Mechanics

    Science.gov (United States)

    Hartmann, Alexander K.; Weigt, Martin

    2005-10-01

    A concise, comprehensive introduction to the topic of statistical physics of combinatorial optimization, bringing together theoretical concepts and algorithms from computer science with analytical methods from physics. The result bridges the gap between statistical physics and combinatorial optimization, investigating problems taken from theoretical computing, such as the vertex-cover problem, with the concepts and methods of theoretical physics. The authors cover rapid developments and analytical methods that are both extremely complex and spread by word-of-mouth, providing all the necessary basics in required detail. Throughout, the algorithms are shown with examples and calculations, while the proofs are given in a way suitable for graduate students, post-docs, and researchers. Ideal for newcomers to this young, multidisciplinary field.

  20. Mechanisms of sound seattering by biological targets and their aggregates

    Directory of Open Access Journals (Sweden)

    Natalia Gorska

    2006-03-01

    Full Text Available Natalia Gorska's thesis is based on a set of 9 papers published in scientific journals (Gorska & Klusek 1998, Gorska 2000, Gorska & Chu 2001a, b, Gorska & Ona 2003a, b and conference proceedings (Gorska & Klusek 1994, Gorska 1999, Gorska & Chu 2000, which broadly summarise her integrated research achievements in underwater acoustics from 1994 to 2003. She is the sole author of two of the articles (Gorska 1999, 2000, and is the first co-author, taking a leading part, in the others (Gorska & Klusek 1994, 1998, Gorska & Chu 2000, Gorska & Chu 200la, b, Gorska & Ona 2003a, b.     Her research objective was to work out the theoretical background to certain problems of sound scattering by biological targets - single individuals and aggregated layers of fish and zooplankton - in relation to environmental conditions in the sea. In the study she focused on acoustical extinction and backscattering, including the phenomenon of echo interference. In conjunction wit h the co-authors of papers Gorska & Ona 2003a, b, Gorska & Chu 2001a, b and Gorska & Chu 2000, she was able to apply and verify her theoretical results empirically.

  1. Basic research on mechanism of BN inclusion in improving the machinability of steel

    International Nuclear Information System (INIS)

    Ya-nan, C.; Yan-ping, B.; Min, W.; Xiao-feng, C.; Lin-jing, W.; Li-hua, Z.

    2014-01-01

    Boron nitride-added eco-friendly free cutting steel has recently drawn more and more attention. But, the mechanisms explaining the role of BN inclusions improving the machinability of steels is not very clear. In this investigation, the material removal mechanism for cutting of BN inclusions in steels is explored, using a combination of theoretical analysis and a series of experiments. First, the actual shape of BN inclusions is observed and the amount and distribution of BN inclusions is quantitatively analyzed. Subsequently, the cutting performance of the steel is determined by cutting experimental tests. Moreover, the micro mechanical properties and the material removal mechanisms for cutting of BN inclusions are investigated by means of nano indentation. The results revealed that the BN inclusions are hexagonal and are uniformly distributed, their average content is 23.2 per unit area and their volume fraction is 0.51% in the steel with 74 ppm B and 180 ppm N. It is shown that BN inclusions can improve the cutting performance of steel significantly, and a model describing the material removal mechanism for cutting of BN inclusions is proposed. BN inclusions act as stress concentration source, lubrication and wrap page of hard particles. (Author)

  2. Basic research on mechanism of BN inclusion in improving the machinability of steel

    Energy Technology Data Exchange (ETDEWEB)

    Ya-nan, C.; Yan-ping, B.; Min, W.; Xiao-feng, C.; Lin-jing, W.; Li-hua, Z.

    2014-07-01

    Boron nitride-added eco-friendly free cutting steel has recently drawn more and more attention. But, the mechanisms explaining the role of BN inclusions improving the machinability of steels is not very clear. In this investigation, the material removal mechanism for cutting of BN inclusions in steels is explored, using a combination of theoretical analysis and a series of experiments. First, the actual shape of BN inclusions is observed and the amount and distribution of BN inclusions is quantitatively analyzed. Subsequently, the cutting performance of the steel is determined by cutting experimental tests. Moreover, the micro mechanical properties and the material removal mechanisms for cutting of BN inclusions are investigated by means of nano indentation. The results revealed that the BN inclusions are hexagonal and are uniformly distributed, their average content is 23.2 per unit area and their volume fraction is 0.51% in the steel with 74 ppm B and 180 ppm N. It is shown that BN inclusions can improve the cutting performance of steel significantly, and a model describing the material removal mechanism for cutting of BN inclusions is proposed. BN inclusions act as stress concentration source, lubrication and wrap page of hard particles. (Author)

  3. Basic Knowledge for Market Principle: Approaches to the Price Coordination Mechanism by Using Optimization Theory and Algorithm

    Science.gov (United States)

    Aiyoshi, Eitaro; Masuda, Kazuaki

    On the basis of market fundamentalism, new types of social systems with the market mechanism such as electricity trading markets and carbon dioxide (CO2) emission trading markets have been developed. However, there are few textbooks in science and technology which present the explanation that Lagrange multipliers can be interpreted as market prices. This tutorial paper explains that (1) the steepest descent method for dual problems in optimization, and (2) Gauss-Seidel method for solving the stationary conditions of Lagrange problems with market principles, can formulate the mechanism of market pricing, which works even in the information-oriented modern society. The authors expect readers to acquire basic knowledge on optimization theory and algorithms related to economics and to utilize them for designing the mechanism of more complicated markets.

  4. A three-scale model of basic mechanical properties of Nafion

    Czech Academy of Sciences Publication Activity Database

    Kafka, Vratislav; Vokoun, David

    2015-01-01

    Roč. 50, č. 6 (2015), s. 763-776 ISSN 0191-5665 R&D Projects: GA ČR(CZ) GAP108/10/1296; GA ČR(CZ) GA103/09/2101 Institutional support: RVO:68378297 ; RVO:68378271 Keywords : Nafion * mechanical properties * mesomechanics * material structure * hydration Subject RIV: JL - Material s Fatigue, Friction Mechanics; JJ - Other Material s (FZU-D) Impact factor: 0.729, year: 2015 http://link.springer.com/article/10.1007%2Fs11029-015-9466-y

  5. Magneto-mechanical trapping systems for biological target detection

    International Nuclear Information System (INIS)

    Li, Fuquan; Kodzius, Rimantas; Gooneratne, Chinthaka P.; Foulds, Ian G.; Kosel, Jürgen

    2014-01-01

    We demonstrate a magnetic microsystem capable of detecting nucleic acids via the size difference between bare magnetic beads and bead compounds. The bead compounds are formed through linking nonmagnetic beads and magnetic beads by the target nucleic acids. The system comprises a tunnel magneto-resistive (TMR) sensor, a trapping well, and a bead-concentrator. The TMR sensor detects the stray field of magnetic beads inside the trapping well, while the sensor output depends on the number of beads. The size of the bead compounds is larger than that of bare magnetic beads, and fewer magnetic beads are required to fill the trapping well. The bead-concentrator, in turn, is capable of filling the trap in a controlled fashion and so to shorten the assay time. The bead-concentrator includes conducting loops surrounding the trapping well and a conducting line underneath. The central conducting line serves to attract magnetic beads in the trapping well and provides a magnetic field to magnetize them so to make them detectable by the TMR sensor. This system excels by its simplicity in that the DNA is incubated with magnetic and nonmagnetic beads, and the solution is then applied to the chip and analyzed in a single step. In current experiments, a signal-to-noise ratio of 40.3 dB was obtained for a solution containing 20.8 nM of DNA. The sensitivity and applicability of this method can be controlled by the size or concentration of the nonmagnetic bead, or by the dimension of the trapping well. (author)

  6. Magneto-mechanical trapping systems for biological target detection

    KAUST Repository

    Li, Fuquan

    2014-03-29

    We demonstrate a magnetic microsystem capable of detecting nucleic acids via the size difference between bare magnetic beads and bead compounds. The bead compounds are formed through linking nonmagnetic beads and magnetic beads by the target nucleic acids. The system comprises a tunnel magneto-resistive (TMR) sensor, a trapping well, and a bead-concentrator. The TMR sensor detects the stray field of magnetic beads inside the trapping well, while the sensor output depends on the number of beads. The size of the bead compounds is larger than that of bare magnetic beads, and fewer magnetic beads are required to fill the trapping well. The bead-concentrator, in turn, is capable of filling the trap in a controlled fashion and so to shorten the assay time. The bead-concentrator includes conducting loops surrounding the trapping well and a conducting line underneath. The central conducting line serves to attract magnetic beads in the trapping well and provides a magnetic field to magnetize them so to make them detectable by the TMR sensor. This system excels by its simplicity in that the DNA is incubated with magnetic and nonmagnetic beads, and the solution is then applied to the chip and analyzed in a single step. In current experiments, a signal-to-noise ratio of 40.3 dB was obtained for a solution containing 20.8 nM of DNA. The sensitivity and applicability of this method can be controlled by the size or concentration of the nonmagnetic bead, or by the dimension of the trapping well.

  7. Autogenous shrinkage in high-performance cement paste: An evaluation of basic mechanisms

    International Nuclear Information System (INIS)

    Lura, Pietro; Jensen, Ole Mejlhede; Breugel, Klaas van

    2003-01-01

    In this paper, various mechanisms suggested to cause autogenous shrinkage are presented. The mechanisms are evaluated from the point of view of their soundness and applicability to quantitative modeling of autogenous shrinkage. The capillary tension approach is advantageous, because it has a sound mechanical and thermodynamical basis. Furthermore, this mechanism is easily applicable in a numerical model when dealing with a continuously changing microstructure. In order to test the numerical model, autogenous deformation and internal relative humidity (RH) of a Portland cement paste were measured during the first week of hardening. The isothermal heat evolution was also recorded to monitor the progress of hydration and the elastic modulus in compression was measured. RH change, degree of hydration and elastic modulus were used as input data for the calculation of autogenous deformation based on the capillary tension approach. Because a part of the RH drop in the cement paste is due to dissolved salts in the pore solution, a method is suggested to separate this effect from self-desiccation and to calculate the actual stress in the pore fluid associated with menisci formation

  8. Derivation of Performance Statements for the Automotive Mechanics Basic Trade Course: Research Documentation.

    Science.gov (United States)

    Fox, A. P.; Kuhl, D. H.

    A project was conducted to derive a comprehensive list of the performances of a competence mechanic to satisfy the planning needs of automotive engineering lecturers, curriculum committees, researchers, course designers, and staff developers. A list of 127 tasks together with information about their relative importance and the frequency with which…

  9. RISK FACTORS FOR PANCREATIC CANCER: UNDERLYING MECHANISMS AND POTENTIAL TARGETS

    Directory of Open Access Journals (Sweden)

    Thomas eKolodecik

    2014-01-01

    Full Text Available Purpose of the review:Pancreatic cancer is extremely aggressive, forming highly chemo-resistant tumors, and has one of the worst prognoses. The evolution of this cancer is multi-factorial. Repeated acute pancreatic injury and inflammation are important contributing factors in the development of pancreatic cancer. This article attempts to understand the common pathways linking pancreatitis to pancreatic cancer.Recent Findings:Intracellular activation of both pancreatic enzymes and the transcription factor NF-kB are important mechanisms that induce acute pancreatitis. Recurrent pancreatic injury due to genetic susceptibility, environmental factors such as smoking, alcohol intake, and conditions such as obesity lead to increases in oxidative stress, impaired autophagy and constitutive activation of inflammatory pathways. These processes can stimulate pancreatic stellate cells, thereby increasing fibrosis and encouraging chronic disease development. Activation of oncogneic Kras mutations through inflammation, coupled with altered levels of tumor suppressor proteins (p53 and p16 can ultimately lead to development of pancreatic cancer. Summary:Although our understanding of pancreatitis and pancreatic cancer has tremendously increased over many years, much remains to be elucidated in terms of common pathways linking these conditions.

  10. Basic rock properties for the thermo-hydro-mechanical analysis of a high-level radioactive waste repository

    International Nuclear Information System (INIS)

    Kim, Jhin Wung; Kang, Chul Hyung

    1999-04-01

    Deep geological radioactive waste disposal is generally based on the isolation of the waste from the biosphere by multiple barriers. The host rock is one of these barriers which should provide a stable mechanical and chemical environment for the engineered barriers. In the evaluation of the safety of the high-level radioactive waste disposal systems, an important part of the safety analysis is an assessment of the coupling or interaction between thermal, hydrological, and mechanical effects. In order to do this assessment, adequate data on the characteristics of different host rocks are necessary. The properties of the rock and rock discontinuity are very complex and their values vary in a wide range. The accuracy of the result of the assessment depends on the values of these properties used. The present study is an attempt to bring together and condense data for the basic properties of various rock masses, which are needed in the thermo-hydro-mechanical analysis for the deep geological radioactive waste repository. The testing and measurement methods for these basic properties are also presented. Domestic data for deep geological media should be supplemented in the future, due to the insufficiency and the lack of accuracy of the data available at present. (author). 28 refs., 21 figs

  11. Basic rock properties for the thermo-hydro-mechanical analysis of a high-level radioactive waste repository

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jhin Wung; Kang, Chul Hyung

    1999-04-01

    Deep geological radioactive waste disposal is generally based on the isolation of the waste from the biosphere by multiple barriers. The host rock is one of these barriers which should provide a stable mechanical and chemical environment for the engineered barriers. In the evaluation of the safety of the high-level radioactive waste disposal systems, an important part of the safety analysis is an assessment of the coupling or interaction between thermal, hydrological, and mechanical effects. In order to do this assessment, adequate data on the characteristics of different host rocks are necessary. The properties of the rock and rock discontinuity are very complex and their values vary in a wide range. The accuracy of the result of the assessment depends on the values of these properties used. The present study is an attempt to bring together and condense data for the basic properties of various rock masses, which are needed in the thermo-hydro-mechanical analysis for the deep geological radioactive waste repository. The testing and measurement methods for these basic properties are also presented. Domestic data for deep geological media should be supplemented in the future, due to the insufficiency and the lack of accuracy of the data available at present. (author). 28 refs., 21 figs.

  12. Dressed dibaryon production as a new mechanism for basic nuclear force and meson-exchange currents

    International Nuclear Information System (INIS)

    Kukulin, V.I.

    2003-01-01

    A novel concept for the nuclear force is introduced. The approach assumes that a specific dressed six-quark state (dressed dibaryon) is generated in NN collision at intermediate and short ranges. The new dressing mechanism providing π-, σ-, ρ- and ω-meson clouds around the six quark core is discussed. These novel components produce both strong intermediate-range attraction and short-range repulsion in the NN sector due to the s-channel exchange mechanism which is supplemented with conventional π- and 2π- Yukawa exchanges at intermediate and long ranges. The model developed is demonstrated to lead to numerous new effects and contributions in many fields of nuclear physics. (author)

  13. Basic hydraulics

    CERN Document Server

    Smith, P D

    1982-01-01

    BASIC Hydraulics aims to help students both to become proficient in the BASIC programming language by actually using the language in an important field of engineering and to use computing as a means of mastering the subject of hydraulics. The book begins with a summary of the technique of computing in BASIC together with comments and listing of the main commands and statements. Subsequent chapters introduce the fundamental concepts and appropriate governing equations. Topics covered include principles of fluid mechanics; flow in pipes, pipe networks and open channels; hydraulic machinery;

  14. Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes–2

    Directory of Open Access Journals (Sweden)

    Diego Muñoz-Torrero

    2017-12-01

    Full Text Available Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of Editorials, which are published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal Molecules [...

  15. Development of composite calcium hydroxide sorbent in mechanical operations and evaluation of its basic sorption properties

    Directory of Open Access Journals (Sweden)

    Gara Paweł

    2017-01-01

    Full Text Available This article presents the results of research carried out on the possibility of obtaining composite calcium hydroxide sorbent in the process of two-step granulation, containing additional compounds of Al, Mg and Fe, and their textural and sorption studies. For this purpose, attempts were undertaken to compact commercial calcium hydroxide powder with six additives in the laboratory roll press. The resulting compacts were crushed and sieved in order to achieve the assumed sieve fraction. Based on the obtained results, basic parameters of the process of formation of composite sorbent have been determined. Both, the selected composite sorbents fractions and additives were subsequently subjected to textural studies (determination of the specific surface area and porosity and sorption capacity performance. In addition, for the better interpretation of the results, thermogravimetric studies were carried out both for the additives and composite sorbents, as well as the grain size distribution of the additives. The results of the physicochemical tests of the obtained composite sorbents were compared with analogic results from the study on fine-grained hydroxide sorbent without additives and carbonate sorbent. The presented results showed that in a two-step granulation process it is possible to obtain the granular Ca(OH2 sorbent, as well as composite sorbents possessing better SO2 sorption capacity in comparison to the powder Ca(OH2 and/or to the calcium carbonate sorbent. This can be attributed to the combination of capability of the sorbent to appropriate thermal decomposition and the formation of a group of pores in the range of 0.07-0.3 microns.

  16. Nucleolar targeting of proteins by the tandem array of basic amino acid stretches identified in the RNA polymerase I-associated factor PAF49

    International Nuclear Information System (INIS)

    Ushijima, Ryujiro; Matsuyama, Toshifumi; Nagata, Izumi; Yamamoto, Kazuo

    2008-01-01

    There is accumulating evidence to indicate that the regulation of subnuclear compartmentalization plays important roles in cellular processes. The RNA polymerase I-associated factor PAF49 has been shown to accumulate in the nucleolus in growing cells, but disperse into the nucleoplasm in growth-arrested cells. Serial deletion analysis revealed that amino acids 199-338 were necessary for the nucleolar localization of PAF49. Combinatorial point mutation analysis indicated that the individual basic amino acid stretches (BS) within the central (BS1-4) and the C-terminal (BS5 and 6) regions may cooperatively confer the nucleolar localization of PAF49. Addition of the basic stretches in tandem to a heterologous protein, such as the interferon regulatory factor-3, translocated the tagged protein into the nucleolus, even in the presence of an intrinsic nuclear export sequence. Thus, tandem array of the basic amino acid stretches identified here functions as a dominant nucleolar targeting sequence

  17. Examination of the relationship between preservice science teachers' scientific reasoning and problem solving skills on basic mechanics

    Science.gov (United States)

    Yuksel, Ibrahim; Ates, Salih

    2018-02-01

    The purpose of this study is to determine relationship between scientific reasoning and mechanics problem solving skills of students in science education program. Scientific Reasoning Skills Test (SRST) and Basic Mechanics Knowledge Test (BMKT) were applied to 90 second, third and fourth grade students who took Scientific Reasoning Skills course at science teaching program of Gazi Faculty of Education for three successive fall semesters of 2014, 2015 and 2016 academic years. It was found a statistically significant positive (p = 0.038 <0.05) but a low correlation (r = 0.219) between SRST and BMKT. There were no significant relationship among Conservation Laws, Proportional Thinking, Combinational Thinking, Correlational Thinking, Probabilistic Thinking subskills of reasoning and BMKT. There were significant and positive correlation among Hypothetical Thinking and Identifying and Controlling Variables subskills of reasoning and BMKT. The findings of the study were compared with other studies in the field and discussed.

  18. Basic research on mechanism of BN inclusion in improving the machinability of steel

    Directory of Open Access Journals (Sweden)

    Ya-nan, Chen

    2014-12-01

    Full Text Available Boron nitride-added eco-friendly free cutting steel has recently drawn more and more attention. But, the mechanisms explaining the role of BN inclusions improving the machinability of steels is not very clear. In this investigation, the material removal mechanism for cutting of BN inclusions in steels is explored, using a combination of theoretical analysis and a series of experiments. First, the actual shape of BN inclusions is observed and the amount and distribution of BN inclusions is quantitatively analyzed. Subsequently, the cutting performance of the steel is determined by cutting experimental tests. Moreover, the micro mechanical properties and the material removal mechanisms for cutting of BN inclusions are investigated by means of nanoindentation. The results revealed that the BN inclusions are hexagonal and are uniformly distributed, their average content is 23.2 per unit area and their volume fraction is 0.51% in the steel with 74 ppm B and 180 ppm N. It is shown that BN inclusions can improve the cutting performance of steel significantly, and a model describing the material removal mechanism for cutting of BN inclusions is proposed. BN inclusions act as stress concentration source, lubrication and wrappage of hard particles.Los aceros de fácil mecanizado o corte libre con nitruro de boro agregado han despertado un gran interés. Sin embargo, aún no se han determinado los mecanismos que explican el papel de las inclusiones de BN en la mejora de la maquinabilidad de estos aceros. En este trabajo, se investigan los mecanismos de corte de las inclusiones BN en aceros mediante la combinación de un análisis teórico y una serie de experimentos. En primer lugar, se determina la morfología de las inclusiones BN y se analiza cuantitativamente la cantidad y distribución de las mismas. Posteriormente, el rendimiento de corte del acero se determina mediante ensayos de corte. Por otra parte, las propiedades mecánicas locales y los

  19. Basic Physical – Mechanical Properties of Geopolymers Depending on the Content of Ground Fly Ash and Fines of Sludge

    Directory of Open Access Journals (Sweden)

    Sičáková Alena

    2017-06-01

    Full Text Available The binding potential of fly ash (FA as a typical basic component of building mixtures can be improved in mechanical way, which unfolds new possibilities of its utilization. This paper presents the possibilities of preparing the geopolymer mixtures based on ground (dm = 31.0 μm FA, used in varying percentages to the original (unground; dm = 74.1 μm one. As a modification, fine-grain sludge from the process of washing the crushed aggregates was used as filler in order to obtain mortar-type material. The basic physical-mechanical properties of mixtures are presented and discussed in the paper, focusing on time dependence. The following standard tests were executed after 2, 7, 28, and 120 days: density, total water absorption, flexural strength, and compressive strength. Ground FA provided for positive effect in all tested parameters, while incorporation of fine portion of sludge into the geopolymer mixture does not offer a significant technical profit. On the other hand, it does not cause the decline in the properties, so the environmental effect (reduction of environmental burden can be applied through its incorporation into the geopolymer mixtures.

  20. Basic Physical - Mechanical Properties of Geopolymers Depending on the Content of Ground Fly Ash and Fines of Sludge

    Science.gov (United States)

    Sičáková, Alena; Števulová, Nadežda

    2017-06-01

    The binding potential of fly ash (FA) as a typical basic component of building mixtures can be improved in mechanical way, which unfolds new possibilities of its utilization. This paper presents the possibilities of preparing the geopolymer mixtures based on ground (dm = 31.0 μm) FA, used in varying percentages to the original (unground; dm = 74.1 μm) one. As a modification, fine-grain sludge from the process of washing the crushed aggregates was used as filler in order to obtain mortar-type material. The basic physical-mechanical properties of mixtures are presented and discussed in the paper, focusing on time dependence. The following standard tests were executed after 2, 7, 28, and 120 days: density, total water absorption, flexural strength, and compressive strength. Ground FA provided for positive effect in all tested parameters, while incorporation of fine portion of sludge into the geopolymer mixture does not offer a significant technical profit. On the other hand, it does not cause the decline in the properties, so the environmental effect (reduction of environmental burden) can be applied through its incorporation into the geopolymer mixtures.

  1. Theoretical Analysis of Pore Pressure Diffusion in Some Basic Rock Mechanics Experiments

    Science.gov (United States)

    Braun, Philipp; Ghabezloo, Siavash; Delage, Pierre; Sulem, Jean; Conil, Nathalie

    2018-05-01

    Non-homogeneity of the pore pressure field in a specimen is an issue for characterization of the thermo-poromechanical behaviour of low-permeability geomaterials, as in the case of the Callovo-Oxfordian claystone ( k radioactive waste disposal in France. In tests with drained boundary conditions, excess pore pressure can result in significant errors in the measurement of material parameters. Analytical solutions are presented for the change in time of the pore pressure field in a specimen submitted to various loading paths and different rates. The pore pressure field in mechanical and thermal undrained tests is simulated with a 1D finite difference model taking into account the dead volume of the drainage system of the triaxial cell connected to the specimen. These solutions provide a simple and efficient tool for the estimation of the conditions that must hold for reliable determination of material parameters and for optimization of various test conditions to minimize the experimental duration, while keeping the measurement errors at an acceptable level.

  2. Basic Characteristics of Hemimorphite and Its Transformation Mechanism with Na2CO3

    Directory of Open Access Journals (Sweden)

    Qihong Wang

    2018-04-01

    Full Text Available The crystal of hemimorphite is a non-conductor. The Si–O bond in the crystal is strong, whereas the Zn–O bond is weak. These properties lead to the easy breakage of the Zn–O bond in the crushing process of hemimorphite. Thus, the interaction between minerals and polar water molecules is strong, and natural floatability of ores is poor. This study systematically investigated the characteristics of hemimorphite and its action mechanism with Na2CO3. Results of SEM-EDS showed that the surface of hemimorphite dissolved after interacting with Na2CO3, and the contents of Si and O decreased, whereas Zn and C increased. XPS analysis showed that the carbonate group was detected. The interaction between CO32− and hemimorphite was calculated using the first principles calculation based on density functional theory. The results indicate that an O atom in CO32− interacted with Zn2+ from the (100 plane of hemimorphite. The interaction between Zn and O atoms was not strong, and the Zn atoms were not completely displaced, which was proven by density of state analysis and the EDS and XPS results. The Mulliken population showed that the O–Zn bond was the atomic bonding of CO32− with Zn2+ and exhibited properties of ionic bonds. Thus, hemimorphite transformed to smithsonite-like mineral (ZnCO3 when acting with CO32−.

  3. Basic mechanisms of atomic displacement production in cubic silicon carbide: A molecular dynamics study

    International Nuclear Information System (INIS)

    Malerba, L.; Perlado, J.M.

    2002-01-01

    Studying the effects of radiation in silicon carbide (SiC) is important for its possible use in both nuclear and electronic technology. One of the most important parameters to describe radiation damage in a material is the threshold displacement energy (TDE). In this paper, the computational technique known as molecular dynamics (MD) is used to determine the TDE's along different crystallographic directions for Si and C atoms in SiC, also allowing for irradiation temperature effects, and to study in detail the mechanisms of atomic displacement production in this material. For this purpose, the widely tested Tersoff potential, implemented in a MD code optimized to study the interaction of high-energy ions with crystals, is used to describe the interatomic forces in SiC. It is found that it is difficult to define a single threshold for this material. Instead, the introduction of two thresholds, upper and lower, becomes necessary. These two thresholds delimit an uncertainty band, within which the displacement may or may not be produced, because the Frenkel pairs generated in such a transferred-kinetic-energy range are metastable. The Arrhenius law expressing the lifetime of one of these metastable defects has also been deduced from the simulation. Finally, on the basis of the results of the simulation, possible values for the recombination distance and the average threshold energy (E d,Si and E d,C ) in SiC are proposed and discussed

  4. Relating Deformation and Thermodynamics: An Opportunity for Rethinking Basic Concepts of Continuum Mechanics

    Directory of Open Access Journals (Sweden)

    Giuseppe Guzzetta

    2013-06-01

    Full Text Available In order to treat deformation as one of the processes taking place in an irreversible thermodynamic transformation, two main conditions must be satisfied: (1 strain and stress should be defined in such a way that the modification of the symmetry of these tensorial quantities reflects that of the structure of the actual material of which the deforming ideal continuum is the counterpart; and (2 the unique decomposition of the above tensors into the algebraic sum of an isotropic and an anisotropic part with different physical meanings should be recognized. The first condition allows the distinction of the energy balance in irrotational and rotational deformations; the second allows the description of a thermodynamic transformation involving deformation as a function of both process quantities, whose values depend on the specific transition, or path, between two equilibrium states, and of state quantities, which describe equilibrium states of a system quantitatively. One of the main conclusions that can be drawn is that, dealing with deformable materials, the quantities that must appear in thermodynamic equations cannot be tensorial quantities, such as the stress tensor and the infinitesimal or finite strain tensor usually considered in continuum mechanics (or, even worse, their components. The appropriate quantities should be invariants involved by the strain and stress tensors here defined. Another important conclusion is that, from a thermodynamic point of view, the consideration of the measurable volume change occurring in an isothermal deformation does not itself give any meaningful information.

  5. Basic thermal-mechanical properties and thermal shock, fatigue resistance of swaged + rolled potassium doped tungsten

    Science.gov (United States)

    Zhang, Xiaoxin; Yan, Qingzhi; Lang, Shaoting; Xia, Min; Ge, Changchun

    2014-09-01

    The potassium doped tungsten (W-K) grade was achieved via swaging + rolling process. The swaged + rolled W-K alloy exhibited acceptable thermal conductivity of 159.1 W/m K and ductile-to-brittle transition temperature of about 873 K while inferior mechanical properties attributed to the coarse pores and small deformation degree. Then the thermal shock, fatigue resistance of the W-K grade were characterized by an electron beam facility. Thermal shock tests were conducted at absorbed power densities varied from 0.22 to 1.1 GW/m2 in a step of 0.22 GW/m2. The cracking threshold was in the range of 0.44-0.66 GW/m2. Furthermore, recrystallization occurred in the subsurface of the specimens tested at 0.66-1.1 GW/m2 basing on the analysis of microhardness and microstructure. Thermal fatigue tests were performed at 0.44 GW/m2 up to 1000 cycles and no cracks emerged throughout the tests. Moreover, recrystallization occurred after 1000 cycles.

  6. [Basic mechanisms of QRS voltage changes on ECG of healthy subjects during the exercise test].

    Science.gov (United States)

    Saltykova, M M

    2015-01-01

    Electrocardiography is the most commonly used technique for detection stress-induced myocardial ischemia. However, the sensitivity of ECG-criteria is not high. One of the major problem is the difficulty in differentiating ECG changes caused by various factors. The aim of this study was to evaluate the dependence of the QRS voltage changes during exercise on parameters of central hemodynamics, gender particularities and to reveal mechanisms causing these changes. To eliminate the effect of changes in cardiomyocytes transmembrane potentials under the influence of the neurotransmitters of the autonomic nervous system during stepwise increasing exercises and/or due to a lack of ATP results from inadequate myocardial blood flow only healthy subjects not older than 35 years were included in the study (7 men and 7 women) and only periods of ventricular depolarization (QRS complex on the ECG) were included in the analysis. We compared the changes of QRS waves during exercise sessions with two upper and one lower limbs in both men and women. The exercise load was twice bigger in exercise with one leg relative to exercise with two arms. Responses of heart rate and systolic arterial pressure were similar. Amplitude of S-wave in left chest leads significantly increased in both sessions without significant difference between augmentations in the sessions and in groups of men and women. Significant relationship between the S wave augmentation and the peak systolic arterial pressure were revealed. Furthermore, the QRS changes during the exercise with vertical and a horizontal torso position were compared to assess the impact of diastolic arterial pressure and displacement of the diaphragm and heart rotation due to increase of abdominal pressure during the last steps of exercise. The obtained results allow us to exclude the impact of the heart position and size changes, as well as the exercise load on S-wave changes and make a conclusion about the dependence of this parameter on

  7. Absolute Configuration Determination by Quantum Mechanical Calculation of Chiroptical Spectra: Basics and Applications to Fungal Metabolites.

    Science.gov (United States)

    Superchi, Stefano; Scafato, Patrizia; Gorecki, Marcin; Pescitelli, Gennaro

    2018-01-01

    Quantum mechanical simulations of chiroptical properties, such as electronic circular dichroism (ECD), optical rotation (OR), and vibrational circular dichroism (VCD), have rapidly become very popular to assign the absolute configuration of novel natural products. We review the application of the ECD/OR/VCD computational methodology to chiral metabolites of fungal origin. First, we summarize the fundamentals of the three spectroscopies; then, we focus on the specific experimental and computational issues allied to the application of their calculations. We surveyed the entire literature describing the use of ECD/OR/VCD computations for fungal metabolites, and catalogued all papers according to the method employed and to the structural family of compounds. Then, we chose several examples to illustrate the use of the techniques and highlight the practical application of the computational approach. Our literature survey demonstrates that the simulation of ECD/OR/VCD spectra is nowadays widespread and accessible also to non-experts, although a good computational practice is necessary to avoid wrong assignments. ECD is still the most common technique used in the context of fungal metabolites. OR and VCD may be profitably employed when the compound of interest lacks chromophoric groups. Our examples illustrate that the combination of two or more chiroptical methods is strongly advisable in some cases, especially in the presence of high conformational flexibility, where a single technique does not lead to a safe conclusion. The ECD/OR/VCD computational approach is a reliable and versatile method to assign the absolute configuration of fungal metabolites and related natural products. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Basic thermal–mechanical properties and thermal shock, fatigue resistance of swaged + rolled potassium doped tungsten

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xiaoxin; Yan, Qingzhi, E-mail: qzyan@ustb.edu.cn; Lang, Shaoting; Xia, Min; Ge, Changchun

    2014-09-15

    Highlights: • The potassium doped tungsten grade was achieved via swaging + rolling process. • The cracking threshold of the W–K alloy was in the range of 0.44–0.66 GW/m{sup 2}. • Recrystallization occurred at 0.66–1.1 GW/m{sup 2} during the thermal shock tests. • No cracks emerged during the thermal fatigue tests (0.44 GW/m{sup 2}, 1000 cycles). • Recrystallization occurred after 1000 cycles during the thermal fatigue tests. - Abstract: The potassium doped tungsten (W–K) grade was achieved via swaging + rolling process. The swaged + rolled W–K alloy exhibited acceptable thermal conductivity of 159.1 W/m K and ductile-to-brittle transition temperature of about 873 K while inferior mechanical properties attributed to the coarse pores and small deformation degree. Then the thermal shock, fatigue resistance of the W–K grade were characterized by an electron beam facility. Thermal shock tests were conducted at absorbed power densities varied from 0.22 to 1.1 GW/m{sup 2} in a step of 0.22 GW/m{sup 2}. The cracking threshold was in the range of 0.44–0.66 GW/m{sup 2}. Furthermore, recrystallization occurred in the subsurface of the specimens tested at 0.66–1.1 GW/m{sup 2} basing on the analysis of microhardness and microstructure. Thermal fatigue tests were performed at 0.44 GW/m{sup 2} up to 1000 cycles and no cracks emerged throughout the tests. Moreover, recrystallization occurred after 1000 cycles.

  9. Basic science and pathogenesis of ageing with HIV: potential mechanisms and biomarkers.

    Science.gov (United States)

    Lagathu, Claire; Cossarizza, Andrea; Béréziat, Véronique; Nasi, Milena; Capeau, Jacqueline; Pinti, Marcello

    2017-06-01

    : The increased prevalence of age-related comorbidities and mortality is worrisome in ageing HIV-infected patients. Here, we aim to analyse the different ageing mechanisms with regard to HIV infection. Ageing results from the time-dependent accumulation of random cellular damage. Epigenetic modifications and mitochondrial DNA haplogroups modulate ageing. In antiretroviral treatment-controlled patients, epigenetic clock appears to be advanced, and some haplogroups are associated with HIV infection severity. Telomere shortening is enhanced in HIV-infected patients because of HIV and some nucleoside analogue reverse transcriptase inhibitors. Mitochondria-related oxidative stress and mitochondrial DNA mutations are increased during ageing and also by some nucleoside analogue reverse transcriptase inhibitors. Overall, increased inflammation or 'inflammageing' is a major driver of ageing and could result from cell senescence with secreted proinflammatory mediators, altered gut microbiota, and coinfections. In HIV-infected patients, the level of inflammation and innate immunity activation is enhanced and related to most comorbidities and to mortality. This status could result, in addition to age, from the virus itself or viral protein released from reservoirs, from HIV-enhanced gut permeability and dysbiosis, from antiretroviral treatment, from frequent cytomegalovirus and hepatitis C virus coinfections, and also from personal and environmental factors, as central fat accumulation or smoking. Adaptive immune activation and immunosenescence are associated with comorbidities and mortality in the general population but are less predictive in HIV-infected patients. Biomarkers to evaluate ageing in HIV-infected patients are required. Numerous systemic or cellular inflammatory, immune activation, oxidative stress, or senescence markers can be tested in serum or peripheral blood mononuclear cells. The novel European Study to Establish Biomarkers of Human Ageing MARK

  10. Segmentation of foreground apple targets by fusing visual attention mechanism and growth rules of seed points

    Energy Technology Data Exchange (ETDEWEB)

    Qu, W.; Shang, W.; Shao, Y.; Wang, D.; Yu, X.; Song, H.

    2015-07-01

    Accurate segmentation of apple targets is one of the most important problems to be solved in the vision system of apple picking robots. This work aimed to solve the difficulties that background targets often bring to foreground targets segmentation, by fusing the visual attention mechanism and the growth rule of seed points. Background targets could be eliminated by extracting the ROI (region of interest) of apple targets; the ROI was roughly segmented on the HSV color space, and then each of the pixels was used as a seed growing point. The growth rule of the seed points was adopted to obtain the whole area of apple targets from seed growing points. The proposed method was tested with 20 images captured in a natural scene, including 54 foreground apple targets and approximately 84 background apple targets. Experimental results showed that the proposed method can remove background targets and focus on foreground targets, while the k-means algorithm and the chromatic aberration algorithm cannot. Additionally, its average segmentation error rate was 13.23%, which is 2.71% higher than that of the k-means algorithm and 2.95% lower than that of the chromatic aberration algorithm. In conclusion, the proposed method contributes to the vision system of apple-picking robots to locate foreground apple targets quickly and accurately under a natural scene. (Author)

  11. Rac1 in human diseases: The therapeutic potential of targeting Rac1 signaling regulatory mechanisms.

    Science.gov (United States)

    Marei, Hadir; Malliri, Angeliki

    2017-07-03

    Abnormal Rac1 signaling is linked to a number of debilitating human diseases, including cancer, cardiovascular diseases and neurodegenerative disorders. As such, Rac1 represents an attractive therapeutic target, yet the search for effective Rac1 inhibitors is still underway. Given the adverse effects associated with Rac1 signaling perturbation, cells have evolved several mechanisms to ensure the tight regulation of Rac1 signaling. Thus, characterizing these mechanisms can provide invaluable information regarding major cellular events that lead to aberrant Rac1 signaling. Importantly, this information can be utilized to further facilitate the development of effective pharmacological modulators that can restore normal Rac1 signaling. In this review, we focus on the pathological role of Rac1 signaling, highlighting the benefits and potential drawbacks of targeting Rac1 in a clinical setting. Additionally, we provide an overview of available compounds that target key Rac1 regulatory mechanisms and discuss future therapeutic avenues arising from our understanding of these mechanisms.

  12. Mechanisms involved in the transport of mercuric ions in target tissues

    Science.gov (United States)

    Bridges, Christy C.; Zalups, Rudolfs K.

    2016-01-01

    Mercury exists in the environment in various forms, all of which pose a risk to human health. Despite guidelines regulating the industrial release of mercury into the environment, humans continue to be exposed regularly to various forms of this metal via inhalation or ingestion. Following exposure, mercuric ions are taken up by and accumulate in numerous organs, including brain, intestine, kidney, liver, and placenta. In order to understand the toxicological effects of exposure to mercury, a thorough understanding of the mechanisms that facilitate entry of mercuric ions into target cells must first be obtained. A number of mechanisms for the transport of mercuric ions into target cells and organs have been proposed in recent years. However, the ability of these mechanisms to transport mercuric ions and the regulatory features of these carriers have not been characterized completely. The purpose of this review is to summarize the current findings related to the mechanisms that may be involved in the transport of inorganic and organic forms of mercury in target tissues and organs. This review will describe mechanisms known to be involved in the transport of mercury and will also propose additional mechanisms that may potentially be involved in the transport of mercuric ions into target cells. PMID:27422290

  13. Atherosclerotic plaque targeting mechanism of long-circulating nanoparticles established by multimodal imaging

    DEFF Research Database (Denmark)

    Lobatto, Mark E; Calcagno, Claudia; Millon, Antoine

    2015-01-01

    Atherosclerosis is a major cause of global morbidity and mortality that could benefit from novel targeted therapeutics. Recent studies have shown efficient and local drug delivery with nanoparticles, although the nanoparticle targeting mechanism for atherosclerosis has not yet been fully elucidated...... enhanced magnetic resonance imaging and nanoparticle plaque accumulation with subsequent nanoparticle distribution throughout the vessel wall. These key observations will enable the development of nanotherapeutic strategies for atherosclerosis....

  14. Basic Retention Mechanisms

    DEFF Research Database (Denmark)

    Jensen, Bror Skytte; Jensen, H.

    1986-01-01

    The effect of multiple cation competition on the adsorption of Sr onto two synthetic ion-exchange resins, i. e. DOWEX 50W and DOWEX CCR-2, as well as onto the clay mineral, kaolinite has been studied. The results for DOWEX 50W, and under certain experimental conditions also for DOWEX CCR-2 were...

  15. A universal entropy-driven mechanism for thioredoxin–target recognition

    Science.gov (United States)

    Palde, Prakash B.; Carroll, Kate S.

    2015-01-01

    Cysteine residues in cytosolic proteins are maintained in their reduced state, but can undergo oxidation owing to posttranslational modification during redox signaling or under conditions of oxidative stress. In large part, the reduction of oxidized protein cysteines is mediated by a small 12-kDa thiol oxidoreductase, thioredoxin (Trx). Trx provides reducing equivalents for central metabolic enzymes and is implicated in redox regulation of a wide number of target proteins, including transcription factors. Despite its importance in cellular redox homeostasis, the precise mechanism by which Trx recognizes target proteins, especially in the absence of any apparent signature binding sequence or motif, remains unknown. Knowledge of the forces associated with the molecular recognition that governs Trx–protein interactions is fundamental to our understanding of target specificity. To gain insight into Trx–target recognition, we have thermodynamically characterized the noncovalent interactions between Trx and target proteins before S-S reduction using isothermal titration calorimetry (ITC). Our findings indicate that Trx recognizes the oxidized form of its target proteins with exquisite selectivity, compared with their reduced counterparts. Furthermore, we show that recognition is dependent on the conformational restriction inherent to oxidized targets. Significantly, the thermodynamic signatures for multiple Trx targets reveal favorable entropic contributions as the major recognition force dictating these protein–protein interactions. Taken together, our data afford significant new insight into the molecular forces responsible for Trx–target recognition and should aid the design of new strategies for thiol oxidoreductase inhibition. PMID:26080424

  16. Mechanism of SOS-induced targeted and untargeted mutagenesis in E. coli

    International Nuclear Information System (INIS)

    Maenhaut-Michel, G.

    1985-01-01

    This paper retraces the evolution of hypotheses concerning mechanisms of SOS induced mutagenesis. Moreover, it reports some recent data which support a new model for the mechanism of targeted and untargeted mutagenesis in E. coli. In summary, the SOS mutator effect, which is responsible for untargeted mutagenesis and perhaps for the misincorporation step in targeted mutagenesis, is believed to involve a fidelity function associated with DNA polymerase III and does not require the umuC gene product. umuC and umuD gene products are probably required specifically for elongation of DNA synthesis past blocking lesions, i.e. to allow mutagenic replication of damaged DNA

  17. Basic features of electromagnetic pulse generated in a laser-target chamber at 3-TW laser facility PALS

    International Nuclear Information System (INIS)

    De Marco, M; Pfeifer, M; Krousky, E; Krasa, J; Cikhardt, J; Klir, D; Nassisi, V

    2014-01-01

    We describe the radiofrequency emission taking place when 300 ps laser pulses irradiate various solid targets with an intensity of 10 16 W/cm 2 . The emission of intense electromagnetic pulses was observed outside the laser target chamber by two loop antennas up to 1 GHz. Electromagnetic pulses can be 800 MHz transients, which decay from a peak electromagnetic field of E 0 ≊ 7 kV/m and H 0 ≊ 15 A/m. The occurrence of these electromagnetic pulses is associated with generation of hard x-rays with photon energies extending beyond 1 MeV. This contribution reports the first observation of this effect at the PALS facility.

  18. Virtual laboratory learning media development to improve science literacy skills of mechanical engineering students on basic physics concept of material measurement

    Science.gov (United States)

    Jannati, E. D.; Setiawan, A.; Siahaan, P.; Rochman, C.

    2018-05-01

    This study aims to determine the description of virtual laboratory learning media development to improve science literacy skills of Mechanical Engineering students on the concept of basic Physics. Quasi experimental method was employed in this research. The participants of this research were first semester students of mechanical engineering in Majalengka University. The research instrument was readability test of instructional media. The results of virtual laboratory learning media readability test show that the average score is 78.5%. It indicates that virtual laboratory learning media development are feasible to be used in improving science literacy skill of Mechanical Engineering students in Majalengka University, specifically on basic Physics concepts of material measurement.

  19. Mechanism of energy release from nucleus-target in hadron-nucleus collision

    International Nuclear Information System (INIS)

    Strugalski, Z.; Strugalska-Gola, E.

    2000-01-01

    The collisions of hadrons (protons, mesons) with 131 Xe nucleus and arising light nuclear fragments as nuclear refraction products have been observed in bubble chamber. Mechanism of energy release during these collisions has been discussed. The quantitative calculations has proved that this phenomena can be treated as potential energy source with use of many different target materials

  20. Manifestations and mechanisms of non-targeted effects of ionizing radiation

    International Nuclear Information System (INIS)

    Wright, Eric G.

    2010-01-01

    A well-established radiobiological paradigm is that the biological effects of ionizing radiation occur in irradiated cells as a consequence of the DNA damage they incur. However, many observations of, so-called, non-targeted effects indicate that genetic alterations are not restricted to directly irradiated cells. Non-targeted effects are responses exhibited by non-irradiated cells that are the descendants of irradiated cells (radiation-induced genomic instability) or by cells that have communicated with irradiated cells (radiation-induced bystander effects). Radiation-induced genomic instability is characterized by chromosomal abnormalities, gene mutations and cell death. Similar effects, as well as responses that may be regarded as protective, have been attributed to bystander mechanisms. The majority of studies to date have used in vitro systems but some non-targeted effects have been demonstrated in vivo and there is also evidence for radiation-induced instability in the mammalian germ line. However, there may be situations where radiation-induced genomic instability in vivo may not necessarily identify genomically unstable somatic cells but the manifestation of responses to ongoing production of damaging signals generated by genotype-dependent mechanisms having properties in common with inflammatory processes. Non-targeted mechanisms have significant implications for understanding mechanisms of radiation action but the current state of knowledge does not permit definitive statements about whether these phenomena have implications for assessing radiation risk.

  1. Mastery versus the standard proficiency target for basic laparoscopic skill training: effect on skill transfer and retention.

    Science.gov (United States)

    Kolozsvari, Nicoleta O; Kaneva, Pepa; Brace, Chantalle; Chartrand, Genevieve; Vaillancourt, Marilou; Cao, Jiguo; Banaszek, Daniel; Demyttenaere, Sebastian; Vassiliou, Melina C; Fried, Gerald M; Feldman, Liane S

    2011-07-01

    Little evidence exists to guide educators in the best way to implement simulation within surgical skills curricula. This study investigated whether practicing a basic Fundamentals of Laparoscopic Surgery (FLS) simulator task [peg transfer (PT)] facilitates learning a more complex skill [intracorporeal suturing (ICS)] and compared the effect of PT training to mastery with training to the passing level on PT retention and on learning ICS. For this study, 98 surgically naïve subjects were randomized to one of three PT training groups: control, standard training, and overtraining. All the participants then trained in ICS. The learning curves for ICS were analyzed by estimating the learning plateau and rate using nonlinear regression. Skill retention was assessed by retesting participants 1 month after training. The groups were compared using analysis of variance (ANOVA). Effectiveness of skill transfer was calculated using the transfer effectiveness ratio (TER). Data are presented as mean±standard deviation (pstandard, and 23 overtrained subjects). The ICS learning plateau rose with increasing PT training (452±10 vs. 459±10 vs. 467±10; p0.5). The PT training took 20±10 min for standard training and 39±20 min for overtraining (pstandard training group, suggesting that PT overtraining took longer than the time saved on ICS training. For surgically naïve subjects, part-task training with PT alone was associated with slight improvements in the learning curve for ICS. However, overtraining with PT did not improve skill retention, and peg training alone was not an efficient strategy for learning ICS.

  2. From light polarization to the basic ideas of Quantum Mechanics. Experience carried out in a Technical Institute in Scampia (Naples)

    International Nuclear Information System (INIS)

    Moretti, M.

    2014-01-01

    The article focuses on teaching/learning Quantum Mechanics (QM) in secondary schools and involves two fundamental aspects: teacher training and experimentation in the classroom, carefully reflecting on the content and highlighting innovation in the teaching methodology. The experience of training took place within a second level post-graduate Master course for Physics teachers (The II level post-graduate Master course in Didactic Innovation in Physics and Guidance (Innovazione Didattica in Fisica e Orientamento IDIFO) http://www.fisica.uniud.it/ URDF/laurea/index.htm) is directed by M. Michelini. The University of Udine organizes the course with the collaboration of the Physiscs Education Research Groups of eighteen Italian Universities, and is a part of a training project addressed to physics teachers focused on modern physics. IDIFO is part of a national plan of the Ministry of Education, Research and University for the Scientific Degrees project (Piano Lauree Scientifiche)), based on a module dedicated to teaching/learning QM according to the fundamental concepts of Dirac theory. The teacher achieved formation attending three e-learning courses about teaching/learning quantum mechanics in secondary schools, researching and discussing research materials of physics education, planning an intervention module and experimenting in a real classroom the planned innovative path for a situated formation. The experimentation, carried out in a fifth class of a Technical Institute at Scampia (Naples), made the conclusive phase and gave data concerning the thinking ways of the students about some basic concepts of QM collected and evaluated. In particular, average students focused more the functional/applicative aspects of formal and conceptual constructs rather than on their physical meanings.

  3. Electric and mechanical basic parameters to elaborate a process for a technical verification of safety related design modifications

    International Nuclear Information System (INIS)

    Lamuno Fernandez, Mercedes; La Roca Mallofre, GISEL; Bano Azcon, Alberto

    2010-01-01

    This paper presents a systematic process to check a design in order to achieve all the requirements that regulations demand. Nuclear engineers must verify that a design is done according to the safety requirements, and this paper presents how we have elaborated a process to improve the technical project verification. For a faster, better and easier verification process, here we summarize how to select the electric and mechanical basic parameters, which ensure the correct project verification of safety related design modifications. This process considers different aspects, which guarantee that the design preserves the availability, reliability and functional capability of the Structures, Systems and Components needed to operate the Nuclear Power Station with security. Electric and mechanical reference parameters are identified and discussed as well as others related ones, which are critical to safety. The implementation procedure to develop tasks performed in any company that has a quality plan is a requirement. On the engineering business, it is important not to use the personal criteria to do a technical analysis of a project; although, many times it is the checker's criteria and knowledge responsibility to ensure the correct development of a design modification. Then, the checker capabilities are the basis of the modification verification. This kind of procedure's development is not easy, because in an engineering project with important technical contents, there are multiple scenarios, but lots of them have a common basis. If we can identify the technical common basis of these projects, we will make good project verification but there are many difficulties we can encounter along this process. (authors)

  4. Effect of viscosity, basicity and organic content of composite flocculant on the decolorization performance and mechanism for reactive dyeing wastewater

    Institute of Scientific and Technical Information of China (English)

    Yuanfang Wang; Baoyu Gao; Qinyan Yue; Yah Wang

    2011-01-01

    A coagulation/flocculation process using the composite floceulant polyaluminum chloride-epichlorohydrin dimethylamine (PAC-EPI-DMA) was employed for the treatment of an anionic azo dye (Reactive Brilliant Red K-2BP dye).The effect of viscosity (η),basicity (B =[OH]/[Al]) and organic content (Wp) on the flocculation performance as well as the mechanism of PAC-EPI-DMA flocculant were investigated.The η was the key factor affecting the dye removal efficiency of PAC-EPI-DMA.PAC-EPI-DMA with an intermediate η (2400 mPa-sec) gave higher decolorization efficiency by adsorption bridging and charge neutralization due to the co-effect of PAC and EPI-DMA polymers.The Wp of the composite flocculant was a minor important factor for the flocculation.The adsorption bridging of PAC-EPI-DMA with η of 300 or 4300 mPa.sec played an important role with the increase of Wp,whereasthe charge neutralization of them was weaker with the increase of Wp.There was interaction between Wp and B on the removal of reactive dye.The composite flocculant with intermediate viscosity and organic content was effective for the treatment of reactive dyeing wastewater,which could achieve high reactive dye removal efficiency with low organic dosage.

  5. Internal and External Triggering Mechanism of "Smart" Nanoparticle-Based DDSs in Targeted Tumor Therapy.

    Science.gov (United States)

    Qiana, Xian-Ling; Li, Jun; Wei, Ran; Lin, Hui; Xiong, Li-Xia

    2018-05-09

    Anticancer chemotherapeutics have a lot of problems via conventional drug delivery systems (DDSs), including non-specificity, burst release, severe side-effects, and damage to normal cells. Owing to its potential to circumventing these problems, nanotechnology has gained increasing attention in targeted tumor therapy. Chemotherapeutic drugs or genes encapsulated in nanoparticles could be used to target therapies to the tumor site in three ways: "passive", "active", and "smart" targeting. To summarize the mechanisms of various internal and external "smart" stimulating factors on the basis of findings from in vivo and in vitro studies. A thorough search of PubMed was conducted in order to identify the majority of trials, studies and novel articles related to the subject. Activated by internal triggering factors (pH, redox, enzyme, hypoxia, etc.) or external triggering factors (temperature, light of different wavelengths, ultrasound, magnetic fields, etc.), "smart" DDSs exhibit targeted delivery to the tumor site, and controlled release of chemotherapeutic drugs or genes. In this review article, we summarize and classify the internal and external triggering mechanism of "smart" nanoparticle-based DDSs in targeted tumor therapy, and the most recent research advances are illustrated for better understanding. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. High-resolution remotely sensed small target detection by imitating fly visual perception mechanism.

    Science.gov (United States)

    Huang, Fengchen; Xu, Lizhong; Li, Min; Tang, Min

    2012-01-01

    The difficulty and limitation of small target detection methods for high-resolution remote sensing data have been a recent research hot spot. Inspired by the information capture and processing theory of fly visual system, this paper endeavors to construct a characterized model of information perception and make use of the advantages of fast and accurate small target detection under complex varied nature environment. The proposed model forms a theoretical basis of small target detection for high-resolution remote sensing data. After the comparison of prevailing simulation mechanism behind fly visual systems, we propose a fly-imitated visual system method of information processing for high-resolution remote sensing data. A small target detector and corresponding detection algorithm are designed by simulating the mechanism of information acquisition, compression, and fusion of fly visual system and the function of pool cell and the character of nonlinear self-adaption. Experiments verify the feasibility and rationality of the proposed small target detection model and fly-imitated visual perception method.

  7. High-Resolution Remotely Sensed Small Target Detection by Imitating Fly Visual Perception Mechanism

    Directory of Open Access Journals (Sweden)

    Fengchen Huang

    2012-01-01

    Full Text Available The difficulty and limitation of small target detection methods for high-resolution remote sensing data have been a recent research hot spot. Inspired by the information capture and processing theory of fly visual system, this paper endeavors to construct a characterized model of information perception and make use of the advantages of fast and accurate small target detection under complex varied nature environment. The proposed model forms a theoretical basis of small target detection for high-resolution remote sensing data. After the comparison of prevailing simulation mechanism behind fly visual systems, we propose a fly-imitated visual system method of information processing for high-resolution remote sensing data. A small target detector and corresponding detection algorithm are designed by simulating the mechanism of information acquisition, compression, and fusion of fly visual system and the function of pool cell and the character of nonlinear self-adaption. Experiments verify the feasibility and rationality of the proposed small target detection model and fly-imitated visual perception method.

  8. Target duality in N= 8 superconformal mechanics and the coupling of dual pairs

    Energy Technology Data Exchange (ETDEWEB)

    Gonzales, Marcelo [Carrera de Física Universidad Autónoma Tomás Frías, Av. Del Maestro s/n, Casilla 36, Potosí (Bolivia, Plurinational State of); Khodaee, Sadi; Toppan, Francesco [TEO, CBPF Rua Dr. Xavier Sigaud 150 (Urca), Rio de Janeiro (RJ), cep 22290-180 (Brazil); Lechtenfeld, Olaf [Institut für Theoretische Physik and Riemann Center for Geometry and Physics, Leibniz Universität Hannover, Appelstraße 2, 30167 Hannover (Germany); Centre for Quantum Engineering and Space-Time Research, Leibniz Universität Hannover, Welfengarten 1, 30167 Hannover (Germany)

    2013-07-15

    We couple dual pairs of N= 8 superconformal mechanics with conical targets of dimension d and 8−d. The superconformal coupling generates an oscillator-type potential on each of the two target factors, with a frequency depending on the respective dual coordinates. In the case of the inhomogeneous (3,8,5) model, which entails a monopole background, it is necessary to add an extra supermultiplet of constants for half of the supersymmetry. The N= 4 analog, joining an inhomogeneous (1,4,3) with a (3,4,1) multiplet, is also analyzed in detail.

  9. Microwave radiation mechanism in a pulse-laser-irradiated Cu foil target revisited

    International Nuclear Information System (INIS)

    Chen Ziyu; Li Jianfeng; Li Jun; Peng Qixian

    2011-01-01

    The microwave radiation mechanism in a Cu-based foil target irradiated by an intense laser pulse has been investigated. Microwave emission in the frequency range 0.5-4 GHz has been observed from a 200 ps laser pulse of intensity about 10 12 W cm -2 normally incident on the target surface. The total microwave power and energy emitted from the interaction were found to be about 0.4 W and 2 nJ, respectively, corresponding to an efficiency of coupling laser energy to microwave energy of 2x10 -8 . The result agrees well with quadrupole radiation calculated based on a circuit model of a laser plasma, which indicates that the radiative process can be explained by magnetic dipole or electric quadrupole radiation from the laser-produced symmetric poloidal current distribution at the plasma-target interface.

  10. Microwave radiation mechanism in a pulse-laser-irradiated Cu foil target revisited

    Energy Technology Data Exchange (ETDEWEB)

    Chen Ziyu; Li Jianfeng; Li Jun; Peng Qixian, E-mail: ziyuch@gmail.com [Institute of Fluid Physics, China Academy of Engineering Physics, Mianyang 621900 (China)

    2011-05-01

    The microwave radiation mechanism in a Cu-based foil target irradiated by an intense laser pulse has been investigated. Microwave emission in the frequency range 0.5-4 GHz has been observed from a 200 ps laser pulse of intensity about 10{sup 12} W cm{sup -2} normally incident on the target surface. The total microwave power and energy emitted from the interaction were found to be about 0.4 W and 2 nJ, respectively, corresponding to an efficiency of coupling laser energy to microwave energy of 2x10{sup -8}. The result agrees well with quadrupole radiation calculated based on a circuit model of a laser plasma, which indicates that the radiative process can be explained by magnetic dipole or electric quadrupole radiation from the laser-produced symmetric poloidal current distribution at the plasma-target interface.

  11. Structure-mechanism-based engineering of chemical regulators targeting distinct pathological factors in Alzheimer's disease.

    Science.gov (United States)

    Beck, Michael W; Derrick, Jeffrey S; Kerr, Richard A; Oh, Shin Bi; Cho, Woo Jong; Lee, Shin Jung C; Ji, Yonghwan; Han, Jiyeon; Tehrani, Zahra Aliakbar; Suh, Nayoung; Kim, Sujeong; Larsen, Scott D; Kim, Kwang S; Lee, Joo-Yong; Ruotolo, Brandon T; Lim, Mi Hee

    2016-10-13

    The absence of effective therapeutics against Alzheimer's disease (AD) is a result of the limited understanding of its multifaceted aetiology. Because of the lack of chemical tools to identify pathological factors, investigations into AD pathogenesis have also been insubstantial. Here we report chemical regulators that demonstrate distinct specificity towards targets linked to AD pathology, including metals, amyloid-β (Aβ), metal-Aβ, reactive oxygen species, and free organic radicals. We obtained these chemical regulators through a rational structure-mechanism-based design strategy. We performed structural variations of small molecules for fine-tuning their electronic properties, such as ionization potentials and mechanistic pathways for reactivity towards different targets. We established in vitro and/or in vivo efficacies of the regulators for modulating their targets' reactivities, ameliorating toxicity, reducing amyloid pathology, and improving cognitive deficits. Our chemical tools show promise for deciphering AD pathogenesis and discovering effective drugs.

  12. Mechanisms of resistance to quinolones: target alterations, decreased accumulation and DNA gyrase protection.

    Science.gov (United States)

    Ruiz, Joaquim

    2003-05-01

    Quinolones are broad-spectrum antibacterial agents, commonly used in both clinical and veterinary medicine. Their extensive use has resulted in bacteria rapidly developing resistance to these agents. Two mechanisms of quinolone resistance have been established to date: alterations in the targets of quinolones, and decreased accumulation due to impermeability of the membrane and/or an overexpression of efflux pump systems. Recently, mobile elements have also been described, carrying the qnr gene, which confers resistance to quinolones.

  13. Mechanical activation of mammalian target of rapamycin pathway is required for cartilage development

    OpenAIRE

    Guan, Yingjie; Yang, Xu; Yang, Wentian; Charbonneau, Cherie; Chen, Qian

    2014-01-01

    Mechanical stress regulates development by modulating cell signaling and gene expression. However, the cytoplasmic components mediating mechanotransduction remain unclear. In this study, elimination of muscle contraction during chicken embryonic development resulted in a reduction in the activity of mammalian target of rapamycin (mTOR) in the cartilaginous growth plate. Inhibition of mTOR activity led to significant inhibition of chondrocyte proliferation, cartilage tissue growth, and express...

  14. Mechanisms and biomaterials in pH-responsive tumour targeted drug delivery: A review.

    Science.gov (United States)

    Kanamala, Manju; Wilson, William R; Yang, Mimi; Palmer, Brian D; Wu, Zimei

    2016-04-01

    As the mainstay in the treatment of various cancers, chemotherapy plays a vital role, but still faces many challenges, such as poor tumour selectivity and multidrug resistance (MDR). Targeted drug delivery using nanotechnology has provided a new strategy for addressing the limitations of the conventional chemotherapy. In the last decade, the volume of research published in this area has increased tremendously, especially with functional nano drug delivery systems (nanocarriers). Coupling a specific stimuli-triggered drug release mechanism with these delivery systems is one of the most prevalent approaches for improving therapeutic outcomes. Among the various stimuli, pH triggered delivery is regarded as the most general strategy, targeting the acidic extracellular microenvironment and intracellular organelles of solid tumours. In this review, we discuss recent advances in the development of pH-sensitive nanocarriers for tumour-targeted drug delivery. The review focuses on the chemical design of pH-sensitive biomaterials, which are used to fabricate nanocarriers for extracellular and/or intracellular tumour site-specific drug release. The pH-responsive biomaterials bring forth conformational changes in these nanocarriers through various mechanisms such as protonation, charge reversal or cleavage of a chemical bond, facilitating tumour specific cell uptake or drug release. A greater understanding of these mechanisms will help to design more efficient drug delivery systems to address the challenges encountered in conventional chemotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Mindfulness Training Targets Neurocognitive Mechanisms of Addiction at the Attention-Appraisal-Emotion Interface

    Science.gov (United States)

    Garland, Eric L.; Froeliger, Brett; Howard, Matthew O.

    2014-01-01

    Prominent neuroscience models suggest that addictive behavior occurs when environmental stressors and drug-relevant cues activate a cycle of cognitive, affective, and psychophysiological mechanisms, including dysregulated interactions between bottom-up and top-down neural processes, that compel the user to seek out and use drugs. Mindfulness-based interventions (MBIs) target pathogenic mechanisms of the risk chain linking stress and addiction. This review describes how MBIs may target neurocognitive mechanisms of addiction at the attention-appraisal-emotion interface. Empirical evidence is presented suggesting that MBIs ameliorate addiction by enhancing cognitive regulation of a number of key processes, including: clarifying cognitive appraisal and modulating negative emotions to reduce perseverative cognition and emotional arousal; enhancing metacognitive awareness to regulate drug-use action schema and decrease addiction attentional bias; promoting extinction learning to uncouple drug-use triggers from conditioned appetitive responses; reducing cue-reactivity and increasing cognitive control over craving; attenuating physiological stress reactivity through parasympathetic activation; and increasing savoring to restore natural reward processing. Treatment and research implications of our neurocognitive framework are presented. We conclude by offering a temporally sequenced description of neurocognitive processes targeted by MBIs through a hypothetical case study. Our neurocognitive framework has implications for the optimization of addiction treatment with MBIs. PMID:24454293

  16. Targeted toxicological screening for acidic, neutral and basic substances in postmortem and antemortem whole blood using simple protein precipitation and UPLC-HR-TOF-MS

    DEFF Research Database (Denmark)

    Telving, Rasmus; Hasselstrøm, Jørgen Bo; Andreasen, Mette Findal

    2016-01-01

    -HR-TOF-MS was achieved in one injection. This method covered basic substances, substances traditionally analyzed in negative ESI (e.g., salicylic acid), small highly polar substances such as beta- and gamma-hydroxybutyric acid (BHB and GHB, respectively) and highly non-polar substances such as amiodarone. The new method......A broad targeted screening method based on broadband collision-induced dissociation (bbCID) ultra-performance liquid chromatography high-resolution time-of-flight mass spectrometry (UPLC-HR-TOF-MS) was developed and evaluated for toxicological screening of whole blood samples. The acidic, neutral...... was performed on spiked whole blood samples and authentic postmortem and antemortem whole blood samples. For most of the basic drugs, the established cut-off limits were very low, ranging from 0.25ng/g to 50ng/g. The established cut-off limits for most neutral and acidic drugs, were in the range from 50ng...

  17. Targeting essential pathways in trypanosomatids gives insights into protozoan mechanisms of cell death

    Directory of Open Access Journals (Sweden)

    Fasel Nicolas

    2010-11-01

    Full Text Available Abstract Apoptosis is a normal component of the development and health of multicellular organisms. However, apoptosis is now considered a prerogative of unicellular organisms, including the trypanosomatids of the genera Trypanosoma spp. and Leishmania spp., causative agents of some of the most important neglected human diseases. Trypanosomatids show typical hallmarks of apoptosis, although they lack some of the key molecules contributing to this process in metazoans, like caspase genes, Bcl-2 family genes and the TNF-related family of receptors. Despite the lack of these molecules, trypanosomatids appear to have the basic machinery to commit suicide. The components of the apoptotic execution machinery of these parasites are slowly coming into light, by targeting essential processes and pathways with different apoptogenic agents and inhibitors. This review will be confined to the events known to drive trypanosomatid parasites to apoptosis.

  18. Fetal Alcohol Spectrum Disorder (FASD) Associated Neural Defects: Complex Mechanisms and Potential Therapeutic Targets.

    Science.gov (United States)

    Muralidharan, Pooja; Sarmah, Swapnalee; Zhou, Feng C; Marrs, James A

    2013-06-19

    Fetal alcohol spectrum disorder (FASD), caused by prenatal alcohol exposure, can result in craniofacial dysmorphism, cognitive impairment, sensory and motor disabilities among other defects. FASD incidences are as high as 2% to 5 % children born in the US, and prevalence is higher in low socioeconomic populations. Despite various mechanisms being proposed to explain the etiology of FASD, the molecular targets of ethanol toxicity during development are unknown. Proposed mechanisms include cell death, cell signaling defects and gene expression changes. More recently, the involvement of several other molecular pathways was explored, including non-coding RNA, epigenetic changes and specific vitamin deficiencies. These various pathways may interact, producing a wide spectrum of consequences. Detailed understanding of these various pathways and their interactions will facilitate the therapeutic target identification, leading to new clinical intervention, which may reduce the incidence and severity of these highly prevalent preventable birth defects. This review discusses manifestations of alcohol exposure on the developing central nervous system, including the neural crest cells and sensory neural placodes, focusing on molecular neurodevelopmental pathways as possible therapeutic targets for prevention or protection.

  19. Fetal Alcohol Spectrum Disorder (FASD Associated Neural Defects: Complex Mechanisms and Potential Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    James A. Marrs

    2013-06-01

    Full Text Available Fetal alcohol spectrum disorder (FASD, caused by prenatal alcohol exposure, can result in craniofacial dysmorphism, cognitive impairment, sensory and motor disabilities among other defects. FASD incidences are as high as 2% to 5 % children born in the US, and prevalence is higher in low socioeconomic populations. Despite various mechanisms being proposed to explain the etiology of FASD, the molecular targets of ethanol toxicity during development are unknown. Proposed mechanisms include cell death, cell signaling defects and gene expression changes. More recently, the involvement of several other molecular pathways was explored, including non-coding RNA, epigenetic changes and specific vitamin deficiencies. These various pathways may interact, producing a wide spectrum of consequences. Detailed understanding of these various pathways and their interactions will facilitate the therapeutic target identification, leading to new clinical intervention, which may reduce the incidence and severity of these highly prevalent preventable birth defects. This review discusses manifestations of alcohol exposure on the developing central nervous system, including the neural crest cells and sensory neural placodes, focusing on molecular neurodevelopmental pathways as possible therapeutic targets for prevention or protection.

  20. TIM-3 as a Target for Cancer Immunotherapy and Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Wenwen Du

    2017-03-01

    Full Text Available Cancer immunotherapy has produced impressive clinical results in recent years. Despite the success of the checkpoint blockade strategies targeting cytotoxic T lymphocyte antigen 4 (CTLA-4 and programmed death receptor 1 (PD-1, a large portion of cancer patients have not yet benefited from this novel therapy. T cell immunoglobulin and mucin domain 3 (TIM-3 has been shown to mediate immune tolerance in mouse models of infectious diseases, alloimmunity, autoimmunity, and tumor Immunity. Thus, targeting TIM-3 emerges as a promising approach for further improvement of current immunotherapy. Despite a large amount of experimental data showing an immune suppressive function of TIM-3 in vivo, the exact mechanisms are not well understood. To enable effective targeting of TIM-3 for tumor immunotherapy, further in-depth mechanistic studies are warranted. These studies will also provide much-needed insight for the rational design of novel combination therapy with other checkpoint blockers. In this review, we summarize key evidence supporting an immune regulatory role of TIM-3 and discuss possible mechanisms of action.

  1. Integrated network analysis reveals potentially novel molecular mechanisms and therapeutic targets of refractory epilepsies.

    Directory of Open Access Journals (Sweden)

    Hongwei Chu

    Full Text Available Epilepsy is a complex neurological disorder and a significant health problem. The pathogenesis of epilepsy remains obscure in a significant number of patients and the current treatment options are not adequate in about a third of individuals which were known as refractory epilepsies (RE. Network medicine provides an effective approach for studying the molecular mechanisms underlying complex diseases. Here we integrated 1876 disease-gene associations of RE and located those genes to human protein-protein interaction (PPI network to obtain 42 significant RE-associated disease modules. The functional analysis of these disease modules showed novel molecular pathological mechanisms of RE, such as the novel enriched pathways (e.g., "presynaptic nicotinic acetylcholine receptors", "signaling by insulin receptor". Further analysis on the relationships between current drug targets and the RE-related disease genes showed the rational mechanisms of most antiepileptic drugs. In addition, we detected ten potential novel drug targets (e.g., KCNA1, KCNA4-6, KCNC3, KCND2, KCNMA1, CAMK2G, CACNB4 and GRM1 located in three RE related disease modules, which might provide novel insights into the new drug discovery for RE therapy.

  2. Epigenetic Mechanisms Regulating Adaptive Responses to Targeted Kinase Inhibitors in Cancer.

    Science.gov (United States)

    Angus, Steven P; Zawistowski, Jon S; Johnson, Gary L

    2018-01-06

    Although targeted inhibition of oncogenic kinase drivers has achieved remarkable patient responses in many cancers, the development of resistance has remained a significant challenge. Numerous mechanisms have been identified, including the acquisition of gatekeeper mutations, activating pathway mutations, and copy number loss or gain of the driver or alternate nodes. These changes have prompted the development of kinase inhibitors with increased selectivity, use of second-line therapeutics to overcome primary resistance, and combination treatment to forestall resistance. In addition to genomic resistance mechanisms, adaptive transcriptional and signaling responses seen in tumors are gaining appreciation as alterations that lead to a phenotypic state change-often observed as an epithelial-to-mesenchymal shift or reversion to a cancer stem cell-like phenotype underpinned by remodeling of the epigenetic landscape. This epigenomic modulation driving cell state change is multifaceted and includes modulation of repressive and activating histone modifications, DNA methylation, enhancer remodeling, and noncoding RNA species. Consequently, the combination of kinase inhibitors with drugs targeting components of the transcriptional machinery and histone-modifying enzymes has shown promise in preclinical and clinical studies. Here, we review mechanisms of resistance to kinase inhibition in cancer, with special emphasis on the rewired kinome and transcriptional signaling networks and the potential vulnerabilities that may be exploited to overcome these adaptive signaling changes.

  3. Acute myeloid leukemia-targeted toxin activates both apoptotic and necroptotic death mechanisms.

    Directory of Open Access Journals (Sweden)

    Henrick Horita

    Full Text Available BACKGROUND: Acute myelogenous leukemia (AML is the second most common leukemia with approximately 13,410 new cases and 8,990 deaths annually in the United States. A novel fusion toxin treatment, diphtheria toxin GM-CSF (DT-GMCSF has been shown to selectively eliminate leukemic repopulating cells that are critical for the formation of AML. We previously showed that DT-GMCSF treatment of U937 cells, an AML cell line, causes activation of caspases and the induction of apoptosis. METHODS AND FINDINGS: In this study we further investigate the mechanisms of cell death induced by DT-GMCSF and show that, in addition to the activation of caspase-dependent apoptosis, DT-GMCSF also kills AML cells by simultaneously activating caspase-independent necroptosis. These mechanisms depend on the ability of the targeted toxin to inhibit protein synthesis, and are not affected by the receptor that is targeted or the mechanism through which protein synthesis is blocked. CONCLUSIONS: We conclude that fusion toxin proteins may be effective for treating AML cells whether or not they are defective in apoptosis.

  4. A new type of liquid-3He target system using small mechanical refrigerators

    International Nuclear Information System (INIS)

    Kato, S.; Kobayashi, K.; Maruyama, K.; Okuno, H.; Konno, O.; Suda, T.; Maki, T.; Asami, H.; Koizumi, T.

    1991-04-01

    A new type of liquid- 3 He target has been developed for photoabsorption experiments at intermediate energies. Using the cooling power of liquid 4 He at reduced vapour pressure, 3 He gas is liquefied into a cylindrical target cell of 180 ml and is maintained at 2.0 K during the experiment. Evaporated 4 He gas is evacuated by a rotary pump and returned into the 4 He bath in the cryostat, where two small mechanical refrigerators with cooling capacities of 3 W at 4.3 K and 10 W at 20 K are operated for the purpose of 4 He recondensation. A maintenance-free operation of more than 1,000 hours has become possible by adopting the 4 He circulation system. (author)

  5. Mechanical activation of mammalian target of rapamycin pathway is required for cartilage development.

    Science.gov (United States)

    Guan, Yingjie; Yang, Xu; Yang, Wentian; Charbonneau, Cherie; Chen, Qian

    2014-10-01

    Mechanical stress regulates development by modulating cell signaling and gene expression. However, the cytoplasmic components mediating mechanotransduction remain unclear. In this study, elimination of muscle contraction during chicken embryonic development resulted in a reduction in the activity of mammalian target of rapamycin (mTOR) in the cartilaginous growth plate. Inhibition of mTOR activity led to significant inhibition of chondrocyte proliferation, cartilage tissue growth, and expression of chondrogenic genes, including Indian hedgehog (Ihh), a critical mediator of mechanotransduction. Conversely, cyclic loading (1 Hz, 5% matrix deformation) of embryonic chicken growth plate chondrocytes in 3-dimensional (3D) collagen scaffolding induced sustained activation of mTOR. Mechanical activation of mTOR occurred in serum-free medium, indicating that it is independent of growth factor or nutrients. Treatment of chondrocytes with Rapa abolished mechanical activation of cell proliferation and Ihh gene expression. Cyclic loading of chondroprogenitor cells deficient in SH2-containing protein tyrosine phosphatase 2 (Shp2) further enhanced mechanical activation of mTOR, cell proliferation, and chondrogenic gene expression. This result suggests that Shp2 is an antagonist of mechanotransduction through inhibition of mTOR activity. Our data demonstrate that mechanical activation of mTOR is necessary for cell proliferation, chondrogenesis, and cartilage growth during bone development, and that mTOR is an essential mechanotransduction component modulated by Shp2 in the cytoplasm. © FASEB.

  6. Mechanism of duplex DNA destabilization by RNA-guided Cas9 nuclease during target interrogation.

    Science.gov (United States)

    Mekler, Vladimir; Minakhin, Leonid; Severinov, Konstantin

    2017-05-23

    The prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9 (Cas9) endonuclease cleaves double-stranded DNA sequences specified by guide RNA molecules and flanked by a protospacer adjacent motif (PAM) and is widely used for genome editing in various organisms. The RNA-programmed Cas9 locates the target site by scanning genomic DNA. We sought to elucidate the mechanism of initial DNA interrogation steps that precede the pairing of target DNA with guide RNA. Using fluorometric and biochemical assays, we studied Cas9/guide RNA complexes with model DNA substrates that mimicked early intermediates on the pathway to the final Cas9/guide RNA-DNA complex. The results show that Cas9/guide RNA binding to PAM favors separation of a few PAM-proximal protospacer base pairs allowing initial target interrogation by guide RNA. The duplex destabilization is mediated, in part, by Cas9/guide RNA affinity for unpaired segments of nontarget strand DNA close to PAM. Furthermore, our data indicate that the entry of double-stranded DNA beyond a short threshold distance from PAM into the Cas9/single-guide RNA (sgRNA) interior is hindered. We suggest that the interactions unfavorable for duplex DNA binding promote DNA bending in the PAM-proximal region during early steps of Cas9/guide RNA-DNA complex formation, thus additionally destabilizing the protospacer duplex. The mechanism that emerges from our analysis explains how the Cas9/sgRNA complex is able to locate the correct target sequence efficiently while interrogating numerous nontarget sequences associated with correct PAMs.

  7. Mechanisms in endocrinology: micro-RNAs: targets for enhancing osteoblast differentiation and bone formation.

    Science.gov (United States)

    Taipaleenmäki, Hanna; Bjerre Hokland, Lea; Chen, Li; Kauppinen, Sakari; Kassem, Moustapha

    2012-03-01

    Osteoblast differentiation and bone formation (osteogenesis) are regulated by transcriptional and post-transcriptional mechanisms. Recently, a novel class of regulatory factors termed micro-RNAs (miRNAs) has been identified as playing an important role in the regulation of many aspects of osteoblast biology including proliferation, differentiation, metabolism and apoptosis. Also, preliminary data from animal disease models suggest that targeting miRNAs in bone can be a novel approach to increase bone mass. This review highlights the current knowledge of miRNA biology and their role in bone formation and discusses their potential use in future therapeutic applications for metabolic bone diseases.

  8. Target-oriented mechanisms of novel herbal therapeutics in the chemotherapy of gastrointestinal cancer and inflammation.

    Science.gov (United States)

    Ko, Joshua K; Auyeung, Kathy K

    2013-01-01

    A prominent group of effective cancer chemopreventive drugs has been derived from natural products having low toxicity while possessing apparent benefit in the disease process. It is plausible that there are multiple target molecules critical to cancer cell survival. Herbal terpenoids have demonstrated excellent target-specific anti-neoplastic functions by suppression of cell proliferation and induction of apoptosis. Transcriptional molecules in the NF-κB, MEK/ERK and PI3K/Akt/mTOR pathways are important molecular targets of chemotherapy that play distinctive roles in modulating the apoptosis cascades. It is recently suggested that NSAID-activated gene (NAG-1), a novel proapoptotic protein, is the upstream anti-carcinogenic target of NSAIDs, PPAR ligands and herbal chemotherapeutic agents that triggers some of the events mentioned above. Besides, angiogenesis, oxidative stress as well as inflammation are important factors that contribute to the development and metastasis of cancer, which could be actively modulated by novel agents of plant origin. The aim of the present review is to discuss and summarize the contemporary use of herbal therapeutics and phytochemicals in the treatment of human cancers, in particular that of the colon. The major events and signaling pathways in the carcinogenesis process being potentially modulated by natural products and novel herbal compounds will be evaluated, with emphasis on some terpenoids. Advances in eliciting the precise cellular and molecular mechanisms during the anti-tumorigenic process of novel herbal therapeutics will be of imperative clinical significance to increase the efficacy and reduce prominent adverse drug effects in cancer patients through target-specific therapy.

  9. Fc-receptor-mediated phagocytosis is regulated by mechanical properties of the target

    Science.gov (United States)

    Beningo, Karen A.; Wang, Yu-li

    2002-01-01

    Phagocytosis is an actin-based process used by macrophages to clear particles greater than 0.5 microm in diameter. In addition to its role in immunological responses, phagocytosis is also necessary for tissue remodeling and repair. To prevent catastrophic autoimmune reactions, phagocytosis must be tightly regulated. It is commonly assumed that the recognition/selection of phagocytic targets is based solely upon receptor-ligand binding. Here we report an important new criterion, that mechanical parameters of the target can dramatically affect the efficiency of phagocytosis. When presented with particles of identical chemical properties but different rigidity, macrophages showed a strong preference to engulf rigid objects. Furthermore, phagocytosis of soft particles can be stimulated with the microinjection of constitutively active Rac1 but not RhoA, and with lysophosphatidic acid, an agent known to activate the small GTP-binding proteins of the Rho family. These data suggest a Rac1-dependent mechanosensory mechanism for phagocytosis, which probably plays an important role in a number of physiological and pathological processes from embryonic development to autoimmune diseases.

  10. Molecular Mechanisms of Diabetic Retinopathy, General Preventive Strategies, and Novel Therapeutic Targets

    Science.gov (United States)

    Safi, Sher Zaman; Kumar, Selva; Ismail, Ikram Shah Bin

    2014-01-01

    The growing number of people with diabetes worldwide suggests that diabetic retinopathy (DR) and diabetic macular edema (DME) will continue to be sight threatening factors. The pathogenesis of diabetic retinopathy is a widespread cause of visual impairment in the world and a range of hyperglycemia-linked pathways have been implicated in the initiation and progression of this condition. Despite understanding the polyol pathway flux, activation of protein kinase C (KPC) isoforms, increased hexosamine pathway flux, and increased advanced glycation end-product (AGE) formation, pathogenic mechanisms underlying diabetes induced vision loss are not fully understood. The purpose of this paper is to review molecular mechanisms that regulate cell survival and apoptosis of retinal cells and discuss new and exciting therapeutic targets with comparison to the old and inefficient preventive strategies. This review highlights the recent advancements in understanding hyperglycemia-induced biochemical and molecular alterations, systemic metabolic factors, and aberrant activation of signaling cascades that ultimately lead to activation of a number of transcription factors causing functional and structural damage to retinal cells. It also reviews the established interventions and emerging molecular targets to avert diabetic retinopathy and its associated risk factors. PMID:25105142

  11. Nuclear-breakup mechanisms in the interaction of relativistic projectiles with heavy targets

    International Nuclear Information System (INIS)

    Steinberg, E.P.

    1982-01-01

    The breakup of a Au nucleus under bombardment with relativistic p, α, and 20 Ne has been investigated in an extensive, multi-detector study. The present discussion addresses some of the many aspects of the experimental results. A broad distribution of coincident fragment masses is observed, with the total fragment kinetic energy being higher than expected for a fission mechanism for total fragment mass less than or equal to 120. The formation of light fragments is shown to be inconsistent with a binary breakup mechanism, and a multi-fragment target breakup is suggested. In general, the results indicate a broad spectrum of violence in the collisions, from gentle, leading to the production of heavy spallation products and fission, to essentially explosive, leading to multi-fragment breakup into light mas products. These aspects of the reactions represent a late-stage breakup of the target residues and are positively correlated with the violence of the initial fast stage of the collision as measured by the charged particle multiplicity

  12. Methotrexate transport mechanisms: the basis for targeted drug delivery and ß-folate-receptor-specific treatment.

    Science.gov (United States)

    Fiehn, C

    2010-01-01

    Methotrexate (MTX) plays a pivotal role in the treatment of rheumatoid arthritis (RA). The transport mechanisms with which MTX reaches is target after application are an important part of MTX pharmacology and its concentration in target tissue such as RA synovial membrane might strongly influence the effectiveness of the drug. Physiological plasma protein binding of MTX to albumin is important for the distribution of MTX in the body and relative high concentrations of the drug are found in the liver. However, targeted drug delivery into inflamed joints and increased anti-arthritic efficiency can be obtained by covalent coupling of MTX ex-vivo to human serum albumin (MTX-HSA) or in-vivo to endogenous albumin mediated through the MTX-pro-drug AWO54. High expression of the folate receptor β (FR-β) on synovial macrophages of RA patients and its capacity to mediate binding and uptake of MTX has been demonstrated. To further improve drug treatment of RA, FR-β specific drugs have been developed and were characterised for their therapeutic potency in synovial inflammation. Therefore, different approaches to improve folate inhibitory and FR-β specific therapy of RA beyond MTX are in development and will be described.

  13. Muddled mechanisms: recent progress towards antimalarial target identification [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Rachel L. Edwards

    2016-10-01

    Full Text Available In the past decade, malaria rates have plummeted as a result of aggressive infection control measures and the adoption of artemisinin-based combination therapies (ACTs. However, a potential crisis looms ahead. Treatment failures to standard antimalarial regimens have been reported in Southeast Asia, and devastating consequences are expected if resistance spreads to the African continent. To prevent a potential public health emergency, the antimalarial arsenal must contain therapeutics with novel mechanisms of action (MOA. An impressive number of high-throughput screening (HTS campaigns have since been launched, identifying thousands of compounds with activity against one of the causative agents of malaria, Plasmodium falciparum. Now begins the difficult task of target identification, for which studies are often tedious, labor intensive, and difficult to interpret. In this review, we highlight approaches that have been instrumental in tackling the challenges of target assignment and elucidation of the MOA for hit compounds. Studies that apply these innovative techniques to antimalarial target identification are described, as well as the impact of the data in the field.

  14. ESAM: Endocrine inspired Sensor Activation Mechanism for multi-target tracking in WSNs

    Science.gov (United States)

    Adil Mahdi, Omar; Wahab, Ainuddin Wahid Abdul; Idris, Mohd Yamani Idna; Znaid, Ammar Abu; Khan, Suleman; Al-Mayouf, Yusor Rafid Bahar

    2016-10-01

    Target tracking is a significant application of wireless sensor networks (WSNs) in which deployment of self-organizing and energy efficient algorithms is required. The tracking accuracy increases as more sensor nodes are activated around the target but more energy is consumed. Thus, in this study, we focus on limiting the number of sensors by forming an ad-hoc network that operates autonomously. This will reduce the energy consumption and prolong the sensor network lifetime. In this paper, we propose a fully distributed algorithm, an Endocrine inspired Sensor Activation Mechanism for multi target-tracking (ESAM) which reflecting the properties of real life sensor activation system based on the information circulating principle in the endocrine system of the human body. Sensor nodes in our network are secreting different hormones according to certain rules. The hormone level enables the nodes to regulate an efficient sleep and wake up cycle of nodes to reduce the energy consumption. It is evident from the simulation results that the proposed ESAM in autonomous sensor network exhibits a stable performance without the need of commands from a central controller. Moreover, the proposed ESAM generates more efficient and persistent results as compared to other algorithms for tracking an invading object.

  15. Mechanisms and Implications of Dual-Acting Methotrexate in Folate-Targeted Nanotherapeutic Delivery

    Directory of Open Access Journals (Sweden)

    Pamela T. Wong

    2015-01-01

    Full Text Available The rational design of a nanoplatform in drug delivery plays a crucial role in determining its targeting specificity and efficacy in vivo. A conventional approach relies on the surface conjugation of a nanometer-sized particle with two functionally distinct types of molecules, one as a targeting ligand, and the other as a therapeutic agent to be delivered to the diseased cell. However, an alternative simplified approach can be used, in which a single type of molecule displaying dual function as both a targeting ligand and therapeutic agent is conjugated to the nanoparticle. In this review, we evaluate the validity of this new strategy by using methotrexate, which displays multifunctional mechanisms of action. Methotrexate binds to the folate receptor, a surface biomarker frequently overexpressed in tumor cells, and also inhibits dihydrofolate reductase, an enzyme critical for cell survival and division. Thus we describe a series of fifth generation poly(amido amine dendrimers conjugated with methotrexate, and discuss several lines of evidence supporting the efficacy of this new platform strategy based on surface plasmon resonance spectroscopy, enzyme activity assays, and cell-based studies with folate receptor (+ KB cancer cells.

  16. Tumor blood flow modifying effects of electrochemotherapy. A potential vascular targeted mechanism

    International Nuclear Information System (INIS)

    Sersa, G.; Cemazar, M.; Miklavcic, D.

    2003-01-01

    Background. The aim of this study was to determine the tumor blood flow modifying, and potential vascular targeted effect of electrochemotherapy with bleomycin or cisplatin. Materials and methods. Electrochemotherapy was performed by application of short intense electric pulses to the tumors after systemic administration of bleomycin or cisplatin. Evaluated were antitumor effectiveness of electrochemotherapy by tumor measurement, tumor blood flow modifying effect by Patent blue staining technique, and sensitivity of endothelial and tumor cells to the drugs and electrochemotherapy by clonogenicity assay. Results. Electrochemotherapy was effective in treatment of SA-1 tumors in A/J mice resulting in substantial tumor growth delay and also tumor cures. Tumor blood flow reduction following electrochemotherapy correlated well with its antitumor effectiveness. Virtually complete shut down of the tumor blood flow was observed already at 24 h after electrochemotherapy with bleomycin whereas only 50% reduction was observed after electrochemotherapy with cisplatin. Sensitivity of human endothelial HMEC-1 cells to electrochemotherapy suggests a vascular targeted effect for electrochemotherapy in vivo with bleomycin as well as with cisplatin. Conclusion. These results show that, in addition to direct electroporation of tumor cells, other vascular targeted mechanisms are involved in electrochemotherapy with bleomycin or cisplatin, potentially mediated by tumor blood flow reduction, and enhanced tumor cell death as a result of endothelial damage by electrochemotherapy. (author)

  17. Mechanism of ad5 vaccine immunity and toxicity: fiber shaft targeting of dendritic cells.

    Directory of Open Access Journals (Sweden)

    Cheng Cheng

    2007-02-01

    Full Text Available Recombinant adenoviral (rAd vectors elicit potent cellular and humoral immune responses and show promise as vaccines for HIV-1, Ebola virus, tuberculosis, malaria, and other infections. These vectors are now widely used and have been generally well tolerated in vaccine and gene therapy clinical trials, with many thousands of people exposed. At the same time, dose-limiting adverse responses have been observed, including transient low-grade fevers and a prior human gene therapy fatality, after systemic high-dose recombinant adenovirus serotype 5 (rAd5 vector administration in a human gene therapy trial. The mechanism responsible for these effects is poorly understood. Here, we define the mechanism by which Ad5 targets immune cells that stimulate adaptive immunity. rAd5 tropism for dendritic cells (DCs was independent of the coxsackievirus and adenovirus receptor (CAR, its primary receptor or the secondary integrin RGD receptor, and was mediated instead by a heparin-sensitive receptor recognized by a distinct segment of the Ad5 fiber, the shaft. rAd vectors with CAR and RGD mutations did not infect a variety of epithelial and fibroblast cell types but retained their ability to transfect several DC types and stimulated adaptive immune responses in mice. Notably, the pyrogenic response to the administration of rAd5 also localized to the shaft region, suggesting that this interaction elicits both protective immunity and vector-induced fevers. The ability of replication-defective rAd5 viruses to elicit potent immune responses is mediated by a heparin-sensitive receptor that interacts with the Ad5 fiber shaft. Mutant CAR and RGD rAd vectors target several DC and mononuclear subsets and induce both adaptive immunity and toxicity. Understanding of these interactions facilitates the development of vectors that target DCs through alternative receptors that can improve safety while retaining the immunogenicity of rAd vaccines.

  18. Basic Financial Accounting

    DEFF Research Database (Denmark)

    Wiborg, Karsten

    This textbook on Basic Financial Accounting is targeted students in the economics studies at universities and business colleges having an introductory subject in the external dimension of the company's economic reporting, including bookkeeping, etc. The book includes the following subjects...

  19. Aberrant regulation of DNA methylation in amyotrophic lateral sclerosis: a new target of disease mechanisms.

    Science.gov (United States)

    Martin, Lee J; Wong, Margaret

    2013-10-01

    Amyotrophic lateral sclerosis (ALS) is the third most common adult-onset neurodegenerative disease. A diagnosis is fatal owing to degeneration of motor neurons in brain and spinal cord that control swallowing, breathing, and movement. ALS can be inherited, but most cases are not associated with a family history of the disease. The mechanisms causing motor neuron death in ALS are still unknown. Given the suspected complex interplay between multiple genes, the environment, metabolism, and lifestyle in the pathogenesis of ALS, we have hypothesized that the mechanisms of disease in ALS involve epigenetic contributions that can drive motor neuron degeneration. DNA methylation is an epigenetic mechanism for gene regulation engaged by DNA methyltransferase (Dnmt)-catalyzed methyl group transfer to carbon-5 in cytosine residues in gene regulatory promoter and nonpromoter regions. Recent genome-wide analyses have found differential gene methylation in human ALS. Neuropathologic assessments have revealed that motor neurons in human ALS show significant abnormalities in Dnmt1, Dnmt3a, and 5-methylcytosine. Similar changes are seen in mice with motor neuron degeneration, and Dnmt3a was found abundantly at synapses and in mitochondria. During apoptosis of cultured motor neuron-like cells, Dnmt1 and Dnmt3a protein levels increase, and 5-methylcytosine accumulates. Enforced expression of Dnmt3a, but not Dnmt1, induces degeneration of cultured neurons. Truncation mutation of the Dnmt3a catalytic domain and Dnmt3a RNAi blocks apoptosis of cultured neurons. Inhibition of Dnmt catalytic activity with small molecules RG108 and procainamide protects motor neurons from excessive DNA methylation and apoptosis in cell culture and in a mouse model of ALS. Thus, motor neurons can engage epigenetic mechanisms to cause their degeneration, involving Dnmts and increased DNA methylation. Aberrant DNA methylation in vulnerable cells is a new direction for discovering mechanisms of ALS

  20. Multi-agent Negotiation Mechanisms for Statistical Target Classification in Wireless Multimedia Sensor Networks

    Science.gov (United States)

    Wang, Xue; Bi, Dao-wei; Ding, Liang; Wang, Sheng

    2007-01-01

    The recent availability of low cost and miniaturized hardware has allowed wireless sensor networks (WSNs) to retrieve audio and video data in real world applications, which has fostered the development of wireless multimedia sensor networks (WMSNs). Resource constraints and challenging multimedia data volume make development of efficient algorithms to perform in-network processing of multimedia contents imperative. This paper proposes solving problems in the domain of WMSNs from the perspective of multi-agent systems. The multi-agent framework enables flexible network configuration and efficient collaborative in-network processing. The focus is placed on target classification in WMSNs where audio information is retrieved by microphones. To deal with the uncertainties related to audio information retrieval, the statistical approaches of power spectral density estimates, principal component analysis and Gaussian process classification are employed. A multi-agent negotiation mechanism is specially developed to efficiently utilize limited resources and simultaneously enhance classification accuracy and reliability. The negotiation is composed of two phases, where an auction based approach is first exploited to allocate the classification task among the agents and then individual agent decisions are combined by the committee decision mechanism. Simulation experiments with real world data are conducted and the results show that the proposed statistical approaches and negotiation mechanism not only reduce memory and computation requirements in WMSNs but also significantly enhance classification accuracy and reliability. PMID:28903223

  1. Extending in silico mechanism-of-action analysis by annotating targets with pathways: application to cellular cytotoxicity readouts.

    Science.gov (United States)

    Liggi, Sonia; Drakakis, Georgios; Koutsoukas, Alexios; Cortes-Ciriano, Isidro; Martínez-Alonso, Patricia; Malliavin, Thérèse E; Velazquez-Campoy, Adrian; Brewerton, Suzanne C; Bodkin, Michael J; Evans, David A; Glen, Robert C; Carrodeguas, José Alberto; Bender, Andreas

    2014-01-01

    An in silico mechanism-of-action analysis protocol was developed, comprising molecule bioactivity profiling, annotation of predicted targets with pathways and calculation of enrichment factors to highlight targets and pathways more likely to be implicated in the studied phenotype. The method was applied to a cytotoxicity phenotypic endpoint, with enriched targets/pathways found to be statistically significant when compared with 100 random datasets. Application on a smaller apoptotic set (10 molecules) did not allowed to obtain statistically relevant results, suggesting that the protocol requires modification such as analysis of the most frequently predicted targets/annotated pathways. Pathway annotations improved the mechanism-of-action information gained by target prediction alone, allowing a better interpretation of the predictions and providing better mapping of targets onto pathways.

  2. Tendon injury and repair - A perspective on the basic mechanisms of tendon disease and future clinical therapy

    NARCIS (Netherlands)

    Snedeker, J.G.; Foolen, J.

    2017-01-01

    Tendon is an intricately organized connective tissue that efficiently transfers muscle force to the bony skeleton. Its structure, function, and physiology reflect the extreme, repetitive mechanical stresses that tendon tissues bear. These mechanical demands also lie beneath high clinical rates of

  3. Vitiligo blood transcriptomics provides new insights into disease mechanisms and identifies potential novel therapeutic targets.

    Science.gov (United States)

    Dey-Rao, Rama; Sinha, Animesh A

    2017-01-28

    Significant gaps remain regarding the pathomechanisms underlying the autoimmune response in vitiligo (VL), where the loss of self-tolerance leads to the targeted killing of melanocytes. Specifically, there is incomplete information regarding alterations in the systemic environment that are relevant to the disease state. We undertook a genome-wide profiling approach to examine gene expression in the peripheral blood of VL patients and healthy controls in the context of our previously published VL-skin gene expression profile. We used several in silico bioinformatics-based analyses to provide new insights into disease mechanisms and suggest novel targets for future therapy. Unsupervised clustering methods of the VL-blood dataset demonstrate a "disease-state"-specific set of co-expressed genes. Ontology enrichment analysis of 99 differentially expressed genes (DEGs) uncovers a down-regulated immune/inflammatory response, B-Cell antigen receptor (BCR) pathways, apoptosis and catabolic processes in VL-blood. There is evidence for both type I and II interferon (IFN) playing a role in VL pathogenesis. We used interactome analysis to identify several key blood associated transcriptional factors (TFs) from within (STAT1, STAT6 and NF-kB), as well as "hidden" (CREB1, MYC, IRF4, IRF1, and TP53) from the dataset that potentially affect disease pathogenesis. The TFs overlap with our reported lesional-skin transcriptional circuitry, underscoring their potential importance to the disease. We also identify a shared VL-blood and -skin transcriptional "hot spot" that maps to chromosome 6, and includes three VL-blood dysregulated genes (PSMB8, PSMB9 and TAP1) described as potential VL-associated genetic susceptibility loci. Finally, we provide bioinformatics-based support for prioritizing dysregulated genes in VL-blood or skin as potential therapeutic targets. We examined the VL-blood transcriptome in context with our (previously published) VL-skin transcriptional profile to address

  4. On the chemistry of ethanol on basic oxides: revising mechanisms and intermediates in the Lebedev and Guerbet reactions.

    Science.gov (United States)

    Chieregato, Alessandro; Velasquez Ochoa, Juliana; Bandinelli, Claudia; Fornasari, Giuseppe; Cavani, Fabrizio; Mella, Massimo

    2015-01-01

    A common way to convert ethanol into chemicals is by upgrading it over oxide catalysts with basic features; this method makes it possible to obtain important chemicals such as 1-butanol (Guerbet reaction) and 1,3-butadiene (Lebedev reaction). Despite their long history in chemistry, the details of the close inter-relationship of these reactions have yet to be discussed properly. Our present study focuses on reactivity tests, in situ diffuse reflectance infrared Fourier transform spectroscopy, MS analysis, and theoretical modeling. We used MgO as a reference catalyst with pure basic features to explore ethanol conversion from its very early stages. Based on the obtained results, we formulate a new mechanistic theory able to explain not only our results but also most of the scientific literature on Lebedev and Guerbet chemistry. This provides a rational description of the intermediates shared by the two reaction pathways as well as an innovative perspective on the catalyst requirements to direct the reaction pathway toward 1-butanol or butadiene. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. MECHANICAL PROPERTIES OF THIN GDP SHELLS USED AS CRYOGENIC DIRECT DRIVE TARGETS AT OMEGA

    International Nuclear Information System (INIS)

    NIKROO, A.; CZECHOWICZ, D.; CHEN, K.C.; DICKEN, M.; MORRIS, C.; ANDREWS, R.; GREENWOOD, A.L; CASTILLO, E.

    2003-09-01

    OAK-B135 Thin glow discharge polymer (GDP) shells are currently used as the targets for cryogenic direct drive laser fusion experiments. These shells need to be filled with nearly 1000 atm of D 2 and cooled to cryogenic temperatures without failing due to buckling and bursting pressures they experience in this process. Therefore, the mechanical and permeation properties of these shells are of utmost importance in successful and rapid filling with D 2 . In this paper, they present an overview of buckle and burst pressures of several different types of GDP shells. These include those made using traditional GDP deposition parameters (standard GDP) using a high deposition pressure and using modified parameters (strong GDP) of low deposition pressure that leads to more robust shells

  6. Mechanical design of experimental apparatus for FIREX cryo-target cooling

    Science.gov (United States)

    Iwamoto, A.; Norimatsu, T.; Nakai, M.; Sakagami, H.; Fujioka, S.; Shiraga, H.; Azechi, H.

    2016-05-01

    Mechanical design of an experimental apparatus for FIREX cryo-target cooling is described. Gaseous helium (GHe) sealing system at a cryogenic environment is an important issue for laser fusion experiments. The dedicated loading system was designed for a metal gasket. We take U-TIGHTSEAL® (Usui Kokusai Sangyo Kaisha. Ltd.) with an indium plated copper jacket as an example. According to its specification, a linear load of 110 N/m along its circumference is the optimum compression; however a lower load would still maintain helium (He) leak below the required level. Its sealing performance was investigated systematically. Our system demanded 27 N/mm of the load to keep He leak tightness in a cryogenic environment. Once leak tightness was obtained, it could be reduced to 9.5 N/mm.

  7. Targeting GLI by GANT61 involves mechanisms dependent on inhibition of both transcription and DNA licensing.

    Science.gov (United States)

    Zhang, Ruowen; Wu, Jiahui; Ferrandon, Sylvain; Glowacki, Katie J; Houghton, Janet A

    2016-12-06

    The GLI genes are transcription factors and in cancers are oncogenes, aberrantly and constitutively activated. GANT61, a specific GLI inhibitor, has induced extensive cytotoxicity in human models of colon cancer. The FOXM1 promoter was determined to be a transcriptional target of GLI1. In HT29 cells, inhibition of GLI1 binding at the GLI consensus sequence by GANT61 led to inhibited binding of Pol II, the pause-release factors DSIF, NELF and p-TEFb. The formation of R-loops (RNA:DNA hybrids, ssDNA), were reduced by GANT61 at the FOXM1 promoter. Pretreatment of HT29 cells with α-amanitin reduced GANT61-induced γH2AX foci. Co-localization of GLI1 and BrdU foci, inhibited by GANT61, indicated GLI1 and DNA replication to be linked. By co-immunoprecipitation and confocal microscopy, GLI1 co-localized with the DNA licensing factors ORC4, CDT1, and MCM2. Significant co-localization of GLI1 and ORC4 was inhibited by GANT61, and enrichment of ORC4 occurred at the GLI binding site in the FOXM1 promoter. CDT1 was found to be a transcription target of GLI1. Overexpression of CDT1 in HT29 and SW480 cells reduced GANT61-induced cell death, gH2AX foci, and cleavage of caspase-3. Data demonstrate involvement of transcription and of DNA replication licensing factors by non-transcriptional and transcriptional mechanisms in the GLI-dependent mechanism of action of GANT61.

  8. Thioredoxin and Thioredoxin Target Proteins: From Molecular Mechanisms to Functional Significance

    Science.gov (United States)

    Lee, Samuel; Kim, Soo Min

    2013-01-01

    Abstract The thioredoxin (Trx) system is one of the central antioxidant systems in mammalian cells, maintaining a reducing environment by catalyzing electron flux from nicotinamide adenine dinucleotide phosphate through Trx reductase to Trx, which reduces its target proteins using highly conserved thiol groups. While the importance of protecting cells from the detrimental effects of reactive oxygen species is clear, decades of research in this field revealed that there is a network of redox-sensitive proteins forming redox-dependent signaling pathways that are crucial for fundamental cellular processes, including metabolism, proliferation, differentiation, migration, and apoptosis. Trx participates in signaling pathways interacting with different proteins to control their dynamic regulation of structure and function. In this review, we focus on Trx target proteins that are involved in redox-dependent signaling pathways. Specifically, Trx-dependent reductive enzymes that participate in classical redox reactions and redox-sensitive signaling molecules are discussed in greater detail. The latter are extensively discussed, as ongoing research unveils more and more details about the complex signaling networks of Trx-sensitive signaling molecules such as apoptosis signal-regulating kinase 1, Trx interacting protein, and phosphatase and tensin homolog, thus highlighting the potential direct and indirect impact of their redox-dependent interaction with Trx. Overall, the findings that are described here illustrate the importance and complexity of Trx-dependent, redox-sensitive signaling in the cell. Our increasing understanding of the components and mechanisms of these signaling pathways could lead to the identification of new potential targets for the treatment of diseases, including cancer and diabetes. Antioxid. Redox Signal. 18, 1165–1207. PMID:22607099

  9. Mechanism of microRNA-target interaction: molecular dynamics simulations and thermodynamics analysis.

    Directory of Open Access Journals (Sweden)

    Yonghua Wang

    Full Text Available MicroRNAs (miRNAs are endogenously produced approximately 21-nt riboregulators that associate with Argonaute (Ago proteins to direct mRNA cleavage or repress the translation of complementary RNAs. Capturing the molecular mechanisms of miRNA interacting with its target will not only reinforce the understanding of underlying RNA interference but also fuel the design of more effective small-interfering RNA strands. To address this, in the present work the RNA-bound (Ago-miRNA, Ago-miRNA-target and RNA-free Ago forms were analyzed by performing both molecular dynamics simulations and thermodynamic analysis. Based on the principal component analysis results of the simulation trajectories as well as the correlation analysis in fluctuations of residues, we discover that: 1 three important (PAZ, Mid and PIWI domains exist in Argonaute which define the global dynamics of the protein; 2 the interdomain correlated movements are so crucial for the interaction of Ago-RNAs that they not only facilitate the relaxation of the interactions between residues surrounding the RNA binding channel but also induce certain conformational changes; and 3 it is just these conformational changes that expand the cavity of the active site and open putative pathways for both the substrate uptake and product release. In addition, by thermodynamic analysis we also discover that for both the guide RNA 5'-end recognition and the facilitated site-specific cleavage of the target, the presence of two metal ions (of Mg(2+ plays a predominant role, and this conclusion is consistent with the observed enzyme catalytic cleavage activity in the ternary complex (Ago-miRNA-mRNA. Our results find that it is the set of arginine amino acids concentrated in the nucleotide-binding channel in Ago, instead of the conventionally-deemed seed base-paring, that makes greater contributions in stabilizing the binding of the nucleic acids to Ago.

  10. Mechanism of microRNA-target interaction: molecular dynamics simulations and thermodynamics analysis.

    Science.gov (United States)

    Wang, Yonghua; Li, Yan; Ma, Zhi; Yang, Wei; Ai, Chunzhi

    2010-07-29

    MicroRNAs (miRNAs) are endogenously produced approximately 21-nt riboregulators that associate with Argonaute (Ago) proteins to direct mRNA cleavage or repress the translation of complementary RNAs. Capturing the molecular mechanisms of miRNA interacting with its target will not only reinforce the understanding of underlying RNA interference but also fuel the design of more effective small-interfering RNA strands. To address this, in the present work the RNA-bound (Ago-miRNA, Ago-miRNA-target) and RNA-free Ago forms were analyzed by performing both molecular dynamics simulations and thermodynamic analysis. Based on the principal component analysis results of the simulation trajectories as well as the correlation analysis in fluctuations of residues, we discover that: 1) three important (PAZ, Mid and PIWI) domains exist in Argonaute which define the global dynamics of the protein; 2) the interdomain correlated movements are so crucial for the interaction of Ago-RNAs that they not only facilitate the relaxation of the interactions between residues surrounding the RNA binding channel but also induce certain conformational changes; and 3) it is just these conformational changes that expand the cavity of the active site and open putative pathways for both the substrate uptake and product release. In addition, by thermodynamic analysis we also discover that for both the guide RNA 5'-end recognition and the facilitated site-specific cleavage of the target, the presence of two metal ions (of Mg(2+)) plays a predominant role, and this conclusion is consistent with the observed enzyme catalytic cleavage activity in the ternary complex (Ago-miRNA-mRNA). Our results find that it is the set of arginine amino acids concentrated in the nucleotide-binding channel in Ago, instead of the conventionally-deemed seed base-paring, that makes greater contributions in stabilizing the binding of the nucleic acids to Ago.

  11. Multi-targeted mechanisms underlying the endothelial protective effects of the diabetic-safe sweetener erythritol.

    Directory of Open Access Journals (Sweden)

    Daniëlle M P H J Boesten

    Full Text Available Diabetes is characterized by hyperglycemia and development of vascular pathology. Endothelial cell dysfunction is a starting point for pathogenesis of vascular complications in diabetes. We previously showed the polyol erythritol to be a hydroxyl radical scavenger preventing endothelial cell dysfunction onset in diabetic rats. To unravel mechanisms, other than scavenging of radicals, by which erythritol mediates this protective effect, we evaluated effects of erythritol in endothelial cells exposed to normal (7 mM and high glucose (30 mM or diabetic stressors (e.g. SIN-1 using targeted and transcriptomic approaches. This study demonstrates that erythritol (i.e. under non-diabetic conditions has minimal effects on endothelial cells. However, under hyperglycemic conditions erythritol protected endothelial cells against cell death induced by diabetic stressors (i.e. high glucose and peroxynitrite. Also a number of harmful effects caused by high glucose, e.g. increased nitric oxide release, are reversed. Additionally, total transcriptome analysis indicated that biological processes which are differentially regulated due to high glucose are corrected by erythritol. We conclude that erythritol protects endothelial cells during high glucose conditions via effects on multiple targets. Overall, these data indicate a therapeutically important endothelial protective effect of erythritol under hyperglycemic conditions.

  12. Mechanisms of adaptation to intensive loads of 400 meters’ hurdles runners at stage of initial basic training

    Directory of Open Access Journals (Sweden)

    A.S. Rovniy

    2015-08-01

    Full Text Available Purpose: is study of adaptation mechanisms of 400 meter’ hurdles-runners to intensive physical loads. Material: in the research 13 - 400 meters’ hurdles-runners and 13 - 400 meters’ runners participated. Results: it was found that physiological cost of sportsmen’s special workability has fragmentary character. We presented results of physiological and bio-chemical adaptation mechanisms to dozed work. The received results have no confident distinctions and can not objectively characterize mechanisms of sportsmen’s special workability. We did not detect definite differences in indicators of mechanisms, ensuring sportsmen’s special workability under dozed loads. We found, that level of anaerobic glycolysis is an objective criterion of 400 meter’ hurdles-runners’ special workability. It was shown that for determination of functional potentials for such kind of functioning it is necessary to apply special loads. Conclusions: the received results deepen information about mechanisms of adaptation to specific competition functioning. Correct approaches to processing and analysis of the research’s results permit to more specifically determine sportsmen’s functional potentials in different kinds of competition functioning.

  13. Hygiene Basics

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Hygiene Basics KidsHealth / For Teens / Hygiene Basics What's in this article? Oily Hair Sweat ... smell, anyway? Read below for information on some hygiene basics — and learn how to deal with greasy ...

  14. IFMIF Li target back-plate design integration and thermo-mechanical analysis

    International Nuclear Information System (INIS)

    Riccardi, B.; Roccella, S.; Micciche, G.

    2006-01-01

    The International Fusion Materials Irradiation Facility (IFMIF) is an accelerator-driven intense neutron source where fusion reactor candidate materials will be tested. The neutron flux is produced by means of a deuteron beam (current 250 mA, energy 40 MeV) that strikes a liquid lithium target circulating in a lithium loop. The support on which the liquid lithium flows, i.e. the back-plate, is the most heavily exposed component to neutron flux. A '' bayonet '' concept solution for the back-plate was proposed by ENEA with the objectives of improving the back-plate reliability and simplifying the remote handling procedures. On the base of this concept, a back-plate mock-up was fabricated and validated. Starting from the findings of the mock up design, a back-plate design integration exercise was carried out in order to check if the back-plate geometrical features are compatible with the target assembly and the Vertical Test Assemblies (VTA). The work carried out has demonstrated that even with the changes operated for the design integration (increase of in-plane dimensions and reduction of thickness) the bayonet concept is able to guarantee a tight connection to the target assembly. A thermo-mechanical analysis of the back-plate has been carried out by means of ABAQUS code. The thermal load used as input for the calculations, i.e. the neutron heat generation, has been estimated by means of Monte Carlo Mc-Delicious code. The two boundary constraint cases (full and minimum contact with target assembly) considered for each back-plate geometry option represent the extreme cases of the real operating condition of the plate. The influence of the contact heat exchange coefficient and the back-plate thickness has been also evaluated. For all these reasons, the results of the analysis can be considered as the domain of variability of the real working conditions. The results show that AISI 316L steel is not suitable as black-plate material: the stress induced in the plate, in

  15. Study of Reaction Mechanism in the Interaction 86 MeV/A $^{12}$C with Heavy Targets

    CERN Multimedia

    2002-01-01

    Using the thin target-thin catcher techniques and the off-line analysis of the activities induced in the irradiated foils by means of singles and coincidences spectra recorded with Ge(Li) @g-rays and Si X-rays detectors, we will measure: 1) The target fragment mass and charge distribution from the interact 2) 86 MeV/A |1|2C with silver, tin and gold. 3) The target fragment average kinetic energy. 4) The target fragment angular and differential kinetic energy distributions. These measurements should allow us to better understand the heavy ion reaction mechanisms at intermediate energy.

  16. Targeting the epidermal growth factor receptor in radiotherapy: radiobiological mechanisms, preclinical and clinical results

    International Nuclear Information System (INIS)

    Baumann, Michael; Krause, Mechthild

    2004-01-01

    Background and purpose: Inhibition of the epidermal growth factor receptor (EGFR) is a fastly developing field in preclinical and clinical cancer research. This review presents the current status of knowledge and discusses radiobiological mechanisms which may underly the efficacy of EGFR inhibitors combined with irradiation. Materials and methods: Preclinical and clinical results on combined targeting of the EGFR and irradiation from the literature and from this laboratory are reviewed. Focus is given to the radiobiological rationale of this approach and to endpoints of experimental radiotherapy. Results: Overexpression of the EGFR is associated with decreased local tumour control after radiotherapy, especially when the overall treatment time is long. Inhibition of the EGFR either alone or in combination with irradiation decreases the growth rate of tumours expressing this receptor. Preclinical data provide proof-of-principle that local tumour control may be improved by combining irradiation with C225 mAb. In a randomised phase III clinical trial, simultaneous irradiation and treatment with the EGFR antibody Cetuximab (Erbitux[reg]; C225) in head and neck cancer patients resulted in significantly improved locoregional tumour control and survival compared to curative irradiation alone. Acute skin reactions increased in the experimental arm. The underlying mechanisms of enhanced radiation effects of combined EGFR inhibition with irradiation and of the partly conflicting results in different studies are poorly understood. There is increasing evidence, that important intertumoral heterogeneity in the response to EGFR inhibition alone and combined with irradiation exists, which appears to be at least partly dependent on specific mutations of the receptor as well as of molecules that are involved in the intracellular signal transduction pathway. Conclusions and outlook: Further investigations at all levels of the translational research chain exploring the mechanisms of

  17. Determination of Basic Structure-Property Relations for Processing and Modeling in Advanced Nuclear Fuel: Microstructure Evolution and Mechanical Properties

    International Nuclear Information System (INIS)

    Wheeler, Kirk; Parra, Manuel; Peralta, Pedro

    2009-01-01

    The project objective is to study structure-property relations in solid solutions of nitrides and oxides with surrogate elements to simulate the behavior of fuels of inert matrix fuels of interest to the Advanced Fuel Cycle Initiative (AFCI), with emphasis in zirconium-based materials. Work with actual fuels will be carried out in parallel in collaboration with Los Alamos National Laboratory (LANL). Three key aspects will be explored: microstructure characterization through measurement of global texture evolution and local crystallographic variations using Electron Backscattering Diffraction (EBSD); determination of mechanical properties, including fracture toughness, quasi-static compression strength, and hardness, as functions of load and temperature, and, finally, development of structure-property relations to describe mechanical behavior of the fuels based on experimental data. Materials tested will be characterized to identify the mechanisms of deformation and fracture and their relationship to microstructure and its evolution. New aspects of this research are the inclusion of crystallographic information into the evaluation of fuel performance and the incorporation of statistical variations of microstructural variables into simplified models of mechanical behavior of fuels that account explicitly for these variations. The work is expected to provide insight into processing conditions leading to better fuel performance and structural reliability during manufacturing and service, as well as providing a simplified testing model for future fuel production

  18. A basic study of the influence of surface topography on mechanisms of liquid lubrication in metal forming

    DEFF Research Database (Denmark)

    Sørensen, C. G.; Bech, Jakob Ilsted; Andreasen, Jan Lasson

    1998-01-01

    ) and Micro Plasto HydroStatic Lubrication (MPHSL) is observed and quantified experimentally with respect to the lubricant pocket parameters, shape, volume, and angle to the edge. The two mechanisms have proved to depend very differently upon these parameters. The level at which the hydrostatic pressure...

  19. A basic study of the influence of surface topography on mechanisms of liquid lubrication in metal forming

    DEFF Research Database (Denmark)

    Sørensen, C. G; Andreasen, Jan Lasson; Bech, Jakob Ilsted

    1999-01-01

    ) and Micro Plasto Hydrostatic Lubrication (MPHSL) is observed and quantified experimentally with respect to the lubricant pocket parameters, shape, volume, and angle to the edge. The two mechanisms have proved to depend very differently upon these parameters. The level at which the hydrostatic pressure...

  20. Mechanism-based design of parasite-targeted artemisinin derivatives: synthesis and antimalarial activity of new diamine containing analogues.

    Science.gov (United States)

    Hindley, Stephen; Ward, Stephen A; Storr, Richard C; Searle, Natalie L; Bray, Patrick G; Park, B Kevin; Davies, Jill; O'Neill, Paul M

    2002-02-28

    The potent antimalarial activity of chloroquine against chloroquine-sensitive strains can be attributed, in part, to its high accumulation in the acidic environment of the heme-rich parasite food vacuole. A key component of this intraparasitic chloroquine accumulation mechanism is a weak base "ion-trapping" effect whereupon the basic drug is concentrated in the acidic food vacuole in its membrane-impermeable diprotonated form. By the incorporation of amino functionality into target artemisinin analogues, we hoped to prepare a new series of analogues that, by virtue of increased accumulation into the ferrous-rich vacuole, would display enhanced antimalarial potency. The initial part of the project focused on the preparation of piperazine-linked analogues (series 1 (7-16)). Antimalarial evaluation of these derivatives demonstrated potent activity versus both chloroquine-sensitive and chloroquine-resistant parasites. On the basis of these observations, we then set about preparing a series of C-10 carba-linked amino derivatives. Optimization of the key synthetic step using a newly developed coupling protocol provided a key intermediate, allyldeoxoartemisinin (17) in 90% yield. Further elaboration, in three steps, provided nine target C-10 carba analogues (series 2 (21-29)) in good overall yields. Antimalarial assessment demonstrated that these compounds were 4-fold more potent than artemisinin and about twice as active as artemether in vitro versus chloroquine-resistant parasites. On the basis of the products obtained from biomimetic Fe(II) degradation of the C-10 carba analogue (23), we propose that these analogues may have a mode of action subtly different from that of the parent drug artemisinin (series 1 (7-16)) and other C-10 ether derivatives such as artemether. Preliminary in vivo testing by the WHO demonstrated that four of these compounds are active orally at doses of less than 10 mg/kg. Since these analogues are available as water-soluble salts and cannot

  1. Basic mechanisms of photosynthesis and applications to improved production and conversion of biomass to fuels and chemical products

    Energy Technology Data Exchange (ETDEWEB)

    El-Sayed, M. [Georgia Institute of Tech., Atlanta, GA (United States); Greenbaum, E. [Oak Ridge National Laboratory, TN (United States); Wasielewski, M. [Argonne National Lab., IL (United States)

    1996-09-01

    Natural photosynthesis, the result of 3.5 billion years of evolutionary experimentation, is the best proven, functional solar energy conversion technology. It is responsible for filling the vast majority of humanity`s energy, nutritional, and materials needs. Understanding the basic physical chemical principles underlying photosynthesis as a working model system is vital to further exploitation of this natural technology. These principles can be used to improve or modify natural photosynthesis so that it is more efficient or so that it can produce unusual products such as hydrogen, methane, methanol, ethanol, diesel fuel substitutes, biodegradable materials, or other high value chemical products. Principles garnered from the natural process can also be used to design artificial photosynthetic devices that employ analogs of natural antenna and reaction center function, self-assembly and repair concepts, photoinduced charge transfer processes, photoprotection, and dark reactions that facilitate catalytic action to convert light into, useful chemical or electrical energy. The present broad understanding of many structural and functional aspects of photosynthesis has resulted from rapid recent research progress. X-ray structures of several key photosynthetic reaction centers and antenna systems are available, and the overall principles controlling photoinduced energy and electron transfer are being established.

  2. Metabolic and Target-Site Mechanisms Combine to Confer Strong DDT Resistance in Anopheles gambiae

    Science.gov (United States)

    Mitchell, Sara N.; Rigden, Daniel J.; Dowd, Andrew J.; Lu, Fang; Wilding, Craig S.; Weetman, David; Dadzie, Samuel; Jenkins, Adam M.; Regna, Kimberly; Boko, Pelagie; Djogbenou, Luc; Muskavitch, Marc A. T.; Ranson, Hilary; Paine, Mark J. I.; Mayans, Olga; Donnelly, Martin J.

    2014-01-01

    The development of resistance to insecticides has become a classic exemplar of evolution occurring within human time scales. In this study we demonstrate how resistance to DDT in the major African malaria vector Anopheles gambiae is a result of both target-site resistance mechanisms that have introgressed between incipient species (the M- and S-molecular forms) and allelic variants in a DDT-detoxifying enzyme. Sequencing of the detoxification enzyme, Gste2, from DDT resistant and susceptible strains of An. gambiae, revealed a non-synonymous polymorphism (I114T), proximal to the DDT binding domain, which segregated with strain phenotype. Recombinant protein expression and DDT metabolism analysis revealed that the proteins from the susceptible strain lost activity at higher DDT concentrations, characteristic of substrate inhibition. The effect of I114T on GSTE2 protein structure was explored through X-ray crystallography. The amino acid exchange in the DDT-resistant strain introduced a hydroxyl group nearby the hydrophobic DDT-binding region. The exchange does not result in structural alterations but is predicted to facilitate local dynamics and enzyme activity. Expression of both wild-type and 114T alleles the allele in Drosophila conferred an increase in DDT tolerance. The 114T mutation was significantly associated with DDT resistance in wild caught M-form populations and acts in concert with target-site mutations in the voltage gated sodium channel (Vgsc-1575Y and Vgsc-1014F) to confer extreme levels of DDT resistance in wild caught An. gambiae. PMID:24675797

  3. Dissolution-modulating mechanism of pH modifiers in solid dispersion containing weakly acidic or basic drugs with poor water solubility.

    Science.gov (United States)

    Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Lee, Kyoung-Ho; Kim, Dong-Jin; Lee, Beom-Jin

    2010-05-01

    Although the solid dispersion method has been known to increase the dissolution rate of poorly water-soluble drugs by dispersing them in hydrophilic carriers, one obstacle of the solid dispersion method is its limited solubilization capacity, especially for pH-dependent soluble drugs. pH-modified solid dispersion, in which pH modifiers are incorporated, may be a useful method for increasing the dissolution rate of weakly acidic or basic drugs. Sufficient research, including the most recent reports, was undertaken in this review. How could the inclusion of the pH the pH modifiers in the solid dispersion system change drug structural behaviors, molecular interactions, microenvironmental pH, and/or release rate of pH modifiers, relating with the enhanced dissolution of weakly acidic or weakly basic drugs with poor water solubility? These questions have been investigated to determine the dissolution-modulating mechanism of pH modifiers in solid dispersion containing weakly acidic or basic drugs. It is believed that step-by-step mechanistic approaches could provide the ultimate solution for solubilizing several poorly water-soluble drugs with pH-dependent solubility from a solid dispersion system, as well as provide ideas for developing future dosage systems.

  4. Benralizumab: From the Basic Mechanism of Action to the Potential Use in the Biological Therapy of Severe Eosinophilic Asthma

    Directory of Open Access Journals (Sweden)

    Corrado Pelaia

    2018-01-01

    Full Text Available Asthma is a very frequent chronic airway disease that includes many different clinical phenotypes and inflammatory patterns. In particular, eosinophilic bronchial inflammation is often associated with allergic as well as nonallergic asthma. The most important cytokine involved in the induction, maintenance, and amplification of airway eosinophilia in asthma is interleukin-5 (IL-5, released by both T helper 2 (Th2 lymphocytes and group 2 innate lymphoid cells (ILC2. Hence, IL-5 and its receptor are suitable targets for selective biologic drugs which can play a key role in add-on treatment of severe eosinophilic asthma refractory to corticosteroids. Within such a context, the anti-IL-5 monoclonal antibodies mepolizumab and reslizumab have been developed and approved for biological therapy of uncontrolled eosinophilic asthma. In this regard, on the basis of several successful randomized controlled trials, the anti-IL-5 receptor benralizumab has also recently obtained the approval from US Food and Drug Administration (FDA.

  5. Food and Natural Materials Target Mechanisms to Effectively Regulate Allergic Responses.

    Science.gov (United States)

    Shin, Hee Soon; Shon, Dong-Hwa

    2015-01-01

    An immune hypersensitivity disorder called allergy is caused by diverse allergens entering the body via skin contact, injection, ingestion, and/or inhalation. These allergic responses may develop into allergic disorders, including inflammations such as atopic dermatitis, asthma, anaphylaxis, food allergies, and allergic rhinitis. Several drugs have been developed to treat these allergic disorders; however, long-term intake of these drugs could have adverse effects. As an alternative to these medicines, food and natural materials that ameliorate allergic disorder symptoms without producing any side effects can be consumed. Food and natural materials can effectively regulate successive allergic responses in an allergic chain-reaction mechanism in the following ways: [1] Inhibition of allergen permeation via paracellular diffusion into epithelial cells, [2] suppression of type 2 T-helper (Th) cell-related cytokine production by regulating Th1/Th2 balance, [3] inhibition of pathogenic effector CD4(+) T cell differentiation by inducing regulatory T cells (Treg), and [4] inhibition of degranulation in mast cells. The immunomodulatory effects of food and natural materials on each target mechanism were scientifically verified and shown to alleviate allergic disorder symptoms. Furthermore, consumption of certain food and natural materials such as fenugreek, skullcap, chitin/chitosan, and cheonggukjang as anti-allergics have merits such as safety (no adverse side effects), multiple suppressive effects (as a mixture would contain various components that are active against allergic responses), and ease of consumption when required. These merits and anti-allergic properties of food and natural materials help control various allergic disorders.

  6. Immune mechanisms in polymyositis and dermatomyositis and potential targets for therapy.

    Science.gov (United States)

    Venalis, Paulius; Lundberg, Ingrid E

    2014-03-01

    PM and DM are characterized clinically by weakness and low endurance of skeletal muscle. Other organs are frequently involved, suggesting that idiopathic inflammatory myopathies (IIMs) are systemic inflammatory diseases. Involvement of immune mechanisms in IIMs is supported by the presence of T cells, macrophages and dendritic cells in muscle tissue, by the presence of autoantibodies and by HLA-DR being a strong genetic risk factor. T cells may have direct and indirect toxic effects on muscle fibres, causing muscle fibre necrosis and muscle weakness, but the target of the immune reaction is not known. A newly identified T cell subset, CD28(null) T cells, may have cytotoxic effects in the CD4(+) and CD8(+) T cell phenotype. These cells are apoptosis resistant and may contribute to treatment resistance. Several myositis-specific autoantibodies have been identified, but they are all directed against ubiquitously expressed autoantigens and the specificity of the T cell reactivity is not known. These autoantibodies are associated with distinct clinical phenotypes and some with distinct molecular pathways; e.g. sera from patients with anti-Jo-1 autoantibodies may activate the type I IFN system and these sera also contain high levels of B cell activating factor compared with other IIM subsets. The characterization of patients into subgroups based on autoantibody profiles seems to be a promising way to learn more about the specificities of the immune reactions. Careful phenotyping of infiltrating immune cells in muscle tissue before and after specific therapies and relating the molecular findings to clinical outcome measures may be another way to improve knowledge on specific immune mechanism in IIMs. Such information will be important for the development of new therapies.

  7. Development of low enriched uranium target plates by thermo-mechanical processing of UAl2–Al matrix for production of 99Mo in Pakistan

    International Nuclear Information System (INIS)

    Ali, Kanwar Liaqat; Khan, Akhlaque Ahmad; Mushtaq, Ahmad; Imtiaz, Farhan; Ziai, Maratab Ali; Gulzar, Amir; Farooq, Muhammad; Hussain, Nazar; Ahmed, Nisar; Pervez, Shahid; Zaidi, Jamshed Hussain

    2013-01-01

    Uranium aluminide predominated with UAl 2 phase was prepared by arc-melting procedures and comminuted to required particle size. UAl 2 and Al powders were blended and compacted to achieve LEU fuel density of 2.17 g/cm 3 . The picture-frame technique was used to clad the dispersions (UAl 2 –Al) with aluminum. A few target plates were fabricated by thermo-mechanical processing (hot rolling and annealing) of UAl 2 –Al matrix contained in roll billet of Al. The fabricated plates were characterized by destructive and some of non-destructive testing techniques and then annealed to achieve required phase of uranium aluminide for proper dissolution in basic media

  8. Molecular Targets of Antihypertensive Peptides: Understanding the Mechanisms of Action Based on the Pathophysiology of Hypertension

    Directory of Open Access Journals (Sweden)

    Kaustav Majumder

    2014-12-01

    Full Text Available There is growing interest in using functional foods or nutraceuticals for the prevention and treatment of hypertension or high blood pressure. Although numerous preventive and therapeutic pharmacological interventions are available on the market, unfortunately, many patients still suffer from poorly controlled hypertension. Furthermore, most pharmacological drugs, such as inhibitors of angiotensin-I converting enzyme (ACE, are often associated with significant adverse effects. Many bioactive food compounds have been characterized over the past decades that may contribute to the management of hypertension; for example, bioactive peptides derived from various food proteins with antihypertensive properties have gained a great deal of attention. Some of these peptides have exhibited potent in vivo antihypertensive activity in both animal models and human clinical trials. This review provides an overview about the complex pathophysiology of hypertension and demonstrates the potential roles of food derived bioactive peptides as viable interventions targeting specific pathways involved in this disease process. This review offers a comprehensive guide for understanding and utilizing the molecular mechanisms of antihypertensive actions of food protein derived peptides.

  9. Exploring Pharmacological Mechanisms of Lavender (Lavandula angustifolia Essential Oil on Central Nervous System Targets

    Directory of Open Access Journals (Sweden)

    Víctor López

    2017-05-01

    Full Text Available Lavender essential oil is traditionally used and approved by the European Medicines Agency (EMA as herbal medicine to relieve stress and anxiety. Some animal and clinical studies reveal positive results in models of anxiety and depression although very little research has been done on molecular mechanisms. Our work consisted of evaluating the effects of lavender (Lavandula angustifolia essential oil on central nervous system well-established targets, such as MAO-A, SERT, GABAAand NMDA receptors as well as in vitro models of neurotoxicity. The results showed that lavender essential oil and its main components exert affinity for the glutamate NMDA-receptor in a dose-dependent manner with an IC50 value of 0.04 μl/mL for lavender oil. In addition, lavender and linalool were also able to bind the serotonin transporter (SERT whereas they did not show affinity for GABAA-benzodiazepine receptor. In three different models of neurotoxicity, lavender did not enhance the neurotoxic insult and improved viability of SH-SY5Y cells treated with hydrogen peroxide. According to our data, the anxiolytic and antidepressant-like effects attributed to lavender may be due to an antagonism on the NMDA-receptor and inhibition of SERT. This study suggests that lavender essential oil may exert pharmacological properties via modulating the NMDA receptor, the SERT as well as neurotoxicity induced by hydrogen peroxide.

  10. Exploring Pharmacological Mechanisms of Lavender (Lavandula angustifolia) Essential Oil on Central Nervous System Targets

    Science.gov (United States)

    López, Víctor; Nielsen, Birgitte; Solas, Maite; Ramírez, Maria J.; Jäger, Anna K.

    2017-01-01

    Lavender essential oil is traditionally used and approved by the European Medicines Agency (EMA) as herbal medicine to relieve stress and anxiety. Some animal and clinical studies reveal positive results in models of anxiety and depression although very little research has been done on molecular mechanisms. Our work consisted of evaluating the effects of lavender (Lavandula angustifolia) essential oil on central nervous system well-established targets, such as MAO-A, SERT, GABAAand NMDA receptors as well as in vitro models of neurotoxicity. The results showed that lavender essential oil and its main components exert affinity for the glutamate NMDA-receptor in a dose-dependent manner with an IC50 value of 0.04 μl/mL for lavender oil. In addition, lavender and linalool were also able to bind the serotonin transporter (SERT) whereas they did not show affinity for GABAA-benzodiazepine receptor. In three different models of neurotoxicity, lavender did not enhance the neurotoxic insult and improved viability of SH-SY5Y cells treated with hydrogen peroxide. According to our data, the anxiolytic and antidepressant-like effects attributed to lavender may be due to an antagonism on the NMDA-receptor and inhibition of SERT. This study suggests that lavender essential oil may exert pharmacological properties via modulating the NMDA receptor, the SERT as well as neurotoxicity induced by hydrogen peroxide. PMID:28579958

  11. Basic electrotechnology

    CERN Document Server

    Ashen, R A

    2013-01-01

    BASIC Electrotechnology discusses the applications of Beginner's All-purpose Symbolic Instruction Code (BASIC) in engineering, particularly in solving electrotechnology-related problems. The book is comprised of six chapters that cover several topics relevant to BASIC and electrotechnology. Chapter 1 provides an introduction to BASIC, and Chapter 2 talks about the use of complex numbers in a.c. circuit analysis. Chapter 3 covers linear circuit analysis with d.c. and sinusoidal a.c. supplies. The book also discusses the elementary magnetic circuit theory. The theory and performance of two windi

  12. Mechanistic Target of Rapamycin Is a Novel Molecular Mechanism Linking Folate Availability and Cell Function.

    Science.gov (United States)

    Silva, Elena; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

    2017-07-01

    Folate deficiency has been linked to a wide range of disorders, including cancer, neural tube defects, and fetal growth restriction. Folate regulates cellular function mediated by its involvement in the synthesis of nucleotides, which are needed for DNA synthesis, and its function as a methyl donor, which is critical for DNA methylation. Here we review current data showing that folate sensing by mechanistic target of rapamycin (mTOR) constitutes a novel and distinct pathway by which folate modulates cell functions such as nutrient transport, protein synthesis, and mitochondrial respiration. The mTOR signaling pathway responds to growth factors and changes in nutrient availability to control cell growth, proliferation, and metabolism. mTOR exists in 2 complexes, mTOR complex (mTORC) 1 and mTORC2, which have distinct upstream regulators and downstream targets. Folate deficiency in pregnant mice caused a marked inhibition of mTORC1 and mTORC2 signaling in multiple maternal and fetal tissues, downregulation of placental amino acid transporters, and fetal growth restriction. In addition, folate deficiency in primary human trophoblast (PHT) cells resulted in inhibition of mTORC1 and mTORC2 signaling and decreased the activity of key amino acid transporters. Folate sensing by mTOR in PHT cells is independent of the accumulation of homocysteine and requires the proton-coupled folate transporter (PCFT; solute carrier 46A1). Furthermore, mTORC1 and mTORC2 regulate trophoblast folate uptake by modulating the cell surface expression of folate receptor α and the reduced folate carrier. These findings, which provide a novel link between folate availability and cell function, growth, and proliferation, may have broad biological significance given the critical role of folate in normal cell function and the multiple diseases that have been associated with decreased or excessive folate availability. Low maternal folate concentrations are linked to restricted fetal growth, and we

  13. Anesthesia Basics

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Anesthesia Basics KidsHealth / For Teens / Anesthesia Basics What's in ... español Conceptos básicos sobre la anestesia What Is Anesthesia? No doubt about it, getting an operation can ...

  14. BASIC Programming.

    Science.gov (United States)

    Jennings, Carol Ann

    Designed for use by both secondary- and postsecondary-level business teachers, this curriculum guide consists of 10 units of instructional materials dealing with Beginners All-Purpose Symbol Instruction Code (BASIC) programing. Topics of the individual lessons are numbering BASIC programs and using the PRINT, END, and REM statements; system…

  15. The Mechanism of Synchronous Precise Regulation of Two Shrimp White Spot Syndrome Virus Targets by a Viral MicroRNA

    Science.gov (United States)

    He, Yaodong; Ma, Tiantian; Zhang, Xiaobo

    2017-01-01

    MicroRNAs (miRNAs), important factors in animal innate immunity, suppress the expressions of their target genes by binding to target mRNA’s 3′ untranslated regions (3′UTRs). However, the mechanism of synchronous regulation of multiple targets by a single miRNA remains unclear. In this study, the interaction between a white spot syndrome virus (WSSV) miRNA (WSSV-miR-N32) and its two viral targets (wsv459 and wsv322) was characterized in WSSV-infected shrimp. The outcomes indicated that WSSV-encoded miRNA (WSSV-miR-N32) significantly inhibited virus infection by simultaneously targeting wsv459 and wsv322. The silencing of wsv459 or wsv322 by siRNA led to significant decrease of WSSV copies in shrimp, showing that the two viral genes were required for WSSV infection. WSSV-miR-N32 could mediate 5′–3′ exonucleolytic digestion of its target mRNAs, which stopped at the sites of target mRNA 3′UTRs close to the sequence complementary to the miRNA seed sequence. The complementary bases (to the target mRNA sequence) of a miRNA 9th–18th non-seed sequence were essential for the miRNA targeting. Therefore, our findings presented novel insights into the mechanism of miRNA-mediated suppression of target gene expressions, which would be helpful for understanding the roles of miRNAs in innate immunity of invertebrate. PMID:29230209

  16. Basic study on safety conditions for MR imaging. Mechanism of burn injury associated with electrode loops during MR scanning

    International Nuclear Information System (INIS)

    Nakamura, Tatsuo; Fukuda, Koji; Hayakawa, Katsumi

    1994-01-01

    Reports of severe burns associated with the clinical use of MRI scanning have continued to appear. However, the precise mechanism responsible for these injuries has not yet been clarified. Since MR imaging exposes the human body not only to a strong H 0 magnetic field but also high-frequency RF pulses (microwave range), and since previously reported burns have occurred only in the area of attachment to monitor cables, the burns have been considered to be due to electro-magnetic induction in the cables caused by the RF pulses. In the study, therefore, using conventional monitor cables, a variety of loops were prepared and the electromagnetic induction within them by RF pulses was checked with an oscilloscope. For a single turn loop (S=0.124 m 2 ) and a 10-roll loop (S=1.24 m 2 ), the peak induced in these loops were 75 V and 45 V, respectively. When a 50 Ω resistance was connected to the ends of the loop to make it a closed circuit, the voltages across the 50 Ω load were 60 V and 30 V, respectively. Furthermore, even under conditions where a circuit was interrupted at the center of the loop, a similar voltage was observed at the ends of the loop. These results indicate that a simple model of electromagnetic induction in the loop of a monitor cable cannot alone explain the cause of the burns associated with MRI. (author)

  17. A study on elongation/contraction behavior and mechanical properties of oxy-polyacrylonitrile(PAN) fiber in basic/acidic solution for artificial muscle applications

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y.K.; Kim, S.W.; Lee, K.S.; Cho, I.H.; Lee, J.H.; Lee, J.W. [Sungkyunkwan University, Suwon (Korea); Kim, K.J. [University of Nevada, Reno (United States); Nam, J.D. [Sungkyunkwan University, Suwon (Korea)

    2002-07-01

    Oxy-PAN fiber prepared from the preoxidation and saponification of raw PAN fiber is known to elongate and contract when immersed in basic and acidic solutions, respectively. In this study, about 30% elongation in NaOH solution and 30{approx}50% contraction in HCl solution have been observed. In mechanical test, the mechanical properties of oxy-PAN fiber in the contracted state was stronger than that in the elongated state. These behaviors and mechanical properties are compared to those of living muscle and linear actuator. The change of length in NaOH and HCl solutions is due to switching between a hydrophilic and a hydrophobic structure. Other reasons are exchange of ion and water in/out of oxy-PAN fiber, and osmotic pressure difference associated with relevant ions. Much studies are needed to clarify the effective factors on but the oxy-PAN fiber's elongation/contraction behavior and mechanical properties, but the oxy-PAN fiber prepared in our laboratory has a sufficient potential for application as artificial muscle and linear actuator. (author). 20 refs., 1 tab., 9 figs.

  18. Luminescent microporous metal–organic framework with functional Lewis basic sites on the pore surface: Quantifiable evaluation of luminescent sensing mechanisms towards Fe{sup 3+}

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Jun-Cheng [Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, Shaanxi Key Laboratory of Physico-Inorganic Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China); Technology Promotion Center of Nano Composite Material of Biomimetic Sensor and Detecting Technology, Preparation and Application, Anhui Provincial Laboratory West Anhui University, Anhui 237012 (China); Guo, Rui-Li; Zhang, Wen-Yan [Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, Shaanxi Key Laboratory of Physico-Inorganic Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China); Jiang, Chen [Technology Promotion Center of Nano Composite Material of Biomimetic Sensor and Detecting Technology, Preparation and Application, Anhui Provincial Laboratory West Anhui University, Anhui 237012 (China); Wang, Yao-Yu, E-mail: wyaoyu@nwu.edu.cn [Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, Shaanxi Key Laboratory of Physico-Inorganic Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China)

    2016-11-15

    A systematic study has been conducted on a novel luminescent metal-organic framework, ([Zn(bpyp)(L-OH)]·DMF·2H{sub 2}O){sub n} (1), to explore its sensing mechanisms to Fe{sup 3+}. Structure analyses show that compound 1 exist pyridine N atoms and -OH groups on the pore surface for specific sensing of metal ions via Lewis acid-base interactions. On this consideration, the quenching mechanisms are studied and the processes are controlled by multiple mechanisms in which dynamic and static mechanisms are calculated, achieving the quantification evaluation of the quenching process. This work not only achieves the quantitative evaluation of the luminescence quenching but also provides certain insights into the quenching process, and the possible mechanisms explored in this work may inspire future research and design of target luminescent metal-organic frameworks (LMOFs) with specific functions. - Graphical abstract: A systematic study has been conducted on a novel luminescent metal-organic framework to explore its sensing mechanisms to Fe{sup 3+}. The quenching mechanisms are studied and the processes are controlled by multiple mechanisms in which dynamic and static mechanisms are calculated, achieving the quantification evaluation of the quenching process. - Highlights: • A novel porous luminescent MOF containing uncoordinated groups in interlayer channels was successfully synthesized. • The compound 1 can exhibit significant luminescent sensitivity to Fe{sup 3+}, which make its good candidate as luminescent sensor. • The corresponding dynamic and static quenching constants are calculated, achieving the quantification evaluation of the quenching process.

  19. Als and Ftd: Insights into the disease mechanisms and therapeutic targets.

    Science.gov (United States)

    Liscic, Rajka M

    2017-12-15

    Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative disorders, related by signs of deteriorating motor and cognitive functions, and short survival. The causes are still largely unknown and no effective treatment currently exists. It has been shown that FTLD may coexist with ALS. The overlap between ALS and frontotemporal dementia (FTD), the clinical syndrome associated with FTLD, occurs at clinical, genetic, and pathological levels. The hallmark proteins of the pathognomonic inclusions are SOD-1, TDP-43 or FUS, rarely the disease is caused by mutations in the respective genes. Frontotemporal lobar degenerations (FTLD) is genetically, neuropathologically and clinically heterogeneous and may present with behavioural, language and occasionally motor disorder, respectively. Almost all cases of ALS, as well as tau-negative FTLD share a common neuropathology, neuronal and glial inclusion bodies containing abnormal TDP-43 protein, collectively called TDP-43 proteinopathy. Recent discoveries in genetics (e.g. C9orf72 hexanucleotide expansion) and the subsequent neuropathological characterization have revealed remarkable overlap between ALS and FTLD-TDP indicating common pathways in pathogenesis. For ALS, an anti-glutamate agent riluzole may be offered to slow disease progression (Level A), and a promising molecule, arimoclomol, is currently in clinical trials. Other compounds, however, are being trailed and some have shown encouraging results. As new therapeutic approaches continue to emerge by targeting SOD1, TDP-43, or GRN, we present some advances that are being made in our understanding of the molecular mechanisms of these diseases, which together with gene and stem cell therapies may translate into new treatment options. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Capillary electrophoretic enantioseparation of basic drugs using a new single-isomer cyclodextrin derivative and theoretical study of the chiral recognition mechanism.

    Science.gov (United States)

    Liu, Yongjing; Deng, Miaoduo; Yu, Jia; Jiang, Zhen; Guo, Xingjie

    2016-05-01

    A novel single-isomer cyclodextrin derivative, heptakis {2,6-di-O-[3-(1,3-dicarboxyl propylamino)-2-hydroxypropyl]}-β-cyclodextrin (glutamic acid-β-cyclodextrin) was synthesized and used as a chiral selector in capillary electrophoresis for the enantioseparation of 12 basic drugs, including terbutaline, clorprenaline, tulobuterol, clenbuterol, procaterol, carvedilol, econazole, miconazole, homatropine methyl bromide, brompheniramine, chlorpheniramine and pheniramine. The primary factors affecting separation efficiency, which include the background electrolyte pH, the concentration of glutamic acid-β-cyclodextrin and phosphate buffer concentration, were investigated. Satisfactory enantioseparations were obtained using an uncoated fused-silica capillary of 50 cm (effective length 40 cm) × 50 μm id with 120 mM phosphate buffer (pH 2.5-4.0) containing 0.5-4.5 mM glutamic acid-β-cyclodextrin as background electrolyte. A voltage of 20 kV was applied and the capillary temperature was kept at 20°C. The results proved that glutamic acid-β-cyclodextrin was an effective chiral selector for studied 12 basic drugs. Moreover, the possible chiral recognition mechanism of brompheniramine, chlorpheniramine and pheniramine on glutamic acid-β-cyclodextrin was investigated using the semi-empirical Parametric Method 3. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Dead-blow hammer design applied to a calibration target mechanism to dampen excessive rebound

    Science.gov (United States)

    Lim, Brian Y.

    1991-01-01

    An existing rotary electromagnetic driver was specified to be used to deploy and restow a blackbody calibration target inside of a spacecraft infrared science instrument. However, this target was much more massive than any other previously inherited design applications. The target experienced unacceptable bounce when reaching its stops. Without any design modification, the momentum generated by the driver caused the target to bounce back to its starting position. Initially, elastomeric dampers were used between the driver and the target. However, this design could not prevent the bounce, and it compromised the positional accuracy of the calibration target. A design that successfully met all the requirements incorporated a sealed pocket 85 percent full of 0.75 mm diameter stainless steel balls in the back of the target to provide the effect of a dead-blow hammer. The energy dissipation resulting from the collision of balls in the pocket successfully dampened the excess momentum generated during the target deployment. The disastrous effects of new requirements on a design with a successful flight history, the modifications that were necessary to make the device work, and the tests performed to verify its functionality are described.

  2. An alternative bactericidal mechanism of action for lantibiotic peptides that target lipid II

    NARCIS (Netherlands)

    Hasper, Hester E.; Kramer, Naomi E.; Smith, James L.; Hillman, J. D.; Zachariah, Cherian; Kuipers, Oscar P.; de Kruijff, Ben; Breukink, Eefjan

    2006-01-01

    Lantibiotics are polycyclic peptides containing unusual amino acids, which have binding specificity for bacterial cells, targeting the bacterial cell wall component lipid II to form pores and thereby lyse the cells. Yet several members of these lipid II - targeted lantibiotics are too short to be

  3. Basic Finance

    Science.gov (United States)

    Vittek, J. F.

    1972-01-01

    A discussion of the basic measures of corporate financial strength, and the sources of the information is reported. Considered are: balance sheet, income statement, funds and cash flow, and financial ratios.

  4. A modified high-intensity Cs sputter negative-ion source with multi-target mechanism

    International Nuclear Information System (INIS)

    Si Houzhi; Zhang Weizhong; Zhu Jinhau; Du Guangtian; Zhang Tiaorong; Gao Xiang

    1993-01-01

    The source is based on Middleton's high-intensity mode, but modified to a multi-target version. It is equipped with a spherical molybdenum ionizer, a 20-position target wheel and a vacuum lock for loading and unloading sample batches. A metal-ceramic bonded section protected by a specially designed labyrinth shielding system results in reliable insulation of the cathode and convenient control of cesium vapor. The latter is particularly important when an oversupply of cesium occurs. The source was developed for accelerator mass spectrometry (AMS) applications. Recently, three versions based on the prototype of the source have been successfully tested to meet different requirements: (a) Single target version, (b) multi-target version with manual sample change, and (c) multi-target version with remote control sample change. Some details of the technical and operational characteristics are presented. (orig.)

  5. Setting reinspection intervals for seam welded piping by use of probabilistic fracture mechanics and target reliability values

    International Nuclear Information System (INIS)

    Harris, D.O.; Dedhia, D.

    1995-01-01

    The purpose of this paper is to describe a procedure for the selection of a reinspection interval for defects found during an inspection. The procedure is based on probabilistic fracture mechanics calculations of the reliability of the component into the future and selection of an inspection time based on maintaining the target value reliability. The selection of a target value based on the risk of everyday activities is discussed. The procedure is applied to high temperature seam welded piping as an example, because the probabilistic fracture mechanics tools are relatively readily available and this is a problem of great current interest. The results obtained in the example problem indicate reinspection intervals much shorter than field experience would suggest. This indicates a conservatism in the fracture mechanics procedures and/or lack of accurate characterization of scatter in material properties due to lack of data. The general procedure should prove useful in the disposition of detected cracks in a wide variety of situations

  6. Structural integrity of heavy liquid-metal target installed in spallation neutron facility. Part 4: Consideration by fracture mechanics of target container window

    International Nuclear Information System (INIS)

    Ishikura, Syuichi; Kogawa, Hiroyuki; Futakawa, Masatoshi; Kikuchi, Kenji; Haga, Katsuhiro; Kaminaga, Masanori; Hino, Ryutaro

    2004-01-01

    Developments of the neutron scattering facility is carried out under the high-intensity proton accelerator project promoted by JAERI and KEK. To estimate the structural integrity of the heavy liquid-metal (mercury) target used as a spallation neutron source in a MW-class neutron scattering facility, static and dynamic stress (including pressure wave in mercury) behaviors due to the incident of 1MW-pulsed proton beam (Maximum heat density is 461W/cc) were analyzed. In the analyses, two type target containers with semi-cylindrical type and flat-type beam windows were used as analytical models. As a result, it is confirmed that the stress generated by the pressure wave becomes the largest at the center of the beam window, and the flat-type beam window is more advantageous from the structural viewpoint than the semi-cylindrical type beam window. It has been understood that the stress generated in the beam window by the pressure wave can be treated as the secondary stress. Then, it has been understood that the stress and the stress range generated in the target window were bellow the allowable stress level defined by the standard of JIS on the maximum stress and fatigue strength. It has been experimentally confirmed that a cavitation was generated by generating the negative pressure in mercury near the target beam window and a collapse of cavitation damaged to the target container material, as pits. Then, the fracture mechanical analyses were carried out on the pit and a crack on pit tip. Consequently, it was clarified that the crack would not propagate because the inner surface of the beam window was become the compressive stress field due to the steady state thermal stress. Moreover, the evaluation technique of the cavitation which would be needed in the future was summarized. (author)

  7. Integrative Analysis of Genetic, Genomic, and Phenotypic Data for Ethanol Behaviors: A Network-Based Pipeline for Identifying Mechanisms and Potential Drug Targets.

    Science.gov (United States)

    Bogenpohl, James W; Mignogna, Kristin M; Smith, Maren L; Miles, Michael F

    2017-01-01

    Complex behavioral traits, such as alcohol abuse, are caused by an interplay of genetic and environmental factors, producing deleterious functional adaptations in the central nervous system. The long-term behavioral consequences of such changes are of substantial cost to both the individual and society. Substantial progress has been made in the last two decades in understanding elements of brain mechanisms underlying responses to ethanol in animal models and risk factors for alcohol use disorder (AUD) in humans. However, treatments for AUD remain largely ineffective and few medications for this disease state have been licensed. Genome-wide genetic polymorphism analysis (GWAS) in humans, behavioral genetic studies in animal models and brain gene expression studies produced by microarrays or RNA-seq have the potential to produce nonbiased and novel insight into the underlying neurobiology of AUD. However, the complexity of such information, both statistical and informational, has slowed progress toward identifying new targets for intervention in AUD. This chapter describes one approach for integrating behavioral, genetic, and genomic information across animal model and human studies. The goal of this approach is to identify networks of genes functioning in the brain that are most relevant to the underlying mechanisms of a complex disease such as AUD. We illustrate an example of how genomic studies in animal models can be used to produce robust gene networks that have functional implications, and to integrate such animal model genomic data with human genetic studies such as GWAS for AUD. We describe several useful analysis tools for such studies: ComBAT, WGCNA, and EW_dmGWAS. The end result of this analysis is a ranking of gene networks and identification of their cognate hub genes, which might provide eventual targets for future therapeutic development. Furthermore, this combined approach may also improve our understanding of basic mechanisms underlying gene x

  8. Basic electronics

    CERN Document Server

    Holbrook, Harold D

    1971-01-01

    Basic Electronics is an elementary text designed for basic instruction in electricity and electronics. It gives emphasis on electronic emission and the vacuum tube and shows transistor circuits in parallel with electron tube circuits. This book also demonstrates how the transistor merely replaces the tube, with proper change of circuit constants as required. Many problems are presented at the end of each chapter. This book is comprised of 17 chapters and opens with an overview of electron theory, followed by a discussion on resistance, inductance, and capacitance, along with their effects on t

  9. Multimodal Nanomedicine Strategies for Targeting Cancer Cells as well as Cancer Stem Cell Signalling Mechanisms.

    Science.gov (United States)

    Kanwar, Jagat R; Samarasinghe, Rasika M; Kamalapuram, Sishir K; Kanwar, Rupinder K

    2017-01-01

    Increasing evidence suggests that stem cells, a small population of cells with unique selfrenewable and tumour regenerative capacity, are aiding tumour re-growth and multidrug resistance. Conventional therapies are highly ineffective at eliminating these cells leading to relapse of disease and formation of chemoresistance tumours. Cancer and stem cells targeted therapies that utilizes nanotherapeutics to delivery anti-cancer drugs to specific sites are continuously investigated. This review focuses on recent research using nanomedicine and targeting entities to eliminate cancer cells and cancer stem cells. Current nanotherapeutics in clinical trials along with more recent publications on targeted therapies are addressed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. The movable polarized target as a basic equipment for high energy spin physics experiments at the JINR-Dubna accelerator complex

    Energy Technology Data Exchange (ETDEWEB)

    Lehar, F.; Adiasevich, B.; Androsov, V.P.; Angelov, N.; Anischenko, N.; Antonenko, V.; Ball, J.; Baryshevsky, V.G.; Bazhanov, N.A.; Belyaev, A.A.; Benda, B.; Bodyagin, V.; Borisov, N.; Borzunov, Yu.; Bradamante, F.; Bunyatova, E.; Burinov, V.; Chernykh, E.; Combet, M.; Datskov, A.; Durand, G.; Dzyubak, A.P.; Fontaine, J.M.; Get`man, V.A.; Giorgi, M.; Golovanov, L.; Grebenyuk, V.; Grosnick, D.; Gurevich, G.; Hasegawa, T.; Hill, D.; Horikawa, N.; Igo, G.; Janout, Z.; Kalinnikov, V.A.; Karnaukhov, I.M.; Kasprzyk, T.; Khachaturov, B.A.; Kirillov, A.; Kisselev, Yu.; Kousmine, E.S.; Kovalenko, A.; Kovaljov, A.I.; Ladygin, V.P.; Lazarev, A.; Leconte, P.; Lesquen, A. de; Lukhanin, A.A.; Mango, S.; Martin, A.; Matafonov, V.N.; Matyushevsky, E.; Mironov, S.; Neganov, A.B.; Neganov, B.S.; Nomofilov, A.; Perelygin, V.; Plis, Yu.; Pilipenko, Yu.; Pisarev, I.L.; Piskunov, N.; Polunin, Yu.; Popkov, Yu.P.; Propov, A.A.; Prokofiev, A.N.; Rekalo, M.P.; Rukoyatkin, P.; Sans, J.L.; Sapozhnikov, M.G.; Sharov, V.; Shilov, S.; Shishov, Yu.; Sitnik, I.M.; Sorokin, P.V.; Spinka, H.; Sporov, E.A.; Strunov, L.N.; Svetov, A.; De Swart, J.J.; Telegin, Yu.P.; Tolmashov, I.; Trentalange, S.; Tsvinev, A.; Usov, Yu.A.; Vikhrov, V.V.; Whitten, C.A.; Zaporozhets, S.; Zarubin, A.; Zhdanov, A.A.; Zolin, L. [CEA Centre d`Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette (France). Dept. d`Astrophysique, de Physique des Particules, de Physique Nucleaire et de l`Instrumentation Associee]|[I.V. Kurchatov Inst. of Atomic Energy, Moscow (Russian Federation)]|[Kharkov Inst. of Physics and Technology (Russian Federation)]|[Lab. of Nuclear Problems, JINR, Dubna (Russian Federation)]|[Lab. of High Energy Physics, JINR, Dubna (Russian Federation)]|[Lab. National SATURNE, CNRS, 91 - Gif-sur-Yvette (France)]|[Inst. of Physics, Belarus Academy of Sciences, Minsk (Belarus)]|[Dept. of Physics, Petersburg Nuclear Physics Inst., Gatchina (Russian Federation)

    1995-03-01

    A movable polarized proton target is planned to be installed in polarized beams of the Synchrophasotron-Nuclotron complex in order to carry out a spin physics experimental program at Dubna. The project is described and the first proposed experiments are discussed. ((orig.))

  11. The movable polarized target as a basic equipment for high energy spin physics experiments at the JINR-Dubna accelerator complex

    International Nuclear Information System (INIS)

    Lehar, F.; Adiasevich, B.; Androsov, V.P.; Angelov, N.; Anischenko, N.; Antonenko, V.; Ball, J.; Baryshevsky, V.G.; Bazhanov, N.A.; Belyaev, A.A.; Benda, B.; Bodyagin, V.; Borisov, N.; Borzunov, Yu.; Bradamante, F.; Bunyatova, E.; Burinov, V.; Chernykh, E.; Combet, M.; Datskov, A.; Durand, G.; Dzyubak, A.P.; Fontaine, J.M.; Get'man, V.A.; Giorgi, M.; Golovanov, L.; Grebenyuk, V.; Grosnick, D.; Gurevich, G.; Hasegawa, T.; Hill, D.; Horikawa, N.; Igo, G.; Janout, Z.; Kalinnikov, V.A.; Karnaukhov, I.M.; Kasprzyk, T.; Khachaturov, B.A.; Kirillov, A.; Kisselev, Yu.; Kousmine, E.S.; Kovalenko, A.; Kovaljov, A.I.; Ladygin, V.P.; Lazarev, A.; Leconte, P.; Lesquen, A. de; Lukhanin, A.A.; Mango, S.; Martin, A.; Matafonov, V.N.; Matyushevsky, E.; Mironov, S.; Neganov, A.B.; Neganov, B.S.; Nomofilov, A.; Perelygin, V.; Plis, Yu.; Pilipenko, Yu.; Pisarev, I.L.; Piskunov, N.; Polunin, Yu.; Popkov, Yu.P.; Propov, A.A.; Prokofiev, A.N.; Rekalo, M.P.; Rukoyatkin, P.; Sans, J.L.; Sapozhnikov, M.G.; Sharov, V.; Shilov, S.; Shishov, Yu.; Sitnik, I.M.; Sorokin, P.V.; Spinka, H.; Sporov, E.A.; Strunov, L.N.; Svetov, A.; De Swart, J.J.; Telegin, Yu.P.; Tolmashov, I.; Trentalange, S.; Tsvinev, A.; Usov, Yu.A.; Vikhrov, V.V.; Whitten, C.A.; Zaporozhets, S.; Zarubin, A.; Zhdanov, A.A.; Zolin, L.

    1995-01-01

    A movable polarized proton target is planned to be installed in polarized beams of the Synchrophasotron-Nuclotron complex in order to carry out a spin physics experimental program at Dubna. The project is described and the first proposed experiments are discussed. ((orig.))

  12. Basic concepts

    International Nuclear Information System (INIS)

    Dorner, B.

    1999-01-01

    The basic concepts of neutron scattering as a tool for studying the structure and the dynamics of condensed matter. Theoretical aspects are outlined, the two different cases of coherent and incoherent scattering are presented. The issue of resolution, coherence volume and the role of monochromators are also discussed. (K.A.)

  13. Body Basics

    Science.gov (United States)

    ... learn more about how the body works, what basic human anatomy is, and what happens when parts of ... consult your doctor. © 1995- The Nemours Foundation. All rights reserved. Images provided by The Nemours Foundation, iStock, Getty Images, Veer, Shutterstock, and Clipart.com.

  14. Basic Thermodynamics

    International Nuclear Information System (INIS)

    Duthil, P

    2014-01-01

    The goal of this paper is to present a general thermodynamic basis that is useable in the context of superconductivity and particle accelerators. The first part recalls the purpose of thermodynamics and summarizes its important concepts. Some applications, from cryogenics to magnetic systems, are covered. In the context of basic thermodynamics, only thermodynamic equilibrium is considered

  15. Basic Thermodynamics

    Energy Technology Data Exchange (ETDEWEB)

    Duthil, P [Orsay, IPN (France)

    2014-07-01

    The goal of this paper is to present a general thermodynamic basis that is useable in the context of superconductivity and particle accelerators. The first part recalls the purpose of thermodynamics and summarizes its important concepts. Some applications, from cryogenics to magnetic systems, are covered. In the context of basic thermodynamics, only thermodynamic equilibrium is considered.

  16. Ethanol Basics

    Energy Technology Data Exchange (ETDEWEB)

    None

    2015-01-30

    Ethanol is a widely-used, domestically-produced renewable fuel made from corn and other plant materials. More than 96% of gasoline sold in the United States contains ethanol. Learn more about this alternative fuel in the Ethanol Basics Fact Sheet, produced by the U.S. Department of Energy's Clean Cities program.

  17. Mechanical and IL-1β Responsive miR-365 Contributes to Osteoarthritis Development by Targeting Histone Deacetylase 4

    Directory of Open Access Journals (Sweden)

    Xu Yang

    2016-03-01

    Full Text Available Mechanical stress plays an important role in the initiation and progression of osteoarthritis. Studies show that excessive mechanical stress can directly damage the cartilage extracellular matrix and shift the balance in chondrocytes to favor catabolic activity over anabolism. However, the underlying mechanism remains unknown. MicroRNAs (miRNAs are emerging as important regulators in osteoarthritis pathogenesis. We have found that mechanical loading up-regulated microRNA miR-365 in growth plate chondrocytes, which promotes chondrocyte differentiation. Here, we explored the role of the mechanical responsive microRNA miR-365 in pathogenesis of osteoarthritis (OA. We found that miR-365 was up-regulated by cyclic loading and IL-1β stimulation in articular chondrocytes through a mechanism that involved the transcription factor NF-κB. miR-365 expressed significant higher level in rat anterior cruciate ligament (ACL surgery induced OA cartilage as well as human OA cartilage from primary OA patients and traumatic OA Patients. Overexpression of miR-365 in chondrocytes increases gene expression of matrix degrading enzyme matrix metallopeptidase 13 (MMP13 and collagen type X (Col X. The increase in miR-365 expression in OA cartilage and in response to IL-1 may contribute to the abnormal gene expression pattern characteristic of OA. Inhibition of miR-365 down-regulated IL-1β induced MMP13 and Col X gene expression. We further showed histone deacetylase 4 (HDAC4 is a direct target of miR-365, which mediates mechanical stress and inflammation in OA pathogenesis. Thus, miR-365 is a critical regulator of mechanical stress and pro-inflammatory responses, which contributes cartilage catabolism. Manipulation of the expression of miR-365 in articular chondrocytes by miR-365 inhibitor may be a potent therapeutic target for the prevention and treatment of osteoarthritis.

  18. A tale of two approaches: complementary mechanisms of cytotoxic and targeted therapy resistance may inform next-generation cancer treatments

    Science.gov (United States)

    Masui, Kenta; Gini, Beatrice; Wykosky, Jill; Zanca, Ciro; Cavenee, Webster K.

    2013-01-01

    Chemotherapy and molecularly targeted approaches represent two very different modes of cancer treatment and each is associated with unique benefits and limitations. Both types of therapy share the overarching limitation of the emergence of drug resistance, which prevents these drugs from eliciting lasting clinical benefit. This review will provide an overview of the various mechanisms of resistance to each of these classes of drugs and examples of drug combinations that have been tested clinically. This analysis supports the contention that understanding modes of resistance to both chemotherapy and molecularly targeted therapies may be very useful in selecting those drugs of each class that will have complementing mechanisms of sensitivity and thereby represent reasonable combination therapies. PMID:23455378

  19. Study of the thermo-mechanical performances of the IFMIF-EVEDA Lithium Test Loop target assembly

    Energy Technology Data Exchange (ETDEWEB)

    Di Maio, P.A., E-mail: dimaio@din.unipa.it [Dipartimento dell' Energia, Universita di Palermo, Viale delle Scienze, 90128 Palermo (Italy); Arena, P.; Bongiovi, G. [Dipartimento dell' Energia, Universita di Palermo, Viale delle Scienze, 90128 Palermo (Italy); Giammusso, R.; Micciche, G.; Tincani, A. [ENEA C. R. Brasimone, 40032 Camugnano, Bologna (Italy)

    2012-08-15

    Highlights: Black-Right-Pointing-Pointer IFMIF-EVEDA target assembly thermo-mechanical behavior has been investigated. Black-Right-Pointing-Pointer Finite element method has been followed and a commercial code has been used. Black-Right-Pointing-Pointer Nominal, design and pressure test steady state scenarios and start-up transient conditions have been investigated. Black-Right-Pointing-Pointer Steady state results have shown that back-plate yielding may occur only under the design scenario. Black-Right-Pointing-Pointer Transient analysis has indicated that TA start-up lasts for {approx}60 h. - Abstract: Within the framework of the IFMIF R and D program and in close cooperation with ENEA-Brasimone, at the Department of Energy of the University of Palermo a research campaign has been launched to investigate the thermo-mechanical behavior of the target assembly under both steady state and start-up transient conditions. A theoretical approach based on the finite element method (FEM) has been followed and a well-known commercial code has been adopted. A realistic 3D FEM model of the target assembly has been set-up and optimized by running a mesh independency analysis. A proper set of loads and boundary conditions, mainly concerned with radiation heat transfer between the target assembly external walls and the inner walls of its containment vessel, have been considered and the target assembly thermo-mechanical behavior under nominal, design and pressure test steady state scenarios and start-up transient conditions has been investigated. Results are herewith reported and discussed.

  20. Phenotype switching : tumor cell plasticity as a resistance mechanism and target for therapy

    NARCIS (Netherlands)

    Kemper, K.; de Goeje, P.L.; Peeper, D.S.; van Amerongen, R.

    2014-01-01

    Mutations in BRAF are present in the majority of patients with melanoma, rendering these tumors sensitive to targeted therapy with BRAF and MEK inhibitors. Unfortunately, resistance almost invariably develops. Recently, a phenomenon called "phenotype switching" has been identified as an escape

  1. Inhibitory mechanism of peptides and antibodies targeting murine urokinase-type plasminogen activator

    DEFF Research Database (Denmark)

    Liu, Zhuo

    2012-01-01

    drugs, a detailed mechanistic understanding must be obtained. One peptide and two antibodies were studied in this thesis. First, an engineered cyclic peptide, mupain-1-16 with an unnatural amino acid in the P1 position and the sequence CPAYS[L-3-(N-Amidino-4-piperidyl)alanine]YLDC was investigated...... different conformational and inhibitory mechanisms both in vivo and in vitro. Their similar epitopes, but different functions revealed two different allosteric regulation mechanisms for antibodies binding to serine proteases. Both the peptidic inhibitors and the allosteric mechanisms of uPA are believed...

  2. Targeting of TAM Receptors Ameliorates Fibrotic Mechanisms in Idiopathic Pulmonary Fibrosis.

    Science.gov (United States)

    Espindola, Milena S; Habiel, David M; Narayanan, Rohan; Jones, Isabelle; Coelho, Ana L; Murray, Lynne A; Jiang, Dianhua; Noble, Paul W; Hogaboam, Cory M

    2018-06-01

    Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant lung remodeling, which progressively abolishes lung function in an RTK (receptor tyrosine kinase)-dependent manner. Gas6 (growth arrest-specific 6) ligand, Tyro3 (TYRO3 protein tyrosine kinase 3), and Axl (anexelekto) RTK expression and activity are increased in IPF. To determine if targeting these RTK pathways would inhibit fibroblast activation and the development of pulmonary fibrosis. Quantitative genomic, proteomic, and functional analyses were used to determine Gas6/TAM (Tyro3, Axl, and Mertk [MER proto-oncogene, tyrosine kinase]) RTK expression and activation in tissues and fibroblasts from normal and IPF lungs. The profibrotic impact of these RTK pathways were also examined in bleomycin-induced pulmonary fibrosis and in SCID/Bg mice that developed pulmonary fibrosis after the intravenous administration of primary IPF fibroblasts. Gas6, Axl, and Tyro3 were increased in both rapidly and slowly progressive IPF compared with normal lung samples and fibroblasts. Targeting these pathways with either specific antibodies directed at Gas6 or Axl, or with small-molecule TAM inhibitors indicated that the small molecule-mediated targeting approach was more efficacious in both in vitro and in vivo studies. Specifically, the TAM receptor inhibitor R428 (also known as BGB324) significantly inhibited the synthetic, migratory, and proliferative properties of IPF fibroblasts compared with the other Gas6/TAM receptor targeting agents. Finally, loss of Gas6 expression decreased lung fibrotic responses to bleomycin and treatment with R428 inhibited pulmonary fibrosis in humanized SCID/Bg mice. Gas6/TAM receptor activity contributes to the activation of pulmonary fibroblasts in IPF, suggesting that targeting this RTK pathway might be an effective antifibrotic strategy in this disease.

  3. Practice of mechanical ventilation in cardiac arrest patients and effects of targeted temperature management: A substudy of the targeted temperature management trial.

    Science.gov (United States)

    Harmon, Matthew B A; van Meenen, David M P; van der Veen, Annelou L I P; Binnekade, Jan M; Dankiewicz, Josef; Ebner, Florian; Nielsen, Niklas; Pelosi, Paolo; Schultz, Marcus J; Horn, Janneke; Friberg, Hans; Juffermans, Nicole P

    2018-05-12

    Mechanical ventilation practices in patients with cardiac arrest are not well described. Also, the effect of temperature on mechanical ventilation settings is not known. The aims of this study were 1) to describe practice of mechanical ventilation and its relation with outcome 2) to determine effects of different target temperatures strategies (33 °C versus 36 °C) on mechanical ventilation settings. This is a substudy of the TTM-trial in which unconscious survivors of a cardiac arrest due to a cardiac cause were randomized to two TTM strategies, 33 °C (TTM33) and 36 °C (TTM36). Mechanical ventilation data were obtained at three time points: 1) before TTM; 2) at the end of TTM (before rewarming) and 3) after rewarming. Logistic regression was used to determine an association between mechanical ventilation variables and outcome. Repeated-measures mixed modelling was performed to determine the effect of TTM on ventilation settings. Mechanical ventilation data was available for 567 of the 950 TTM patients. Of these, 81% was male with a mean (SD) age of 64 (12) years. At the end of TTM median tidal volume was 7.7 ml/kg predicted body weight (PBW)(6.4-8.7) and 60% of patients were ventilated with a tidal volume ≤ 8 ml/kg PBW. Median PEEP was 7.7cmH 2 O (6.4-8.7) and mean driving pressure was 14.6 cmH 2 O (±4.3). The median FiO 2 fraction was 0.35 (0.30-0.45). Multivariate analysis showed an independent relationship between increased respiratory rate and 28-day mortality. TTM33 resulted in lower end-tidal CO 2 (Pgroup = 0.0003) and higher alveolar dead space fraction (Pgroup = 0.003) compared to TTM36, while PCO 2 levels and respiratory minute volume were similar between groups. In the majority of the cardiac arrest patients, protective ventilation settings are applied, including low tidal volumes and driving pressures. High respiratory rate was associated with mortality. TTM33 results in lower end-tidal CO 2 levels and a higher alveolar dead

  4. siRNA as a tool to improve the treatment of brain diseases: Mechanism, targets and delivery.

    Science.gov (United States)

    Gomes, Maria João; Martins, Susana; Sarmento, Bruno

    2015-05-01

    As the population ages, brain pathologies such as neurodegenerative diseases and brain cancer increase their incidence, being the need to find successful treatments of upmost importance. Drug delivery to the central nervous system (CNS) is required in order to reach diseases causes and treat them. However, biological barriers, mainly blood-brain barrier (BBB), are the key obstacles that prevent the effectiveness of possible treatments due to their ability to strongly limit the perfusion of compounds into the brain. Over the past decades, new approaches towards overcoming BBB and its efflux transporters had been proposed. One of these approaches here reviewed is through small interfering RNA (siRNA), which is capable to specifically target one gene and silence it in a post-transcriptional way. There are different possible functional proteins at the BBB, as the ones responsible for transport or just for its tightness, which could be a siRNA target. As important as the effective silence is the way to delivery siRNA to its anatomical site of action. This is where nanotechnology-based systems may help, by protecting siRNA circulation and providing cell/tissue-targeting and intracellular siRNA delivery. After an initial overview on incidence of brain diseases and basic features of the CNS, BBB and its efflux pumps, this review focuses on recent strategies to reach brain based on siRNA, and how to specifically target these approaches in order to treat brain diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Wavelet basics

    CERN Document Server

    Chan, Y T

    1995-01-01

    Since the study of wavelets is a relatively new area, much of the research coming from mathematicians, most of the literature uses terminology, concepts and proofs that may, at times, be difficult and intimidating for the engineer. Wavelet Basics has therefore been written as an introductory book for scientists and engineers. The mathematical presentation has been kept simple, the concepts being presented in elaborate detail in a terminology that engineers will find familiar. Difficult ideas are illustrated with examples which will also aid in the development of an intuitive insight. Chapter 1 reviews the basics of signal transformation and discusses the concepts of duals and frames. Chapter 2 introduces the wavelet transform, contrasts it with the short-time Fourier transform and clarifies the names of the different types of wavelet transforms. Chapter 3 links multiresolution analysis, orthonormal wavelets and the design of digital filters. Chapter 4 gives a tour d'horizon of topics of current interest: wave...

  6. Chronic lymphocytic leukemia and infection risk in the era of targeted therapies: Linking mechanisms with infections.

    Science.gov (United States)

    Hilal, Talal; Gea Banacloche, Juan C; Leis, Jose F

    2018-03-16

    Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the world. Patient with CLL are at particular risk for infections due to inherent disease-related immune dysfunction in addition to the effect of certain systemic therapies on the immune system. The advent of B-cell receptor (BCR) inhibitors such as ibrutinib and idelalisib has led to a practice change that utilizes these targeted agents in the treatment of CLL, either in place of chemoimmunotherapy (CIT) or in later line settings. In this paper, we review the pathophysiology of immune dysfunction in CLL, the spectrum of immunodeficiency with the various therapeutic agents along with prevention strategies with a focus on targeted therapies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Molecular mechanisms underlying radio-induced fibro-genic differentiation and fibrosis targeted therapies

    International Nuclear Information System (INIS)

    Bourgier, C.

    2008-01-01

    Intestinal complications after radiotherapy are caused by transmural fibrosis (RIF) that impaired the quality of life of cancer patient survivors and considered permanent and irreversible until recently but recent molecular characterization of RIF offered new targeted opportunities for the development of anti-fibrotic therapies. In this thesis work, we identified activation of the Rho/ROCK pathway which is involved in the persistence of fibro-genic signals. In addition, among the new anti-fibrotic targeted therapies, we asked whether specific inhibition of Rho pathway, by Pravastatin could elicit anti-fibrotic action. Therefore, the therapeutic relevance of pravastatin as anti-fibrotic strategy was validated using two different models of intestinal and lung fibrosis. As statins are safe and well tolerated compounds, phase II clinical trial is envisioned within the next months to reverse established fibrosis after radiotherapy. (author)

  8. Reactive Oxygen Species-Mediated Mechanisms of Action of Targeted Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Hanna-Riikka Teppo

    2017-01-01

    Full Text Available Targeted cancer therapies, involving tyrosine kinase inhibitors and monoclonal antibodies, for example, have recently led to substantial prolongation of survival in many metastatic cancers. Compared with traditional chemotherapy and radiotherapy, where reactive oxygen species (ROS have been directly linked to the mediation of cytotoxic effects and adverse events, the field of oxidative stress regulation is still emerging in targeted cancer therapies. Here, we provide a comprehensive review regarding the current evidence of ROS-mediated effects of antibodies and tyrosine kinase inhibitors, use of which has been indicated in the treatment of solid malignancies and lymphomas. It can be concluded that there is rapidly emerging evidence of ROS-mediated effects of some of these compounds, which is also relevant in the context of drug resistance and how to overcome it.

  9. Education: The Basics. The Basics

    Science.gov (United States)

    Wood, Kay

    2011-01-01

    Everyone knows that education is important, we are confronted daily by discussion of it in the media and by politicians, but how much do we really know about education? "Education: The Basics" is a lively and engaging introduction to education as an academic subject, taking into account both theory and practice. Covering the schooling system, the…

  10. The Mechanisms to Consolidate Staff Efforts in the Targeting of Increasing the Competitive Potential of Enterprise

    Directory of Open Access Journals (Sweden)

    Legominova Svitlana V.

    2017-10-01

    Full Text Available The topicality of focusing efforts to improve the competitive potential of enterprise through intellectualization of its staff, using continuous training in accordance with technological regimes and modern trends, has been rationalized. The author has analyzed the structural features of intellectual capital, determining the need for their efficient interaction to gain competitive value. A combination of behavioristic and cognitive approaches has been proposed, using a holistic model of human resources management in order to ensure efficient management and consideration of specific characteristics of cognitive behavior. It has been proven that the competitive potential of enterprise is directly dependent on the accumulation and diffusion of knowledge, should be of permanent nature, ensuring a stable increase in the competitive potential of enterprise and creating the ground for the formation of leadership positions, thus determining the basic mainstreams of development.

  11. Monoaminergic Mechanisms in Epilepsy May Offer Innovative Therapeutic Opportunity for Monoaminergic Multi-Target Drugs

    Directory of Open Access Journals (Sweden)

    Dubravka Svob Strac

    2016-11-01

    Full Text Available A large body of experimental and clinical evidence has strongly suggested that monoamines play an important role in regulating epileptogenesis, seizure susceptibility, convulsions and comorbid psychiatric disorders commonly seen in people with epilepsy. However, neither the relative significance of individual monoamines nor their interaction has yet been fully clarified due to the complexity of these neurotransmitter systems. In addition, epilepsy is diverse, with many different seizure types and epilepsy syndromes, and the role played by monoamines may vary from one condition to another. In this review, we will focus on the role of serotonin, dopamine, noradrenaline, histamine and melatonin in epilepsy. Recent experimental, clinical and genetic evidence, will be reviewed in consideration of the mutual relationship of monoamines with the other putative neurotransmitters. The complexity of epileptic pathogenesis may explain why the currently available drugs, developed according to the classic drug discovery paradigm of one-molecule-one-target, have turned out to be effective only in a percentage of people with epilepsy. Although no antiepileptic drugs currently target specifically monoaminergic systems, multi-target directed ligands acting on different monoaminergic proteins present on both neurons and glia cells may represent a new approach in the management of seizures and their generation as well as comorbid neuropsychiatric disorders.

  12. Monoaminergic Mechanisms in Epilepsy May Offer Innovative Therapeutic Opportunity for Monoaminergic Multi-Target Drugs

    Science.gov (United States)

    Svob Strac, Dubravka; Pivac, Nela; Smolders, Ilse J.; Fogel, Wieslawa A.; De Deurwaerdere, Philippe; Di Giovanni, Giuseppe

    2016-01-01

    A large body of experimental and clinical evidence has strongly suggested that monoamines play an important role in regulating epileptogenesis, seizure susceptibility, convulsions, and comorbid psychiatric disorders commonly seen in people with epilepsy (PWE). However, neither the relative significance of individual monoamines nor their interaction has yet been fully clarified due to the complexity of these neurotransmitter systems. In addition, epilepsy is diverse, with many different seizure types and epilepsy syndromes, and the role played by monoamines may vary from one condition to another. In this review, we will focus on the role of serotonin, dopamine, noradrenaline, histamine, and melatonin in epilepsy. Recent experimental, clinical, and genetic evidence will be reviewed in consideration of the mutual relationship of monoamines with the other putative neurotransmitters. The complexity of epileptic pathogenesis may explain why the currently available drugs, developed according to the classic drug discovery paradigm of “one-molecule-one-target,” have turned out to be effective only in a percentage of PWE. Although, no antiepileptic drugs currently target specifically monoaminergic systems, multi-target directed ligands acting on different monoaminergic proteins, present on both neurons and glia cells, may represent a new approach in the management of seizures, and their generation as well as comorbid neuropsychiatric disorders. PMID:27891070

  13. EGFR-targeted anti-cancer drugs in radiotherapy: Preclinical evaluation of mechanisms

    International Nuclear Information System (INIS)

    Baumann, Michael; Krause, Mechthild; Dikomey, Ekkehard; Dittmann, Klaus; Doerr, Wolfgang; Kasten-Pisula, Ulla; Rodemann, H. Peter

    2007-01-01

    Preclinical and clinical results indicate that the EGFR can mediate radioresistance in different solid human tumours. Combination of radiotherapy and EGFR inhibitors can improve local tumour control compared to irradiation alone and has been introduced into clinical radiotherapy practice. So far several mechanisms have been identified in preclinical studies to contribute to improved local tumour control after radiation combined with EGFR inhibitors. These include direct kill of cancer stem cells by EGFR inhibitors, cellular radiosensitization through modified signal transduction, inhibition of repair of DNA damage, reduced repopulation and improved reoxygenation during fractionated radiotherapy. Effects and mechanisms may differ for different classes of EGFR inhibitors, for different tumours and for normal tissues. The mechanisms underlying this heterogeneity are currently poorly understood, and predictive assays are not available yet. Importantly, mechanisms and predictors for the combined effects of radiation with EGFR inhibitors appear to be considerably different to those for application of EGFR inhibitors alone or in combination with chemotherapy. Therefore to further evaluate the efficacy and mechanisms of EGFR-inhibition in combined treatments, radiotherapy-specific preclinical research strategies, which include in vivo experiments using local tumour control as an endpoint, as well as animal studies on normal tissue toxicity are needed

  14. [Study on correction of data bias caused by different missing mechanisms in survey of medical expenditure among students enrolling in Urban Resident Basic Medical Insurance].

    Science.gov (United States)

    Zhang, Haixia; Zhao, Junkang; Gu, Caijiao; Cui, Yan; Rong, Huiying; Meng, Fanlong; Wang, Tong

    2015-05-01

    The study of the medical expenditure and its influencing factors among the students enrolling in Urban Resident Basic Medical Insurance (URBMI) in Taiyuan indicated that non response bias and selection bias coexist in dependent variable of the survey data. Unlike previous studies only focused on one missing mechanism, a two-stage method to deal with two missing mechanisms simultaneously was suggested in this study, combining multiple imputation with sample selection model. A total of 1 190 questionnaires were returned by the students (or their parents) selected in child care settings, schools and universities in Taiyuan by stratified cluster random sampling in 2012. In the returned questionnaires, 2.52% existed not missing at random (NMAR) of dependent variable and 7.14% existed missing at random (MAR) of dependent variable. First, multiple imputation was conducted for MAR by using completed data, then sample selection model was used to correct NMAR in multiple imputation, and a multi influencing factor analysis model was established. Based on 1 000 times resampling, the best scheme of filling the random missing values is the predictive mean matching (PMM) method under the missing proportion. With this optimal scheme, a two stage survey was conducted. Finally, it was found that the influencing factors on annual medical expenditure among the students enrolling in URBMI in Taiyuan included population group, annual household gross income, affordability of medical insurance expenditure, chronic disease, seeking medical care in hospital, seeking medical care in community health center or private clinic, hospitalization, hospitalization canceled due to certain reason, self medication and acceptable proportion of self-paid medical expenditure. The two-stage method combining multiple imputation with sample selection model can deal with non response bias and selection bias effectively in dependent variable of the survey data.

  15. Chemical and radiation carcinogenesis - basic mechanisms and establishment of biomedical risk-assessment systems. Technical progress report, February 15, 1981-June 1, 1982

    International Nuclear Information System (INIS)

    1982-01-01

    In the past, the characterization of both perturbation and response has been done at the cellular level, and therefore, has only been semi-quantitative, descriptive, and time-consuming. We are rapidly developing the molecular basis of determining the perturbation and the biological response at the molecular level. This is made possible through extensive application of monoclonal antibodies and recombinant DNA as well as other modern molecular biology techniques. Previous studies on somatic mutation and neoplastic transformation have been sufficiently quantitative to indicate the inadequate understanding of the basic mechanisms in the biological system when only focused on these two approaches. For the first time, our studies have been focused on two additional important issues: (1) consideration of differentiation and (2) the importance of stem cells in culture and in the host. We have begun to focus not only on cellular studies in culture but on the establishment of a system which embraces both in vivo and in vitro studies. The two systems which we have chosen to investigate are the embryo-skin cell system and the embryonic-hematopoietic system. The experimental approaches and procedures will involve the study of the problem at the molecular level, and will be extended to the study from cells to tissues to host

  16. Specification of Change Mechanisms in Pregnant Smokers for Malleable Target Identification: A Novel Approach to a Tenacious Public Health Problem

    Directory of Open Access Journals (Sweden)

    Suena H. Massey

    2017-09-01

    Full Text Available Maternal smoking during pregnancy (MSDP continues to be a leading modifiable risk factor for perinatal complications and a range of neurodevelopmental and cardio-metabolic outcomes across the lifespan. Despite 40 years of intervention research less than one in five pregnant smokers who receive an intervention quit by delivery. Within this context, recognition of pregnancy is commonly associated with abrupt suspension or reduction of smoking in the absence of intervention, yet has not been investigated as a volitional target. The goal of this article is to provide the empirical foundation for a novel direction of research aimed at identifying malleable targets for intervention through the specification of behavior change mechanisms specific to pregnant women. To do so, we: (1 summarize progress on MSDP in the United States generated from conventional empirical approaches to health behavior change; (2 discuss the phenomenon of spontaneous change in the absence of intervention among pregnant smokers to illustrate the need for mechanistic specification of behavior change motivated by concern for fetal well-being; (3 summarize component processes in neurobiological models of parental and non-parental social behaviors as a conceptual framework for understanding change mechanisms during pregnancy; (4 discuss the evidence for the malleability of these processes to support their translational relevance for preventive interventions; and (5 propose a roadmap for validating the proposed change mechanism using an experimental medicine approach. A greater understanding of social and interpersonal processes that facilitate health behavior change among expectant mothers and how these processes differ interindividually could yield novel volitional targets for prenatal interventions. More broadly, explicating other-oriented mechanisms of behavior change during pregnancy could serve as a paradigm for understanding how social and interpersonal processes

  17. Ecological Interventionist Causal Models in Psychosis: Targeting Psychological Mechanisms in Daily Life.

    Science.gov (United States)

    Reininghaus, Ulrich; Depp, Colin A; Myin-Germeys, Inez

    2016-03-01

    Integrated models of psychotic disorders have posited a number of putative psychological mechanisms that may contribute to the development of psychotic symptoms, but it is only recently that a modest amount of experience sampling research has provided evidence on their role in daily life, outside the research laboratory. A number of methodological challenges remain in evaluating specificity of potential causal links between a given psychological mechanism and psychosis outcomes in a systematic fashion, capitalizing on longitudinal data to investigate temporal ordering. In this article, we argue for testing ecological interventionist causal models that draw on real world and real-time delivered, ecological momentary interventions for generating evidence on several causal criteria (association, time order, and direction/sole plausibility) under real-world conditions, while maximizing generalizability to social contexts and experiences in heterogeneous populations. Specifically, this approach tests whether ecological momentary interventions can (1) modify a putative mechanism and (2) produce changes in the mechanism that lead to sustainable changes in intended psychosis outcomes in individuals' daily lives. Future research using this approach will provide translational evidence on the active ingredients of mobile health and in-person interventions that promote sustained effectiveness of ecological momentary interventions and, thereby, contribute to ongoing efforts that seek to enhance effectiveness of psychological interventions under real-world conditions. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  18. Ecological Interventionist Causal Models in Psychosis: Targeting Psychological Mechanisms in Daily Life

    Science.gov (United States)

    Reininghaus, Ulrich; Depp, Colin A.; Myin-Germeys, Inez

    2016-01-01

    Integrated models of psychotic disorders have posited a number of putative psychological mechanisms that may contribute to the development of psychotic symptoms, but it is only recently that a modest amount of experience sampling research has provided evidence on their role in daily life, outside the research laboratory. A number of methodological challenges remain in evaluating specificity of potential causal links between a given psychological mechanism and psychosis outcomes in a systematic fashion, capitalizing on longitudinal data to investigate temporal ordering. In this article, we argue for testing ecological interventionist causal models that draw on real world and real-time delivered, ecological momentary interventions for generating evidence on several causal criteria (association, time order, and direction/sole plausibility) under real-world conditions, while maximizing generalizability to social contexts and experiences in heterogeneous populations. Specifically, this approach tests whether ecological momentary interventions can (1) modify a putative mechanism and (2) produce changes in the mechanism that lead to sustainable changes in intended psychosis outcomes in individuals’ daily lives. Future research using this approach will provide translational evidence on the active ingredients of mobile health and in-person interventions that promote sustained effectiveness of ecological momentary interventions and, thereby, contribute to ongoing efforts that seek to enhance effectiveness of psychological interventions under real-world conditions. PMID:26707864

  19. Protective immune mechanisms against pre-erythrocytic forms of Plasmodium berghei depend on the target antigen

    Directory of Open Access Journals (Sweden)

    Elke S. Bergmann-Leitner

    2014-01-01

    Full Text Available Pre-erythrocytic malaria vaccines are believed to either stop the injected sporozoites from reaching the liver or to direct cellular immune responses towards eliminating infected hepatocytes. The present study reveals for the first time the anatomical sites at which these immune mechanisms act against the malaria parasites. To determine the mechanisms leading to protection mediated by two previously characterized vaccines against either the circumsporozoite protein (CSP or the cell traversal protein for ookinetes and sporozoites (CelTOS, mice were immunized and subsequently challenged by subcutaneous injection of salivary gland sporozoites of luciferase-transgenic Plasmodium berghei parasites. The In Vivo Imaging System (IVIS was used to identify the anatomical site where the vaccine-induced immune response eliminates sporozoites after injection. The data demonstrate that CSP-based immunity acts at the site of infection (skin whereas CelTOS-based immunity is only partially efficient in the skin and allows reduced levels of liver infection that can be subsequently cleared. The results of this study challenge assumptions regarding CSP-mediated immune mechanisms and call into question the validity of some commonly used assays to evaluate anti-CSP immune responses. The knowledge of the mechanism and events leading to infection or immune defense will guide supportive treatment with drugs or combination therapies and thus accelerate the development of effective antimalarial strategies.

  20. Targeting Cellular Stress Mechanisms and Metabolic Homeostasis by Chinese Herbal Drugs for Neuroprotection

    Directory of Open Access Journals (Sweden)

    Hsiao-Chien Ting

    2018-01-01

    Full Text Available Traditional Chinese medicine has been practiced for centuries in East Asia. Herbs are used to maintain health and cure disease. Certain Chinese herbs are known to protect and improve the brain, memory, and nervous system. To apply ancient knowledge to modern science, some major natural therapeutic compounds in herbs were extracted and evaluated in recent decades. Emerging studies have shown that herbal compounds have neuroprotective effects or can ameliorate neurodegenerative diseases. To understand the mechanisms of herbal compounds that protect against neurodegenerative diseases, we summarize studies that discovered neuroprotection by herbal compounds and compound-related mechanisms in neurodegenerative disease models. Those compounds discussed herein show neuroprotection through different mechanisms, such as cytokine regulation, autophagy, endoplasmic reticulum (ER stress, glucose metabolism, and synaptic function. The interleukin (IL-1β and tumor necrosis factor (TNF-α signaling pathways are inhibited by some compounds, thus attenuating the inflammatory response and protecting neurons from cell death. As to autophagy regulation, herbal compounds show opposite regulatory effects in different neurodegenerative models. Herbal compounds that inhibit ER stress prevent neuronal death in neurodegenerative diseases. Moreover, there are compounds that protect against neuronal death by affecting glucose metabolism and synaptic function. Since the progression of neurodegenerative diseases is complicated, and compound-related mechanisms for neuroprotection differ, therapeutic strategies may need to involve multiple compounds and consider the type and stage of neurodegenerative diseases.

  1. Targeting of nucleotide-binding proteins by HAMLET--a conserved tumor cell death mechanism.

    Science.gov (United States)

    Ho, J C S; Nadeem, A; Rydström, A; Puthia, M; Svanborg, C

    2016-02-18

    HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) kills tumor cells broadly suggesting that conserved survival pathways are perturbed. We now identify nucleotide-binding proteins as HAMLET binding partners, accounting for about 35% of all HAMLET targets in a protein microarray comprising 8000 human proteins. Target kinases were present in all branches of the Kinome tree, including 26 tyrosine kinases, 10 tyrosine kinase-like kinases, 13 homologs of yeast sterile kinases, 4 casein kinase 1 kinases, 15 containing PKA, PKG, PKC family kinases, 15 calcium/calmodulin-dependent protein kinase kinases and 13 kinases from CDK, MAPK, GSK3, CLK families. HAMLET acted as a broad kinase inhibitor in vitro, as defined in a screen of 347 wild-type, 93 mutant, 19 atypical and 17 lipid kinases. Inhibition of phosphorylation was also detected in extracts from HAMLET-treated lung carcinoma cells. In addition, HAMLET recognized 24 Ras family proteins and bound to Ras, RasL11B and Rap1B on the cytoplasmic face of the plasma membrane. Direct cellular interactions between HAMLET and activated Ras family members including Braf were confirmed by co-immunoprecipitation. As a consequence, oncogenic Ras and Braf activity was inhibited and HAMLET and Braf inhibitors synergistically increased tumor cell death in response to HAMLET. Unlike most small molecule kinase inhibitors, HAMLET showed selectivity for tumor cells in vitro and in vivo. The results identify nucleotide-binding proteins as HAMLET targets and suggest that dysregulation of the ATPase/kinase/GTPase machinery contributes to cell death, following the initial, selective recognition of HAMLET by tumor cells. The findings thus provide a molecular basis for the conserved tumoricidal effect of HAMLET, through dysregulation of kinases and oncogenic GTPases, to which tumor cells are addicted.

  2. Chemical Genomics and Emerging DNA Technologies in the Identification of Drug Mechanisms and Drug Targets

    DEFF Research Database (Denmark)

    Olsen, Louise Cathrine Braun; Færgeman, Nils J.

    2012-01-01

    and validate therapeutic targets and to discover drug candidates for rapidly and effectively generating new interventions for human diseases. The recent emergence of genomic technologies and their application on genetically tractable model organisms like Drosophila melanogaster,Caenorhabditis elegans...... critical roles in the genomic age of biological research and drug discovery. In the present review we discuss how simple biological model organisms can be used as screening platforms in combination with emerging genomic technologies to advance the identification of potential drugs and their molecular...

  3. Specific Cell Targeting Therapy Bypasses Drug Resistance Mechanisms in African Trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    Juan D Unciti-Broceta

    2015-06-01

    Full Text Available African trypanosomiasis is a deadly neglected disease caused by the extracellular parasite Trypanosoma brucei. Current therapies are characterized by high drug toxicity and increasing drug resistance mainly associated with loss-of-function mutations in the transporters involved in drug import. The introduction of new antiparasitic drugs into therapeutic use is a slow and expensive process. In contrast, specific targeting of existing drugs could represent a more rapid and cost-effective approach for neglected disease treatment, impacting through reduced systemic toxicity and circumventing resistance acquired through impaired compound uptake. We have generated nanoparticles of chitosan loaded with the trypanocidal drug pentamidine and coated by a single domain nanobody that specifically targets the surface of African trypanosomes. Once loaded into this nanocarrier, pentamidine enters trypanosomes through endocytosis instead of via classical cell surface transporters. The curative dose of pentamidine-loaded nanobody-chitosan nanoparticles was 100-fold lower than pentamidine alone in a murine model of acute African trypanosomiasis. Crucially, this new formulation displayed undiminished in vitro and in vivo activity against a trypanosome cell line resistant to pentamidine as a result of mutations in the surface transporter aquaglyceroporin 2. We conclude that this new drug delivery system increases drug efficacy and has the ability to overcome resistance to some anti-protozoal drugs.

  4. Targeting oxidant-dependent mechanisms for the treatment of COPD and its comorbidities.

    Science.gov (United States)

    Bernardo, Ivan; Bozinovski, Steven; Vlahos, Ross

    2015-11-01

    Chronic obstructive pulmonary disease (COPD) is an incurable global health burden and is characterised by progressive airflow limitation and loss of lung function. In addition to the pulmonary impact of the disease, COPD patients often develop comorbid diseases such as cardiovascular disease, skeletal muscle wasting, lung cancer and osteoporosis. One key feature of COPD, yet often underappreciated, is the contribution of oxidative stress in the onset and development of the disease. Patients experience an increased burden of oxidative stress due to the combined effects of excess reactive oxygen species (ROS) and nitrogen species (RNS) generation, antioxidant depletion and reduced antioxidant enzyme activity. Currently, there is a lack of effective treatments for COPD, and an even greater lack of research regarding interventions that treat both COPD and its comorbidities. Due to the involvement of oxidative stress in the pathogenesis of COPD and many of its comorbidities, a unique therapeutic opportunity arises where the treatment of a multitude of diseases may be possible with only one therapeutic target. In this review, oxidative stress and the roles of ROS/RNS in the context of COPD and comorbid cardiovascular disease, skeletal muscle wasting, lung cancer, and osteoporosis are discussed and the potential for therapeutic benefit of anti-oxidative treatment in these conditions is outlined. Because of the unique interplay between oxidative stress and these diseases, oxidative stress represents a novel target for the treatment of COPD and its comorbidities. Copyright © 2015. Published by Elsevier Inc.

  5. Basic principles

    International Nuclear Information System (INIS)

    Wilson, P.D.

    1996-01-01

    Some basic explanations are given of the principles underlying the nuclear fuel cycle, starting with the physics of atomic and nuclear structure and continuing with nuclear energy and reactors, fuel and waste management and finally a discussion of economics and the future. An important aspect of the fuel cycle concerns the possibility of ''closing the back end'' i.e. reprocessing the waste or unused fuel in order to re-use it in reactors of various kinds. The alternative, the ''oncethrough'' cycle, discards the discharged fuel completely. An interim measure involves the prolonged storage of highly radioactive waste fuel. (UK)

  6. Basic electronics

    CERN Document Server

    Tayal, DC

    2010-01-01

    The second edition of this book incorporates the comments and suggestions of my friends and students who have critically studied the first edition. In this edition the changes and additions have been made and subject matter has been rearranged at some places. The purpose of this text is to provide a comprehensive and up-to-date study of the principles of operation of solid state devices, their basic circuits and application of these circuits to various electronic systems, so that it can serve as a standard text not only for universities and colleges but also for technical institutes. This book

  7. Targeting health subsidies through a non-price mechanism: A randomized controlled trial in Kenya

    Science.gov (United States)

    Dupas, Pascaline; Hoffmann, Vivian; Kremer, Michael; Zwane, Alix Peterson

    2016-01-01

    Free provision of preventive health products can dramatically increase access in low income countries. A cost concern about free provision is that some recipients may not use the product, wasting resources (over-inclusion). Yet charging a price to screen out non-users may screen out poor people who need and would use the product (over-exclusion). We report on a randomized controlled trial of a screening mechanism that combines the free provision of chlorine solution for water treatment with a small non-monetary cost (household vouchers that need to be redeemed monthly in order). Relative to a non-voucher free distribution program, this mechanism reduces the quantity of chlorine procured by 60 percentage points, but reduces the share of households whose stored water tests positive for chlorine residual by only one percentage point, dramatically improving the tradeoff between over-inclusion and over-exclusion. PMID:27563091

  8. Structural Insights into the Mechanisms of Action of Short-Peptide HIV-1 Fusion Inhibitors Targeting the Gp41 Pocket

    Directory of Open Access Journals (Sweden)

    Xiujuan Zhang

    2018-02-01

    Full Text Available The deep hydrophobic pocket of HIV-1 gp41 has been considered a drug target, but short-peptides targeting this site usually lack potent antiviral activity. By applying the M-T hook structure, we previously generated highly potent short-peptide fusion inhibitors that specifically targeted the pocket site, such as MT-SC22EK, HP23L, and LP-11. Here, the crystal structures of HP23L and LP-11 bound to the target mimic peptide N36 demonstrated the critical intrahelical and interhelical interactions, especially verifying that the hook-like conformation was finely adopted while the methionine residue was replaced by the oxidation-less prone residue leucine, and that addition of an extra glutamic acid significantly enhanced the binding and inhibitory activities. The structure of HP23L bound to N36 with two mutations (E49K and L57R revealed the critical residues and motifs mediating drug resistance and provided new insights into the mechanism of action of inhibitors. Therefore, the present data help our understanding for the structure-activity relationship (SAR of HIV-1 fusion inhibitors and facilitate the development of novel antiviral drugs.

  9. Bitter melon juice targets molecular mechanisms underlying gemcitabine resistance in pancreatic cancer cells

    OpenAIRE

    SOMASAGARA, RANGANATHA R.; DEEP, GAGAN; SHROTRIYA, SANGEETA; PATEL, MANISHA; AGARWAL, CHAPLA; AGARWAL, RAJESH

    2015-01-01

    Pancreatic cancer (PanC) is one of the most lethal malignancies, and resistance towards gemcitabine, the front-line chemotherapy, is the main cause for dismal rate of survival in PanC patients; overcoming this resistance remains a major challenge to treat this deadly malignancy. Whereas several molecular mechanisms are known for gemcitabine resistance in PanC cells, altered metabolism and bioenergetics are not yet studied. Here, we compared metabolic and bioenergetic functions between gemcita...

  10. Mechanisms Modulating Inflammatory Osteolysis: A Review with Insights into Therapeutic Targets

    OpenAIRE

    Wei, Shi; Siegal, Gene P.

    2008-01-01

    Inflammatory osteolysis is a relatively frequent and incapacitating complication of rheumatoid arthritis and multiple other inflammation-associated bone diseases. It is thought to operate through an ultimate common pathway of accelerated osteoclast recruitment and activation under the control of cytokines produced in the inflammatory environment. Over the past decade, there have been major advances in our understanding of the mechanisms of osteoclastogenesis. It is now clear that the interact...

  11. Study of mechanism improving target course traceability in G-Vectoring Control

    Science.gov (United States)

    Yamakado, Makoto; Abe, Masato; Kano, Yoshio; Umetsu, Daisuke; Yoshioka, Thoru

    2018-05-01

    Production-type G-Vectoring Control vehicles are now being put on the market. Customers and reviewers have praised the handling quality and course traceability of these vehicles. This paper clarifies the mechanism behind this improvement in handling quality using a simple bicycle model and driver model analysis. It focuses on the residual yaw angular acceleration when the steering speed is zero and shows that GVC reduces its value. This result provides evidence for improved handling quality in GVC vehicles.

  12. Facility target insert shielding assessment

    Energy Technology Data Exchange (ETDEWEB)

    Mocko, Michal [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-10-06

    Main objective of this report is to assess the basic shielding requirements for the vertical target insert and retrieval port. We used the baseline design for the vertical target insert in our calculations. The insert sits in the 12”-diameter cylindrical shaft extending from the service alley in the top floor of the facility all the way down to the target location. The target retrieval mechanism is a long rod with the target assembly attached and running the entire length of the vertical shaft. The insert also houses the helium cooling supply and return lines each with 2” diameter. In the present study we focused on calculating the neutron and photon dose rate fields on top of the target insert/retrieval mechanism in the service alley. Additionally, we studied a few prototypical configurations of the shielding layers in the vertical insert as well as on the top.

  13. Multi-agent Negotiation Mechanisms for Statistical Target Classification in Wireless Multimedia Sensor Networks

    Directory of Open Access Journals (Sweden)

    Sheng Wang

    2007-10-01

    Full Text Available The recent availability of low cost and miniaturized hardware has allowedwireless sensor networks (WSNs to retrieve audio and video data in real worldapplications, which has fostered the development of wireless multimedia sensor networks(WMSNs. Resource constraints and challenging multimedia data volume makedevelopment of efficient algorithms to perform in-network processing of multimediacontents imperative. This paper proposes solving problems in the domain of WMSNs fromthe perspective of multi-agent systems. The multi-agent framework enables flexible networkconfiguration and efficient collaborative in-network processing. The focus is placed ontarget classification in WMSNs where audio information is retrieved by microphones. Todeal with the uncertainties related to audio information retrieval, the statistical approachesof power spectral density estimates, principal component analysis and Gaussian processclassification are employed. A multi-agent negotiation mechanism is specially developed toefficiently utilize limited resources and simultaneously enhance classification accuracy andreliability. The negotiation is composed of two phases, where an auction based approach isfirst exploited to allocate the classification task among the agents and then individual agentdecisions are combined by the committee decision mechanism. Simulation experiments withreal world data are conducted and the results show that the proposed statistical approachesand negotiation mechanism not only reduce memory and computation requi

  14. Androgen receptor-dependent and -independent mechanisms driving prostate cancer progression: Opportunities for therapeutic targeting from multiple angles

    Science.gov (United States)

    Hoang, David T; Iczkowski, Kenneth A; Kilari, Deepak; See, William; Nevalainen, Marja T

    2017-01-01

    Despite aggressive treatment for localized cancer, prostate cancer (PC) remains a leading cause of cancer-related death for American men due to a subset of patients progressing to lethal and incurable metastatic castrate-resistant prostate cancer (CRPC). Organ-confined PC is treated by surgery or radiation with or without androgen deprivation therapy (ADT), while options for locally advanced and disseminated PC include radiation combined with ADT, or systemic treatments including chemotherapy. Progression to CRPC results from failure of ADT, which targets the androgen receptor (AR) signaling axis and inhibits AR-driven proliferation and survival pathways. The exact mechanisms underlying the transition from androgen-dependent PC to CRPC remain incompletely understood. Reactivation of AR has been shown to occur in CRPC despite depletion of circulating androgens by ADT. At the same time, the presence of AR-negative cell populations in CRPC has also been identified. While AR signaling has been proposed as the primary driver of CRPC, AR-independent signaling pathways may represent additional mechanisms underlying CRPC progression. Identification of new therapeutic strategies to target both AR-positive and AR-negative PC cell populations and, thereby, AR-driven as well as non-AR-driven PC cell growth and survival mechanisms would provide a two-pronged approach to eliminate CRPC cells with potential for synthetic lethality. In this review, we provide an overview of AR-dependent and AR-independent molecular mechanisms which drive CRPC, with special emphasis on the role of the Jak2-Stat5a/b signaling pathway in promoting castrate-resistant growth of PC through both AR-dependent and AR-independent mechanisms. PMID:27741508

  15. Targeting vascular NADPH oxidase 1 blocks tumor angiogenesis through a PPARα mediated mechanism.

    Directory of Open Access Journals (Sweden)

    Sarah Garrido-Urbani

    Full Text Available Reactive oxygen species, ROS, are regulators of endothelial cell migration, proliferation and survival, events critically involved in angiogenesis. Different isoforms of ROS-generating NOX enzymes are expressed in the vasculature and provide distinct signaling cues through differential localization and activation. We show that mice deficient in NOX1, but not NOX2 or NOX4, have impaired angiogenesis. NOX1 expression and activity is increased in primary mouse and human endothelial cells upon angiogenic stimulation. NOX1 silencing decreases endothelial cell migration and tube-like structure formation, through the inhibition of PPARα, a regulator of NF-κB. Administration of a novel NOX-specific inhibitor reduced angiogenesis and tumor growth in vivo in a PPARα dependent manner. In conclusion, vascular NOX1 is a critical mediator of angiogenesis and an attractive target for anti-angiogenic therapies.

  16. Melanin targets LC3-associated phagocytosis (LAP): A novel pathogenetic mechanism in fungal disease.

    Science.gov (United States)

    Chamilos, Georgios; Akoumianaki, Tonia; Kyrmizi, Irene; Brakhage, Axel; Beauvais, Anne; Latge, Jean-Paul

    2016-05-03

    Intracellular swelling of conidia of the major human airborne fungal pathogen Aspergillus fumigatus results in surface exposure of immunostimulatory pathogen-associated molecular patterns (PAMPs) and triggers activation of a specialized autophagy pathway called LC3-associated phagocytosis (LAP) to promote fungal killing. We have recently discovered that, apart from PAMPs exposure, cell wall melanin removal during germination of A. fumigatus is a prerequisite for activation of LAP. Importantly, melanin promotes fungal pathogenicity via targeting LAP, as a melanin-deficient A. fumigatus mutant restores its virulence upon conditional inactivation of Atg5 in hematopoietic cells of mice. Mechanistically, fungal cell wall melanin selectively excludes the CYBA/p22phox subunit of NADPH oxidase from the phagosome to inhibit LAP, without interfering with signaling regulating cytokine responses. Notably, inhibition of LAP is a general property of melanin pigments, a finding with broad physiological implications.

  17. Cognitive mechanisms of change in delusions: an experimental investigation targeting reasoning to effect change in paranoia.

    Science.gov (United States)

    Garety, Philippa; Waller, Helen; Emsley, Richard; Jolley, Suzanne; Kuipers, Elizabeth; Bebbington, Paul; Dunn, Graham; Fowler, David; Hardy, Amy; Freeman, Daniel

    2015-03-01

    Given the evidence that reasoning biases contribute to delusional persistence and change, several research groups have made systematic efforts to modify them. The current experiment tested the hypothesis that targeting reasoning biases would result in change in delusions. One hundred and one participants with current delusions and schizophrenia spectrum psychosis were randomly allocated to a brief computerized reasoning training intervention or to a control condition involving computer-based activities of similar duration. The primary hypotheses tested were that the reasoning training intervention, would improve (1) data gathering and belief flexibility and (2) delusional thinking, specifically paranoia. We then tested whether the changes in paranoia were mediated by changes in data gathering and flexibility, and whether working memory and negative symptoms moderated any intervention effects. On an intention-to-treat analysis, there were significant improvements in state paranoia and reasoning in the experimental compared with the control condition. There was evidence that changes in reasoning mediated changes in paranoia, although this effect fell just outside the conventional level of significance after adjustment for baseline confounders. Working memory and negative symptoms significantly moderated the effects of the intervention on reasoning. The study demonstrated the effectiveness of a brief reasoning intervention in improving both reasoning processes and paranoia. It thereby provides proof-of-concept evidence that reasoning is a promising intermediary target in interventions to ameliorate delusions, and thus supports the value of developing this approach as a longer therapeutic intervention. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

  18. On mechanism of low-energy heavy ions scattering on a target surface with small atomic mass

    Energy Technology Data Exchange (ETDEWEB)

    Umarov, F.F. E-mail: farid1945@yahoo.com; Bazarbaev, N.N.; Kudryashova, L.B.; Krylov, N.M

    2002-11-01

    In the present work, an experimental study of low-energy (E{sub 0}=20-500 eV) heavy Cs{sup +} ions scattering on target surfaces with small atomic masses (Al, Si, Ni) has been performed for more accurate definition of mechanism of scattering and evaluation of an opportunity for use of heavy ions scattering as a tool of surface layer analysis. It is shown that the dependence of the relative energies of scattered ions versus the initial energy E/E{sub 0} (E{sub 0}) for Si (E{sub b}=4.64 eV/atom) and Ni (E{sub b}=4.43 eV/atom) approximately coincide despite the fact that the mass of Ni atom is twice as large as that of the Si atom mass. At the same time their binding energies E{sub b} are approximately equal to each other. It is found that the scattering angles of Cs{sup +} ions considerably exceed a limiting scattering angle {theta}{sub lim} in a single collision. It has been established that the scattering of low-energy heavy ions by light targets is described by a non-binary mechanism of many-particle interactions (simultaneous ion interaction with several target atoms). It has been shown that during the many-particle interactions the structure of energy spectra disappears; high relative energy of scattering ions and their dependence on energy of bombardment is observed. It has been found that the energy of scattered ions depends on binding energy, melting temperature and packing density of target atoms.

  19. The intensity of non-target site mechanisms influences the level of resistance of sourgrass to glyphosate

    Directory of Open Access Journals (Sweden)

    Flávia Regina da Costa

    2014-02-01

    Full Text Available Non-target site mechanisms are involved in the resistance of sourgrass (Digitaria insularis to glyphosate. Studies on the 14C-glyphosate absorption and translocation as well as the detection of glyphosate and its metabolites in sourgrass plants were carried out under controlled conditions to investigate if the differential response of resistant sourgrass biotypes (R1 and R2 is derived from the intensity of non-target site mechanisms involved in the resistance to glyphosate. Different pattern of absorption was observed between S (susceptible and R2 from 12 up to 48 hours after treatment with glyphosate (HAT, and between S and R1 just at 12 HAT. The initial difference in glyphosate absorption among the biotypes did not maintained at 96 HAT and afterwards. Smaller amount of herbicide left the treated leaf into the rest of shoot and roots in R2 (25% than in S (58% and R1 (52%. In addition, slight difference in glyphosate translocation was observed between S and R1. We found high percentage (81% of glyphosate in the S biotype up to 168 HAT, while just 44% and 2% of glyphosate was recovered from R1 and R2 plant tissues. In addition, high percentage of glyphosate metabolites was found in R2 (98% and R1 (56% biotypes, while a very low percentage (11% was found in the S biotype. As previous studies indicated resistant factors of 3.5 and 5.6 for R1 and R2, respectively, we conclude that the differential response of sourgrass biotypes is derived from the intensity of the non-target site mechanisms involved in the resistance to glyphosate.

  20. Elucidating the mechanism of action of pregabalin: α(2)δ as a therapeutic target in anxiety.

    Science.gov (United States)

    Micó, Juan-Antonio; Prieto, Rita

    2012-08-01

    This review provides a brief summary of what is known about the anxiolytic mechanism of action of pregabalin, a highly selective, high-affinity ligand of the P/Q type of voltage-gated calcium channel (CaV). Evidence from in vivo models of neuronal hyperexcitability suggests that pregabalin reduces synaptic release of neurotransmitters in selected CNS regions including the cortex, olfactory bulb, hypothalamus, amygdala, hippocampus, cerebellum and dorsal horn of the spinal cord. Release of neurotransmitters from the synaptic vesicle, and propagation of neurotransmission, requires the vesicle to fuse with the presynaptic membrane. Pregabalin binding to the α(2)δ type 1 protein of the P/Q type CaV reduces the availability of Ca2+ required for membrane fusion and exocytosis of neurotransmitters. Evidence that the anxiolytic mechanism of action of pregabalin is mediated by binding to the α(2)δ type 1 protein comes from animal models, which have demonstrated a structure-activity relationship between the affinity of ligands for the α(2)δ type 1 protein and their potency in models of anxiety such as the Vogel conflict test. Furthermore, the anxiolytic activity of pregabalin is lost in transgenic mice with specific point mutations in the CaV α(2)δ type 1 protein. Pregabalin-mediated reduction in calcium currents has also been shown to result in a significant inhibition of the release of neurotransmitters implicated in pathological anxiety such as glutamate and monoamine neurotransmitters. However, further research is needed to confirm that these effects contribute to the anxiolytic mechanism of action of pregabalin. Finally, pregabalin may also act by inhibiting synaptogenesis of excitatory neurons formed in response to chronic stress or anxiety, or more acutely inhibit the trafficking of CaV to the plasma membrane.

  1. Basic Financial Accounting

    DEFF Research Database (Denmark)

    Wiborg, Karsten

    This textbook on Basic Financial Accounting is targeted students in the economics studies at universities and business colleges having an introductory subject in the external dimension of the company's economic reporting, including bookkeeping, etc. The book includes the following subjects......: business entities, the transformation process, types of businesses, stakeholders, legislation, the annual report, the VAT system, double-entry bookkeeping, inventories, and year-end cast flow analysis....

  2. Proposal of measuring the mechanisms of nuclear excitation leading to fission with the ADONE jet-target tagged photon beam

    International Nuclear Information System (INIS)

    Lucherini, V.; Bianchi, N.; De Sanctis, E.; Guaraldo, C.; Levi Sandri, P.; Muccifora, V.; Polli, E.; Reolon, A.R.; Aiello, S.; De Filippo, E.; Lanzano', G.; Lo Nigro, S.; Milone, C.; Pagano, A.; Botvina, A.S.; Iljinov, A.S.; Mebel, M.V.

    1990-01-01

    The mechanisms of excitation with subsequent fission of heavy nuclei can be conveniently studied by means of photons, since this probe is able to interact deeply inside the nucleus. We propose the use of the (200-1200 MeV) tagged photon beam from the ADONE Jet Target in order to study the mass-energy and total momentum distributions of fission fragments, to obtain experimental information on the configurations (excitation energy and nucleonic composition) of produced compound nuclei and on their decay channels

  3. EMT blockage strategies: Targeting Akt dependent mechanisms for breast cancer metastatic behaviour modulation.

    Science.gov (United States)

    Rafael, D; Doktorovová, S; Florindo, H F; Gener, P; Abasolo, I; Schwartz, S; Videira, M A

    2015-01-01

    Epithelial Mesenchymal Transition (EMT) is an event where epithelial cells acquire mesenchymal-like phenotype. EMT can occur as a physiological phenomenon during tissue development and wound healing, but most importantly, EMT can confer highly invasive properties to epithelial carcinoma cells. The impairment of E-cadherin expression, an essential cell-cell adhesion protein, together with an increase in the expression of mesenchymal markers, such as N-cadherin, vimentin, and fibronectin, characterize the EMT process and are usually correlated with tumor migration, and metastization. A wide range of micro-environmental and intracellular factors regulate tumor development and progression. The dynamic cross-talk between the adhesion-related proteins such as E-cadherin and the EMT-related transcription factors, with special focus on TWIST, will be discussed here, with the aim of finding a suitable biological pathway to be used as potential target for cancer therapy. Emerging concepts such as the role of the PI3K/AKT/TWIST pathway in the regulation of the E-cadherin expression will be highlighted, since it seems to be consistently involved in cells EMT. The well-known efficacy of the RNA interference as a tool to silence the expression of specific proteins has come into focus as a strategy to control different tumor sub-populations. Despite the oligonucleotides enormous sensitivity and low in vivo stability, new (nano)technological solutions are expected to enable RNAi clinical application in cancer therapy.

  4. Ebselen, a promising antioxidant drug: mechanisms of action and targets of biological pathways.

    Science.gov (United States)

    Azad, Gajendra Kumar; Tomar, Raghuvir S

    2014-08-01

    Ebselen, an organoselenium compound, mimics glutathione peroxidase activity. It is a multifunctional compound, which catalyzes several essential reactions for the protection of cellular components from oxidative and free radical damage. Based on a number of in vitro and in vivo studies, various mechanisms are proposed to understand the biomedical actions of ebselen in health and diseases. It modulates metallo-proteins, enzymatic cofactors, gene expression, epigenetics, antioxidant defenses and immune systems. Owing to these properties, ebselen is currently under clinical trials for the prevention and treatment of various disorders such as cardiovascular diseases, arthritis, stroke, atherosclerosis, and cancer. A few ebselen-based pharmaceutical agents are under extensive investigation. As ebselen has been shown to have significant cellular toxicity, appropriate studies are needed to redesign the ebselen-based therapy for clinical trials. This review summarizes current understanding of the biochemical and molecular properties, and pharmacological applications of ebselen and future directions in this area of research.

  5. Fracture mechanical analysis of tungsten armor failure of a water-cooled divertor target

    Energy Technology Data Exchange (ETDEWEB)

    Li, Muyuan; Werner, Ewald [Lehrstuhl für Werkstoffkunde und Werkstoffmechanik, Technische Universität München, Boltzmannstr. 15, 85748 Garching (Germany); You, Jeong-Ha, E-mail: you@ipp.mpg.de [Max-Planck-Institut für Plasmaphysik, Boltzmannstr. 2, 85748 Garching (Germany)

    2014-11-15

    Highlights: • The FEM-based VCE method and XFEM were employed for computing K{sub I} (or J-integral) and predicting progressive cracking, respectively. • The most probable pattern of crack formation is radial cracking in the tungsten armor block. • The most probable site of cracking is the upper interfacial region of the tungsten armor block adjacent to the top position of the copper interlayer. • The initiation of a major crack becomes likely, only when the strength of tungsten armor block is significantly reduced from its original strength. - Abstract: The inherent brittleness of tungsten at low temperature and the embrittlement by neutron irradiation are its most critical weaknesses for fusion applications. In the current design of the ITER and DEMO divertor, the high heat flux loads during the operation impose a strong constraint on the structure–mechanical performance of the divertor. Thus, the combination of brittleness and the thermally induced stress fields due to the high heat flux loads raises a serious reliability issue in terms of the structural integrity of tungsten armor. In this study, quantitative estimates of the vulnerability of the tungsten monoblock armor cracking under stationary high heat flux loads are presented. A comparative fracture mechanical investigation has been carried out by means of two different types of computational approaches, namely, the extended finite element method (XFEM) and the finite element method (FEM)-based virtual crack tip extension (VCE) method. The fracture analysis indicates that the most probable pattern of crack formation is radial cracking in the tungsten armor starting from the interface to tube and the most probable site of cracking is the upper interfacial region of the tungsten armor adjacent to the top position of the copper interlayer. The strength threshold for crack initiation and the high heat flux load threshold for crack propagation are evaluated based on XFEM simulations and computations

  6. Dry age-related macular degeneration: mechanisms, therapeutic targets, and imaging.

    Science.gov (United States)

    Bowes Rickman, Catherine; Farsiu, Sina; Toth, Cynthia A; Klingeborn, Mikael

    2013-12-13

    Age-related macular degeneration is the leading cause of irreversible visual dysfunction in individuals over 65 in Western Society. Patients with AMD are classified as having early stage disease (early AMD), in which visual function is affected, or late AMD (generally characterized as either "wet" neovascular AMD, "dry" atrophic AMD or both), in which central vision is severely compromised or lost. Until recently, there have been no therapies available to treat the disorder(s). Now, the most common wet form of late-stage AMD, choroidal neovascularization, generally responds to treatment with anti-vascular endothelial growth factor therapies. Nevertheless, there are no current therapies to restore lost vision in eyes with advanced atrophic AMD. Oral supplementation with the Age-Related Eye Disease Study (AREDS) or AREDS2 formulation (antioxidant vitamins C and E, lutein, zeaxanthin, and zinc) has been shown to reduce the risk of progression to advanced AMD, although the impact was in neovascular rather than atrophic AMD. Recent findings, however, have demonstrated several features of early AMD that are likely to be druggable targets for treatment. Studies have established that much of the genetic risk for AMD is associated with complement genes. Consequently, several complement-based therapeutic treatment approaches are being pursued. Potential treatment strategies against AMD deposit formation and protein and/or lipid deposition will be discussed, including anti-amyloid therapies. In addition, the role of autophagy in AMD and prevention of oxidative stress through modulation of the antioxidant system will be explored. Finally, the success of these new therapies in clinical trials and beyond relies on early detection, disease typing, and predicting disease progression, areas that are currently being rapidly transformed by improving imaging modalities and functional assays.

  7. Targeting extinction and reconsolidation mechanisms to combat the impact of drug cues on addiction.

    Science.gov (United States)

    Taylor, Jane R; Olausson, Peter; Quinn, Jennifer J; Torregrossa, Mary M

    2009-01-01

    Drug addiction is a progressive and compulsive disorder, where recurrent craving and relapse to drug-seeking occur even after long periods of abstinence. A major contributing factor to relapse is drug-associated cues. Here we review behavioral and pharmacological studies outlining novel methods of effective and persistent reductions in cue-induced relapse behavior in animal models. We focus on extinction and reconsolidation of cue-drug associations as the memory processes that are the most likely targets for interventions. Extinction involves the formation of new inhibitory memories rather than memory erasure; thus, it should be possible to facilitate the extinction of cue-drug memories to reduce relapse. We propose that context-dependency of extinction might be altered by mnemonic agents, thereby enhancing the efficacy of cue-exposure therapy as treatment strategy. In contrast, interfering with memory reconsolidation processes can disrupt the integrity or strength of specific cue-drug memories. Reconsolidation is argued to be a distinct process that occurs over a brief time period after memory is reactivated/retrieved - when the memory becomes labile and vulnerable to disruption. Reconsolidation is thought to be an independent, perhaps opposing, process to extinction and disruption of reconsolidation has recently been shown to directly affect subsequent cue-drug memory retrieval in an animal model of relapse. We hypothesize that a combined approach aimed at both enhancing the consolidation of cue-drug extinction and interfering with the reconsolidation of cue-drug memories will have a greater potential for persistently inhibiting cue-induced relapse than either treatment alone.

  8. Dry Age-Related Macular Degeneration: Mechanisms, Therapeutic Targets, and Imaging

    Science.gov (United States)

    Bowes Rickman, Catherine; Farsiu, Sina; Toth, Cynthia A.; Klingeborn, Mikael

    2013-01-01

    Age-related macular degeneration is the leading cause of irreversible visual dysfunction in individuals over 65 in Western Society. Patients with AMD are classified as having early stage disease (early AMD), in which visual function is affected, or late AMD (generally characterized as either “wet” neovascular AMD, “dry” atrophic AMD or both), in which central vision is severely compromised or lost. Until recently, there have been no therapies available to treat the disorder(s). Now, the most common wet form of late-stage AMD, choroidal neovascularization, generally responds to treatment with anti–vascular endothelial growth factor therapies. Nevertheless, there are no current therapies to restore lost vision in eyes with advanced atrophic AMD. Oral supplementation with the Age-Related Eye Disease Study (AREDS) or AREDS2 formulation (antioxidant vitamins C and E, lutein, zeaxanthin, and zinc) has been shown to reduce the risk of progression to advanced AMD, although the impact was in neovascular rather than atrophic AMD. Recent findings, however, have demonstrated several features of early AMD that are likely to be druggable targets for treatment. Studies have established that much of the genetic risk for AMD is associated with complement genes. Consequently, several complement-based therapeutic treatment approaches are being pursued. Potential treatment strategies against AMD deposit formation and protein and/or lipid deposition will be discussed, including anti-amyloid therapies. In addition, the role of autophagy in AMD and prevention of oxidative stress through modulation of the antioxidant system will be explored. Finally, the success of these new therapies in clinical trials and beyond relies on early detection, disease typing, and predicting disease progression, areas that are currently being rapidly transformed by improving imaging modalities and functional assays. PMID:24335072

  9. Basic characteristics of simultaneous color contrast revisited.

    Science.gov (United States)

    Ekroll, Vebjørn; Faul, Franz

    2012-10-01

    In this article, we present evidence supporting the hypothesis that the local mechanism of simultaneous color contrast is the same as the mechanism responsible for the crispening effect and the gamut expansion effect. A theoretically important corollary of this hypothesis is that the basic characteristics of simultaneous contrast are at odds with traditional laws. First, this hypothesis implies that the direction of the simultaneous contrast effect in color space is given by the vector from surround to target and not--as traditionally assumed--by the hue complementary to that of the surround. Second, it implies that the size of the simultaneous contrast effect depends on the difference between the target and surround colors in a way that challenges Kirschmann's fourth law. The widespread belief in the traditional laws, we argue, is due to the confounding influence of temporal adaptation.

  10. On mechanism of low-energy heavy ions scattering on a target surface with small atomic mass

    CERN Document Server

    Umarov, F F; Kudryashova, L B; Krylov, N M

    2002-01-01

    In the present work, an experimental study of low-energy (E sub 0 =20-500 eV) heavy Cs sup + ions scattering on target surfaces with small atomic masses (Al, Si, Ni) has been performed for more accurate definition of mechanism of scattering and evaluation of an opportunity for use of heavy ions scattering as a tool of surface layer analysis. It is shown that the dependence of the relative energies of scattered ions versus the initial energy E/E sub 0 (E sub 0) for Si (E sub b =4.64 eV/atom) and Ni (E sub b =4.43 eV/atom) approximately coincide despite the fact that the mass of Ni atom is twice as large as that of the Si atom mass. At the same time their binding energies E sub b are approximately equal to each other. It is found that the scattering angles of Cs sup + ions considerably exceed a limiting scattering angle theta sub l sub i sub m in a single collision. It has been established that the scattering of low-energy heavy ions by light targets is described by a non-binary mechanism of many-particle inter...

  11. Mechanism of Genome Interrogation: How CRISPR RNA-Guided Cas9 Proteins Locate Specific Targets on DNA.

    Science.gov (United States)

    Shvets, Alexey A; Kolomeisky, Anatoly B

    2017-10-03

    The ability to precisely edit and modify a genome opens endless opportunities to investigate fundamental properties of living systems as well as to advance various medical techniques and bioengineering applications. This possibility is now close to reality due to a recent discovery of the adaptive bacterial immune system, which is based on clustered regularly interspaced short palindromic repeats (CRISPR)-associated proteins (Cas) that utilize RNA to find and cut the double-stranded DNA molecules at specific locations. Here we develop a quantitative theoretical approach to analyze the mechanism of target search on DNA by CRISPR RNA-guided Cas9 proteins, which is followed by a selective cleavage of nucleic acids. It is based on a discrete-state stochastic model that takes into account the most relevant physical-chemical processes in the system. Using a method of first-passage processes, a full dynamic description of the target search is presented. It is found that the location of specific sites on DNA by CRISPR Cas9 proteins is governed by binding first to protospacer adjacent motif sequences on DNA, which is followed by reversible transitions into DNA interrogation states. In addition, the search dynamics is strongly influenced by the off-target cutting. Our theoretical calculations allow us to explain the experimental observations and to give experimentally testable predictions. Thus, the presented theoretical model clarifies some molecular aspects of the genome interrogation by CRISPR RNA-guided Cas9 proteins. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  12. Protective role of Nrf2 against mechanical-stretch-induced apoptosis in mouse fibroblasts: a potential therapeutic target of mechanical-trauma-induced stress urinary incontinence.

    Science.gov (United States)

    Li, Qiannan; Li, Bingshu; Liu, Cheng; Wang, Linlin; Tang, Jianming; Hong, Li

    2018-01-10

    We investigated the protective effect and underlying molecular mechanism of nuclear factor-E2-related factor 2 (Nrf2) against mechanical-stretch-induced apoptosis in mouse fibroblasts. Normal cells, Nrf2 silencing cells, and Nrf2 overexpressing cells were respectively divided into two groups-nonintervention and cyclic mechanical strain (CMS)-subjected to CMS of 5333 μ (1.0 Hz for 4 h), six groups in total (control, CMS, shNfe212, shNfe212 + CMS, LV-shNfe212, and LV-shNfe212 + CMS). After treatment, cell apoptosis; cell-cycle distribution; expressions of Nrf2, Bax, Bcl-2, Cyt-C, caspase-3, caspase-9, cleaved-caspase-3, and cleaved-caspase-9; mitochondrial membrane potential (ΔΨm); reactive oxygen species (ROS); and malondialdehyde (MDA) levels were measured. Thirty virgin female C57BL/6 mice were divided into two groups: control (without intervention) and vaginal distension (VD) groups, which underwent VD for 1 h with an 8-mm dilator (0.3 ml saline). Leak-point pressure (LPP) was tested on day 7 after VD; Nrf2 expression, apoptosis, and MDA levels were then measured in urethra and anterior vaginal wall. Mechanical stretch decreased Nrf2 messenger RNA (mRNA) and protein expressions. Overexpression of Nrf2 alleviated mechanical-stretch-induced cell apoptosis; S-phase arrest of cell cycle; up-regulation of Bax, cytochrome C (Cyt-C), ROS, MDA, ratio of cleaved-caspase-3/caspase-3 and cleaved-caspase-9/caspase-9; and exacerbated the decrease of Bcl2 and ΔΨm in L929 cells. On the contrary, silencing of Nrf2 showed opposite effects. Besides, VD reduced LPP levels and Nrf2 expression and increased cell apoptosis and MDA generation in the urethra and anterior vaginal wall. Nrf2 exhibits a protective role against mechanical-stretch -induced apoptosis on mouse fibroblasts, which might indicate a potential therapeutic target of mechanical-trauma-induced stress urinary incontinence (SUI).

  13. Inflation Basics

    Energy Technology Data Exchange (ETDEWEB)

    Green, Dan [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States)

    2014-03-01

    inflation since metrical fluctuations, both scalar and tensor, are also produced in inflationary models. Thus, the time appears to be appropriate for a very basic and simple exposition of the inflationary model written from a particle physics perspective. Only the simplest scalar model will be explored because it is easy to understand and contains all the basic elements of the inflationary model.

  14. Inflation Basics

    International Nuclear Information System (INIS)

    Green, Dan

    2014-01-01

    waves imprinted on the CMB. These would be a ''smoking gun'' for inflation since metrical fluctuations, both scalar and tensor, are also produced in inflationary models. Thus, the time appears to be appropriate for a very basic and simple exposition of the inflationary model written from a particle physics perspective. Only the simplest scalar model will be explored because it is easy to understand and contains all the basic elements of the inflationary model.

  15. Neuroinflammatory Mechanisms of Connective Tissue Fibrosis: Targeting Neurogenic and Mast Cell Contributions

    Science.gov (United States)

    Monument, Michael J.; Hart, David A.; Salo, Paul T.; Befus, A. Dean; Hildebrand, Kevin A.

    2015-01-01

    Significance: The pathogenesis of fibrogenic wound and connective tissue healing is complex and incompletely understood. Common observations across a vast array of human and animal models of fibroproliferative conditions suggest neuroinflammatory mechanisms are important upstream fibrogenic events. Recent Advances: As detailed in this review, mast cell hyperplasia is a common observation in fibrotic tissue. Recent investigations in human and preclinical models of hypertrophic wound healing and post-traumatic joint fibrosis provides evidence that fibrogenesis is governed by a maladaptive neuropeptide-mast cell-myofibroblast signaling pathway. Critical Issues: The blockade and manipulation of these factors is providing promising evidence that if timed correctly, the fibrogenic process can be appropriately regulated. Clinically, abnormal fibrogenic healing responses are not ubiquitous to all patients and the identification of those at-risk remains an area of priority. Future Directions: Ultimately, an integrated appreciation of the common pathobiology shared by many fibrogenic connective tissue conditions may provide a scientific framework to facilitate the development of novel antifibrotic prevention and treatment strategies. PMID:25785237

  16. Molecular Mechanisms of Foot-and-Mouth Disease Virus Targeting the Host Antiviral Response.

    Science.gov (United States)

    Rodríguez Pulido, Miguel; Sáiz, Margarita

    2017-01-01

    Foot-and-mouth disease virus (FMDV) is the causative agent of an acute vesicular disease affecting pigs, cattle and other domestic, and wild animals worldwide. The aim of the host interferon (IFN) response is to limit viral replication and spread. Detection of the viral genome and products by specialized cellular sensors initiates a signaling cascade that leads to a rapid antiviral response involving the secretion of type I- and type III-IFNs and other antiviral cytokines with antiproliferative and immunomodulatory functions. During co-evolution with their hosts, viruses have acquired strategies to actively counteract host antiviral responses and the balance between innate response and viral antagonism may determine the outcome of disease and pathogenesis. FMDV proteases Lpro and 3C have been found to antagonize the host IFN response by a repertoire of mechanisms. Moreover, the putative role of other viral proteins in IFN antagonism is being recently unveiled, uncovering sophisticated immune evasion strategies different to those reported to date for other members of the Picornaviridae family. Here, we review the interplay between antiviral responses induced by FMDV infection and viral countermeasures to block them. Research on strategies used by viruses to modulate immunity will provide insights into the function of host pathways involved in defense against pathogens and will also lead to development of new therapeutic strategies to fight virus infections.

  17. Nanobodies targeting norovirus capsid reveal functional epitopes and potential mechanisms of neutralization.

    Directory of Open Access Journals (Sweden)

    Anna D Koromyslova

    2017-11-01

    Full Text Available Norovirus is the leading cause of gastroenteritis worldwide. Despite recent developments in norovirus propagation in cell culture, these viruses are still challenging to grow routinely. Moreover, little is known on how norovirus infects the host cells, except that histo-blood group antigens (HBGAs are important binding factors for infection and cell entry. Antibodies that bind at the HBGA pocket and block attachment to HBGAs are believed to neutralize the virus. However, additional neutralization epitopes elsewhere on the capsid likely exist and impeding the intrinsic structural dynamics of the capsid could be equally important. In the current study, we investigated a panel of Nanobodies in order to probe functional epitopes that could trigger capsid rearrangement and/ or interfere with HBGA binding interactions. The precise binding sites of six Nanobodies (Nano-4, Nano-14, Nano-26, Nano-27, Nano-32, and Nano-42 were identified using X-ray crystallography. We showed that these Nanobodies bound on the top, side, and bottom of the norovirus protruding domain. The impact of Nanobody binding on norovirus capsid morphology was analyzed using electron microscopy and dynamic light scattering. We discovered that distinct Nanobody epitopes were associated with varied changes in particle structural integrity and assembly. Interestingly, certain Nanobody-induced capsid morphological changes lead to the capsid protein degradation and viral RNA exposure. Moreover, Nanobodies employed multiple inhibition mechanisms to prevent norovirus attachment to HBGAs, which included steric obstruction (Nano-14, allosteric interference (Nano-32, and violation of normal capsid morphology (Nano-26 and Nano-85. Finally, we showed that two Nanobodies (Nano-26 and Nano-85 not only compromised capsid integrity and inhibited VLPs attachment to HBGAs, but also recognized a broad panel of norovirus genotypes with high affinities. Consequently, Nano-26 and Nano-85 have a great

  18. Nanobodies targeting norovirus capsid reveal functional epitopes and potential mechanisms of neutralization

    Science.gov (United States)

    2017-01-01

    Norovirus is the leading cause of gastroenteritis worldwide. Despite recent developments in norovirus propagation in cell culture, these viruses are still challenging to grow routinely. Moreover, little is known on how norovirus infects the host cells, except that histo-blood group antigens (HBGAs) are important binding factors for infection and cell entry. Antibodies that bind at the HBGA pocket and block attachment to HBGAs are believed to neutralize the virus. However, additional neutralization epitopes elsewhere on the capsid likely exist and impeding the intrinsic structural dynamics of the capsid could be equally important. In the current study, we investigated a panel of Nanobodies in order to probe functional epitopes that could trigger capsid rearrangement and/ or interfere with HBGA binding interactions. The precise binding sites of six Nanobodies (Nano-4, Nano-14, Nano-26, Nano-27, Nano-32, and Nano-42) were identified using X-ray crystallography. We showed that these Nanobodies bound on the top, side, and bottom of the norovirus protruding domain. The impact of Nanobody binding on norovirus capsid morphology was analyzed using electron microscopy and dynamic light scattering. We discovered that distinct Nanobody epitopes were associated with varied changes in particle structural integrity and assembly. Interestingly, certain Nanobody-induced capsid morphological changes lead to the capsid protein degradation and viral RNA exposure. Moreover, Nanobodies employed multiple inhibition mechanisms to prevent norovirus attachment to HBGAs, which included steric obstruction (Nano-14), allosteric interference (Nano-32), and violation of normal capsid morphology (Nano-26 and Nano-85). Finally, we showed that two Nanobodies (Nano-26 and Nano-85) not only compromised capsid integrity and inhibited VLPs attachment to HBGAs, but also recognized a broad panel of norovirus genotypes with high affinities. Consequently, Nano-26 and Nano-85 have a great potential to

  19. Cell signaling heterogeneity is modulated by both cell-intrinsic and -extrinsic mechanisms: An integrated approach to understanding targeted therapy.

    Science.gov (United States)

    Kim, Eunjung; Kim, Jae-Young; Smith, Matthew A; Haura, Eric B; Anderson, Alexander R A

    2018-03-01

    During the last decade, our understanding of cancer cell signaling networks has significantly improved, leading to the development of various targeted therapies that have elicited profound but, unfortunately, short-lived responses. This is, in part, due to the fact that these targeted therapies ignore context and average out heterogeneity. Here, we present a mathematical framework that addresses the impact of signaling heterogeneity on targeted therapy outcomes. We employ a simplified oncogenic rat sarcoma (RAS)-driven mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase-protein kinase B (PI3K-AKT) signaling pathway in lung cancer as an experimental model system and develop a network model of the pathway. We measure how inhibition of the pathway modulates protein phosphorylation as well as cell viability under different microenvironmental conditions. Training the model on this data using Monte Carlo simulation results in a suite of in silico cells whose relative protein activities and cell viability match experimental observation. The calibrated model predicts distributional responses to kinase inhibitors and suggests drug resistance mechanisms that can be exploited in drug combination strategies. The suggested combination strategies are validated using in vitro experimental data. The validated in silico cells are further interrogated through an unsupervised clustering analysis and then integrated into a mathematical model of tumor growth in a homogeneous and resource-limited microenvironment. We assess posttreatment heterogeneity and predict vast differences across treatments with similar efficacy, further emphasizing that heterogeneity should modulate treatment strategies. The signaling model is also integrated into a hybrid cellular automata (HCA) model of tumor growth in a spatially heterogeneous microenvironment. As a proof of concept, we simulate tumor responses to targeted therapies in a spatially segregated tissue structure containing tumor

  20. Japan's new basic energy plan

    International Nuclear Information System (INIS)

    Duffield, John S.; Woodall, Brian

    2011-01-01

    In June 2010, the Japanese cabinet adopted a new Basic Energy Plan (BEP). This was the third such plan that the government has approved since the passage of the Basic Act on Energy Policy in 2002, and it represents the most significant statement of Japanese energy policy in more than four years, since the publication of the New National Energy Strategy (NNES) in 2006. Perhaps more than its predecessors, moreover, the new plan establishes a number of ambitious targets as well as more detailed measures for achieving those targets. Among the targets are a doubling of Japan's 'energy independence ratio,' a doubling of the percentage of electricity generated by renewable sources and nuclear power, and a 30 percent reduction in energy-related CO 2 emissions, all by 2030. This paper explains the origins of the 2010 BEP and why it was adopted. It then describes the content of the plan and how it differs from the NNES. A third section analyzes the appropriateness of the new goals and targets contained in the BEP and their feasibility, finding that achievement of many of the targets was likely to be quite challenging even before the March 2011 earthquake, tsunami, and nuclear crisis. - Highlights: → Origins of Japan's new Basic Energy Plan. → Content of Japan's new Basic Energy Plan. → Feasibility of achieving the targets in Japan's new Basic Energy Plan. → Impact of 2011 earthquake and tsunami on Japanese energy policy.

  1. Mechanics

    CERN Document Server

    Chester, W

    1979-01-01

    When I began to write this book, I originally had in mind the needs of university students in their first year. May aim was to keep the mathematics simple. No advanced techniques are used and there are no complicated applications. The emphasis is on an understanding of the basic ideas and problems which require expertise but do not contribute to this understanding are not discussed. How­ ever, the presentation is more sophisticated than might be considered appropri­ ate for someone with no previous knowledge of the subject so that, although it is developed from the beginning, some previous acquaintance with the elements of the subject would be an advantage. In addition, some familiarity with element­ ary calculus is assumed but not with the elementary theory of differential equations, although knowledge of the latter would again be an advantage. It is my opinion that mechanics is best introduced through the motion of a particle, with rigid body problems left until the subject is more fully developed. Howev...

  2. Structural effects and competition mechanisms targeting the interactions between p53 and MDM2 for cancer therapy

    Science.gov (United States)

    Liu, Shu-Xia; Geng, Yi-Zhao; Yan, Shi-Wei

    2017-06-01

    Approximately half of all human cancers show normal TP53 gene expression but aberrant overexpression of MDM2 and/or MDMX. This fact suggests a promising cancer therapeutic strategy in targeting the interactions between p53 and MDM2/MDMX. To help realize the goal of developing effective inhibitors to disrupt the p53-MDM2/MDMX interaction, we systematically investigated the structural and interaction characteristics of p53 with inhibitors of its interactions with MDM2 and MDMX from an atomistic perspective using stochastic molecular dynamics simulations. We found that some specific α helices in the structures of MDM2 and MDMX play key roles in their binding to inhibitors, and that the hydrogen bond formed by the Trp23 residue of p53 with its counterpart in MDM2 or MDMX determines the dynamic competition processes of the disruption of the MDM2-p53 interaction and replacement of p53 from the MDM2-p53 complex in vivo. The results reported in this paper are expected to provide basic information for designing functional inhibitors and realizing new strategies of cancer gene therapy.

  3. Basic of Neutron NDA

    Energy Technology Data Exchange (ETDEWEB)

    Trahan, Alexis Chanel [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-09-15

    The objectives of this presentation are to introduce the basic physics of neutron production, interactions and detection; identify the processes that generate neutrons; explain the most common neutron mechanism, spontaneous and induced fission and (a,n) reactions; describe the properties of neutron from different sources; recognize advantages of neutron measurements techniques; recognize common neutrons interactions; explain neutron cross section measurements; describe the fundamental of 3He detector function and designs; and differentiate between passive and active assay techniques.

  4. MicroRNAs upregulated during HIV infection target peroxisome biogenesis factors: Implications for virus biology, disease mechanisms and neuropathology.

    Directory of Open Access Journals (Sweden)

    Zaikun Xu

    2017-06-01

    Full Text Available HIV-associated neurocognitive disorders (HAND represent a spectrum neurological syndrome that affects up to 25% of patients with HIV/AIDS. Multiple pathogenic mechanisms contribute to the development of HAND symptoms including chronic neuroinflammation and neurodegeneration. Among the factors linked to development of HAND is altered expression of host cell microRNAs (miRNAs in brain. Here, we examined brain miRNA profiles among HIV/AIDS patients with and without HAND. Our analyses revealed differential expression of 17 miRNAs in brain tissue from HAND patients. A subset of the upregulated miRNAs (miR-500a-5p, miR-34c-3p, miR-93-3p and miR-381-3p, are predicted to target peroxisome biogenesis factors (PEX2, PEX7, PEX11B and PEX13. Expression of these miRNAs in transfected cells significantly decreased levels of peroxisomal proteins and concomitantly decreased peroxisome numbers or affected their morphology. The levels of miR-500a-5p, miR-34c-3p, miR-93-3p and miR-381-3p were not only elevated in the brains of HAND patients, but were also upregulated during HIV infection of primary macrophages. Moreover, concomitant loss of peroxisomal proteins was observed in HIV-infected macrophages as well as in brain tissue from HIV-infected patients. HIV-induced loss of peroxisomes was abrogated by blocking the functions of the upregulated miRNAs. Overall, these findings point to previously unrecognized miRNA expression patterns in the brains of HIV patients. Targeting peroxisomes by up-regulating miRNAs that repress peroxisome biogenesis factors may represent a novel mechanism by which HIV-1 subverts innate immune responses and/or causes neurocognitive dysfunction.

  5. FUNCTIONAL GENOMICS IDENTIFIES TIS21-DEPENDENT MECHANISMS AND PUTATIVE CANCER DRUG TARGETS UNDERLYING MEDULLOBLASTOMA SHH-TYPE DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Giulia Gentile

    2016-11-01

    Full Text Available We have recently generated a novel medulloblastoma (MB mouse model with activation of the Shh pathway and lacking the MB suppressor Tis21 (Patched1+-Tis21KO.ts main phenotype is a defect of migration of the cerebellar granule precursor cells (GCPs. By genomic analysis of GCPs in vivo, we identified as drug target and major responsible of this defect the down-regulation of the promigratory chemokine Cxcl3. Consequently, the GCPs remain longer in the cerebellum proliferative area, and the MB frequency is enhanced. Here, we further analyzed the genes deregulated in a Tis21-dependent manner (Patched1+-is21 wild-type versus Ptch1+-Tis21 knockout, among which are a number of down-regulated tumor inhibitors and up-regulated tumor facilitators, focusing on pathways potentially involved in the tumorigenesis and on putative new drug targets.The data analysis using bioinformatic tools revealed: i a link between the Shh signaling and the Tis21-dependent impairment of the GCPs migration, through a Shh-dependent deregulation of the clathrin-mediated chemotaxis operating in the primary cilium through the Cxcl3-Cxcr2 axis; ii a possible lineage shift of Shh-type GCPs toward retinal precursor phenotype the neural cell type involved in group 3 MB; iii the identification of a subset of putative drug targets for MB, involved, among the others, in the regulation of Hippo signaling and centrosome assembly. Finally, our findings define also the role of Tis21 in the regulation of gene expression, through epigenetic and RNA processing mechanisms, influencing the fate of the GCPs.

  6. A Connection Model between the Positioning Mechanism and Ultrasonic Measurement System via a Web Browser to Assess Acoustic Target Strength

    Science.gov (United States)

    Ishii, Ken; Imaizumi, Tomohito; Abe, Koki; Takao, Yoshimi; Tamura, Shuko

    This paper details a network-controlled measurement system for use in fisheries engineering. The target strength (TS) of fish is important in order to convert acoustic integration values obtained during acoustic surveys into estimates of fish abundance. The target strength pattern is measured with the combination of the rotation system for the aspect of the sample and the echo data acquisition system using the underwater supersonic wave. The user interface of the network architecture is designed for collaborative use with researchers in other organizations. The flexible network architecture is based on the web direct-access model for the rotation mechanism. The user interface is available for monitoring and controlling via a web browser that is installed in any terminal PC (personal computer). Previously the combination of two applications was performed not by a web browser but by the exclusive interface program. So a connection model is proposed between two applications by indirect communication via the DCOM (Distributed Component Object Model) server and added in the web direct-access model. A prompt report system in the TS measurement system and a positioning and measurement system using an electric flatcar via a web browser are developed. By a secure network architecture, DCOM communications via both Intranet and LAN are successfully certificated.

  7. Targeting multiple pathogenic mechanisms with polyphenols for the treatment of Alzheimer’s disease: Experimental approach and therapeutic implications

    Directory of Open Access Journals (Sweden)

    Jun eWang

    2014-03-01

    Full Text Available Alzheimer’s disease (AD is the most prevalent neurodegenerative disease of aging and currently has no cure. Its onset and progression are influenced by multiple factors. There is growing consensus that successful treatment will rely on simultaneously targeting multiple pathological features of AD. Polyphenol compounds have many proven health benefits. In this study, we tested the hypothesis that combining three polyphenolic preparations (grape seed extract, resveratrol and Concord grape juice extract, with different polyphenolic compositions and partially redundant bioactivities, may simultaneously and synergistically mitigate amyloid-β (Aβ mediated neuropathology and cognitive impairments in a mouse model of AD. We found that administration of the polyphenols in combination did not alter the profile of bioactive polyphenol metabolites in the brain. We also found that combination treatment resulted in better protection against cognitive impairments compared to individual treatments, in J20 AD mice. Electrophysiological examination showed that acute treatment with select brain penetrating polyphenol metabolites, derived from these polyphenols, improved oligomeric Aβ (oAβ-induced long term potentiation (LTP deficits in hippocampal slices. Moreover, we found greatly reduced total amyloid content in the brain following combination treatment. Our studies provided experimental evidence that application of polyphenols targeting multiple disease-mechanisms may yield a greater likelihood of therapeutic efficacy.

  8. Using Mechanical Turk to recruit participants for internet intervention research: experience from recruitment for four trials targeting hazardous alcohol consumption.

    Science.gov (United States)

    Cunningham, John A; Godinho, Alexandra; Kushnir, Vladyslav

    2017-12-01

    Mechanical Turk (MTurk) is an online portal operated by Amazon where 'requesters' (individuals or businesses) can submit jobs for 'workers.' MTurk is used extensively by academics as a quick and cheap means of collecting questionnaire data, including information on alcohol consumption, from a diverse sample of participants. We tested the feasibility of recruiting for alcohol Internet intervention trials through MTurk. Participants, 18 years or older, who drank at least weekly were recruited for four intervention trials (combined sample size, N = 11,107). The same basic recruitment strategy was employed for each trial - invite participants to complete a survey about alcohol consumption (less than 15 min in length, US$1.50 payment), identify eligible participants who drank in a hazardous fashion, invite those eligible to complete a follow-up survey ($10 payment), randomize participants to be sent or not sent information to access an online intervention for hazardous alcohol use. Procedures where put in place to optimize the chances that participants could only complete the baseline survey once. There was a substantially slower rate of recruitment by the fourth trial compared to the earlier trials. Demographic characteristics also varied across trials (age, sex, employment and marital status). Patterns of alcohol consumption, while displaying some differences, did not appear to vary in a linear fashion between trials. It is possible to recruit large (but not inexhaustible) numbers of people who drink in a hazardous fashion. Issues for online intervention research when employing this sample are discussed.

  9. Mitochondrial ADP/ATP exchange inhibition: a novel off-target mechanism underlying ibipinabant-induced myotoxicity.

    Science.gov (United States)

    Schirris, Tom J J; Ritschel, Tina; Herma Renkema, G; Willems, Peter H G M; Smeitink, Jan A M; Russel, Frans G M

    2015-09-29

    Cannabinoid receptor 1 (CB1R) antagonists appear to be promising drugs for the treatment of obesity, however, serious side effects have hampered their clinical application. Rimonabant, the first in class CB1R antagonist, was withdrawn from the market because of psychiatric side effects. This has led to the search for more peripherally restricted CB1R antagonists, one of which is ibipinabant. However, this 3,4-diarylpyrazoline derivative showed muscle toxicity in a pre-clinical dog study with mitochondrial dysfunction. Here, we studied the molecular mechanism by which ibipinabant induces mitochondrial toxicity. We observed a strong cytotoxic potency of ibipinabant in C2C12 myoblasts. Functional characterization of mitochondria revealed increased cellular reactive oxygen species generation and a decreased ATP production capacity, without effects on the catalytic activities of mitochondrial enzyme complexes I-V or the complex specific-driven oxygen consumption. Using in silico off-target prediction modelling, combined with in vitro validation in isolated mitochondria and mitoplasts, we identified adenine nucleotide translocase (ANT)-dependent mitochondrial ADP/ATP exchange as a novel molecular mechanism underlying ibipinabant-induced toxicity. Minor structural modification of ibipinabant could abolish ANT inhibition leading to a decreased cytotoxic potency, as observed with the ibipinabant derivative CB23. Our results will be instrumental in the development of new types of safer CB1R antagonists.

  10. New mechanisms for non-porative ultrasound stimulation of cargo delivery to cell cytosol with targeted perfluorocarbon nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Soman, N R; Marsh, J N; Lanza, G M; Wickline, S A [Washington University School of Medicine, Consortium for Translational Research in Advanced Imaging and Nanomedicine, CTRAIN, Campus Box 8215, St Louis, MO 63110 (United States)], E-mail: saw@wuphys.wustl.edu

    2008-05-07

    The cell membrane constitutes a major barrier for non-endocytotic intracellular delivery of therapeutic molecules from drug delivery vehicles. Existing approaches to breaching the cell membrane include cavitational ultrasound (with microbubbles), electroporation and cell-penetrating peptides. We report the use of diagnostic ultrasound for intracellular delivery of therapeutic bulky cargo with the use of molecularly targeted liquid perfluorocarbon (PFC) nanoparticles. To demonstrate the concept, we used a lipid with a surrogate polar head group, nanogold-DPPE, incorporated into the nanoparticle lipid monolayer. Melanoma cells were incubated with nanogold particles and this was followed by insonication with continuous wave ultrasound (2.25 MHz, 5 min, 0.6 MPa). Cells not exposed to ultrasound showed gold particles partitioned only in the outer bilayer of the cell membrane with no evidence of the intracellular transit of nanogold. However, the cells exposed to ultrasound exhibited numerous nanogold-DPPE components inside the cell that appeared polarized inside intracellular vesicles demonstrating cellular uptake and trafficking. Further, ultrasound-exposed cells manifested no incorporation of calcein or the release of lactate dehydrogenase. These observations are consistent with a mechanism that suggests that ultrasound is capable of stimulating the intracellular delivery of therapeutic molecules via non-porative mechanisms. Therefore, non-cavitational adjunctive ultrasound offers a novel paradigm in intracellular cargo delivery from PFC nanoparticles.

  11. New mechanisms for non-porative ultrasound stimulation of cargo delivery to cell cytosol with targeted perfluorocarbon nanoparticles

    International Nuclear Information System (INIS)

    Soman, N R; Marsh, J N; Lanza, G M; Wickline, S A

    2008-01-01

    The cell membrane constitutes a major barrier for non-endocytotic intracellular delivery of therapeutic molecules from drug delivery vehicles. Existing approaches to breaching the cell membrane include cavitational ultrasound (with microbubbles), electroporation and cell-penetrating peptides. We report the use of diagnostic ultrasound for intracellular delivery of therapeutic bulky cargo with the use of molecularly targeted liquid perfluorocarbon (PFC) nanoparticles. To demonstrate the concept, we used a lipid with a surrogate polar head group, nanogold-DPPE, incorporated into the nanoparticle lipid monolayer. Melanoma cells were incubated with nanogold particles and this was followed by insonication with continuous wave ultrasound (2.25 MHz, 5 min, 0.6 MPa). Cells not exposed to ultrasound showed gold particles partitioned only in the outer bilayer of the cell membrane with no evidence of the intracellular transit of nanogold. However, the cells exposed to ultrasound exhibited numerous nanogold-DPPE components inside the cell that appeared polarized inside intracellular vesicles demonstrating cellular uptake and trafficking. Further, ultrasound-exposed cells manifested no incorporation of calcein or the release of lactate dehydrogenase. These observations are consistent with a mechanism that suggests that ultrasound is capable of stimulating the intracellular delivery of therapeutic molecules via non-porative mechanisms. Therefore, non-cavitational adjunctive ultrasound offers a novel paradigm in intracellular cargo delivery from PFC nanoparticles

  12. Target or barrier? The cell wall of early- and later- diverging plants vs cadmium toxicity: differences in the response mechanisms

    Directory of Open Access Journals (Sweden)

    Luigi eParrotta

    2015-03-01

    Full Text Available Increasing industrialization and urbanization result in emission of pollutants in the environment including toxic heavy metals, as cadmium and lead. Among the different heavy metals contaminating the environment, cadmium raises great concern, as it is ecotoxic and as such can heavily impact ecosystems. The cell wall is the first structure of plant cells to come in contact with heavy metals. Its composition, characterized by proteins, polysaccharides and in some instances lignin and other phenolic compounds, confers the ability to bind non-covalently and/or covalently heavy metals via functional groups. A strong body of evidence in the literature has shown the role of the cell wall in heavy metal response: it sequesters heavy metals, but at the same time its synthesis and composition can be severely affected. The present review analyzes the dual property of plant cell walls, i.e. barrier and target of heavy metals, by taking Cd toxicity as example. Following a summary of the known physiological and biochemical responses of plants to Cd, the review compares the wall-related mechanisms in early- and later-diverging land plants, by considering the diversity in cell wall composition. By doing so, common as well as unique response mechanisms to metal/cadmium toxicity are identified among plant phyla and discussed. After discussing the role of hyperaccumulators’ cell walls as a particular case, the review concludes by considering important aspects for plant engineering.

  13. New mechanisms for non-porative ultrasound stimulation of cargo delivery to cell cytosol with targeted perfluorocarbon nanoparticles

    Science.gov (United States)

    Soman, N. R.; Marsh, J. N.; Lanza, G. M.; Wickline, S. A.

    2008-05-01

    The cell membrane constitutes a major barrier for non-endocytotic intracellular delivery of therapeutic molecules from drug delivery vehicles. Existing approaches to breaching the cell membrane include cavitational ultrasound (with microbubbles), electroporation and cell-penetrating peptides. We report the use of diagnostic ultrasound for intracellular delivery of therapeutic bulky cargo with the use of molecularly targeted liquid perfluorocarbon (PFC) nanoparticles. To demonstrate the concept, we used a lipid with a surrogate polar head group, nanogold-DPPE, incorporated into the nanoparticle lipid monolayer. Melanoma cells were incubated with nanogold particles and this was followed by insonication with continuous wave ultrasound (2.25 MHz, 5 min, 0.6 MPa). Cells not exposed to ultrasound showed gold particles partitioned only in the outer bilayer of the cell membrane with no evidence of the intracellular transit of nanogold. However, the cells exposed to ultrasound exhibited numerous nanogold-DPPE components inside the cell that appeared polarized inside intracellular vesicles demonstrating cellular uptake and trafficking. Further, ultrasound-exposed cells manifested no incorporation of calcein or the release of lactate dehydrogenase. These observations are consistent with a mechanism that suggests that ultrasound is capable of stimulating the intracellular delivery of therapeutic molecules via non-porative mechanisms. Therefore, non-cavitational adjunctive ultrasound offers a novel paradigm in intracellular cargo delivery from PFC nanoparticles.

  14. Hypoxemia Episodes during Day and Night and Their Impact on Oxygen Saturation Targeting in Mechanically Ventilated Preterm Infants.

    Science.gov (United States)

    Jain, Deepak; D'Ugard, Carmen; Bello, Jose; Bancalari, Eduardo; Claure, Nelson

    2018-01-01

    Hypoxemia episodes (HE) occur frequently in ventilated preterm infants and hinder the achievement of arterial oxygen saturation (SpO2) targets. These episodes may increase the risk for retinopathy of prematurity and neurodevelopmental disability. There are no data on the variation in HE and SpO2 targeting between day and night. The aim of this study was to evaluate the difference between day and night on the frequency and severity of HE and achievement of SpO2 targets. Twenty-four mechanically ventilated preterm infants with ≥4 episodes of SpO2 day (9 a.m. to 5 p.m.) were compared to the night (9 p.m. to 5 a.m.) for the frequency of HE and proportion of time within and outside the target SpO2 range (90-95%). The frequency of severe HE (SpO2 night compared to the day (1.6 ± 1.0 vs. 2.4 ± 1.3 episodes/h, p = 0.008, and 0.53 ± 0.35 vs. 0.90 ± 0.54 episodes/h, p = 0.018). There was no difference in mean episode duration. The frequency and duration of mild HE (SpO2 night compared to the day (5.9 ± 2.7 vs. 7.1 ± 2.5 episodes/h, p = 0.003, and 72 ± 15 vs. 87 ± 25 s, p = 0.01, respectively). The proportion of time in severe hypoxemia (SpO2 95%) was greater, during the night compared to the day. The mean FiO2 did not differ between day and night. In this group of infants with frequent HE, nighttime was associated with fewer episodes when compared to daytime. This is likely due to less handling and sensory stimulation during the night. The increase in time spent with hyperoxemia during the night is likely to be due to more tolerance of high SpO2 with less proactive weaning of FiO2. © 2017 S. Karger AG, Basel.

  15. Chimeric peptides as modulators of CK2-dependent signaling: Mechanism of action and off-target effects.

    Science.gov (United States)

    Zanin, Sofia; Sandre, Michele; Cozza, Giorgio; Ottaviani, Daniele; Marin, Oriano; Pinna, Lorenzo A; Ruzzene, Maria

    2015-10-01

    Protein kinase CK2 is a tetrameric enzyme composed of two catalytic (α/α') and two regulatory (β) subunits. It has a global prosurvival function, especially in cancer, and represents an attractive therapeutic target. Most CK2 inhibitors available so far are ATP-competitive compounds; however, the possibility to block only the phosphorylation of few substrates has been recently explored, and a compound composed of a Tat cell-penetrating peptide and an active cyclic peptide, selected for its ability to bind to the CK2 substrate E7 protein of human papilloma virus, has been developed [Perea et al., Cancer Res. 2004; 64:7127-7129]. By using a similar chimeric peptide (CK2 modulatory chimeric peptide, CK2-MCP), we performed a study to dissect its molecular mechanism of action and the signaling pathways that it affects in cells. We found that it directly interacts with CK2 itself, counteracting the regulatory and stabilizing functions of the β subunit. Cell treatment with CK2-MCP induces a rapid decrease of the amount of CK2 subunits, as well as of other signaling proteins. Concomitant cell death is observed, more pronounced in tumor cells and not accompanied by apoptotic events. CK2 relocalizes to lysosomes, whose proteases are activated, while the proteasome machinery is inhibited. Several sequence variants of the chimeric peptide have been also synthesized, and their effects compared to those of the parental peptide. Intriguingly, the Tat moiety is essential not only for cell penetration but also for the in vitro efficacy of the peptide. We conclude that this class of chimeric peptides, in addition to altering some properties of CK2 holoenzyme, affects several other cellular targets, causing profound perturbations of cell biology. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. A Potential Bone-Targeting Hypotoxic Platinum(II) Complex with an Unusual Cytostatic Mechanism toward Osteosarcoma Cells.

    Science.gov (United States)

    Zhang, Zhenqin; Zhu, Zhenzhu; Luo, Cheng; Zhu, Chengcheng; Zhang, Changli; Guo, Zijian; Wang, Xiaoyong

    2018-03-19

    Osteosarcoma (OS) is the most common primary pediatric bone tumor lethal to children and adolescents. Chemotherapeutic agents such as cisplatin are not effective for OS because of their poor accessibility to this cancer and severe systemic toxicity. In this study, a lipophilic platinum(II) complex bearing a bisphosphonate bone-targeting moiety, cis-[PtL(NH 3 ) 2 Cl]NO 3 {BPP; L = tetraethyl [2-(pyridin-2-yl)ethane-1,1-diyl]bisphosphonate}, was prepared and characterized by NMR, electrospray ionization mass spectrometry, and single-crystal X-ray crystallography. The cytotoxicity of BPP toward OS cell lines U2OS and MG-63 was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. BPP exhibits moderate inhibition against U2OS cells through a mechanism involving both DNA binding and a mevalonate pathway. The acute toxicity of BPP to mice is 7-fold lower than that of cisplatin. The relative low systemic toxicity may result from the steric hindrance of the ligand, which blocks BPP approaching the bases of DNA. The results suggest that incorporating bisphosphonates into a platinum complex not only enhances its bone-targeting property but also minimizes its reactivity toward DNA and thereby lowers the systematic toxicity of the complex. The diminished cytotoxicity of BPP could be compensated for by increasing the therapeutic dose with marginal harm. This strategy provides a new possibility for overcoming the ineffectiveness and systemic toxicity of platinum drugs in the treatment of OS.

  17. Secondary targets of nitrite-derived reactive nitrogen species: nitrosation/nitration pathways, antioxidant defense mechanisms and toxicological implications.

    Science.gov (United States)

    d'Ischia, Marco; Napolitano, Alessandra; Manini, Paola; Panzella, Lucia

    2011-12-19

    Nitrite, the primary metabolite of nitric oxide (NO) and a widely diffused component of human diet, plays distinct and increasingly appreciated roles in human physiology. However, when exposed to acidic environments, typically in the stomach, or under oxidative stress conditions, it may be converted to a range of reactive nitrogen species (RNS) which in turn can target a variety of biomolecules. Typical consequences of toxicological relevance include protein modification, DNA base deamination and the formation of N-nitrosamines, among the most potent mutagenic and carcinogenic compounds for humans. Besides primary biomolecules, nitrite can cause structural modifications to a variety of endogenous and exogenous organic compounds, ranging from polyunsaturated fatty acids to estrogens, tocopherol, catecholamines, furans, retinoids, dietary phenols, and a range of xenobiotics. The study of the interactions between nitrite and key food components, including phenolic antioxidants, has therefore emerged as an area of great promise for delineating innovative strategies in cancer chemoprevention. Depending on substrates and conditions, diverse reaction pathways may compete to determine product features and distribution patterns. These include nitrosation and nitration but also oxidation, via electron transfer to nitrosonium ion or nitrogen dioxide. This contribution aims to provide an overview of the main classes of compounds that can be targeted by nitrite and to discuss at chemical levels the possible reaction mechanisms under conditions that model those occurring in the stomach. The toxicological implications of the nitrite-modified molecules are finally addressed, and a rational chemical approach to the design of potent antinitrosing agents is illustrated. © 2011 American Chemical Society

  18. Using Mechanical Turk to recruit participants for internet intervention research: experience from recruitment for four trials targeting hazardous alcohol consumption

    Directory of Open Access Journals (Sweden)

    John A. Cunningham

    2017-12-01

    Full Text Available Abstract Background Mechanical Turk (MTurk is an online portal operated by Amazon where ‘requesters’ (individuals or businesses can submit jobs for ‘workers.’ MTurk is used extensively by academics as a quick and cheap means of collecting questionnaire data, including information on alcohol consumption, from a diverse sample of participants. We tested the feasibility of recruiting for alcohol Internet intervention trials through MTurk. Methods Participants, 18 years or older, who drank at least weekly were recruited for four intervention trials (combined sample size, N = 11,107. The same basic recruitment strategy was employed for each trial – invite participants to complete a survey about alcohol consumption (less than 15 min in length, US$1.50 payment, identify eligible participants who drank in a hazardous fashion, invite those eligible to complete a follow-up survey ($10 payment, randomize participants to be sent or not sent information to access an online intervention for hazardous alcohol use. Procedures where put in place to optimize the chances that participants could only complete the baseline survey once. Results There was a substantially slower rate of recruitment by the fourth trial compared to the earlier trials. Demographic characteristics also varied across trials (age, sex, employment and marital status. Patterns of alcohol consumption, while displaying some differences, did not appear to vary in a linear fashion between trials. Conclusions It is possible to recruit large (but not inexhaustible numbers of people who drink in a hazardous fashion. Issues for online intervention research when employing this sample are discussed.

  19. Cytotoxicity and cell death mechanisms induced by the polyamine-vectorized anti-cancer drug F14512 targeting topoisomerase II.

    Science.gov (United States)

    Brel, Viviane; Annereau, Jean-Philippe; Vispé, Stéphane; Kruczynski, Anna; Bailly, Christian; Guilbaud, Nicolas

    2011-12-15

    The polyamines transport system (PTS) is usually enhanced in cancer cells and can be exploited to deliver anticancer drugs. The spermine-conjugated epipodophyllotoxin derivative F14512 is a topoisomerase II poison that exploits the PTS to target preferentially tumor cells. F14512 has been characterized as a potent anticancer drug candidate and is currently in phase 1 clinical trials. Here we have analyzed the mechanisms of cell death induced by F14512, compared to the parent drug etoposide lacking the polyamine tail. F14512 proved to be >30-fold more cytotoxic than etoposide against A549 non-small cell lung cancer cells and triggers less but unrecoverable DNA damages. The cytotoxic action of F14512 is extremely rapid (within 3 h) and does not lead to a marked accumulation in the S-phase of the cell cycle, unlike etoposide. Interestingly, A549 cells treated with F14512 were less prone to undergo apoptosis (neither caspases-dependent nor caspases-independent pathways) or autophagy but preferentially entered into senescence. Drug-induced senescence was characterized qualitatively and quantitatively by an increased β-galactosidase activity, both by cytochemical staining and by flow cytometry. A morphological analysis by electron microscopy revealed the presence of numerous multi-lamellar and vesicular bodies and large electron-lucent (methuosis-like) vacuoles in F14512-treated cell samples. The mechanism of drug-induced cell death is thus distinct for F14512 compared to etoposide, and this difference may account for their distinct pharmacological profiles and the markedly superior activity of F14512 in vivo. This study suggests that senescence markers should be considered as potential pharmacodynamic biomarkers of F14512 antitumor activity. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Clinical efficacy and IL-17 targeting mechanism of Indigo naturalis as a topical agent in moderate psoriasis.

    Science.gov (United States)

    Cheng, Hui-Man; Wu, Yang-Chang; Wang, Qingmin; Song, Michael; Wu, Jackson; Chen, Dion; Li, Katherine; Wadman, Eric; Kao, Shung-Te; Li, Tsai-Chung; Leon, Francisco; Hayden, Karen; Brodmerkel, Carrie; Chris Huang, C

    2017-09-02

    Indigo naturalis is a Traditional Chinese Medicine (TCM) ingredient long-recognized as a therapy for several inflammatory conditions, including psoriasis. However, its mechanism is unknown due to lack of knowledge about the responsible chemical entity. We took a different approach to this challenge by investigating the molecular profile of Indigo naturalis treatment and impacted pathways. A randomized, double-blind, placebo-controlled clinical study was conducted using Indigo naturalis as topical monotherapy to treat moderate plaque psoriasis in a Chinese cohort (n = 24). Patients were treated with Indigo naturalis ointment (n = 16) or matched placebo (n = 8) twice daily for 8 weeks, with 1 week of follow-up. At week 8, significant improvements in Psoriasis Area and Severity Index (PASI) scores from baseline were observed in Indigo naturalis-treated patients (56.3% had 75% improvement [PASI 75] response) compared with placebo (0.0%). A gene expression signature of moderate psoriasis was established from baseline skin biopsies, which included the up-regulation of the interleukin (IL)-17 pathway as a key component; Indigo naturalis treatment resulted in most of these signature genes returning toward normal, including down-regulation of the IL-17 pathway. Using an in vitro keratinocyte assay, an IL-17-inhibitory effect was observed for tryptanthrin, a component of Indigo naturalis. This study demonstrated the clinical efficacy of Indigo naturalis in moderate psoriasis, and exemplified a novel experimental medicine approach to understand TCM targeting mechanisms. NCT01901705 .

  1. Mechanisms of developing post-traumatic stress disorder: new targets for drug development and other potential interventions.

    Science.gov (United States)

    Wimalawansa, Sunil J

    2014-01-01

    The post-traumatic stress disorder (PTSD) is defined as a severe anxiety disorder that develops after exposure to an event with actual, threatened, or perceived death or serious injury, or a threat to the physical integrity of oneself or others that results in significant psychological trauma. Moreover, the ability of people to handle acute severe stress experiences varies among individuals. Depending on the underlying personality and resiliency, therefore, PTSD can occur in individuals exposed to exceedingly stressful incidences or those who have encountered seemingly less overwhelming stressors. In addition to severe stressful exposure, multiple other factors including genetic susceptibility; past experiences; cultural, spiritual, and personal beliefs; bullying and harassments; and lack of support at the workplace, social, and home environement may contribute to the development of PTSD. Author investigated multiple potential mechanisms for the development and sustenance of PTSD based on the recent literature and his own experiences and insight. Based on this search, author indicates that among other pathological and biochemical abnormalities, hormonal aberrations are most likely key mechanisms initiating and the maintenance of the PTSD. These pathophysiological neuro-hormonal changes instigate maladaptive learning processes caused by sustained high levels of anxiety and fear, through a hypo-responsive hypothalamic-pituitary axis and hyper-responsive catecholamine system (persistently elevated blood norepinephrine levels and lower than appropriate glucocorticoid levels). In addition to having inappropriately low serum cortisol levels and high epinephrine and norepinephrine levels, patients with PTSD also have mitochondrial dysfunctions and other hormonal abnormalities. Based on these data, author concluded that these pathological, biochemical and sustained neurohormonal abnormalities are likely to influence the structural brain changes, particularly in the

  2. Multiple insecticide resistance mechanisms involving metabolic changes and insensitive target sites selected in anopheline vectors of malaria in Sri Lanka

    Directory of Open Access Journals (Sweden)

    Karunaratne SHP Parakrama

    2008-08-01

    Full Text Available Abstract Background The current status of insecticide resistance and the underlying resistance mechanisms were studied in the major vector of malaria, Anopheles culicifacies, and the secondary vector, Anopheles subpictus in five districts (Anuradhapura, Kurunegala, Moneragala, Puttalam and Trincomalee of Sri Lanka. Eight other anophelines, Anopheles annularis, Anopheles barbirostris, Anopheles jamesii, Anopheles nigerrimus, Anopheles peditaeniatus, Anopheles tessellatus, Anopheles vagus and Anopheles varuna from Anuradhapura district were also tested. Methods Adult females were exposed to the WHO discriminating dosages of DDT, malathion, fenitrothion, propoxur, λ-cyhalothrin, cyfluthrin, cypermethrin, deltamethrin, permethrin and etofenprox. The presence of metabolic resistance by esterase, glutathione S-transferase (GST and monooxygenase-based mechanisms, and the sensitivity of the acetylcholinesterase target site were assessed using synergists, and biochemical, and metabolic techniques. Results All the anopheline species had high DDT resistance. All An. culicifacies and An. subpictus populations were resistant to malathion, except An. culicifacies from Kurunegala, where there was no malathion carboxylesterase activity. Kurunegala and Puttalam populations of An. culicifacies were susceptible to fenitrothion. All the An. culicifacies populations were susceptible to carbamates. Both species were susceptible to the discriminating dosages of cypermethrin and cyfluthrin, but had different levels of resistance to other pyrethroids. Of the 8 other anophelines, only An. nigerrimus and An. peditaeniatus were resistant to all the insecticides tested, probably due to their high exposure to the insecticides used in agriculture. An. vagus showed some resistance to permethrin. Esterases, GSTs and monooxygenases were elevated in both An. culicifacies and An. subpictus. AChE was most sensitive to insecticides in Kurunegala and Trincomalee An. culicifacies

  3. Basic and clinical immunology

    Science.gov (United States)

    Chinen, Javier; Shearer, William T.

    2003-01-01

    Progress in immunology continues to grow exponentially every year. New applications of this knowledge are being developed for a broad range of clinical conditions. Conversely, the study of primary and secondary immunodeficiencies is helping to elucidate the intricate mechanisms of the immune system. We have selected a few of the most significant contributions to the fields of basic and clinical immunology published between October 2001 and October 2002. Our choice of topics in basic immunology included the description of T-bet as a determinant factor for T(H)1 differentiation, the role of the activation-induced cytosine deaminase gene in B-cell development, the characterization of CD4(+)CD25(+) regulatory T cells, and the use of dynamic imaging to study MHC class II transport and T-cell and dendritic cell membrane interactions. Articles related to clinical immunology that were selected for review include the description of immunodeficiency caused by caspase 8 deficiency; a case series report on X-linked agammaglobulinemia; the mechanism of action, efficacy, and complications of intravenous immunoglobulin; mechanisms of autoimmunity diseases; and advances in HIV pathogenesis and vaccine development. We also reviewed two articles that explore the possible alterations of the immune system caused by spaceflights, a new field with increasing importance as human space expeditions become a reality in the 21st century.

  4. Development of low enriched uranium target plates by thermo-mechanical processing of UAl{sub 2}–Al matrix for production of {sup 99}Mo in Pakistan

    Energy Technology Data Exchange (ETDEWEB)

    Ali, Kanwar Liaqat; Khan, Akhlaque Ahmad [Pakistan Institute of Nuclear Science and Technology (PINSTECH) P.O Nilore, Islamabad (Pakistan); Mushtaq, Ahmad, E-mail: amushtaq1@hotmail.com [Pakistan Institute of Nuclear Science and Technology (PINSTECH) P.O Nilore, Islamabad (Pakistan); Imtiaz, Farhan; Ziai, Maratab Ali; Gulzar, Amir; Farooq, Muhammad; Hussain, Nazar; Ahmed, Nisar; Pervez, Shahid; Zaidi, Jamshed Hussain [Pakistan Institute of Nuclear Science and Technology (PINSTECH) P.O Nilore, Islamabad (Pakistan)

    2013-02-15

    Uranium aluminide predominated with UAl{sub 2} phase was prepared by arc-melting procedures and comminuted to required particle size. UAl{sub 2} and Al powders were blended and compacted to achieve LEU fuel density of 2.17 g/cm{sup 3}. The picture-frame technique was used to clad the dispersions (UAl{sub 2}–Al) with aluminum. A few target plates were fabricated by thermo-mechanical processing (hot rolling and annealing) of UAl{sub 2}–Al matrix contained in roll billet of Al. The fabricated plates were characterized by destructive and some of non-destructive testing techniques and then annealed to achieve required phase of uranium aluminide for proper dissolution in basic media.

  5. The metabolically active subpopulation in Pseudomonas aeruginosa biofilms survives exposure to membrane-targeting antimicrobials via distinct molecular mechanisms

    DEFF Research Database (Denmark)

    Chiang, Wen-Chi; Pamp, Sünje Johanna; Nilsson, Martin

    2012-01-01

    encoding lipopolysaccharide modification enzymes, as well as on the mexAB-oprM, mexCD-oprJ, and muxABC-opmB genes encoding antimicrobial efflux pumps, but does not depend on the mexPQ-opmE efflux pump genes. Development of chlorhexidine-tolerant subpopulations was found to depend on the mexCD-oprJ genes......, but does not depend on the pmr, mexAB-oprM, mexPQ-opmE, or muxABC-opmB genes. Tolerance to SDS and EDTA in P. aeruginosa biofilms is linked to metabolically active cells, but does not depend on the pmr, mexAB, mexCD, mexPQ, or muxABC genes. Our data suggest that the active subpopulation in P. aeruginosa......-targeting compounds colistin, EDTA, SDS, and chlorhexidine resulted in the same spatial distribution of live and dead bacteria, we investigated whether tolerance to these compounds originated from the same molecular mechanisms. Development of colistin-tolerant subpopulations was found to depend on the pmr genes...

  6. Quantum mechanics

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    The book is on quantum mechanics. The emphasis is on the basic concepts and the methodology. The chapters include: Breakdown of classical concepts; Quantum mechanical concepts; Basic postulates of quantum mechanics; solution of problems in quantum mechanics; Simple harmonic oscillator; and Angular Momentum

  7. Basic principles of concrete structures

    CERN Document Server

    Gu, Xianglin; Zhou, Yong

    2016-01-01

    Based on the latest version of designing codes both for buildings and bridges (GB50010-2010 and JTG D62-2004), this book starts from steel and concrete materials, whose properties are very important to the mechanical behavior of concrete structural members. Step by step, analysis of reinforced and prestressed concrete members under basic loading types (tension, compression, flexure, shearing and torsion) and environmental actions are introduced. The characteristic of the book that distinguishes it from other textbooks on concrete structures is that more emphasis has been laid on the basic theories of reinforced concrete and the application of the basic theories in design of new structures and analysis of existing structures. Examples and problems in each chapter are carefully designed to cover every important knowledge point. As a basic course for undergraduates majoring in civil engineering, this course is different from either the previously learnt mechanics courses or the design courses to be learnt. Compa...

  8. The Target Characteristics and Basic Ideas of Modern Tax Culture Construction%现代税务文化建设的目标特征与基本思路

    Institute of Scientific and Technical Information of China (English)

    周海生; 战炤磊

    2013-01-01

    long period of time in our country. The four target features con-struct the basic framework to explore our country tax culture construction as the basic thought.

  9. Understanding the Catalytic Mechanism and the Nature of the Transition State of an Attractive Drug-Target Enzyme (Shikimate Kinase) by Quantum Mechanical/Molecular Mechanical (QM/MM) Studies.

    Science.gov (United States)

    Yao, Jianzhuang; Wang, Xia; Luo, Haixia; Gu, Pengfei

    2017-11-16

    Shikimate kinase (SK) is the fifth bacterial enzyme involved in the shikimate pathway for biosynthesis of life-indispensable components, such as aromatic amino acids. The absence of the shikimate pathway in humans makes SK an attractive target for the rational design of drugs aimed at pathogenesis bacteria, such as Mycobacterium tuberculosis and Helicobacter pylori. However, an effective inhibitor of SK (e.g., a transition-state analogue) is still not available on the market due, at least in part, to a lack of knowledge on the catalytic mechanism and the nature of the rate-limiting transition state. Herein, quantum mechanical/molecular mechanical (QM/MM) reaction coordinate, molecular dynamics (MD), and free-energy simulations have been performed to answer these questions. The results presented herein demonstrate that the phosphoryl-transfer process, which is the rate-limiting step of SK-catalyzed phosphorylation of shikimic acid (SKM), is a concerted one-step reaction proceeding through a loose transition state. The computational results agree well with those of experimental studies, specifically NMR results, X-ray crystal structure observation, and activation free-energy barrier. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Adult Competency Education Kit. Basic Skills in Speaking, Math, and Reading for Employment. Part G. ACE Competency Based Job Descriptions: #22--Refrigerator Mechanic; #24--Motorcycle Repairperson.

    Science.gov (United States)

    San Mateo County Office of Education, Redwood City, CA. Career Preparation Centers.

    This fourth of fifteen sets of Adult Competency Education (ACE) Competency Based Job Descriptions in the ACE kit contains job descriptions for Refrigerator Mechanic and Motorcycle Repairperson. Each begins with a fact sheet that includes this information: occupational title, D.O.T. code, ACE number, career ladder, D.O.T. general educational…

  11. Orofacial pain: basic mechanisms and implication for successful management Dores orofaciais: mecanismos básicos e implicações para um tratamento efetivo

    Directory of Open Access Journals (Sweden)

    Paulo César Rodrigues Conti

    2003-03-01

    Full Text Available Orofacial Pain is the field of dentistry devoted to the diagnosis and management of chronic, complex, facial pain and oromotor disorders. This specialty in dentistry has developed over a number of years out of the need for better understanding of a group of patients who somehow were not clearly suffering from dental pain disorders, but still did not seem to have a clearly defined medical problem. After a long period of treating patients based on the mechanicist aspect of the disease, our profession has realized the importance of basic knowledge and differencial diagnosis in order to proper manage these patients. This modification in the approach has caused severe changes in education as well as in clinical activities. Historically considered as a problem of occlusion, Orofacial Pain, including Temporomandibular Disorders (TMD has recently reached the status of "Specialty" in Brazil. Therefore, this paper aims to discuss the main differences between musculoskeletal and neuropathic pain and the importance of basic knowledge to perform successful management.Dor Orofacial é um campo da odontologia dedicado ao diagnóstico e tratamento de dores orofaciais crônicas e complexas, além d e desordens motoras. Essa especialidade odontológica tem se desenvolvido por vários anos com o objetivo de prover um melhor entendimento de um grupo de pacientes que, de alguma forma, não tinham dores de origem dentária e nem condições óbvias médicas que explicassem suas dores na face. Depois de um longo período propondo tratamentos baseados apenas no aspecto mecanicista da doença, nossa profissão percebeu a importância de entender mecanismos básicos de diagnóstico diferencial para melhor controlar esses casos. Essa mudança de mentalidade tem levado a modificações na educação em odontologia, assim como nos procedimentos clínicos executados. Historicamente considerada como um "problema de oclusão", as dores orofaciais obtiveram recentemente o

  12. Stem Cell Basics

    Science.gov (United States)

    ... Tips Info Center Research Topics Federal Policy Glossary Stem Cell Information General Information Clinical Trials Funding Information Current ... Basics » Stem Cell Basics I. Back to top Stem Cell Basics I. Introduction: What are stem cells, and ...

  13. Synthesis of hierarchically porous perovskite-carbon aerogel composite catalysts for the rapid degradation of fuchsin basic under microwave irradiation and an insight into probable catalytic mechanism

    Science.gov (United States)

    Wang, Yin; Wang, Jiayuan; Du, Baobao; Wang, Yun; Xiong, Yang; Yang, Yiqiong; Zhang, Xiaodong

    2018-05-01

    3D hierarchically porous perovskites LaFe0.5M0.5O3-CA (M = Mn, Cu) were synthesized by a two-step method using PMMA as template and supporting with carbon aerogel, which were characterized with SEM, TEM, XRD, XPS and FT-IR spectroscopy. The as-prepared composites were used in microwave (MW) catalytic degradation of fuchsin basic (FB) dye wastewater. Batch experiment results showed that the catalytic degradation of FB could be remarkably improved by coating with CA. And LaFe0.5Cu0.5O3-CA exhibited higher catalytic performance than LaFe0.5Mn0.5O3-CA, which had a close connection with the activity of substitution metal ion in B site of the catalysts. The FB removal fit pseudo-first-order model and the degradation rate constant increased with initial pH value and MW powder while decreases with initial FB concentration. All catalysts presented favorable recycling and stability in the repeated experiment. Radical scavenger measurements indicated that hydroxyl radicals rather than surface peroxide and hole played an important role in the catalytic process, and its quantity determined the degradation of FB. Furthermore, both Cu and Fe species were involved in the formation of active species, which were responsible to the excellent performance of the LaFe0.5Cu0.5O3-CA/MW system. Therefore, LaFe0.5Cu0.5O3-CA/MW showed to be a promising technology for the removal of organic pollutants in wastewater treatment applications.

  14. Basic modelling of transport in 2D wave-mechanical nanodots and billiards with balanced gain and loss mediated by complex potentials

    Science.gov (United States)

    Berggren, Karl-Fredrik; Tellander, Felix; Yakimenko, Irina

    2018-05-01

    Non-Hermitian quantum mechanics with parity-time (PT) symmetry is presently gaining great interest, especially within the fields of photonics and optics. Here, we give a brief overview of low-dimensional semiconductor nanodevices using the example of a quantum dot with input and output leads, which are mimicked by imaginary potentials for gain and loss, and how wave functions, particle flow, coalescence of levels and associated breaking of PT symmetry may be analysed within such a framework. Special attention is given to the presence of exceptional points and symmetry breaking. Related features for musical string instruments and ‘wolf-notes’ are outlined briefly with suggestions for further experiments.

  15. Current Molecular Targeted Therapy in Advanced Gastric Cancer: A Comprehensive Review of Therapeutic Mechanism, Clinical Trials, and Practical Application

    Directory of Open Access Journals (Sweden)

    Kaichun Li

    2016-01-01

    Full Text Available Despite the great progress in the treatment of gastric cancer, it is still the third leading cause of cancer death worldwide. Patients often miss the opportunity for a surgical cure, because the cancer has already developed into advanced cancer when identified. Compared to best supportive care, chemotherapy can improve quality of life and prolong survival time, but the overall survival is often short. Due to the molecular study of gastric cancer, new molecular targeted drugs have entered the clinical use. Trastuzumab, an antibody targeting human epidermal growth factor receptor 2 (HER2, can significantly improve survival in advanced gastric cancer patients with HER2 overexpression. Second-line treatment of advanced gastric cancer with ramucirumab, an antibody targeting VEGFR-2, alone or in combination with paclitaxel, has been proved to provide a beneficial effect. The VEGFR-2 tyrosine kinase inhibitor, apatinib, can improve the survival of advanced gastric cancer patients after second-line chemotherapy failure. Unfortunately, none of the EGFR targeting antibodies (cetuximab or panitumumab, VEGF targeting monoclonal antibodies (bevacizumab, mTOR inhibitor (everolimus, or HGF/MET pathway targeting drugs has a significant survival benefit. Many other clinical trials based on molecular markers are underway. This review will summarize targeted therapies for advanced gastric cancer.

  16. Theoretical challenges in understanding the inhibition mechanism of aluminum corrosion in basic media in the presence of some p-phenol derivatives

    International Nuclear Information System (INIS)

    Lashgari, Mohsen

    2011-01-01

    Graphical abstract: Display Omitted Research highlights: → Quantum electrochemical/thermodynamical models for inhibition mechanism. → A new insight based on local deactivation of corrosive agents at interface region. → Protonation/deprotonation cycle of phenolic species inside electrical double layer. - Abstract: Using quantum electrochemical/thermodynamical approaches based on coupled cluster/polarized continuum models and density functional theory (CM/PCM-DFT), we investigated the corrosion inhibition mechanism of Al/NaOH system in the presence of some p-phenol derivatives. The influencing parameters on inhibitory action, i.e. charges on oxygen and hydrogen atoms of hydroxyl group, charge transfer, interaction energy, molecular activity and softness, electric dipole moment and de-solvation free energy, were determined for both neutral and deprotonated species at metal|solution interface. A good correlation was observed between these parameters and inhibition efficiency data reported in the literature. By introducing an appropriate thermodynamic procedure, we also determined the proton-loss tendency of the molecules nearby interface. The results were amazing and revealed a complicated protonation/deprotonation cycle for inhibitor species inside electrical double layer; the corrosive agents in the vicinity of metal surface become locally neutralized and pushed away.

  17. From basic physics to mechanisms of toxicity: the ``liquid drop'' approach applied to develop predictive classification models for toxicity of metal oxide nanoparticles

    Science.gov (United States)

    Sizochenko, Natalia; Rasulev, Bakhtiyor; Gajewicz, Agnieszka; Kuz'min, Victor; Puzyn, Tomasz; Leszczynski, Jerzy

    2014-10-01

    Many metal oxide nanoparticles are able to cause persistent stress to live organisms, including humans, when discharged to the environment. To understand the mechanism of metal oxide nanoparticles' toxicity and reduce the number of experiments, the development of predictive toxicity models is important. In this study, performed on a series of nanoparticles, the comparative quantitative-structure activity relationship (nano-QSAR) analyses of their toxicity towards E. coli and HaCaT cells were established. A new approach for representation of nanoparticles' structure is presented. For description of the supramolecular structure of nanoparticles the ``liquid drop'' model was applied. It is expected that a novel, proposed approach could be of general use for predictions related to nanomaterials. In addition, in our study fragmental simplex descriptors and several ligand-metal binding characteristics were calculated. The developed nano-QSAR models were validated and reliably predict the toxicity of all studied metal oxide nanoparticles. Based on the comparative analysis of contributed properties in both models the LDM-based descriptors were revealed to have an almost similar level of contribution to toxicity in both cases, while other parameters (van der Waals interactions, electronegativity and metal-ligand binding characteristics) have unequal contribution levels. In addition, the models developed here suggest different mechanisms of nanotoxicity for these two types of cells.Many metal oxide nanoparticles are able to cause persistent stress to live organisms, including humans, when discharged to the environment. To understand the mechanism of metal oxide nanoparticles' toxicity and reduce the number of experiments, the development of predictive toxicity models is important. In this study, performed on a series of nanoparticles, the comparative quantitative-structure activity relationship (nano-QSAR) analyses of their toxicity towards E. coli and HaCaT cells were

  18. Wire-based laser metal deposition for additive manufacturing of TiAl6V4: basic investigations of microstructure and mechanical properties from build up parts

    Science.gov (United States)

    Klocke, Fritz; Arntz, Kristian; Klingbeil, Nils; Schulz, Martin

    2017-02-01

    The wire-based laser metal deposition (LMD-W) is a new technology which enables to produce complex parts made of titanium for the aerospace and automotive industry. For establishing the LMD-W as a new production process it has to be proven that the properties are comparable or superior to conventional produced parts. The mechanical properties were investigated by analysis of microstructure and tensile test. Therefore, specimens were generated using a 4.5 kW diode laser cladding system integrated in a 5-Axis-machining center. The structural mechanical properties are mainly influence by crystal structure and thereby the thermal history of the work piece. Especially the high affinity to oxide, distortion and dual phase microstructure make titanium grade 5 (TiAl6V4) one of the most challenging material for additive manufacturing. By using a proper local multi-nozzle shielding gas concept the negative influence of oxide in the process could be eliminated. The distortion being marginal at a single bead, accumulated to a macroscopic effect on the work piece. The third critical point for additive processing of titanium, the bimodal microstructure, could not be cleared by the laser process alone. All metallurgical probes showed α-martensitic-structure. Therefore, a thermal treatment became a necessary production step in the additive production chain. After the thermal treatment the microstructure as well as the distortion was analyzed and compared with the status before. Although not all technical issues could be solved, the investigation show that LMD-W of titanium grade 5 is a promising alternative to other additive techniques as electronic beam melting or plasma deposition welding.

  19. A neuro-mechanical model of a single leg joint highlighting the basic physiological role of fast and slow muscle fibres of an insect muscle system.

    Directory of Open Access Journals (Sweden)

    Tibor Istvan Toth

    Full Text Available In legged animals, the muscle system has a dual function: to produce forces and torques necessary to move the limbs in a systematic way, and to maintain the body in a static position. These two functions are performed by the contribution of specialized motor units, i.e. motoneurons driving sets of specialized muscle fibres. With reference to their overall contraction and metabolic properties they are called fast and slow muscle fibres and can be found ubiquitously in skeletal muscles. Both fibre types are active during stepping, but only the slow ones maintain the posture of the body. From these findings, the general hypothesis on a functional segregation between both fibre types and their neuronal control has arisen. Earlier muscle models did not fully take this aspect into account. They either focused on certain aspects of muscular function or were developed to describe specific behaviours only. By contrast, our neuro-mechanical model is more general as it allows functionally to differentiate between static and dynamic aspects of movement control. It does so by including both muscle fibre types and separate motoneuron drives. Our model helps to gain a deeper insight into how the nervous system might combine neuronal control of locomotion and posture. It predicts that (1 positioning the leg at a specific retraction angle in steady state is most likely due to the extent of recruitment of slow muscle fibres and not to the force developed in the individual fibres of the antagonistic muscles; (2 the fast muscle fibres of antagonistic muscles contract alternately during stepping, while co-contraction of the slow muscle fibres takes place during steady state; (3 there are several possible ways of transition between movement and steady state of the leg achieved by varying the time course of recruitment of the fibres in the participating muscles.

  20. Expression and mechanism of mammalian target of rapamycin in age-related renal cell senescence and organ aging.

    Science.gov (United States)

    Zhuo, Li; Cai, Guangyan; Liu, Fuyou; Fu, Bo; Liu, Weiping; Hong, Quan; Ma, Qiang; Peng, Youming; Wang, Jianzhong; Chen, Xiangmei

    2009-10-01

    The mammalian target of rapamycin (mTOR) is relevant to cell senescence and organismal aging. This study firstly showed that the level of mTOR expression increased with aging in rat kidneys, rat mesangial cells and WI-38 cells (P aging-related phenotypes were all reduced in cells treated with rapamycin (an inhibitor of mTOR) than in control cells (P aging, and that mTOR may promote cellular senescence by regulating the cell cycle through p21(WAF1/CIP1/SDI1), which might provide a new target for preventing renal aging.

  1. Mechanics

    CERN Document Server

    Hartog, J P Den

    1961-01-01

    First published over 40 years ago, this work has achieved the status of a classic among introductory texts on mechanics. Den Hartog is known for his lively, discursive and often witty presentations of all the fundamental material of both statics and dynamics (and considerable more advanced material) in new, original ways that provide students with insights into mechanical relationships that other books do not always succeed in conveying. On the other hand, the work is so replete with engineering applications and actual design problems that it is as valuable as a reference to the practicing e

  2. Metabonomics applied in exploring the antitumour mechanism of physapubenolide on hepatocellular carcinoma cells by targeting glycolysis through the Akt-p53 pathway

    OpenAIRE

    Ma, Ting; Fan, Bo-Yi; Zhang, Chao; Zhao, Hui-Jun; Han, Chao; Gao, Cai-Yun; Luo, Jian-Guang; Kong, Ling-Yi

    2016-01-01

    Metabolomics can be used to identify potential markers and discover new targets for future therapeutic interventions. Here, we developed a novel application of the metabonomics method based on gas chromatography-mass spectrometry (GC/MS) analysis and principal component analysis (PCA) for rapidly exploring the anticancer mechanism of physapubenolide (PB), a cytotoxic withanolide isolated from Physalis species. PB inhibited the proliferation of hepatocellular carcinoma cells in vitro and in vi...

  3. Mechanism for the generation of 109 G magnetic fields in the interaction of ultraintense short laser pulse with an overdense plasma target

    International Nuclear Information System (INIS)

    Sudan, R.N.

    1993-01-01

    The physical mechanism for the generation of very high ''dc'' magnetic fields in the interaction of ultraintense short laser pulse with an overdense plasma target originates in the spatial gradients and nonstationary character of the ponderomotive force. A set of model equations to determine the evolution of the ''dc'' fields is derived and it is shown that the ''dc'' magnetic field is of the same order of magnitude as the high frequency laser magnetic field

  4. Targeting Glial Mitochondrial Function for Protection from Cerebral Ischemia: Relevance, Mechanisms, and the Role of MicroRNAs

    Directory of Open Access Journals (Sweden)

    Le Li

    2016-01-01

    Full Text Available Astrocytes and microglia play crucial roles in the response to cerebral ischemia and are effective targets for stroke therapy in animal models. MicroRNAs (miRs are important posttranscriptional regulators of gene expression that function by inhibiting the translation of select target genes. In astrocytes, miR expression patterns regulate mitochondrial function in response to oxidative stress via targeting of Bcl2 and heat shock protein 70 family members. Mitochondria play an active role in microglial activation, and miRs regulate the microglial neuroinflammatory response. As endogenous miR expression patterns can be altered with exogenous mimics and inhibitors, miR-targeted therapies represent a viable intervention to optimize glial mitochondrial function and improve clinical outcome following cerebral ischemia. In the present article, we review the role that astrocytes and microglia play in neuronal function and fate following ischemic stress, discuss the relevance of mitochondria in the glial response to injury, and present current evidence implicating miRs as critical regulators in the glial mitochondrial response to cerebral ischemia.

  5. Basic Research Firing Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Basic Research Firing Facility is an indoor ballistic test facility that has recently transitioned from a customer-based facility to a dedicated basic research...

  6. Fracture Mechanics

    International Nuclear Information System (INIS)

    Jang, Dong Il; Jeong, Gyeong Seop; Han, Min Gu

    1992-08-01

    This book introduces basic theory and analytical solution of fracture mechanics, linear fracture mechanics, non-linear fracture mechanics, dynamic fracture mechanics, environmental fracture and fatigue fracture, application on design fracture mechanics, application on analysis of structural safety, engineering approach method on fracture mechanics, stochastic fracture mechanics, numerical analysis code and fracture toughness test and fracture toughness data. It gives descriptions of fracture mechanics to theory and analysis from application of engineering.

  7. Systemic combinatorial peptide selection yields a non-canonical iron-mimicry mechanism for targeting tumors in a mouse model of human glioblastoma

    Science.gov (United States)

    Staquicini, Fernanda I.; Ozawa, Michael G.; Moya, Catherine A.; Driessen, Wouter H.P.; Barbu, E. Magda; Nishimori, Hiroyuki; Soghomonyan, Suren; Flores, Leo G.; Liang, Xiaowen; Paolillo, Vincenzo; Alauddin, Mian M.; Basilion, James P.; Furnari, Frank B.; Bogler, Oliver; Lang, Frederick F.; Aldape, Kenneth D.; Fuller, Gregory N.; Höök, Magnus; Gelovani, Juri G.; Sidman, Richard L.; Cavenee, Webster K.; Pasqualini, Renata; Arap, Wadih

    2010-01-01

    The management of CNS tumors is limited by the blood-brain barrier (BBB), a vascular interface that restricts the passage of most molecules from the blood into the brain. Here we show that phage particles targeted with certain ligand motifs selected in vivo from a combinatorial peptide library can cross the BBB under normal and pathological conditions. Specifically, we demonstrated that phage clones displaying an iron-mimic peptide were able to target a protein complex of transferrin and transferrin receptor (TfR) through a non-canonical allosteric binding mechanism and that this functional protein complex mediated transport of the corresponding viral particles into the normal mouse brain. We also showed that, in an orthotopic mouse model of human glioblastoma, a combination of TfR overexpression plus extended vascular permeability and ligand retention resulted in remarkable brain tumor targeting of chimeric adeno-associated virus/phage particles displaying the iron-mimic peptide and carrying a gene of interest. As a proof of concept, we delivered the HSV thymidine kinase gene for molecular-genetic imaging and targeted therapy of intracranial xenografted tumors. Finally, we established that these experimental findings might be clinically relevant by determining through human tissue microarrays that many primary astrocytic tumors strongly express TfR. Together, our combinatorial selection system and results may provide a translational avenue for the targeted detection and treatment of brain tumors. PMID:21183793

  8. Basic Cake Decorating Workbook.

    Science.gov (United States)

    Bogdany, Mel

    Included in this student workbook for basic cake decorating are the following: (1) Drawings of steps in a basic way to ice a layer cake, how to make a paper cone, various sizes of flower nails, various sizes and types of tin pastry tubes, and special rose tubes; (2) recipes for basic decorating icings (buttercream, rose paste, and royal icing);…

  9. A theoretical study on predicted protein targets of apple polyphenols and possible mechanisms of chemoprevention in colorectal cancer

    OpenAIRE

    Bernardina Scafuri; Anna Marabotti; Virginia Carbone; Paola Minasi; Serena Dotolo; Angelo Facchiano

    2016-01-01

    We investigated the potential role of apple phenolic compounds in human pathologies by integrating chemical characterization of phenolic compounds in three apple varieties, computational approaches to identify potential protein targets of the compounds, bioinformatics analyses on data from public archive of gene expression data, and functional analyses to hypothesize the effects of the selected compounds in molecular pathways. Starting by the analytic characterization of phenolic compounds in...

  10. The basic corrosion mechanisms of HLW glasses

    International Nuclear Information System (INIS)

    Conradt, R.; Roggendorf, H.; Ostertag, R.

    1986-01-01

    During the years 1975 to 1984, the Commission of the European Communities organized and promoted an R and D programme on the testing and evaluation of solidified high-level waste forms with the purpose of providing a scientific basis for the management and storage of radioactive waste. A fair number of materials were tested under a broad variation of experimental data. The Fraunhofer-Institut fuer Silicatforschung, Wuerzburg, has undertaken to perform a synoptic evaluation of the above data. The purpose of this evaluation is: - to compile the data from the individual national contributors (as presented in the joint annual reports of the EC) with respect to: the materials, or the experimental parameters, or further aspects, and to harmonize them with respect to their presentation, choice of units, etc., - to compare the results to the international state of information, - to elaborate and demonstrate common features of the diverse materials, e.g. common patterns of the corrosion behaviour, - to check the validity of present models, - to define shortcomings and questions that are still open

  11. High heat flux tests of the WENDELSTEIN 7-X pre-series target elements - experimental evaluation of the thermo-mechanical behaviour

    International Nuclear Information System (INIS)

    Greuner, H.; Boeswirth, B.; Boscary, J.; Plankensteiner, A.; Schedler, B.

    2006-01-01

    The HHF testing of WENDELSTEIN 7-X pre-series target elements is an indispensable step in the qualification of the manufacturing process. The finally 890 divertor target elements are made of an actively water-cooled CuCrZr heat sink covered with flat tiles of CFC NB31 as plasma facing material. A set of 20 full scale pre-series elements was manufactured by PLANSEE to validate the materials and manufacturing technologies prior to the start of the series production. Due to the large mismatch in the coefficients of thermal expansion for CFC and CuCrZr - resulting in high residual stresses as well as high operation-induced stresses - the bonding zone between CFC and CuCrZr was detected to be the most critical issue for the operational behaviour of the target elements. To achieve a sufficiently high manufacturing quality together with a high lifetime during operation thermal testing of full scale mockups was performed in combination with extensive FEM analyses. In both cases heat loads were applied similar to the expected heat loads in W7-X. All pre-series elements were tested in the ion beam test facility GLADIS. The elements were tested with 100 cycles of 10 MW/m 2 and several elements with even higher cycle numbers and heat loads up to 24 MW/m 2 . The instrumentation of the targets (thermocouples, strain gages) and the infrared camera observation of the heat loaded surface allow an experimental evaluation of the thermo-mechanical behaviour of the tested elements. The main result is a good agreement between experimental data and numerically computed predictions. Hot spots were, however, observed at the edges of several tiles during the HHF tests indicating local bonding problems. Therefore, a programme of fully 3D nonlinear thermal-mechanical FEM calculations was started to evaluate the thermo-mechanical behavior of the target elements with special focus on the optimization of the stress situation in the bonding zone between the CFC and the CuCrZr heat sink. This

  12. Advances in molecular-based personalized non-small-cell lung cancer therapy: targeting epidermal growth factor receptor and mechanisms of resistance

    International Nuclear Information System (INIS)

    Jotte, Robert M; Spigel, David R

    2015-01-01

    Molecularly targeted therapies, directed against the features of a given tumor, have allowed for a personalized approach to the treatment of advanced non-small-cell lung cancer (NSCLC). The reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib had undergone turbulent clinical development until it was discovered that these agents have preferential activity in patients with NSCLC harboring activating EGFR mutations. Since then, a number of phase 3 clinical trials have collectively shown that EGFR-TKI monotherapy is more effective than combination chemotherapy as first-line therapy for EGFR mutation-positive advanced NSCLC. The next generation of EGFR-directed agents for EGFR mutation-positive advanced NSCLC is irreversible TKIs against EGFR and other ErbB family members, including afatinib, which was recently approved, and dacomitinib, which is currently being tested in phase 3 trials. As research efforts continue to explore the various proposed mechanisms of acquired resistance to EGFR-TKI therapy, agents that target signaling pathways downstream of EGFR are being studied in combination with EGFR TKIs in molecularly selected advanced NSCLC. Overall, the results of numerous ongoing phase 3 trials involving the EGFR TKIs will be instrumental in determining whether further gains in personalized therapy for advanced NSCLC are attainable with newer agents and combinations. This article reviews key clinical trial data for personalized NSCLC therapy with agents that target the EGFR and related pathways, specifically based on molecular characteristics of individual tumors, and mechanisms of resistance

  13. Effect of titanium incorporation on the structural, mechanical and biocompatible properties of DLC thin films prepared by reactive-biased target ion beam deposition method

    Energy Technology Data Exchange (ETDEWEB)

    Bharathy, P. Vijai [Thin Films and Nanomaterials Lab, School of Physical Sciences, Bharathiar University, Coimbatore 641046 (India); Department of Mechanical Engineering, University of Saskatchewan, Saskatoon (Canada); Nataraj, D., E-mail: de.natraj@gmail.com [Thin Films and Nanomaterials Lab, School of Physical Sciences, Bharathiar University, Coimbatore 641046 (India); Chu, Paul K.; Wang, Huaiyu [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon (Hong Kong); Yang, Q. [Department of Mechanical Engineering, University of Saskatchewan, Saskatoon (Canada); Kiran, M.S.R.N. [School of Physics, University of Hyderabad, Hyderabad, Andra Pradesh (India); Silvestre-Albero, J. [Laboratorio de Materiales Avanzados, Departmento de Quimica Inorganica, Universidad de Alicante, Ap 99, E-03080 Alicante (Spain); Mangalaraj, D. [Thin Films and Nanomaterials Lab, School of Physical Sciences, Bharathiar University, Coimbatore 641046 (India)

    2010-10-15

    Amorphous diamond like carbon (DLC) and titanium incorporated diamond like carbon (Ti-DLC) thin films were deposited by using reactive-biased target ion beam deposition method. The effects of Ti incorporation and target bias voltage on the microstructure and mechanical properties of the as-deposited films were investigated by means of X-ray photoelectron spectroscopy, Raman spectroscopy, transmission electron microscopy and nano-indentation. It was found that the Ti content in Ti-DLC films gets increased with increasing target bias voltage. At about 4.2 at.% of Ti, uniform sized well dispersed nanocrystals were seen in the DLC matrix. Using FFT analysis, a facility available in the TEM, it was found that the nanocrystals are in cubic TiC phase. Though at the core, the incorporated Ti atoms react with carbon to form cubic TiC; most of the surface exposed Ti atoms were found to react with the atmospheric oxygen to form weakly bonded Ti-O. The presence of TiC nanocrystals greatly modified the sp{sup 3}/sp{sup 2} hybridized bonding ratio and is reflected in mechanical hardness of Ti-DLC films. These films were then tested for their biocompatibility by an invitro cell culturing test. Morphological observation and the cell proliferation test have demonstrated that the human osteoblast cells well attach and proliferate on the surface of Ti incorporated DLC films, suggesting possible applications in bone related implant coatings.

  14. Effect of titanium incorporation on the structural, mechanical and biocompatible properties of DLC thin films prepared by reactive-biased target ion beam deposition method

    International Nuclear Information System (INIS)

    Bharathy, P. Vijai; Nataraj, D.; Chu, Paul K.; Wang, Huaiyu; Yang, Q.; Kiran, M.S.R.N.; Silvestre-Albero, J.; Mangalaraj, D.

    2010-01-01

    Amorphous diamond like carbon (DLC) and titanium incorporated diamond like carbon (Ti-DLC) thin films were deposited by using reactive-biased target ion beam deposition method. The effects of Ti incorporation and target bias voltage on the microstructure and mechanical properties of the as-deposited films were investigated by means of X-ray photoelectron spectroscopy, Raman spectroscopy, transmission electron microscopy and nano-indentation. It was found that the Ti content in Ti-DLC films gets increased with increasing target bias voltage. At about 4.2 at.% of Ti, uniform sized well dispersed nanocrystals were seen in the DLC matrix. Using FFT analysis, a facility available in the TEM, it was found that the nanocrystals are in cubic TiC phase. Though at the core, the incorporated Ti atoms react with carbon to form cubic TiC; most of the surface exposed Ti atoms were found to react with the atmospheric oxygen to form weakly bonded Ti-O. The presence of TiC nanocrystals greatly modified the sp 3 /sp 2 hybridized bonding ratio and is reflected in mechanical hardness of Ti-DLC films. These films were then tested for their biocompatibility by an invitro cell culturing test. Morphological observation and the cell proliferation test have demonstrated that the human osteoblast cells well attach and proliferate on the surface of Ti incorporated DLC films, suggesting possible applications in bone related implant coatings.

  15. A mitochondrially targeted compound delays aging in yeast through a mechanism linking mitochondrial membrane lipid metabolism to mitochondrial redox biology

    Directory of Open Access Journals (Sweden)

    Michelle T. Burstein

    2014-01-01

    Full Text Available A recent study revealed a mechanism of delaying aging in yeast by a natural compound which specifically impacts mitochondrial redox processes. In this mechanism, exogenously added lithocholic bile acid enters yeast cells, accumulates mainly in the inner mitochondrial membrane, and elicits an age-related remodeling of phospholipid synthesis and movement within both mitochondrial membranes. Such remodeling of mitochondrial phospholipid dynamics progresses with the chronological age of a yeast cell and ultimately causes significant changes in mitochondrial membrane lipidome. These changes in the composition of membrane phospholipids alter mitochondrial abundance and morphology, thereby triggering changes in the age-related chronology of such longevity-defining redox processes as mitochondrial respiration, the maintenance of mitochondrial membrane potential, the preservation of cellular homeostasis of mitochondrially produced reactive oxygen species, and the coupling of electron transport to ATP synthesis.

  16. Differential scanning calorimetry of whole Escherichia coli treated with the antimicrobial peptide MSI-78 indicate a multi-hit mechanism with ribosomes as a novel target

    Directory of Open Access Journals (Sweden)

    Alexander M. Brannan

    2015-12-01

    Full Text Available Differential Scanning Calorimetry (DSC of intact Escherichia coli (E. coli was used to identify non-lipidic targets of the antimicrobial peptide (AMP MSI-78. The DSC thermograms revealed that, in addition to its known lytic properties, MSI-78 also has a striking effect on ribosomes. MSI-78’s effect on DSC scans of bacteria was similar to that of kanamycin, an antibiotic drug known to target the 30S small ribosomal subunit. An in vitro transcription/translation assay helped confirm MSI-78’s targeting of ribosomes. The scrambled version of MSI-78 also affected the ribosome peak of the DSC scans, but required greater amounts of peptide to cause a similar effect to the unscrambled peptide. Furthermore, the effect of the scrambled peptide was not specific to the ribosomes; other regions of the DSC thermogram were also affected. These results suggest that MSI-78’s effects on E. coli are at least somewhat dependent on its particular structural features, rather than a sole function of its overall charge and hydrophobicity. When considered along with earlier work detailing MSI-78’s membrane lytic properties, it appears that MSI-78 operates via a multi-hit mechanism with multiple targets.

  17. Basic concepts of epidemiology

    International Nuclear Information System (INIS)

    Savitz, D.A.

    1984-01-01

    Epidemiology can be defined simply as the science of the distribution and determinants of disease in human populations. As a descriptive tool, epidemiology can aid health care service providers, for example, in allocation of resources. In its analytic capacity, the epidemiologic approach can help identify determinants of disease through the study of human populations. Epidemiology is primarily an observational rather than experimental methodology, with corresponding strengths and limitations. Relative to other approaches for assessing disease etiology and impacts of potential health hazards, epidemiology has a rather unique role that is complementary to, but independent of, both basic biologic sciences and clinical medicine. Experimental biologic sciences such as toxicology and physiology provide critical information on biologic mechanisms of disease required for causal inference. Clinical medicine often serves as the warning system that provides etiologic clues to be pursued through systematic investigation. The advantage of the epidemiologic approach is its reliance on human field experience, that is, the real world. While laboratory experimentation is uniquely well suited to defining potential hazards, it can neither determine whether human populations have actually been affected nor quantify that effect. Building all the complexities of human behavior and external factors into a laboratory study or mathematical model is impossible. By studying the world as it exists, epidemiology examines the integrated, summarized product of the myriad factors influencing health

  18. Positron emission tomography. Basic principles

    International Nuclear Information System (INIS)

    Rodriguez, Jose Luis; Massardo, Teresa; Gonzalez, Patricio

    2001-01-01

    The basic principles of positron emission tomography (PET) technique are reviewed. lt allows to obtain functional images from gamma rays produced by annihilation of a positron, a positive beta particle. This paper analyzes positron emitters production in a cyclotron, its general mechanisms, and the various detection systems. The most important clinical applications are also mentioned, related to oncological uses of fluor-l8-deoxyglucose

  19. DNA-Destabilizing Agents as an Alternative Approach for Targeting DNA: Mechanisms of Action and Cellular Consequences

    Directory of Open Access Journals (Sweden)

    Gaëlle Lenglet

    2010-01-01

    Full Text Available DNA targeting drugs represent a large proportion of the actual anticancer drug pharmacopeia, both in terms of drug brands and prescription volumes. Small DNA-interacting molecules share the ability of certain proteins to change the DNA helix's overall organization and geometrical orientation via tilt, roll, twist, slip, and flip effects. In this ocean of DNA-interacting compounds, most stabilize both DNA strands and very few display helix-destabilizing properties. These types of DNA-destabilizing effect are observed with certain mono- or bis-intercalators and DNA alkylating agents (some of which have been or are being developed as cancer drugs. The formation of locally destabilized DNA portions could interfere with protein/DNA recognition and potentially affect several crucial cellular processes, such as DNA repair, replication, and transcription. The present paper describes the molecular basis of DNA destabilization, the cellular impact on protein recognition, and DNA repair processes and the latter's relationships with antitumour efficacy.

  20. Rice and Bean Targets for Biofortification Combined with High Carotenoid Content Crops Regulate Transcriptional Mechanisms Increasing Iron Bioavailability

    Science.gov (United States)

    Dias, Desirrê Morais; de Castro Moreira, Maria Eliza; Gomes, Mariana Juste Contin; Lopes Toledo, Renata Celi; Nutti, Marilia Regini; Pinheiro Sant’Ana, Helena Maria; Martino, Hércia Stampini Duarte

    2015-01-01

    Iron deficiency affects thousands of people worldwide. Biofortification of staple food crops aims to support the reduction of this deficiency. This study evaluates the effect of combinations of common beans and rice, targets for biofortification, with high carotenoid content crops on the iron bioavailability, protein gene expression, and antioxidant effect. Iron bioavailability was measured by the depletion/repletion method. Seven groups were tested (n = 7): Pontal bean (PB); rice + Pontal bean (R + BP); Pontal bean + sweet potato (PB + SP); Pontal bean + pumpkin (PB + P); Pontal bean + rice + sweet potato (PB + R + P); Pontal bean + rice + sweet potato (PB + R + SP); positive control (Ferrous Sulfate). The evaluations included: hemoglobin gain, hemoglobin regeneration efficiency (HRE), gene expression of divalente metal transporter 1 (DMT-1), duodenal citocromo B (DcytB), ferroportin, hephaestin, transferrin and ferritin and total plasma antioxidant capacity (TAC). The test groups, except the PB, showed higher HRE (p bioavailability and antioxidant capacity. PMID:26610564

  1. A multi-target caffeine derived rhodium(i) N-heterocyclic carbene complex: evaluation of the mechanism of action.

    Science.gov (United States)

    Zhang, Jing-Jing; Muenzner, Julienne K; Abu El Maaty, Mohamed A; Karge, Bianka; Schobert, Rainer; Wölfl, Stefan; Ott, Ingo

    2016-08-16

    A rhodium(i) and a ruthenium(ii) complex with a caffeine derived N-heterocyclic carbene (NHC) ligand were biologically investigated as organometallic conjugates consisting of a metal center and a naturally occurring moiety. While the ruthenium(ii) complex was largely inactive, the rhodium(i) NHC complex displayed selective cytotoxicity and significant anti-metastatic and in vivo anti-vascular activities and acted as both a mammalian and an E. coli thioredoxin reductase inhibitor. In HCT-116 cells it increased the reactive oxygen species level, leading to DNA damage, and it induced cell cycle arrest, decreased the mitochondrial membrane potential, and triggered apoptosis. This rhodium(i) NHC derivative thus represents a multi-target compound with promising anti-cancer potential.

  2. Development and Mechanism of Small Activating RNA Targeting CEBPA, a Novel Therapeutic in Clinical Trials for Liver Cancer.

    Science.gov (United States)

    Voutila, Jon; Reebye, Vikash; Roberts, Thomas C; Protopapa, Pantelitsa; Andrikakou, Pinelopi; Blakey, David C; Habib, Robert; Huber, Hans; Saetrom, Pal; Rossi, John J; Habib, Nagy A

    2017-12-06

    Small activating RNAs (saRNAs) are short double-stranded oligonucleotides that selectively increase gene transcription. Here, we describe the development of an saRNA that upregulates the transcription factor CCATT/enhancer binding protein alpha (CEBPA), investigate its mode of action, and describe its development into a clinical candidate. A bioinformatically directed nucleotide walk around the CEBPA gene identified an saRNA sequence that upregulates CEBPA mRNA 2.5-fold in human hepatocellular carcinoma cells. A nuclear run-on assay confirmed that this upregulation is a transcriptionally driven process. Mechanistic experiments demonstrate that Argonaute-2 (Ago2) is required for saRNA activity, with the guide strand of the saRNA shown to be associated with Ago2 and localized at the CEBPA genomic locus using RNA chromatin immunoprecipitation (ChIP) assays. The data support a sequence-specific on-target saRNA activity that leads to enhanced CEBPA mRNA transcription. Chemical modifications were introduced in the saRNA duplex to prevent activation of the innate immunity. This modified saRNA retains activation of CEBPA mRNA and downstream targets and inhibits growth of liver cancer cell lines in vitro. This novel drug has been encapsulated in a liposomal formulation for liver delivery, is currently in a phase I clinical trial for patients with liver cancer, and represents the first human study of an saRNA therapeutic. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. Chemical proteomics approach reveals the direct targets and the heme-dependent activation mechanism of artemisinin in Plasmodium falciparum using an activity-based artemisinin probe

    Directory of Open Access Journals (Sweden)

    Jigang Wang

    2016-04-01

    Full Text Available Artemisinin and its analogues are currently the most effective anti-malarial drugs. The activation of artemisinin requires the cleavage of the endoperoxide bridge in the presence of iron sources. Once activated, artemisinins attack macromolecules through alkylation and propagate a series of damages, leading to parasite death. Even though several parasite proteins have been reported as artemisinin targets, the exact mechanism of action (MOA of artemisinin is still controversial and its high potency and specificity against the malaria parasite could not be fully accounted for. Recently, we have developed an unbiased chemical proteomics approach to directly probe the MOA of artemisinin in P. falciparum. We synthesized an activity-based artemisinin probe with an alkyne tag, which can be coupled with biotin through click chemistry. This enabled selective purification and identification of 124 protein targets of artemisinin. Many of these targets are critical for the parasite survival. In vitro assays confirmed the specific artemisinin binding and inhibition of selected targets. We thus postulated that artemisinin kills the parasite through disrupting its biochemical landscape. In addition, we showed that artemisinin activation requires heme, rather than free ferrous iron, by monitoring the extent of protein binding using a fluorescent dye coupled with the alkyne-tagged artemisinin. The extremely high level of heme released from the hemoglobin digestion by the parasite makes artemisinin exceptionally potent against late-stage parasites (trophozoite and schizont stages compared to parasites at early ring stage, which have low level of heme, possibly derived from endogenous synthesis. Such a unique activation mechanism also confers artemisinin with extremely high specificity against the parasites, while the healthy red blood cells are unaffected. Our results provide a sound explanation of the MOA of artemisinin and its specificity against malaria

  4. Basic digital signal processing

    CERN Document Server

    Lockhart, Gordon B

    1985-01-01

    Basic Digital Signal Processing describes the principles of digital signal processing and experiments with BASIC programs involving the fast Fourier theorem (FFT). The book reviews the fundamentals of the BASIC program, continuous and discrete time signals including analog signals, Fourier analysis, discrete Fourier transform, signal energy, power. The text also explains digital signal processing involving digital filters, linear time-variant systems, discrete time unit impulse, discrete-time convolution, and the alternative structure for second order infinite impulse response (IIR) sections.

  5. Hydromechanics - basic properties

    International Nuclear Information System (INIS)

    Lee, Sung Tak; Lee, Je Geun

    1987-03-01

    This book tells of hydromechanics, which is about basic properties of hydromechanics such as conception, definition, mass, power and weight, and perfect fluid and perfect gas, hydrostatics with summary, basic equation of hydrostatics, relative balance of hydrostatics, and kinematics of hydromechanics, description method of floating, hydromechanics about basic knowledge, equation of moment, energy equation and application of Bernoulli equation, application of momentum theory, inviscid flow and fluid measuring.

  6. Basic molecular spectroscopy

    CERN Document Server

    Gorry, PA

    1985-01-01

    BASIC Molecular Spectroscopy discusses the utilization of the Beginner's All-purpose Symbolic Instruction Code (BASIC) programming language in molecular spectroscopy. The book is comprised of five chapters that provide an introduction to molecular spectroscopy through programs written in BASIC. The coverage of the text includes rotational spectra, vibrational spectra, and Raman and electronic spectra. The book will be of great use to students who are currently taking a course in molecular spectroscopy.

  7. Ultrasound-targeted transfection of tissue-type plasminogen activator gene carried by albumin nanoparticles to dog myocardium to prevent thrombosis after heart mechanical valve replacement

    Directory of Open Access Journals (Sweden)

    Ji J

    2012-06-01

    Full Text Available Ji Jun, Ji Shang-Yi, Yang Jian-An, He Xia, Yang Xiao-Han, Ling Wen-Ping, Chen Xiao-LingDepartment of Pathology and Cardiovascular Surgery, Shenzhen Sun Yat-Sen Cardiovascular Hospital, Shenzhen, Guangdong, People's Republic of ChinaBackground: There are more than 300,000 prosthetic heart valve replacements each year worldwide. These patients are faced with a higher risk of thromboembolic events after heart valve surgery and long-term or even life-long anticoagulative and antiplatelet therapies are necessary. Some severe complications such as hemorrhaging or rebound thrombosis can occur when the therapy ceases. Tissue-type plasminogen activator (t-PA is a thrombolytic agent. One of the best strategies is gene therapy, which offers a local high expression of t-PA over a prolonged time period to avoid both systemic hemorrhaging and local rebound thrombosis. There are some issues with t-PA that need to be addressed: currently, there is no up-to-date report on how the t-PA gene targets the heart in vivo and the gene vector for t-PA needs to be determined.Aims: To fabricate an albumin nano-t-PA gene ultrasound-targeted agent and investigate its targeting effect on prevention of thrombosis after heart mechanic valve replacement under therapeutic ultrasound.Methods: A dog model of mechanical tricuspid valve replacement was constructed. A highly expressive t-PA gene plasmid was constructed and packaged by nanoparticles prepared with bovine serum albumin. This nanopackaged t-PA gene plasmid was further cross-linked to ultrasonic microbubbles prepared with sucrose and bovine serum albumin to form the ultrasonic-targeted agent for t-PA gene transfection. The agent was given intravenously followed by a therapeutic ultrasound treatment (1 MHz, 1.5 w/cm2, 10 minutes of the heart soon after valve replacement had been performed. The expression of t-PA in myocardium was detected with multiclonal antibodies to t-PA by the indirect immunohistochemical method

  8. Stiff mutant genes of Phycomyces target turgor pressure and wall mechanical properties to regulate elongation growth rate

    Directory of Open Access Journals (Sweden)

    Joseph K. E. Ortega

    2012-05-01

    Full Text Available Regulation of cell growth is paramount to all living organisms. In plants, algae and fungi, regulation of expansive growth of cells is required for development and morphogenesis. Also, many sensory responses of stage IVb sporangiophores of Phycomyces blakesleeanus are produced by regulating elongation growth rate (growth responses and differential elongation growth rate (tropic responses. Stiff mutant sporangiophores exhibit diminished tropic responses and are found to be defective in at least four genes; madD, madE, madF and madG. Prior experimental research suggests that the defective genes affect growth regulation, but this was not verified. All the growth of the single-celled stalk of the stage IVb sporangiophore occurs in a short region termed the growth zone. Prior experimental and theoretical research indicates that elongation growth rate of the stage IVb sporangiophore can be regulated by controlling the cell wall mechanical properties within the growth zone and the magnitude of the turgor pressure. A quantitative biophysical model for elongation growth rate is required to elucidate the relationship between wall mechanical properties and turgor pressure during growth regulation. In this study, it is hypothesized that the mechanical properties of the wall within the growth zone of stiff mutant sporangiophores are different compared to wild type. A biophysical equation for elongation growth rate is derived for fungal and plant cells with a growth zone. Two strains of stiff mutants are studied, C149 madD120 (- and C216 geo- (-. Experimental results demonstrate that turgor pressure is larger but irreversible deformation rates of the wall within the growth zone and growth zone length are smaller for stiff mutant sporangiophores compared to wild type. These findings explain the diminished tropic responses of the stiff mutant sporangiophores and suggest that the defective genes affect the amount of wall-building material delivered to the inner

  9. New approaches to targeted drug delivery to tumour cells

    International Nuclear Information System (INIS)

    Severin, E S

    2015-01-01

    Basic approaches to the design of targeted drugs for the treatment of human malignant tumours have been considered. The stages of the development of these approaches have been described in detail and theoretically substantiated, and basic experimental results have been reported. Considerable attention is paid to the general characteristic of nanopharmacological drugs and to the description of mechanisms of cellular interactions with nanodrugs. The potentialities and limitations of application of nanodrugs for cancer therapy and treatment of other diseases have been considered. The use of nanodrugs conjugated with vector molecules seems to be the most promising trend of targeted therapy of malignant tumours. The bibliography includes 122 references

  10. Rice and Bean Targets for Biofortification Combined with High Carotenoid Content Crops Regulate Transcriptional Mechanisms Increasing Iron Bioavailability

    Directory of Open Access Journals (Sweden)

    Desirrê Morais Dias

    2015-11-01

    Full Text Available Iron deficiency affects thousands of people worldwide. Biofortification of staple food crops aims to support the reduction of this deficiency. This study evaluates the effect of combinations of common beans and rice, targets for biofortification, with high carotenoid content crops on the iron bioavailability, protein gene expression, and antioxidant effect. Iron bioavailability was measured by the depletion/repletion method. Seven groups were tested (n = 7: Pontal bean (PB; rice + Pontal bean (R + BP; Pontal bean + sweet potato (PB + SP; Pontal bean + pumpkin (PB + P; Pontal bean + rice + sweet potato (PB + R + P; Pontal bean + rice + sweet potato (PB + R + SP; positive control (Ferrous Sulfate. The evaluations included: hemoglobin gain, hemoglobin regeneration efficiency (HRE, gene expression of divalente metal transporter 1 (DMT-1, duodenal citocromo B (DcytB, ferroportin, hephaestin, transferrin and ferritin and total plasma antioxidant capacity (TAC. The test groups, except the PB, showed higher HRE (p < 0.05 than the control. Gene expression of DMT-1, DcytB and ferroportin increased (p < 0.05 in the groups fed with high content carotenoid crops (sweet potato or pumpkin. The PB group presented lower (p < 0.05 TAC than the other groups. The combination of rice and common beans, and those with high carotenoid content crops increased protein gene expression, increasing the iron bioavailability and antioxidant capacity.

  11. Targeting Wnt signaling in colorectal cancer. A Review in the Theme: Cell Signaling: Proteins, Pathways and Mechanisms

    Science.gov (United States)

    Novellasdemunt, Laura; Antas, Pedro

    2015-01-01

    The evolutionarily conserved Wnt signaling pathway plays essential roles during embryonic development and tissue homeostasis. Notably, comprehensive genetic studies in Drosophila and mice in the past decades have demonstrated the crucial role of Wnt signaling in intestinal stem cell maintenance by regulating proliferation, differentiation, and cell-fate decisions. Wnt signaling has also been implicated in a variety of cancers and other diseases. Loss of the Wnt pathway negative regulator adenomatous polyposis coli (APC) is the hallmark of human colorectal cancers (CRC). Recent advances in high-throughput sequencing further reveal many novel recurrent Wnt pathway mutations in addition to the well-characterized APC and β-catenin mutations in CRC. Despite attractive strategies to develop drugs for Wnt signaling, major hurdles in therapeutic intervention of the pathway persist. Here we discuss the Wnt-activating mechanisms in CRC and review the current advances and challenges in drug discovery. PMID:26289750

  12. SPARC/osteonectin, an endogenous mechanism for targeting albumin to the blood-cerebrospinal fluid interface during brain development

    DEFF Research Database (Denmark)

    Liddelow, S A; Dziegielewska, K M; Møllgård, K

    2011-01-01

    Specialized populations of choroid plexus epithelial cells have previously been shown to be responsible for the transfer of individual plasma proteins from blood to the cerebrospinal fluid (CSF), contributing to their characteristically high concentrations in CSF of the developing brain. The mech......Specialized populations of choroid plexus epithelial cells have previously been shown to be responsible for the transfer of individual plasma proteins from blood to the cerebrospinal fluid (CSF), contributing to their characteristically high concentrations in CSF of the developing brain....... The mechanism of this protein transfer remains elusive. Using a marsupial, Monodelphis domestica, we demonstrate that the albumin-binding protein SPARC (osteonectin/BM-40/culture-shock protein) is present in a subset of choroid plexus epithelial cells from its first appearance, throughout development...

  13. Insight into PreImplantation Factor (PIF* mechanism for embryo protection and development: target oxidative stress and protein misfolding (PDI and HSP through essential RIKP [corrected] binding site.

    Directory of Open Access Journals (Sweden)

    Eytan R Barnea

    novel utilitarian method for small molecule targets direct identification. Data reveals and completes the understanding of mechanisms involved in PIF-induced autotrophic and protective effects on the embryo.

  14. Finding Basic Writing's Place.

    Science.gov (United States)

    Sheridan-Rabideau, Mary P.; Brossell, Gordon

    1995-01-01

    Posits that basic writing serves a vital function by providing writing support for at-risk students and serves the needs of a growing student population that universities accept yet feel needs additional writing instruction. Concludes that the basic writing classroom is the most effective educational support for at-risk students and their writing.…

  15. Biomass Energy Basics | NREL

    Science.gov (United States)

    Biomass Energy Basics Biomass Energy Basics We have used biomass energy, or "bioenergy" keep warm. Wood is still the largest biomass energy resource today, but other sources of biomass can landfills (which are methane, the main component in natural gas) can be used as a biomass energy source. A

  16. Wind Energy Basics | NREL

    Science.gov (United States)

    Wind Energy Basics Wind Energy Basics We have been harnessing the wind's energy for hundreds of grinding grain. Today, the windmill's modern equivalent-a wind turbine can use the wind's energy to most energy. At 100 feet (30 meters) or more aboveground, they can take advantage of the faster and

  17. Solar Energy Basics | NREL

    Science.gov (United States)

    Solar Energy Basics Solar Energy Basics Solar is the Latin word for sun-a powerful source of energy that can be used to heat, cool, and light our homes and businesses. That's because more energy from the technologies convert sunlight to usable energy for buildings. The most commonly used solar technologies for

  18. Learning Visual Basic NET

    CERN Document Server

    Liberty, Jesse

    2009-01-01

    Learning Visual Basic .NET is a complete introduction to VB.NET and object-oriented programming. By using hundreds of examples, this book demonstrates how to develop various kinds of applications--including those that work with databases--and web services. Learning Visual Basic .NET will help you build a solid foundation in .NET.

  19. Health Insurance Basics

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Health Insurance Basics KidsHealth / For Teens / Health Insurance Basics What's ... thought advanced calculus was confusing. What Exactly Is Health Insurance? Health insurance is a plan that people buy ...

  20. Body Basics Library

    Science.gov (United States)

    ... Body Basics articles explain just how each body system, part, and process works. Use this medical library to find out about basic human anatomy, how ... Teeth Skin, Hair, and Nails Spleen and Lymphatic System ... Visit the Nemours Web site. Note: All information on TeensHealth® is for ...

  1. Molecular mechanisms and signaling pathways of angiotensin II-induced muscle wasting: potential therapeutic targets for cardiac cachexia

    Science.gov (United States)

    Yoshida, Tadashi; Tabony, A. Michael; Galvez, Sarah; Mitch, William E.; Higashi, Yusuke; Sukhanov, Sergiy; Delafontaine, Patrice

    2013-01-01

    Cachexia is a serious complication of many chronic diseases, such as congestive heart failure (CHF) and chronic kidney disease (CKD). Many factors are involved in the development of cachexia, and there is increasing evidence that angiotensin II (Ang II), the main effector molecule of the renin-angiotensin system (RAS), plays an important role in this process. Patients with advanced CHF or CKD often have increased Ang II levels and cachexia, and angiotensin-converting enzyme (ACE) inhibitor treatment improves weight loss. In rodent models, an increase in systemic Ang II leads to weight loss through increased protein breakdown, reduced protein synthesis in skeletal muscle and decreased appetite. Ang II activates the ubiquitin-proteasome system via generation of reactive oxygen species and via inhibition of the insulin-like growth factor-1 signaling pathway. Furthermore, Ang II inhibits 5′ AMP-activated protein kinase (AMPK) activity and disrupts normal energy balance. Ang II also increases cytokines and circulating hormones such as tumor necrosis factor-α, interleukin-6, serum amyloid-A, glucocorticoids and myostatin, which regulate muscle protein synthesis and degradation. Ang II acts on hypothalamic neurons to regulate orexigenic/anorexigenic neuropeptides, such as neuropeptide-Y, orexin and corticotropin-releasing hormone, leading to reduced appetite. Also, Ang II may regulate skeletal muscle regenerative processes. Several clinical studies have indicated that blockade of Ang II signaling via ACE inhibitors or Ang II type 1 receptor blockers prevents weight loss and improves muscle strength. Thus the RAS is a promising target for the treatment of muscle atrophy in patients with CHF and CKD. PMID:23769949

  2. Combustion from basics to applications

    CERN Document Server

    Lackner, Maximilian; Winter, Franz

    2013-01-01

    Combustion, the process of burning, is defined as a chemical reaction between a combustible reactant (the fuel) and an oxidizing agent (such as air) in order to produce heat and in most cases light while new chemical species (e.g., flue gas components) are formed. This book covers a gap on the market by providing a concise introduction to combustion. Most of the other books currently available are targeted towards the experienced users and contain too many details and/or contain knowledge at a fairly high level. This book provides a brief and clear overview of the combustion basics, suitable f

  3. A Novel Energy-Efficient Multi-Sensor Fusion Wake-Up Control Strategy Based on a Biomimetic Infectious-Immune Mechanism for Target Tracking.

    Science.gov (United States)

    Zhou, Jie; Liang, Yan; Shen, Qiang; Feng, Xiaoxue; Pan, Quan

    2018-04-18

    A biomimetic distributed infection-immunity model (BDIIM), inspired by the immune mechanism of an infected organism, is proposed in order to achieve a high-efficiency wake-up control strategy based on multi-sensor fusion for target tracking. The resultant BDIIM consists of six sub-processes reflecting the infection-immunity mechanism: occurrence probabilities of direct-infection (DI) and cross-infection (CI), immunity/immune-deficiency of DI and CI, pathogen amount of DI and CI, immune cell production, immune memory, and pathogen accumulation under immunity state. Furthermore, a corresponding relationship between the BDIIM and sensor wake-up control is established to form the collaborative wake-up method. Finally, joint surveillance and target tracking are formulated in the simulation, in which we show that the energy cost and position tracking error are reduced to 50.8% and 78.9%, respectively. Effectiveness of the proposed BDIIM algorithm is shown, and this model is expected to have a significant role in guiding the performance improvement of multi-sensor networks.

  4. Targeted retrograde transfection of adenovirus vector carrying brain-derived neurotrophic factor gene prevents loss of mouse (twy/twy) anterior horn neurons in vivo sustaining mechanical compression.

    Science.gov (United States)

    Xu, Kan; Uchida, Kenzo; Nakajima, Hideaki; Kobayashi, Shigeru; Baba, Hisatoshi

    2006-08-01

    Immunohistochemical analysis after adenovirus (AdV)-mediated BDNF gene transfer in and around the area of mechanical compression in the cervical spinal cord of the hyperostotic mouse (twy/twy). To investigate the neuroprotective effect of targeted AdV-BDNF gene transfection in the twy mouse with spontaneous chronic compression of the spinal cord motoneurons. Several studies reported the neuroprotective effects of neurotrophins on injured spinal cord. However, no report has described the effect of targeted retrograde neurotrophic gene delivery on motoneuron survival in chronic compression lesions of the cervical spinal cord resembling lesions of myelopathy. LacZ marker gene using adenoviral vector (AdV-LacZ) was used to evaluate retrograde delivery from the sternomastoid muscle in adult twy mice (16-week-old) and (control). Four weeks after the AdV-LacZ or AdV-BDNF injection, the compressed cervical spinal cord was removed en bloc for immunohistologic investigation of b-galactosidase activity and immunoreactivity and immunoblot analyses of BDNF. The number of anterior horn neurons was counted using Nissl, ChAT and AChE staining. Spinal accessory motoneurons between C1 and C3 segments were successfully transfected by AdV-LacZ in both twy and ICR mice after targeted intramuscular injection. Immunoreactivity to BDNF was significantly stronger in AdV-BDNF-gene transfected twy mice than in AdV-LacZ-gene transfected mice. At the cord level showing the maximum compression in AdV-BDNF-transfected twy mice, the number of anterior horn neurons was sinificantly higher in the topographic neuronal cell counting of Nissl-, ChAT-, and AChE-stained samples than in AdV-LacZ-injected twy mice. Targeted AdV-BDNF-gene delivery significantly increased Nissl-stained anterior horn neurons and enhanced cholinergic enzyme activities in the twy. Our results suggest that targeted retrograde AdV-BDNF-gene in vivo delivery may enhance neuronal survival even under chronic mechanical compression.

  5. Mechanical microencapsulation: The best technique in taste masking for the manufacturing scale - Effect of polymer encapsulation on drug targeting.

    Science.gov (United States)

    Al-Kasmi, Basheer; Alsirawan, Mhd Bashir; Bashimam, Mais; El-Zein, Hind

    2017-08-28

    Drug taste masking is a crucial process for the preparation of pediatric and geriatric formulations as well as fast dissolving tablets. Taste masking techniques aim to prevent drug release in saliva and at the same time to obtain the desired release profile in gastrointestinal tract. Several taste masking methods are reported, however this review has focused on a group of promising methods; complexation, encapsulation, and hot melting. The effects of each method on the physicochemical properties of the drug are described in details. Furthermore, a scoring system was established to evaluate each process using recent published data of selected factors. These include, input, process, and output factors that are related to each taste masking method. Input factors include the attributes of the materials used for taste masking. Process factors include equipment type and process parameters. Finally, output factors, include taste masking quality and yield. As a result, Mechanical microencapsulation obtained the highest score (5/8) along with complexation with cyclodextrin suggesting that these methods are the most preferable for drug taste masking. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Targeting Anabolic Impairment in Response to Resistance Exercise in Older Adults with Mobility Impairments: Potential Mechanisms and Rehabilitation Approaches

    Directory of Open Access Journals (Sweden)

    Micah J. Drummond

    2012-01-01

    Full Text Available Muscle atrophy is associated with healthy aging (i.e., sarcopenia and may be compounded by comorbidities, injury, surgery, illness, and physical inactivity. While a bout of resistance exercise increases protein synthesis rates in healthy young skeletal muscle, the effectiveness of resistance exercise to mount a protein synthetic response is less pronounced in older adults. Improving anabolic sensitivity to resistance exercise, thereby enhancing physical function, is most critical in needy older adults with clinical conditions that render them “low responders”. In this paper, we discuss potential mechanisms contributing to anabolic impairment to resistance exercise and highlight the need to improve anabolic responsiveness in low responders. This is followed with evidence suggesting that the recovery period of resistance exercise provides an opportunity to amplify the exercise-induced anabolic response using protein/essential amino acid ingestion. This anabolic strategy, if repeated chronically, may improve lean muscle gains, decrease time to recovery of function during periods of rehabilitation, and overall, maintain/improve physical independence and reduce mortality rates in older adults.

  7. One Target, Two Mechanisms: The Impact of 'Candidatus Liberibacter asiaticus' and Its Vector, Diaphorina citri, on Citrus Leaf Pigments.

    Science.gov (United States)

    Killiny, Nabil; Nehela, Yasser

    2017-07-01

    Huanglongbing (HLB) is currently the largest threat to global citrus production. We examined the effect of HLB pathogen 'Candidatus Liberibacter asiaticus' infection or infestation by its vector, Diaphorina citri, on 'Valencia' sweet orange leaf pigments using high-performance liquid chromatography, followed by gene expression analysis for 46 involved genes in carotenoid and chlorophyll biosynthesis pathways. Both 'Ca. L. asiaticus' and D. citri alter the total citrus leaf pigment balance with a greater impact by 'Ca. L. asiaticus'. Although zeaxanthin was accumulated in 'Ca. L. asiaticus'-infected leaves, chlorophyllide a was increased in D. citri-infested plants. Our findings support the idea that both 'Ca. L. asiaticus' and D. citri affect the citrus pigments and promote symptom development but using two different mechanisms. 'Ca. L. asiaticus' promotes chlorophyll degradation but accelerates the biosynthesis of carotenoid pigments, resulting in accumulation of abscisic acid and its precursor, zeaxanthin. Zeaxanthin also has a photoprotective role. By contrast, D. citri induced the degradation of most carotenoids and accelerated chlorophyll biosynthesis, leading to chlorophyllide a accumulation. Chlorophyllide a might have an antiherbivory role. Accordingly, we suggest that citrus plants try to defend themselves against 'Ca. L. asiaticus' or D. citri using multifaceted defense systems, based on the stressor type. These findings will help in better understanding the tritrophic interactions among plant, pathogen, and vector.

  8. What are the working mechanisms of a web-based workplace sitting intervention targeting psychosocial factors and action planning?

    Science.gov (United States)

    De Cocker, Katrien; De Bourdeaudhuij, Ilse; Cardon, Greet; Vandelanotte, Corneel

    2017-05-03

    Office workers demonstrate high levels of sitting on workdays. As sitting is positively associated with adverse health risks in adults, a theory-driven web-based computer-tailored intervention to influence workplace sitting, named 'Start to Stand,' was developed. The intervention was found to be effective in reducing self-reported workplace sitting among Flemish employees. The aim of this study was to investigate through which mechanisms the web-based computer-tailored intervention influenced self-reported workplace sitting. Employees (n = 155) participated in a clustered randomised controlled trial and reported socio-demographics (age, gender, education), work-related (hours at work, employment duration), health-related (weight and height, workplace sitting and physical activity) and psychosocial (knowledge, attitudes, self-efficacy, social support, intention regarding (changing) sitting behaviours) variables at baseline and 1-month follow-up. The product-of-coefficients test of MacKinnon based on multiple linear regression analyses was conducted to examine the mediating role of five psychosocial factors (knowledge, attitudes, self-efficacy, social support, intention). The influence of one self-regulation skill (action planning) in the association between the intervention and self-reported workplace sitting time was investigated via moderation analyses. The intervention had a positive influence on knowledge (p = 0.040), but none of the psychosocial variables did mediate the intervention effect on self-reported workplace sitting. Action planning was found to be a significant moderator (p workplace sitting only occurred in the group completing an action plan. Future interventions aimed at reducing employees' workplace sitting are suggested to focus on self-regulatory skills and promote action planning when using web-based computer-tailored advice. Clinicaltrials.gov NCT02672215 ; (Archived by WebCite at https://clinicaltrials.gov/ct2/show/NCT02672215 ).

  9. Callous-unemotional traits in children and mechanisms of impaired eye contact during expressions of love: a treatment target?

    Science.gov (United States)

    Dadds, Mark R; Allen, Jennifer L; McGregor, Kimberley; Woolgar, Matthew; Viding, Essi; Scott, Stephen

    2014-07-01

    We previously hypothesised that the early development of psychopathy is associated with a failure to attend to the eyes of attachment figures, and we have presented preliminary data from a parent-child 'love' scenario in support of this. Here, we confirm the association in a larger sample and test mechanisms of impaired eye contact during expressions of love in control and behaviourally disturbed children. Oppositional defiant disorder children, assessed for callous-unemotional (CU) traits, and controls, were observed in a brief interaction task where the mother was asked to show love to her child. Eye contact and affection were measured for each dyad. As predicted, there were no group differences in affection and eye contact expressed by mothers; levels of CU traits predicted low levels of eye contact towards their mothers across all groups of children. As expected, low eye contact was correlated with psychopathic fearlessness in their fathers, and maternal reports of negative feelings towards the child. Independent observations showed that child's behaviour largely drives the low eye contact associated with CU traits, and low eye contact was not associated with independent observations of the quality of attachment-related behaviours in mothers. Impaired eye contact is a unique characteristic of children with CU traits; these impairments are largely independent of maternal behaviour, but associated with psychopathic traits in the fathers. These impairments should be tested for functional significance and amenability to change in longitudinal and treatment studies. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

  10. A Scoping Review Protocol to Explore the Use of Interleukin-1-Targeting Drugs for the Treatment of Dermatological Diseases: Indications, Mechanism of Action, Efficacy, and Safety.

    Science.gov (United States)

    Gómez-García, Francisco; Ruano, Juan; Gay-Mimbrera, Jesús; Aguilar-Luque, Macarena; Sanz-Cabanillas, Juan L; Hernández Romero, José L; Garcia-Nieto, Antonio Velez

    2018-04-06

    The interleukin (IL)-1 pathway has been identified as being involved in inflammatory and neoplastic skin diseases such as psoriasis, atopic dermatitis, neutrophilic dermatosis, melanoma, and squamous cell carcinoma. Drugs developed to target the IL-1 pathway are currently used to treat these pathologies, and although they are becoming more selective, they are not exempt from adverse events and high costs. Integrating the best research evidence with clinical experience and patient needs has been shown to improve care, health, and cost outcomes. This is because evidence-based guidelines rank interventions according to cost-effectiveness. However, evidence on this topic is scarce for several reasons. First, although randomized clinical trials currently provide the best evidence, they are not always available. Second, there are no secondary scientific studies that summarize the use of IL-1-targeting agents in dermatology. We therefore sought to develop an a priori protocol for broadly reviewing the available evidence on the use of IL-1-targeting drugs in the treatment of dermatological diseases. We used the latest methodology to perform a scoping review as described in the Joanna Briggs Institute manual. Developing and applying a methodology for evidence synthesis promotes reproducibility and increases the validity of secondary scientific investigations, making it the optimal strategy for scientifically synthesizing a broad field such as the indications for and the mechanisms of action, efficacies, safety, and costs of IL-1-targeting drugs in the treatment of dermatological diseases. Quantitative synthesis facilitates the detection of knowledge gaps and the identification of new questions that can be addressed through systematic reviews. We present an a priori protocol for exploring the available evidence on this topic.

  11. From basic needs to basic rights.

    Science.gov (United States)

    Facio, A

    1995-06-01

    After arriving at an understanding that basic rights refer to all human needs, it is clear that a recognition of the basic needs of female humans must precede the realization of their rights. The old Women in Development (WID) framework only understood women's needs from an androcentric perspective which was limited to practical interests. Instead, women's primary need is to be free from their subordination to men. Such an understanding places all of women's immediate needs in a new light. A human rights approach to development would see women not as beneficiaries but as people entitled to enjoy the benefits of development. Discussion of what equality before the law should mean to women began at the Third World Conference on Women in Nairobi where the issue of violence against women was first linked to development. While debate continues about the distinction between civil and political rights and economic, social, and cultural rights, the realities of women's lives do not permit such a distinction. The concept of the universality of human rights did not become codified until the UN proclaimed the Universal Declaration of Human Rights in 1948. The declaration has been criticized by feminists because the view of human rights it embodies has been too strongly influenced by a liberal Western philosophy which stresses individual rights and because it is ambiguous on the distinction between human rights and the rights of a citizen. The protection of rights afforded by the Declaration, however, should not be viewed as a final achievement but as an ongoing struggle. International conferences have led to an analysis of the human-rights approach to sustainable development which concludes that women continue to face the routine denial of their rights. Each human right must be redefined from the perspective of women's needs, which must also be redefined. Women must forego challenging the concept of the universality of human rights in order to overcome the argument of cultural

  12. Basic rocks in Finland

    International Nuclear Information System (INIS)

    Piirainen, T.; Gehoer, S.; Iljina, M.; Kaerki, A.; Paakkola, J.; Vuollo, J.

    1992-10-01

    Basic igneous rocks, containing less than 52% SiO 2 , constitute an important part of the Finnish Archaean and Proterozoic crust. In the Archaean crust exist two units which contain the majority of the basic rocks. The Arcaean basic rocks are metavolcanics and situated in the Greenstone Belts of Eastern Finland. They are divided into two units. The greenstones of the lower one are tholeiites, komatiites and basaltic komatiites. The upper consists of bimodal series of volcanics and the basic rocks of which are Fe-tholeiites, basaltic komatiites and komatiites. Proterozoic basic rocks are divided into seven groups according to their ages. The Proterozoic igneous activity started by the volominous basic magmatism 2.44 Ga ago. During this stage formed the layered intrusions and related dykes in the Northern Finland. 2.2 Ga old basic rocks are situated at the margins of Karelian formations. 2.1 Ga aged Fe-tholeiitic magmatic activity is widespread in Eastern and Northern Finland. The basic rocks of 1.97 Ga age group are met within the Karelian Schist Belts as obducted ophiolite complexes but they occur also as tholeiitic diabase dykes cutting the Karelian schists and Archean basement. The intrusions and the volcanics of the 1.9 Ga old basic igneous activity are mostly encountered around the Granitoid Complex of Central Finland. Subjotnian, 1.6 Ga aged tholeiitic diabases are situated around the Rapakivi massifs of Southern Finland, and postjotnian, 1.2 Ga diabases in Western Finland where they form dykes cutting Svecofennian rocks

  13. Fusion target design

    International Nuclear Information System (INIS)

    Bangerter, R.O.

    1978-01-01

    Most detailed fusion target design is done by numerical simulation using large computers. Although numerical simulation is briefly discussed, this lecture deals primarily with the way in which basic physical arguments, driver technology considerations and economical power production requirements are used to guide and augment the simulations. Physics topics discussed include target energetics, preheat, stability and symmetry. A specific design example is discussed

  14. What are the working mechanisms of a web-based workplace sitting intervention targeting psychosocial factors and action planning?

    Directory of Open Access Journals (Sweden)

    Katrien De Cocker

    2017-05-01

    Full Text Available Abstract Background Office workers demonstrate high levels of sitting on workdays. As sitting is positively associated with adverse health risks in adults, a theory-driven web-based computer-tailored intervention to influence workplace sitting, named ‘Start to Stand,’ was developed. The intervention was found to be effective in reducing self-reported workplace sitting among Flemish employees. The aim of this study was to investigate through which mechanisms the web-based computer-tailored intervention influenced self-reported workplace sitting. Methods Employees (n = 155 participated in a clustered randomised controlled trial and reported socio-demographics (age, gender, education, work-related (hours at work, employment duration, health-related (weight and height, workplace sitting and physical activity and psychosocial (knowledge, attitudes, self-efficacy, social support, intention regarding (changing sitting behaviours variables at baseline and 1-month follow-up. The product-of-coefficients test of MacKinnon based on multiple linear regression analyses was conducted to examine the mediating role of five psychosocial factors (knowledge, attitudes, self-efficacy, social support, intention. The influence of one self-regulation skill (action planning in the association between the intervention and self-reported workplace sitting time was investigated via moderation analyses. Results The intervention had a positive influence on knowledge (p = 0.040, but none of the psychosocial variables did mediate the intervention effect on self-reported workplace sitting. Action planning was found to be a significant moderator (p < 0.001 as the decrease in self-reported workplace sitting only occurred in the group completing an action plan. Conclusions Future interventions aimed at reducing employees’ workplace sitting are suggested to focus on self-regulatory skills and promote action planning when using web-based computer-tailored advice. Trial

  15. Quantum electronics basic theory

    CERN Document Server

    Fain, V M; Sanders, J H

    1969-01-01

    Quantum Electronics, Volume 1: Basic Theory is a condensed and generalized description of the many research and rapid progress done on the subject. It is translated from the Russian language. The volume describes the basic theory of quantum electronics, and shows how the concepts and equations followed in quantum electronics arise from the basic principles of theoretical physics. The book then briefly discusses the interaction of an electromagnetic field with matter. The text also covers the quantum theory of relaxation process when a quantum system approaches an equilibrium state, and explai

  16. Basic stress analysis

    CERN Document Server

    Iremonger, M J

    1982-01-01

    BASIC Stress Analysis aims to help students to become proficient at BASIC programming by actually using it in an important engineering subject. It also enables the student to use computing as a means of learning stress analysis because writing a program is analogous to teaching-it is necessary to understand the subject matter. The book begins by introducing the BASIC approach and the concept of stress analysis at first- and second-year undergraduate level. Subsequent chapters contain a summary of relevant theory, worked examples containing computer programs, and a set of problems. Topics c

  17. Hurdles in Basic Science Translation

    Directory of Open Access Journals (Sweden)

    Christina J. Perry

    2017-07-01

    Full Text Available In the past century there have been incredible advances in the field of medical research, but what hinders translation of this knowledge into effective treatment for human disease? There is an increasing focus on the failure of many research breakthroughs to be translated through the clinical trial process and into medical practice. In this mini review, we will consider some of the reasons that findings in basic medical research fail to become translated through clinical trials and into basic medical practices. We focus in particular on the way that human disease is modeled, the understanding we have of how our targets behave in vivo, and also some of the issues surrounding reproducibility of basic research findings. We will also look at some of the ways that have been proposed for overcoming these issues. It appears that there needs to be a cultural shift in the way we fund, publish and recognize quality control in scientific research. Although this is a daunting proposition, we hope that with increasing awareness and focus on research translation and the hurdles that impede it, the field of medical research will continue to inform and improve medical practice across the world.

  18. HIV Treatment: The Basics

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV Treatment Home Understanding HIV/AIDS Fact Sheets HIV ... 4 p.m. ET) Send us an email HIV Treatment: The Basics Last Reviewed: March 22, 2018 ...

  19. Basics of SCI Rehabilitation

    Medline Plus

    Full Text Available ... How Peer Counseling Works Julie Gassaway, MS, RN Pediatric Injuries Pediatric Spinal Cord Injury 101 Lawrence Vogel, MD The Basics of Pediatric SCI Rehabilitation Sara Klaas, MSW Transitions for Children ...

  20. Powassan (POW) Virus Basics

    Science.gov (United States)

    ... Health Professionals Related Topics For International Travelers Powassan Virus Disease Basics Download this fact sheet formatted for ... Virus Disease Fact Sheet (PDF) What is Powassan virus? Powassan virus is a tickborne flavivirus that is ...

  1. Brain Basics: Understanding Sleep

    Science.gov (United States)

    ... You are here Home » Disorders » Patient & Caregiver Education Brain Basics: Understanding Sleep Anatomy of Sleep Sleep Stages ... t form or maintain the pathways in your brain that let you learn and create new memories, ...

  2. Basics of SCI Rehabilitation

    Medline Plus

    Full Text Available ... Counseling Blog About Media Donate Spinal Cord Injury Medical Expert Videos Topics menu Topics The Basics of ... injury? What is a Spinal Cord Injury? SCI Medical Experts People Living With SCI Personal Experiences By ...

  3. Basics of SCI Rehabilitation

    Medline Plus

    Full Text Available ... Topic Resources Peer Counseling Blog About Media Donate Spinal Cord Injury Medical Expert Videos Topics menu Topics The Basics of Spinal Cord Injury Rehabilitation Adult Injuries Spinal Cord Injury 101 David ...

  4. Basics of SCI Rehabilitation

    Medline Plus

    Full Text Available ... RN Pediatric Injuries Pediatric Spinal Cord Injury 101 Lawrence Vogel, MD The Basics of Pediatric SCI Rehabilitation ... Rogers, PT Recreational Therapy after Spinal Cord Injury Jennifer Piatt, PhD Kristine Cichowski, MS Read Bio Founding ...

  5. Basics of SCI Rehabilitation

    Medline Plus

    Full Text Available ... Topic Resources Peer Counseling Blog About Media Donate Spinal Cord Injury Medical Expert Videos Topics menu Topics The Basics of Spinal Cord Injury Rehabilitation Adult Injuries Spinal Cord Injury 101 ...

  6. Basics of SCI Rehabilitation

    Medline Plus

    Full Text Available ... Spinal Cord Injury 101 Lawrence Vogel, MD The Basics of Pediatric SCI Rehabilitation Sara Klaas, MSW Transitions for Children with Spinal Cord Injury Patricia Mucia, RN Family Life After Pediatric Spinal Injury Dawn Sheaffer, MSW Rehabilitation ...

  7. Physical Activity Basics

    Science.gov (United States)

    ... Weight Breastfeeding Micronutrient Malnutrition State and Local Programs Physical Activity Basics Recommend on Facebook Tweet Share Compartir How much physical activity do you need? Regular physical activity helps improve ...

  8. Radionuclide Basics: Iodine

    Science.gov (United States)

    ... Centers Radiation Protection Contact Us Share Radionuclide Basics: Iodine Iodine (chemical symbol I) is a chemical element. ... in the environment Iodine sources Iodine and health Iodine in the Environment All 37 isotopes of iodine ...

  9. Basic Finite Element Method

    International Nuclear Information System (INIS)

    Lee, Byeong Hae

    1992-02-01

    This book gives descriptions of basic finite element method, which includes basic finite element method and data, black box, writing of data, definition of VECTOR, definition of matrix, matrix and multiplication of matrix, addition of matrix, and unit matrix, conception of hardness matrix like spring power and displacement, governed equation of an elastic body, finite element method, Fortran method and programming such as composition of computer, order of programming and data card and Fortran card, finite element program and application of nonelastic problem.

  10. Development NGOs: Basic Facts

    OpenAIRE

    Aldashev, Gani; Navarra, Cecilia

    2017-01-01

    This paper systematizes the results of the empirical literature on development non-governmental organizations (NGOs), drawing both from quantitative and qualitative analyses, and constructs a set of basic facts about these organizations. These basic facts concern the size of the development NGO sector and its evolution, the funding of NGOs, the allocation of NGO aid and projects across beneficiary countries, the relationship of NGOs with beneficiaries, and the phenomenon of globalization of d...

  11. Real-time target tracking of soft tissues in 3D ultrasound images based on robust visual information and mechanical simulation.

    Science.gov (United States)

    Royer, Lucas; Krupa, Alexandre; Dardenne, Guillaume; Le Bras, Anthony; Marchand, Eric; Marchal, Maud

    2017-01-01

    In this paper, we present a real-time approach that allows tracking deformable structures in 3D ultrasound sequences. Our method consists in obtaining the target displacements by combining robust dense motion estimation and mechanical model simulation. We perform evaluation of our method through simulated data, phantom data, and real-data. Results demonstrate that this novel approach has the advantage of providing correct motion estimation regarding different ultrasound shortcomings including speckle noise, large shadows and ultrasound gain variation. Furthermore, we show the good performance of our method with respect to state-of-the-art techniques by testing on the 3D databases provided by MICCAI CLUST'14 and CLUST'15 challenges. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Assessment of cooperation mechanism options: Cost-efficient and sustainable deployment of renewable energy sources towards the 20% target by 2020, and beyond. D3.2

    Energy Technology Data Exchange (ETDEWEB)

    Pade Hansen, L.-L.; Klinge Jacobsen, H.; Skovsgaard Nielsen, L.

    2012-12-15

    The RES Directive 2009/28/EC (European Commission 2009) set legally binding targets for EU Member States on energy consumption from renewable sources - the 2020 RES targets. A part of this can be achieved through the use of cooperation mechanisms: statistical transfer, joint project and joint support schemes. The intention of the cooperation mechanisms is to provide the flexibility needed to achieve Europe's renewable energy targets in a more cost-efficient way. In Task 3 of the RES4Less project we analyse the benefits and challenges of using the two cooperation mechanisms: joint project and joint support schemes. This report is the outcome of the work in Task 3.2 where we analyse how the barriers can be overcome and how different design options can be used under varying conditions and time horizons. Cooperation mechanisms have the potential to reduce the compliance costs of reaching the 2020 RES targets for EU member states. The largest benefits can be achieved under full harmonisation and one joints support scheme. However, the different national objectives along with uneven distribution of benefits and costs make this unrealistic in the near future. Cooperation between pairs or groups of countries with large net benefits that can be relatively easy estimated and shared is attractive and realisable in a shorter time horizon. Joint project cooperation is the most flexible instrument to use as it preserves the national legislation and support schemes (national objectives) and can be easily scaled in size. The drawback is the high transaction costs and some uncertainty regarding which party should carry the project implementation risk and guaranty the support for the projects for the entire lifetime. The joint projects can be realised in a short term horizon and as such pave the way for further cooperation. Large projects has a considerable advantage in the reduced transaction cost relative to project size and governments can be expected to be more willing to

  13. Glatiramer Acetate in Treatment of Multiple Sclerosis: A Toolbox of Random Co-Polymers for Targeting Inflammatory Mechanisms of both the Innate and Adaptive Immune System?

    Directory of Open Access Journals (Sweden)

    Thomas Vorup-Jensen

    2012-11-01

    Full Text Available Multiple sclerosis is a disease of the central nervous system, resulting in the demyelination of neurons, causing mild to severe symptoms. Several anti-inflammatory treatments now play a significant role in ameliorating the disease. Glatiramer acetate (GA is a formulation of random polypeptide copolymers for the treatment of relapsing-remitting MS by limiting the frequency of attacks. While evidence suggests the influence of GA on inflammatory responses, the targeted molecular mechanisms remain poorly understood. Here, we review the multiple pharmacological modes-of-actions of glatiramer acetate in treatment of multiple sclerosis. We discuss in particular a newly discovered interaction between the leukocyte-expressed integrin αMβ2 (also called Mac-1, complement receptor 3, or CD11b/CD18 and perspectives on the GA co-polymers as an influence on the function of the innate immune system.

  14. Dual effect of F-actin targeted carrier combined with antimitotic drug on aggressive colorectal cancer cytoskeleton: Allying dissimilar cell cytoskeleton disrupting mechanisms.

    Science.gov (United States)

    Taranejoo, Shahrouz; Janmaleki, Mohsen; Pachenari, Mohammad; Seyedpour, Seyed Morteza; Chandrasekaran, Ramya; Cheng, Wenlong; Hourigan, Kerry

    2016-11-20

    A recent approach to colon cancer therapy is to employ selective drugs with specific extra/intracellular sites of action. Alteration of cytoskeletal protein reorganization and, subsequently, to cellular biomechanical behaviour during cancer progression highly affects the cancer cell progress. Hence, cytoskeleton targeted drugs are an important class of cancer therapy agents. We have studied viscoelastic alteration of the human colon adenocarcinoma cell line, SW48, after treatment with a drug delivery system comprising chitosan as the carrier and albendazole as the microtubule-targeting agent (MTA). For the first time, we have evaluated the biomechanical characteristics of the cell line, using the micropipette aspiration (MA) method after treatment with drug delivery systems. Surprisingly, employing a chitosan-albendazole pair, in comparison with both neat materials, resulted in more significant change in the viscoelastic parameters of cells, including the elastic constants (K 1 and K 2 ) and the coefficient of viscosity (μ). This difference was more pronounced for cancer cells after 48h of the treatment. Microtubule and actin microfilament (F-actin) contents in the cell line were studied by immunofluorescent staining. Good agreement was observed between the mechanical characteristics results and microtubule/F-actin contents of the treated SW48 cell line, which declined after treatment. The results showed that chitosan affected F-actin more, while MTA was more effective for microtubules. Toxicity studies were performed against two cancer cell lines (SW48 and MCF10CA1h) and compared to normal cells, MCF10A. The results showed cancer selectiveness, safety of formulation, and enhanced anticancer efficacy of the CS/ABZ conjugate. This study suggests that employing such a suitable pair of drug-carriers with dissimilar sites of action, thus allying the different cell cytoskeleton disrupting mechanisms, may provide a more efficient cancer therapy approach. Copyright

  15. Quantitative Proteome Analysis of Mouse Liver Lysosomes Provides Evidence for Mannose 6-phosphate-independent Targeting Mechanisms of Acid Hydrolases in Mucolipidosis II.

    Science.gov (United States)

    Markmann, Sandra; Krambeck, Svenja; Hughes, Christopher J; Mirzaian, Mina; Aerts, Johannes M F G; Saftig, Paul; Schweizer, Michaela; Vissers, Johannes P C; Braulke, Thomas; Damme, Markus

    2017-03-01

    The efficient receptor-mediated targeting of soluble lysosomal proteins to lysosomes requires the modification with mannose 6-phosphate (M6P) residues. Although the absence of M6P results in misrouting and hypersecretion of lysosomal enzymes in many cells, normal levels of lysosomal enzymes have been reported in liver of patients lacking the M6P-generating phosphotransferase (PT). The identity of lysosomal proteins depending on M6P has not yet been comprehensively analyzed. In this study we purified lysosomes from liver of PT-defective mice and 67 known soluble lysosomal proteins were identified that illustrated quantitative changes using an ion mobility-assisted data-independent label-free LC-MS approach. After validation of various differentially expressed lysosomal components by Western blotting and enzyme activity assays, the data revealed a small number of lysosomal proteins depending on M6P, including neuraminidase 1, cathepsin F, Npc2, and cathepsin L, whereas the majority reach lysosomes by alternative pathways. These data were compared with findings on cultured hepatocytes and liver sinusoid endothelial cells isolated from the liver of wild-type and PT-defective mice. Our findings show that the relative expression, targeting efficiency and lysosomal localization of lysosomal proteins tested in cultured hepatic cells resemble their proportion in isolated liver lysosomes. Hypersecretion of newly synthesized nonphosphorylated lysosomal proteins suggest that secretion-recapture mechanisms contribute to maintain major lysosomal functions in liver. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Universal Basic Education and Achievement of Millennium ...

    African Journals Online (AJOL)

    For this reason, targets have been set, and projects, programmes and schemes instituted to achieve zero level of illiteracy. One of such is maximizing access to quality education in all nooks and crannies of Nigeria. This is where the Universal Basic Education (UBE) and Millennium Development Goals (MDGs) stand out ...

  17. Increasing crop yield and resilience with trehalose 6-phosphate: targeting a feast-famine mechanism in cereals for better source-sink optimization.

    Science.gov (United States)

    Paul, Matthew J; Oszvald, Maria; Jesus, Claudia; Rajulu, Charukesi; Griffiths, Cara A

    2017-07-20

    Food security is a pressing global issue. New approaches are required to break through a yield ceiling that has developed in recent years for the major crops. As important as increasing yield potential is the protection of yield from abiotic stresses in an increasingly variable and unpredictable climate. Current strategies to improve yield include conventional breeding, marker-assisted breeding, quantitative trait loci (QTLs), mutagenesis, creation of hybrids, genetic modification (GM), emerging genome-editing technologies, and chemical approaches. A regulatory mechanism amenable to three of these approaches has great promise for large yield improvements. Trehalose 6-phosphate (T6P) synthesized in the low-flux trehalose biosynthetic pathway signals the availability of sucrose in plant cells as part of a whole-plant sucrose homeostatic mechanism. Modifying T6P content by GM, marker-assisted selection, and novel chemistry has improved yield in three major cereals under a range of water availabilities from severe drought through to flooding. Yield improvements have been achieved by altering carbon allocation and how carbon is used. Targeting T6P both temporally and spatially offers great promise for large yield improvements in productive (up to 20%) and marginal environments (up to 120%). This opinion paper highlights this important breakthrough in fundamental science for crop improvement. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  18. Basic Electromagnetism and Materials

    CERN Document Server

    Moliton, André

    2007-01-01

    Basic Electromagnetism and Materials is the product of many years of teaching basic and applied electromagnetism. This textbook can be used to teach electromagnetism to a wide range of undergraduate science majors in physics, electrical engineering or materials science. However, by making lesser demands on mathematical knowledge than competing texts, and by emphasizing electromagnetic properties of materials and their applications, this textbook is uniquely suited to students of materials science. Many competing texts focus on the study of propagation waves either in the microwave or optical domain, whereas Basic Electromagnetism and Materials covers the entire electromagnetic domain and the physical response of materials to these waves. Professor André Moliton is Director of the Unité de Microélectronique, Optoélectronique et Polymères (Université de Limoges, France), which brings together three groups studying the optoelectronics of molecular and polymer layers, micro-optoelectronic systems for teleco...

  19. Final Report on DTRA Basic Research Project #BRCALL08-Per3-C-2-0006 "High-Z Non-Equilibrium Physics and Bright X-ray Sources with New Laser Targets"

    Energy Technology Data Exchange (ETDEWEB)

    Colvin, Jeffrey D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-06-01

    This project had two major goals. Final Goal: obtain spectrally resolved, absolutely calibrated x-ray emission data from uniquely uniform mm-scale near-critical-density high-Z plasmas not in local thermodynamic equilibrium (LTE) to benchmark modern detailed atomic physics models. Scientific significance: advance understanding of non-LTE atomic physics. Intermediate Goal: develop new nano-fabrication techniques to make suitable laser targets that form the required highly uniform non-LTE plasmas when illuminated by high-intensity laser light. Scientific significance: advance understanding of nano-science. The new knowledge will allow us to make x-ray sources that are bright at the photon energies of most interest for testing radiation hardening technologies, the spectral energy range where current x-ray sources are weak. All project goals were met.

  20. Basic properties of semiconductors

    CERN Document Server

    Landsberg, PT

    2013-01-01

    Since Volume 1 was published in 1982, the centres of interest in the basic physics of semiconductors have shifted. Volume 1 was called Band Theory and Transport Properties in the first edition, but the subject has broadened to such an extent that Basic Properties is now a more suitable title. Seven chapters have been rewritten by the original authors. However, twelve chapters are essentially new, with the bulk of this work being devoted to important current topics which give this volume an almost encyclopaedic form. The first three chapters discuss various aspects of modern band theory and the

  1. Basic set theory

    CERN Document Server

    Levy, Azriel

    2002-01-01

    An advanced-level treatment of the basics of set theory, this text offers students a firm foundation, stopping just short of the areas employing model-theoretic methods. Geared toward upper-level undergraduate and graduate students, it consists of two parts: the first covers pure set theory, including the basic motions, order and well-foundedness, cardinal numbers, the ordinals, and the axiom of choice and some of it consequences; the second deals with applications and advanced topics such as point set topology, real spaces, Boolean algebras, and infinite combinatorics and large cardinals. An

  2. Comprehensive basic mathematics

    CERN Document Server

    Veena, GR

    2005-01-01

    Salient Features As per II PUC Basic Mathematics syllabus of Karnataka. Provides an introduction to various basic mathematical techniques and the situations where these could be usefully employed. The language is simple and the material is self-explanatory with a large number of illustrations. Assists the reader in gaining proficiency to solve diverse variety of problems. A special capsule containing a gist and list of formulae titled ''REMEMBER! Additional chapterwise arranged question bank and 3 model papers in a separate section---''EXAMINATION CORNER''.

  3. Ecology and basic laws

    International Nuclear Information System (INIS)

    Mayer-Tasch, P.C.

    1980-01-01

    The author sketches the critical relation between ecology and basic law - critical in more than one sense. He points out the incompatibility of constitutional states and atomic states which is due to constitutional order being jeopardised by nuclear policy. He traces back the continuously rising awareness of pollution and the modern youth movement to their common root i.e. the awakening, the youth movement of the turn of the century. Eventually, he considers an economical, political, and social decentralization as a feasible alternative which would considerably relieve our basic living conditions from the threatening forms of civilization prevailing. (HSCH) [de

  4. Precompound Reactions: Basic Concepts

    International Nuclear Information System (INIS)

    Weidenmueller, H. A.

    2008-01-01

    Because of the non-zero nuclear equilibration time, the compound-nucleus scattering model fails when the incident energy exceeds 10 or 20 MeV, and precompound reactions become important. Basic ideas used in the quantum-statistical approaches to these reactions are described

  5. Basic Tuberculosis Facts

    Centers for Disease Control (CDC) Podcasts

    2012-03-12

    In this podcast, Dr. Kenneth Castro, Director of the Division of Tuberculosis Elimination, discusses basic TB prevention, testing, and treatment information.  Created: 3/12/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 3/12/2012.

  6. Basic Exchange Rate Theories

    NARCIS (Netherlands)

    J.G.M. van Marrewijk (Charles)

    2005-01-01

    textabstractThis four-chapter overview of basic exchange rate theories discusses (i) the elasticity and absorption approach, (ii) the (long-run) implications of the monetary approach, (iii) the short-run effects of monetary and fiscal policy under various economic conditions, and (iv) the transition

  7. Basic SPSS tutorial

    NARCIS (Netherlands)

    Grotenhuis, H.F. te; Matthijssen, A.C.B.

    2015-01-01

    This supplementary book for the social, behavioral, and health sciences helps readers with no prior knowledge of IBM® SPSS® Statistics, statistics, or mathematics learn the basics of SPSS. Designed to reduce fear and build confidence, the book guides readers through point-and-click sequences using

  8. Basic Skills Assessment

    Science.gov (United States)

    Yin, Alexander C.; Volkwein, J. Fredericks

    2010-01-01

    After surveying 1,827 students in their final year at eighty randomly selected two-year and four-year public and private institutions, American Institutes for Research (2006) reported that approximately 30 percent of students in two-year institutions and nearly 20 percent of students in four-year institutions have only basic quantitative…

  9. Basic physics for all

    CERN Document Server

    Kumar, B N

    2012-01-01

    This is a simple, concise book for both student and non-physics students, presenting basic facts in straightforward form and conveying fundamental principles and theories of physics. This book will be helpful as a supplement to class teaching and to aid those who have difficulty in mastering concepts and principles.

  10. Basic pharmaceutical technology

    OpenAIRE

    Angelovska, Bistra; Drakalska, Elena

    2017-01-01

    The lecture deals with basics of pharmaceutical technology as applied discipline of pharmaceutical science, whose main subject of study is formulation and manufacture of drugs. In a broad sense, pharmaceutical technology is science of formulation, preparation, stabilization and determination of the quality of medicines prepared in the pharmacy or in pharmaceutical industry

  11. Basic radiation oncology

    International Nuclear Information System (INIS)

    Beyzadeoglu, M. M.; Ebruli, C.

    2008-01-01

    Basic Radiation Oncology is an all-in-one book. It is an up-to-date bedside oriented book integrating the radiation physics, radiobiology and clinical radiation oncology. It includes the essentials of all aspects of radiation oncology with more than 300 practical illustrations, black and white and color figures. The layout and presentation is very practical and enriched with many pearl boxes. Key studies particularly randomized ones are also included at the end of each clinical chapter. Basic knowledge of all high-tech radiation teletherapy units such as tomotherapy, cyberknife, and proton therapy are also given. The first 2 sections review concepts that are crucial in radiation physics and radiobiology. The remaining 11 chapters describe treatment regimens for main cancer sites and tumor types. Basic Radiation Oncology will greatly help meeting the needs for a practical and bedside oriented oncology book for residents, fellows, and clinicians of Radiation, Medical and Surgical Oncology as well as medical students, physicians and medical physicists interested in Clinical Oncology. English Edition of the book Temel Radyasyon Onkolojisi is being published by Springer Heidelberg this year with updated 2009 AJCC Staging as Basic Radiation Oncology

  12. Bottled Water Basics

    Science.gov (United States)

    Table of Contents Bottled water basics ....................................... pg.2 Advice for people with severely compromised immune systems (Sidebar) ............................. pg2 Know what you’re buying .............................. pg.3 Taste considerations ........................................ pg.4 Bottled water terms (Sidebar) ..................... pg.4 Begin by reading the ...

  13. Monte Carlo: Basics

    OpenAIRE

    Murthy, K. P. N.

    2001-01-01

    An introduction to the basics of Monte Carlo is given. The topics covered include, sample space, events, probabilities, random variables, mean, variance, covariance, characteristic function, chebyshev inequality, law of large numbers, central limit theorem (stable distribution, Levy distribution), random numbers (generation and testing), random sampling techniques (inversion, rejection, sampling from a Gaussian, Metropolis sampling), analogue Monte Carlo and Importance sampling (exponential b...

  14. Ethanol Basics (Fact Sheet)

    Energy Technology Data Exchange (ETDEWEB)

    2015-01-01

    Ethanol is a widely-used, domestically-produced renewable fuel made from corn and other plant materials. More than 96% of gasoline sold in the United States contains ethanol. Learn more about this alternative fuel in the Ethanol Basics Fact Sheet, produced by the U.S. Department of Energy's Clean Cities program.

  15. Basic Soils. Revision.

    Science.gov (United States)

    Montana State Univ., Bozeman. Dept. of Agricultural and Industrial Education.

    This curriculum guide is designed for use in teaching a course in basic soils that is intended for college freshmen. Addressed in the individual lessons of the unit are the following topics: the way in which soil is formed, the physical properties of soil, the chemical properties of soil, the biotic properties of soil, plant-soil-water…

  16. Continuum mechanics

    CERN Document Server

    Spencer, A J M

    2004-01-01

    The mechanics of fluids and the mechanics of solids represent the two major areas of physics and applied mathematics that meet in continuum mechanics, a field that forms the foundation of civil and mechanical engineering. This unified approach to the teaching of fluid and solid mechanics focuses on the general mechanical principles that apply to all materials. Students who have familiarized themselves with the basic principles can go on to specialize in any of the different branches of continuum mechanics. This text opens with introductory chapters on matrix algebra, vectors and Cartesian ten

  17. A transcriptomic computational analysis of mastic oil-treated Lewis lung carcinomas reveals molecular mechanisms targeting tumor cell growth and survival

    Directory of Open Access Journals (Sweden)

    Roussos Charis

    2009-12-01

    Full Text Available Abstract Background Mastic oil from Pistacia lentiscus variation chia, a blend of bioactive terpenes with recognized medicinal properties, has been recently shown to exert anti-tumor growth activity through inhibition of cancer cell proliferation, survival, angiogenesis and inflammatory response. However, no studies have addressed its mechanisms of action at genome-wide gene expression level. Methods To investigate molecular mechanisms triggered by mastic oil, Lewis Lung Carcinoma cells were treated with mastic oil or DMSO and RNA was collected at five distinct time points (3-48 h. Microarray expression profiling was performed using Illumina mouse-6 v1 beadchips, followed by computational analysis. For a number of selected genes, RT-PCR validation was performed in LLC cells as well as in three human cancer cell lines of different origin (A549, HCT116, K562. PTEN specific inhibition by a bisperovanadium compound was applied to validate its contribution to mastic oil-mediated anti-tumor growth effects. Results In this work we demonstrated that exposure of Lewis lung carcinomas to mastic oil caused a time-dependent alteration in the expression of 925 genes. GO analysis associated expression profiles with several biological processes and functions. Among them, modifications on cell cycle/proliferation, survival and NF-κB cascade in conjunction with concomitant regulation of genes encoding for PTEN, E2F7, HMOX1 (up-regulation and NOD1 (down-regulation indicated some important mechanistic links underlying the anti-proliferative, pro-apoptotic and anti-inflammatory effects of mastic oil. The expression profiles of Hmox1, Pten and E2f7 genes were similarly altered by mastic oil in the majority of test cancer cell lines. Inhibition of PTEN partially reversed mastic oil effects on tumor cell growth, indicating a multi-target mechanism of action. Finally, k-means clustering, organized the significant gene list in eight clusters demonstrating a similar

  18. Off-target Effects in CRISPR/Cas9-mediated Genome Engineering

    Directory of Open Access Journals (Sweden)

    Xiao-Hui Zhang

    2015-01-01

    Full Text Available CRISPR/Cas9 is a versatile genome-editing technology that is widely used for studying the functionality of genetic elements, creating genetically modified organisms as well as preclinical research of genetic disorders. However, the high frequency of off-target activity (≥50%—RGEN (RNA-guided endonuclease-induced mutations at sites other than the intended on-target site—is one major concern, especially for therapeutic and clinical applications. Here, we review the basic mechanisms underlying off-target cutting in the CRISPR/Cas9 system, methods for detecting off-target mutations, and strategies for minimizing off-target cleavage. The improvement off-target specificity in the CRISPR/Cas9 system will provide solid genotype–phenotype correlations, and thus enable faithful interpretation of genome-editing data, which will certainly facilitate the basic and clinical application of this technology.

  19. Targets for heavy ion fusion

    International Nuclear Information System (INIS)

    Clauser, M.J.

    1978-01-01

    This paper describes some of the basic principles of fusion target implosions, using some simple targets designed for irradiation by ion beams. Present estimates are that ion beams with 1-5 MJ, and 100-500 TW will be required to ignite high gain targets. (orig.) [de

  20. Targeted impairment of thymidine kinase 2 expression in cells induces mitochondrial DNA depletion and reveals molecular mechanisms of compensation of mitochondrial respiratory activity

    International Nuclear Information System (INIS)

    Villarroya, Joan; Lara, Mari-Carmen; Dorado, Beatriz; Garrido, Marta; Garcia-Arumi, Elena; Meseguer, Anna; Hirano, Michio; Vila, Maya R.

    2011-01-01

    Highlights: → We impaired TK2 expression in Ost TK1 - cells via siRNA-mediated interference (TK2 - ). → TK2 impairment caused severe mitochondrial DNA (mtDNA) depletion in quiescent cells. → Despite mtDNA depletion, TK2 - cells show high cytochrome oxidase activity. → Depletion of mtDNA occurs without imbalance in the mitochondrial dNTP pool. → Nuclear-encoded ENT1, DNA-pol γ, TFAM and TP gene expression is lowered in TK2 - cells. -- Abstract: The mitochondrial DNA (mtDNA) depletion syndrome comprises a clinically heterogeneous group of diseases characterized by reductions of the mtDNA abundance, without associated point mutations or rearrangements. We have developed the first in vitro model to study of mtDNA depletion due to reduced mitochondrial thymidine kinase 2 gene (TK2) expression in order to understand the molecular mechanisms involved in mtDNA depletion syndrome due to TK2 mutations. Small interfering RNA targeting TK2 mRNA was used to decrease TK2 expression in Ost TK1 - cells, a cell line devoid of endogenous thymidine kinase 1 (TK1). Stable TK2-deficient cell lines showed a reduction of TK2 levels close to 80%. In quiescent conditions, TK2-deficient cells showed severe mtDNA depletion, also close to 80% the control levels. However, TK2-deficient clones showed increased cytochrome c oxidase activity, higher cytochrome c oxidase subunit I transcript levels and higher subunit II protein expression respect to control cells. No alterations of the deoxynucleotide pools were found, whereas a reduction in the expression of genes involved in nucleoside/nucleotide homeostasis (human equilibrative nucleoside transporter 1, thymidine phosphorylase) and mtDNA maintenance (DNA-polymerase γ, mitochondrial transcription factor A) was observed. Our findings highlight the importance of cellular compensatory mechanisms that enhance the expression of respiratory components to ensure respiratory activity despite profound depletion in mtDNA levels.

  1. Therapeutic mechanisms of Mindfulness-Oriented Recovery Enhancement for internet gaming disorder: Reducing craving and addictive behavior by targeting cognitive processes.

    Science.gov (United States)

    Li, Wen; Garland, Eric L; Howard, Matthew O

    2018-03-22

    Internet gaming disorder (IGD) is characterized by signs and symptoms similar to substance use and gambling disorders, and associated with psychosocial impairments. Research suggests that maladaptive gaming-related cognitions and coping may be implicated in IGD; therefore, interventions for IGD need to target these underlying mechanisms. Mindfulness-based treatment is effective in changing maladaptive cognitive processes and increasing adaptive coping among people with addictions. This study used data from an RCT of Mindfulness-Oriented Recovery Enhancement (MORE) for IGD to further examine changes in maladaptive gaming-related cognitions and positive reappraisal as mediators of the effects of MORE on IGD signs/symptoms. Participants (N = 30, Age M = 25.0, SD  = 5.4) were randomized to 8-weekly sessions of MORE or a support group (SG) control condition. IGD severity, levels of craving for video game playing, maladaptive gaming-related cognitions, and positive reappraisal were measured at pre-and posttreatment, and 3-month follow-up. Multivariate path analyses revealed that effects of MORE in reducing IGD and craving were statistically mediated by changes in maladaptive gaming-related cognitions. Though changes in positive reappraisal did not significantly mediate effects of MORE on IGD or craving, MORE enhanced positive reappraisal to a significantly greater extent than the SG at posttreatment. Findings suggest that effects of mindfulness treatment in reducing maladaptive gaming-related cognitions might lead to reductions in IGD severity and cravings for video game playing. This cognitive mechanism should be evaluated in a future, full-scale RCT.

  2. Development of distributed target

    CERN Document Server

    Yu Hai Jun; Li Qin; Zhou Fu Xin; Shi Jin Shui; Ma Bing; Chen Nan; Jing Xiao Bing

    2002-01-01

    Linear introduction accelerator is expected to generate small diameter X-ray spots with high intensity. The interaction of the electron beam with plasmas generated at the X-ray converter will make the spot on target increase with time and debase the X-ray dose and the imaging resolving power. A distributed target is developed which has about 24 pieces of thin 0.05 mm tantalum films distributed over 1 cm. due to the structure adoption, the distributed target material over a large volume decreases the energy deposition per unit volume and hence reduces the temperature of target surface, then reduces the initial plasma formalizing and its expansion velocity. The comparison and analysis with two kinds of target structures are presented using numerical calculation and experiments, the results show the X-ray dose and normalized angle distribution of the two is basically the same, while the surface of the distributed target is not destroyed like the previous block target

  3. Transportation Emissions: some basics

    DEFF Research Database (Denmark)

    Kontovas, Christos A.; Psaraftis, Harilaos N.

    2016-01-01

    transportation and especially carbon dioxide emissions are at the center stage of discussion by the world community through various international treaties, such as the Kyoto Protocol. The transportation sector also emits non-CO2 pollutants that have important effects on air quality, climate, and public health......Transportation is the backbone of international trade and a key engine driving globalization. However, there is growing concern that the Earth’s atmospheric composition is being altered by human activities, including transportation, which can lead to climate change. Air pollution from....... The main purpose of this chapter is to introduce some basic concepts that are relevant in the quest of green transportation logistics. First, we present the basics of estimating emissions from transportation activities, the current statistics and future trends, as well as the total impact of air emissions...

  4. Basic Emotions: A Reconstruction

    Science.gov (United States)

    Mason, William A.; Capitanio, John P.

    2016-01-01

    Emotionality is a basic feature of behavior. The argument over whether the expression of emotions is based primarily on culture (constructivism, nurture) or biology (natural forms, nature) will never be resolved because both alternatives are untenable. The evidence is overwhelming that at all ages and all levels of organization, the development of emotionality is epigenetic: The organism is an active participant in its own development. To ascribe these effects to “experience” was the best that could be done for many years. With the rapid acceleration of information on how changes in organization are actually brought about, it is a good time to review, update, and revitalize our views of experience in relation to the concept of basic emotion. PMID:27110280

  5. Basic electronic circuits

    CERN Document Server

    Buckley, P M

    1980-01-01

    In the past, the teaching of electricity and electronics has more often than not been carried out from a theoretical and often highly academic standpoint. Fundamentals and basic concepts have often been presented with no indication of their practical appli­ cations, and all too frequently they have been illustrated by artificially contrived laboratory experiments bearing little relationship to the outside world. The course comes in the form of fourteen fairly open-ended constructional experiments or projects. Each experiment has associated with it a construction exercise and an explanation. The basic idea behind this dual presentation is that the student can embark on each circuit following only the briefest possible instructions and that an open-ended approach is thereby not prejudiced by an initial lengthy encounter with the theory behind the project; this being a sure way to dampen enthusiasm at the outset. As the investigation progresses, questions inevitably arise. Descriptions of the phenomena encounte...

  6. Basic linear algebra

    CERN Document Server

    Blyth, T S

    2002-01-01

    Basic Linear Algebra is a text for first year students leading from concrete examples to abstract theorems, via tutorial-type exercises. More exercises (of the kind a student may expect in examination papers) are grouped at the end of each section. The book covers the most important basics of any first course on linear algebra, explaining the algebra of matrices with applications to analytic geometry, systems of linear equations, difference equations and complex numbers. Linear equations are treated via Hermite normal forms which provides a successful and concrete explanation of the notion of linear independence. Another important highlight is the connection between linear mappings and matrices leading to the change of basis theorem which opens the door to the notion of similarity. This new and revised edition features additional exercises and coverage of Cramer's rule (omitted from the first edition). However, it is the new, extra chapter on computer assistance that will be of particular interest to readers:...

  7. Basics of statistical physics

    CERN Document Server

    Müller-Kirsten, Harald J W

    2013-01-01

    Statistics links microscopic and macroscopic phenomena, and requires for this reason a large number of microscopic elements like atoms. The results are values of maximum probability or of averaging. This introduction to statistical physics concentrates on the basic principles, and attempts to explain these in simple terms supplemented by numerous examples. These basic principles include the difference between classical and quantum statistics, a priori probabilities as related to degeneracies, the vital aspect of indistinguishability as compared with distinguishability in classical physics, the differences between conserved and non-conserved elements, the different ways of counting arrangements in the three statistics (Maxwell-Boltzmann, Fermi-Dirac, Bose-Einstein), the difference between maximization of the number of arrangements of elements, and averaging in the Darwin-Fowler method. Significant applications to solids, radiation and electrons in metals are treated in separate chapters, as well as Bose-Eins...

  8. Emulsion Science Basic Principles

    CERN Document Server

    Leal-Calderon, Fernando; Schmitt, Véronique

    2007-01-01

    Emulsions are generally made out of two immiscible fluids like oil and water, one being dispersed in the second in the presence of surface-active compounds.They are used as intermediate or end products in a huge range of areas including the food, chemical, cosmetic, pharmaceutical, paint, and coating industries. Besides the broad domain of technological interest, emulsions are raising a variety of fundamental questions at the frontier between physics and chemistry. This book aims to give an overview of the most recent advances in emulsion science. The basic principles, covering aspects of emulsions from their preparation to their destruction, are presented in close relation to both the fundamental physics and the applications of these materials. The book is intended to help scientists and engineers in formulating new materials by giving them the basics of emulsion science.

  9. Basics of Computer Networking

    CERN Document Server

    Robertazzi, Thomas

    2012-01-01

    Springer Brief Basics of Computer Networking provides a non-mathematical introduction to the world of networks. This book covers both technology for wired and wireless networks. Coverage includes transmission media, local area networks, wide area networks, and network security. Written in a very accessible style for the interested layman by the author of a widely used textbook with many years of experience explaining concepts to the beginner.

  10. Risk communication basics

    International Nuclear Information System (INIS)

    Corrado, P.G.

    1995-01-01

    In low-trust, high-concern situations, 50% of your credibility comes from perceived empathy and caring, demonstrated in the first 30 s you come in contact with someone. There is no second chance for a first impression. These and other principles contained in this paper provide you with a basic level of understanding of risk communication. The principles identified are time-tested caveats and will assist you in effectively communicating technical information

  11. Risk communication basics

    Energy Technology Data Exchange (ETDEWEB)

    Corrado, P.G. [Lawrence Livermore National Laboratory, CA (United States)

    1995-12-31

    In low-trust, high-concern situations, 50% of your credibility comes from perceived empathy and caring, demonstrated in the first 30 s you come in contact with someone. There is no second chance for a first impression. These and other principles contained in this paper provide you with a basic level of understanding of risk communication. The principles identified are time-tested caveats and will assist you in effectively communicating technical information.

  12. Basic nucleonics. 2. ed.

    International Nuclear Information System (INIS)

    Guzman, M.E.

    1989-01-01

    This book is oriented mainly towards professionals who are not physicists or experts in nuclear sciences, physicians planning to specialize in nuclear medicine or radiotherapy and technicians involved in nuclear applications. The book covers the fundamental concepts of nuclear science and technology in a simple and ordered fashion. Theory is illustrated with appropriate exercises and answers. With 17 chapters plus 3 appendices on mathematics, basic concepts are covered in: nuclear science, radioactivity, radiation and matter, nuclear reactions, X rays, shielding and radioprotection

  13. Shoulder arthroscopy: the basics.

    Science.gov (United States)

    Farmer, Kevin W; Wright, Thomas W

    2015-04-01

    Shoulder arthroscopy is a commonly performed and accepted procedure for a wide variety of pathologies. Surgeon experience, patient positioning, knowledge of surgical anatomy, proper portal placement, and proper use of instrumentation can improve technical success and minimize complication risks. This article details the surgical anatomy, indications, patient positioning, portal placement, instrumentation, and complications for basic shoulder arthroscopy. Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  14. Basic accelerator optics

    CERN Document Server

    CERN. Geneva. Audiovisual Unit

    1985-01-01

    A complete derivation, from first principles, of the concepts and methods applied in linear accelerator and beamline optics will be presented. Particle motion and beam motion in systems composed of linear magnets, as well as weak and strong focusing and special insertions are treated in mathematically simple terms, and design examples for magnets and systems are given. This series of five lectures is intended to provide all the basic tools required for the design and operation of beam optical systems.

  15. Basic concepts in oceanography

    International Nuclear Information System (INIS)

    Small, L.F.

    1997-01-01

    Basic concepts in oceanography include major wind patterns that drive ocean currents, and the effects that the earth's rotation, positions of land masses, and temperature and salinity have on oceanic circulation and hence global distribution of radioactivity. Special attention is given to coastal and near-coastal processes such as upwelling, tidal effects, and small-scale processes, as radionuclide distributions are currently most associated with coastal regions. (author)

  16. Mechanical, Electrical and Magnetic Properties of Ferrogels with Embedded Iron Oxide Nanoparticles Obtained by Laser Target Evaporation: Focus on Multifunctional Biosensor Applications.

    Science.gov (United States)

    Blyakhman, Felix A; Buznikov, Nikita A; Sklyar, Tatyana F; Safronov, Alexander P; Golubeva, Elizaveta V; Svalov, Andrey V; Sokolov, Sergey Yu; Melnikov, Grigory Yu; Orue, Iñaki; Kurlyandskaya, Galina V

    2018-03-15

    Hydrogels are biomimetic materials widely used in the area of biomedical engineering and biosensing. Ferrogels (FG) are magnetic composites capable of functioning as magnetic field sensitive transformers and field assisted drug deliverers. FG can be prepared by incorporating magnetic nanoparticles (MNPs) into chemically crosslinked hydrogels. The properties of biomimetic ferrogels for multifunctional biosensor applications can be set up by synthesis. The properties of these biomimetic ferrogels can be thoroughly controlled in a physical experiment environment which is much less demanding than biotests. Two series of ferrogels (soft and dense) based on polyacrylamide (PAAm) with different chemical network densities were synthesized by free-radical polymerization in aqueous solution with N , N '-methylene-diacrylamide as a cross-linker and maghemite Fe₂O₃ MNPs fabricated by laser target evaporation as a filler. Their mechanical, electrical and magnetic properties were comparatively analyzed. We developed a giant magnetoimpedance (MI) sensor prototype with multilayered FeNi-based sensitive elements deposited onto glass or polymer substrates adapted for FG studies. The MI measurements in the initial state and in the presence of FG with different concentrations of MNPs at a frequency range of 1-300 MHz allowed a precise characterization of the stray fields of the MNPs present in the FG. We proposed an electrodynamic model to describe the MI in multilayered film with a FG layer based on the solution of linearized Maxwell equations for the electromagnetic fields coupled with the Landau-Lifshitz equation for the magnetization dynamics.

  17. Selection, Identification, and Binding Mechanism Studies of an ssDNA Aptamer Targeted to Different Stages of E. coli O157:H7.

    Science.gov (United States)

    Zou, Ying; Duan, Nuo; Wu, Shijia; Shen, Mofei; Wang, Zhouping

    2018-06-06

    Enterohemorrhagic Escherichia coli O157:H7 ( E. coli O157:H7) is known as an important food-borne pathogen related to public health. In this study, aptamers which could bind to different stages of E. coli O157:H7 (adjustment phase, log phase, and stationary phase) with high affinity and specificity were obtained by the whole cell-SELEX method through 14 selection rounds including three counter-selection rounds. Altogether, 32 sequences were obtained, and nine families were classified to select the optimal aptamer. To analyze affinity and specificity by flow cytometer, an ssDNA aptamer named Apt-5 was picked out as the optimal aptamer that recognizes different stages of E. coli O157:H7 specifically with the K d value of 9.04 ± 2.80 nM. In addition, in order to study the binding mechanism, target bacteria were treated by proteinase K and trypsin, indicating that the specific binding site is not protein on the cell membrane. Furthermore, when we treated E. coli O157:H7 with EDTA, the result showed that the binding site might be lipopolysaccharide (LPS) on the outer membrane of E. coli O157:H7.

  18. p97 Composition Changes Caused by Allosteric Inhibition Are Suppressed by an On-Target Mechanism that Increases the Enzyme's ATPase Activity.

    Science.gov (United States)

    Her, Nam-Gu; Toth, Julia I; Ma, Chen-Ting; Wei, Yang; Motamedchaboki, Khatereh; Sergienko, Eduard; Petroski, Matthew D

    2016-04-21

    The AAA ATPase p97/VCP regulates protein homeostasis using a diverse repertoire of cofactors to fulfill its biological functions. Here we use the allosteric p97 inhibitor NMS-873 to analyze its effects on enzyme composition and the ability of cells to adapt to its cytotoxicity. We found that p97 inhibition changes steady state cofactor-p97 composition, leading to the enrichment of a subset of its cofactors and polyubiquitin bound to p97. We isolated cells specifically insensitive to NMS-873 and identified a new mutation (A530T) in p97. A530T is sufficient to overcome the cytotoxicity of NMS-873 and alleviates p97 composition changes caused by the molecule but not other p97 inhibitors. This mutation does not affect NMS-873 binding but increases p97 catalytic efficiency through altered ATP and ADP binding. Collectively, these findings identify cofactor-p97 interactions sensitive to p97 inhibition and reveal a new on-target mechanism to suppress the cytotoxicity of NMS-873. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Oxidative Stress: A Unifying Mechanism for Cell Damage Induced by Noise, (Water-Pipe) Smoking, and Emotional Stress-Therapeutic Strategies Targeting Redox Imbalance.

    Science.gov (United States)

    Golbidi, Saeid; Li, Huige; Laher, Ismail

    2018-03-20

    Modern technologies have eased our lives but these conveniences can impact our lifestyles in destructive ways. Noise pollution, mental stresses, and smoking (as a stress-relieving solution) are some environmental hazards that affect our well-being and healthcare budgets. Scrutinizing their pathophysiology could lead to solutions to reduce their harmful effects. Recent Advances: Oxidative stress plays an important role in initiating local and systemic inflammation after noise pollution, mental stress, and smoking. Lipid peroxidation and release of lysolipid by-products, disturbance in activation and function of nuclear factor erythroid 2-related factor 2 (Nrf2), induction of stress hormones and their secondary effects on intracellular kinases, and dysregulation of intracellular Ca 2+ can all potentially trigger other vicious cycles. Recent clinical data suggest that boosting the antioxidant system through nonpharmacological measures, for example, lifestyle changes that include exercise have benefits that cannot easily be achieved with pharmacological interventions alone. Indiscriminate manipulation of the cellular redox network could lead to a new series of ailments. An ideal approach requires meticulous scrutiny of redox balance mechanisms for individual pathologies so as to create new treatment strategies that target key pathways while minimizing side effects. Extrapolating our understanding of redox balance to other debilitating conditions such as diabetes and the metabolic syndrome could potentially lead to devising a unifying therapeutic strategy. Antioxid. Redox Signal. 28, 741-759.

  20. Chronic subordinate colony housing paradigm: A mouse model for mechanisms of PTSD vulnerability, targeted prevention, and treatment-2016 Curt Richter Award Paper.

    Science.gov (United States)

    Reber, Stefan O; Langgartner, Dominik; Foertsch, Sandra; Postolache, Teodor T; Brenner, Lisa A; Guendel, Harald; Lowry, Christopher A

    2016-12-01

    There is considerable individual variability in vulnerability for developing posttraumatic stress disorder (PTSD); evidence suggests that this variability is related in part to genetic and environmental factors, including adverse early life experience. Interestingly, recent studies indicate that induction of chronic low-grade inflammation may be a common mechanism underlying gene and environment interactions that increase the risk for development of PTSD symptoms, and, therefore, may be a target for novel interventions for prevention or treatment of PTSD. Development of murine models with face, construct, and predictive validity would provide opportunities to investigate in detail complex genetic, environmental, endocrine, and immunologic factors that determine vulnerability to PTSD-like syndromes, and furthermore may provide mechanistic insight leading to development of novel interventions for both prevention and treatment of PTSD symptoms. Here we describe the potential use of the chronic subordinate colony housing (CSC) paradigm in mice as an adequate animal model for development of a PTSD-like syndrome and describe recent studies that suggest novel interventions for the prevention and treatment of PTSD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Mechanical, Electrical and Magnetic Properties of Ferrogels with Embedded Iron Oxide Nanoparticles Obtained by Laser Target Evaporation: Focus on Multifunctional Biosensor Applications

    Directory of Open Access Journals (Sweden)

    Felix A. Blyakhman

    2018-03-01

    Full Text Available Hydrogels are biomimetic materials widely used in the area of biomedical engineering and biosensing. Ferrogels (FG are magnetic composites capable of functioning as magnetic field sensitive transformers and field assisted drug deliverers. FG can be prepared by incorporating magnetic nanoparticles (MNPs into chemically crosslinked hydrogels. The properties of biomimetic ferrogels for multifunctional biosensor applications can be set up by synthesis. The properties of these biomimetic ferrogels can be thoroughly controlled in a physical experiment environment which is much less demanding than biotests. Two series of ferrogels (soft and dense based on polyacrylamide (PAAm with different chemical network densities were synthesized by free-radical polymerization in aqueous solution with N,N’-methylene-diacrylamide as a cross-linker and maghemite Fe2O3 MNPs fabricated by laser target evaporation as a filler. Their mechanical, electrical and magnetic properties were comparatively analyzed. We developed a giant magnetoimpedance (MI sensor prototype with multilayered FeNi-based sensitive elements deposited onto glass or polymer substrates adapted for FG studies. The MI measurements in the initial state and in the presence of FG with different concentrations of MNPs at a frequency range of 1–300 MHz allowed a precise characterization of the stray fields of the MNPs present in the FG. We proposed an electrodynamic model to describe the MI in multilayered film with a FG layer based on the solution of linearized Maxwell equations for the electromagnetic fields coupled with the Landau-Lifshitz equation for the magnetization dynamics.

  2. Criticality safety basics, a study guide

    Energy Technology Data Exchange (ETDEWEB)

    V. L. Putman

    1999-09-01

    This document is a self-study and classroom guide, for criticality safety of activities with fissile materials outside nuclear reactors. This guide provides a basic overview of criticality safety and criticality accident prevention methods divided into three parts: theory, application, and history. Except for topic emphasis, theory and history information is general, while application information is specific to the Idaho National Engineering and Environmental Laboratory (INEEL). Information presented here should be useful to personnel who must know criticality safety basics to perform their assignments safely or to design critically safe equipment or operations. However, the guide's primary target audience is fissile material handler candidates.

  3. Criticality safety basics, a study guide

    International Nuclear Information System (INIS)

    Putman, V.L.

    1999-01-01

    This document is a self-study and classroom guide, for criticality safety of activities with fissile materials outside nuclear reactors. This guide provides a basic overview of criticality safety and criticality accident prevention methods divided into three parts: theory, application, and history. Except for topic emphasis, theory and history information is general, while application information is specific to the Idaho National Engineering and Environmental Laboratory (INEEL). Information presented here should be useful to personnel who must know criticality safety basics to perform their assignments safely or to design critically safe equipment or operations. However, the guide's primary target audience is fissile material handler candidates

  4. Cost-Efficient and Sustainable Deployment of Renewable Energy Sources towards the 20% Target by 2020, and beyond. Summary of case studies for cooperation mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Dalla Longa, F. [ECN Policy Studies, Amsterdam (Netherlands); Klinge Jacobsen, H.; Pade Hnasen, L. [Technical University of Denmark DTU, Lyngby (Denmark); Tantareanu, C. [Center for Promotion of Clean and Efficient Energy ENERO, Bucharest (Romania); Caldes-Gomez, N.; Santamaria-Belda, M. [CIEMAT, Madrid (Spain)

    2012-09-15

    This document is a summary report highlighting the main aspect analyzed in the RES4LESS case studies. The document starts with an introductory chapter where the background that led to the selection of the case studies is outlined. In the following three chapters the case studies are presented, highlighting the most relevant results. A brief chapter concludes the document, giving an outlook on the follow-up activities of the RES4LESS project. This summary is intended not only as an introduction to the RES4LESS cases studies, but also as a guideline to read and interpret the in-depth analysis carried out in the final documents that describe the case studies in detail. These documents will be published in September 2012 on the RES4LESS website, www.res4less.eu. The objective of the RES4LESS project is to develop a Roadmap to cost-efficient deployment of energy from renewable sources (RES) in Europe, via cross-border cooperation mechanisms. The Commission has indicated that the 2020 targets for renewable energy (European Commission 2009) can be achieved through cooperation between Member States. This cooperation could lead to win-win situations, when a country with a large low-cost potential for renewable electricity could sell part of its surplus to a country with a limited and/or expensive potential. In the project, first a scoping exercise has been carried out to identify which countries could be candidates for cooperation. Next, three case studies have been elaborated to give a better view of what these cooperation mechanisms would entail in practice. The analysis has focused on renewable electricity (RES-E), although cooperation mechanisms could also be envisaged for renewable heat. Among the Member States providing the largest and cheapest surpluses Denmark, Romania and Spain have been chosen as Host Countries for the RES4LESS case studies. The technologies considered in the case studies are Offshore Wind for Denmark, Biomass for Romania, and CSP for Spain.

  5. A State Articulated Instructional Objectives Guide for Occupational Education Programs. State Pilot Model for Drafting (Graphic Communications). Part I--Basic. Part II--Specialty Programs. Section A (Mechanical Drafting and Design). Section B (Architectural Drafting and Design).

    Science.gov (United States)

    North Carolina State Dept. of Community Colleges, Raleigh.

    A two-part articulation instructional objective guide for drafting (graphic communications) is provided. Part I contains summary information on seven blocks (courses) of instruction. They are as follow: introduction; basic technical drafting; problem solving in graphics; reproduction processes; freehand drawing and sketching; graphics composition;…

  6. Fundamentals of neurogastroenterology: basic science.

    Science.gov (United States)

    Grundy, David; Al-Chaer, Elie D; Aziz, Qasim; Collins, Stephen M; Ke, Meiyun; Taché, Yvette; Wood, Jackie D

    2006-04-01

    The focus of neurogastroenterology in Rome II was the enteric nervous system (ENS). To avoid duplication with Rome II, only advances in ENS neurobiology after Rome II are reviewed together with stronger emphasis on interactions of the brain, spinal cord, and the gut in terms of relevance for abdominal pain and disordered gastrointestinal function. A committee with expertise in selective aspects of neurogastroenterology was invited to evaluate the literature and provide a consensus overview of the Fundamentals of Neurogastroenterology textbook as they relate to functional gastrointestinal disorders (FGIDs). This review is an abbreviated version of a fuller account that appears in the forthcoming book, Rome III. This report reviews current basic science understanding of visceral sensation and its modulation by inflammation and stress and advances in the neurophysiology of the ENS. Many of the concepts are derived from animal studies in which the physiologic mechanisms underlying visceral sensitivity and neural control of motility, secretion, and blood flow are examined. Impact of inflammation and stress in experimental models relative to FGIDs is reviewed as is human brain imaging, which provides a means for translating basic science to understanding FGID symptoms. Investigative evidence and emerging concepts implicate dysfunction in the nervous system as a significant factor underlying patient symptoms in FGIDs. Continued focus on neurogastroenterologic factors that underlie the development of symptoms will lead to mechanistic understanding that is expected to directly benefit the large contingent of patients and care-givers who deal with FGIDs.

  7. Radiation: Basic life for human

    International Nuclear Information System (INIS)

    Wan Saffiey Wan Abdullah

    2009-01-01

    Basically, radiation is sources for everything in this world. From radiation, many reactions and activities can be done by organisms. The tree can do photosynthesis and at the same time can give oxygen to human and others. In Quran, radiation was mentioned almost 41 times and from that, 12 are preferred to sun, moon, and stars. Radiation can be classified into two groups, mechanical and electromagnetic. Mechanical radiations are produced from vibration process. For example, when we are talking, sound radiation will be produced from vibration of sounds box. The guitar will sounded when we pluck it. Generally, mechanical radiation needs medium for its propagation and the velocity of wave can change and it cannot propagate in vacuum states. Meanwhile, electromagnetic radiations are energy that emitted in wave produced by propagation of electrical charges. This will produce magnetic fields and then if these fields changed, electrical fields will produce. There are two types of radiation in human life, natural radiation and artificially radiation. Radiation can be applied in medical and defend sector. Radiation also can be misuse by some people that want it for other purpose in intention to do something wrong, such as in making bomb and others weapons. In Malaysia, there are one act to control the imports, exports, licensing, transferring and application of ionizing radiation but not for non-ionizing radiation. In future, laser radiations have their own potential to become one of the most important radiations in renewable energy sector, medical and defend.

  8. Basic DTU Wind Energy controller

    DEFF Research Database (Denmark)

    Hansen, Morten Hartvig; Henriksen, Lars Christian

    This report contains a description and documentation, including source code, of the basic DTU Wind Energy controller applicable for pitch-regulated, variable speed wind turbines. The controller features both partial and full load operation capabilities as well as switching mechanisms ensuring......-integral controller to counter the effects of changing dynamics of the wind turbine for different wind speeds. Blade pitch servo and generator models are not included in this controller and should be modeled separately, if they are to be included in the simulations....... dependent minimum blade pitch in partial load operation. The controller uses the collective blade pitch angle and electromagnetic generator torque to control the wind turbine. In full load operation a feedback term from the collective blade pitch angle is used to schedule the gains of the proportional...

  9. Heat Transfer Basics and Practice

    CERN Document Server

    Böckh, Peter

    2012-01-01

    The book provides an easy way to understand the fundamentals of heat transfer. The reader will acquire the ability to design and analyze heat exchangers. Without extensive derivation of the fundamentals, the latest correlations for heat transfer coefficients and their application are discussed. The following topics are presented - Steady state and transient heat conduction - Free and forced convection - Finned surfaces - Condensation and boiling - Radiation - Heat exchanger design - Problem-solving After introducing the basic terminology, the reader is made familiar with the different mechanisms of heat transfer. Their practical application is demonstrated in examples, which are available in the Internet as MathCad files for further use. Tables of material properties and formulas for their use in programs are included in the appendix. This book will serve as a valuable resource for both students and engineers in the industry. The author’s experience indicates that students, after 40 lectures and exercises ...

  10. Catalyst in Basic Oleochemicals

    Directory of Open Access Journals (Sweden)

    Eva Suyenty

    2007-10-01

    Full Text Available Currently Indonesia is the world largest palm oil producer with production volume reaching 16 million tones per annum. The high crude oil and ethylene prices in the last 3 – 4 years contribute to the healthy demand growth for basic oleochemicals: fatty acids and fatty alcohols. Oleochemicals are starting to replace crude oil derived products in various applications. As widely practiced in petrochemical industry, catalyst plays a very important role in the production of basic oleochemicals. Catalytic reactions are abound in the production of oleochemicals: Nickel based catalysts are used in the hydrogenation of unsaturated fatty acids; sodium methylate catalyst in the transesterification of triglycerides; sulfonic based polystyrene resin catalyst in esterification of fatty acids; and copper chromite/copper zinc catalyst in the high pressure hydrogenation of methyl esters or fatty acids to produce fatty alcohols. To maintain long catalyst life, it is crucial to ensure the absence of catalyst poisons and inhibitors in the feed. The preparation methods of nickel and copper chromite catalysts are as follows: precipitation, filtration, drying, and calcinations. Sodium methylate is derived from direct reaction of sodium metal and methanol under inert gas. The sulfonic based polystyrene resin is derived from sulfonation of polystyrene crosslinked with di-vinyl-benzene. © 2007 BCREC UNDIP. All rights reserved.[Presented at Symposium and Congress of MKICS 2007, 18-19 April 2007, Semarang, Indonesia][How to Cite: E. Suyenty, H. Sentosa, M. Agustine, S. Anwar, A. Lie, E. Sutanto. (2007. Catalyst in Basic Oleochemicals. Bulletin of Chemical Reaction Engineering and Catalysis, 2 (2-3: 22-31.  doi:10.9767/bcrec.2.2-3.6.22-31][How to Link/DOI: http://dx.doi.org/10.9767/bcrec.2.2-3.6.22-31 || or local: http://ejournal.undip.ac.id/index.php/bcrec/article/view/6

  11. Uranium: a basic evaluation

    International Nuclear Information System (INIS)

    Crull, A.W.

    1978-01-01

    All energy sources and technologies, including uranium and the nuclear industry, are needed to provide power. Public misunderstanding of the nature of uranium and how it works as a fuel may jeopardize nuclear energy as a major option. Basic chemical facts about uranium ore and uranium fuel technology are presented. Some of the major policy decisions that must be made include the enrichment, stockpiling, and pricing of uranium. Investigations and lawsuits pertaining to uranium markets are reviewed, and the point is made that oil companies will probably have to divest their non-oil energy activities. Recommendations for nuclear policies that have been made by the General Accounting Office are discussed briefly

  12. C# Database Basics

    CERN Document Server

    Schmalz, Michael

    2012-01-01

    Working with data and databases in C# certainly can be daunting if you're coming from VB6, VBA, or Access. With this hands-on guide, you'll shorten the learning curve considerably as you master accessing, adding, updating, and deleting data with C#-basic skills you need if you intend to program with this language. No previous knowledge of C# is necessary. By following the examples in this book, you'll learn how to tackle several database tasks in C#, such as working with SQL Server, building data entry forms, and using data in a web service. The book's code samples will help you get started

  13. Electrical installation calculations basic

    CERN Document Server

    Kitcher, Christopher

    2013-01-01

    All the essential calculations required for basic electrical installation workThe Electrical Installation Calculations series has proved an invaluable reference for over forty years, for both apprentices and professional electrical installation engineers alike. The book provides a step-by-step guide to the successful application of electrical installation calculations required in day-to-day electrical engineering practice. A step-by-step guide to everyday calculations used on the job An essential aid to the City & Guilds certificates at Levels 2 and 3Fo

  14. Basic structural dynamics

    CERN Document Server

    Anderson, James C

    2012-01-01

    A concise introduction to structural dynamics and earthquake engineering Basic Structural Dynamics serves as a fundamental introduction to the topic of structural dynamics. Covering single and multiple-degree-of-freedom systems while providing an introduction to earthquake engineering, the book keeps the coverage succinct and on topic at a level that is appropriate for undergraduate and graduate students. Through dozens of worked examples based on actual structures, it also introduces readers to MATLAB, a powerful software for solving both simple and complex structural d

  15. Basic heat transfer

    CERN Document Server

    Bacon, D H

    2013-01-01

    Basic Heat Transfer aims to help readers use a computer to solve heat transfer problems and to promote greater understanding by changing data values and observing the effects, which are necessary in design and optimization calculations.The book is concerned with applications including insulation and heating in buildings and pipes, temperature distributions in solids for steady state and transient conditions, the determination of surface heat transfer coefficients for convection in various situations, radiation heat transfer in grey body problems, the use of finned surfaces, and simple heat exc

  16. Back to basics audio

    CERN Document Server

    Nathan, Julian

    1998-01-01

    Back to Basics Audio is a thorough, yet approachable handbook on audio electronics theory and equipment. The first part of the book discusses electrical and audio principles. Those principles form a basis for understanding the operation of equipment and systems, covered in the second section. Finally, the author addresses planning and installation of a home audio system.Julian Nathan joined the audio service and manufacturing industry in 1954 and moved into motion picture engineering and production in 1960. He installed and operated recording theaters in Sydney, Austra

  17. Machine shop basics

    CERN Document Server

    Miller, Rex

    2004-01-01

    Use the right tool the right wayHere, fully updated to include new machines and electronic/digital controls, is the ultimate guide to basic machine shop equipment and how to use it. Whether you're a professional machinist, an apprentice, a trade student, or a handy homeowner, this fully illustrated volume helps you define tools and use them properly and safely. It's packed with review questions for students, and loaded with answers you need on the job.Mark Richard Miller is a Professor and Chairman of the Industrial Technology Department at Texas A&M University in Kingsville, T

  18. Basic bladder neurophysiology.

    Science.gov (United States)

    Clemens, J Quentin

    2010-11-01

    Maintenance of normal lower urinary tract function is a complex process that requires coordination between the central nervous system and the autonomic and somatic components of the peripheral nervous system. This article provides an overview of the basic principles that are recognized to regulate normal urine storage and micturition, including bladder biomechanics, relevant neuroanatomy, neural control of lower urinary tract function, and the pharmacologic processes that translate the neural signals into functional results. Finally, the emerging role of the urothelium as a sensory structure is discussed. Copyright © 2010 Elsevier Inc. All rights reserved.

  19. Nova target experiments

    International Nuclear Information System (INIS)

    Drake, R.P.

    1985-11-01

    The Nova laser, at the Lawrence Livermore National Laboratory, provides unique opportunities for target experiments. It has unprecedented energy on target and significant flexibility. The paper presented by John Hunt described the capabilities and the status of Nova. This paper discusses plans for future experiments using Nova, and the present status of target experiments. We plan to perform high-quality physics experiments that exploit the unique capabilities of Nova. Because this is our goal, we are fielding an extensive array of well-characterized target diagnostics to measure the emissions from the target. The first section of this paper discusses the basic target diagnostics. We are also taking care to quantify the performance of the laser

  20. Ethyl p-coumarate exerts antifungal activity in vitro and in vivo against fruit Alternaria alternata via membrane-targeted mechanism.

    Science.gov (United States)

    Li, Wusun; Yuan, Shuzhi; Sun, Jing; Li, Qianqian; Jiang, Weibo; Cao, Jiankang

    2018-08-02

    by the severe occurrence of lipid peroxidation of the pathogen treated with EpCA. Taken together, these results indicated that EpCA exerts antifungal activity via membrane-targeted mechanism and it would be a promising candidate to control postharvest diseases of fruits. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Pro-neurogenic, Memory-Enhancing and Anti-stress Effects of DF302, a Novel Fluorine Gamma-Carboline Derivative with Multi-target Mechanism of Action.

    Science.gov (United States)

    Strekalova, Tatyana; Bahzenova, Nataliia; Trofimov, Alexander; Schmitt-Böhrer, Angelika G; Markova, Nataliia; Grigoriev, Vladimir; Zamoyski, Vladimir; Serkova, Tatiana; Redkozubova, Olga; Vinogradova, Daria; Umriukhin, Alexei; Fisenko, Vladimir; Lillesaar, Christina; Shevtsova, Elena; Sokolov, Vladimir; Aksinenko, Alexey; Lesch, Klaus-Peter; Bachurin, Sergey

    2018-01-01

    A comparative study performed in mice investigating the action of DF302, a novel fluoride-containing gamma-carboline derivative, in comparison to the structurally similar neuroprotective drug dimebon. Drug effects on learning and memory, emotionality, hippocampal neurogenesis and mitochondrial functions, as well as AMPA-mediated currents and the 5-HT6 receptor are reported. In the step-down avoidance and fear-conditioning paradigms, bolus administration of drugs at doses of 10 or 40 mg/kg showed that only the higher dose of DF302 improved long-term memory while dimebon was ineffective at either dosage. Short-term memory and fear extinction remained unaltered across treatment groups. During the 5-day predation stress paradigm, oral drug treatment over a period of 2 weeks at the higher dosage regimen decreased anxiety-like behaviour. Both compounds supressed inter-male aggression in CD1 mice, the most eminent being the effects of DF302 in its highest dose. DF302 at the higher dose decreased floating behaviour in a 2-day swim test and after 21-day ultrasound stress. The density of Ki67-positive cells, a marker of adult neurogenesis, was reduced in the dentate gyrus of stressed dimebon-treated and non-treated mice, but not in DF302-treated mice. Non-stressed mice that received DF302 had a higher density of Ki67-positive cells than controls unlike dimebon-treated mice. Similar to dimebon, DF302 effectively potentiated AMPA receptor-mediated currents, bound to the 5-HT6 receptor, inhibited mitochondrial permeability transition and displayed cytoprotective properties in cellular models of neurodegeneration. Thus, DF302 exerts multi-target effects on the key mechanisms of neurodegenerative pathologies and can be considered as an optimized novel analogue of the neuroprotective agent dimebon.

  2. Basic research projects

    International Nuclear Information System (INIS)

    1979-04-01

    The research programs under the cognizance of the Office of Energy Research (OER) are directed toward discovery of natural laws and new knowledge, and to improved understanding of the physical and biological sciences as related to the development, use, and control of energy. The ultimate goal is to develop a scientific underlay for the overall DOE effort and the fundamental principles of natural phenomena so that these phenomena may be understood, and new principles, formulated. The DOE-OER outlay activities include three major programs: High Energy Physics, Nuclear Physics, and Basic Energy Sciences. Taken together, these programs represent some 30 percent of the Nation's Federal support of basic research in the energy sciences. The research activities of OER involve more than 6,000 scientists and engineers working in some 17 major Federal Research Centers and at more than 135 different universities and industrial firms throughout the United States. Contract holders in the areas of high-energy physics, nuclear physics, materials sciences, nuclear science, chemical sciences, engineering, mathematics geosciences, advanced energy projects, and biological energy research are listed. Funding trends for recent years are outlined

  3. Basic scattering theory

    International Nuclear Information System (INIS)

    Queen, N.M.

    1978-01-01

    This series of lectures on basic scattering theory were given as part of a course for postgraduate high energy physicists and were designed to acquaint the student with some of the basic language and formalism used for the phenomenological description of nuclear reactions and decay processes used for the study of elementary particle interactions. Well established and model independent aspects of scattering theory, which are the basis of S-matrix theory, are considered. The subject is considered under the following headings; the S-matrix, cross sections and decay rates, phase space, relativistic kinematics, the Mandelstam variables, the flux factor, two-body phase space, Dalitz plots, other kinematic plots, two-particle reactions, unitarity, the partial-wave expansion, resonances (single-channel case), multi-channel resonances, analyticity and crossing, dispersion relations, the one-particle exchange model, the density matrix, mathematical properties of the density matrix, the density matrix in scattering processes, the density matrix in decay processes, and the helicity formalism. Some exercises for the students are included. (U.K.)

  4. Mechanical drawing

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Ho Seon; Lee, Geun Hui

    2004-04-15

    This book deals with how to read and draw the mechanical drawing, which includes the basic of drawing like purpose, kinds, and criterion, projection, special projection drawing, omission of the figure, section, and types of section, dimensioning method, writing way of allowable limit size, tolerance of regular size, parts list and assembling drawing, fitting, mechanical elements like screw, key, pin, rivet, spring, bearing, pipe, valve, welding, geometric tolerance and mechanical materials.

  5. Classical mechanics

    CERN Document Server

    Benacquista, Matthew J

    2018-01-01

    This textbook provides an introduction to classical mechanics at a level intermediate between the typical undergraduate and advanced graduate level. This text describes the background and tools for use in the fields of modern physics, such as quantum mechanics, astrophysics, particle physics, and relativity. Students who have had basic undergraduate classical mechanics or who have a good understanding of the mathematical methods of physics will benefit from this book.

  6. Mechanical science

    CERN Document Server

    Bolton, W C

    2013-01-01

    This book gives comprehensive coverage of mechanical science for HNC/HND students taking mechanical engineering courses, including all topics likely to be covered in both years of such courses, as well as for first year undergraduate courses in mechanical engineering. It features 500 problems with answers and 200 worked examples. The third edition includes a new section on power transmission and an appendix on mathematics to help students with the basic notation of calculus and solution of differential equations.

  7. The Global Challenge in Basic Education: Why Continued Investment in Basic Education Is Important

    Science.gov (United States)

    Mertaugh, Michael T.; Jimenez, Emmanuel Y.; Patrinos, Harry A.

    2009-01-01

    This paper documents the importance of continued investment in basic education and argues that investments need to be carefully targeted to address the constraints that limit the coverage and quality of education if they are to provide expected benefits. Part I begins with a discussion of the returns to investment in education. Part II then…

  8. Basics and application of PSpice

    International Nuclear Information System (INIS)

    Choi, Pyeong; Cho, Yong Beom; Mok, Hyeong Su; Baek, Dong CHeol

    2006-03-01

    This book is comprised of nineteenth chapters, which introduces basics and application of PSpice. The contents of this book are PSpice?, PSpice introduction, PSpice simulation, DC analysis, parametric analysis, Transient analysis, parametric analysis and measurements, Monte Carlo analysis, changing of device characteristic, ABM application. The elementary laws of circuit, R.L.C. basic circuit, Diode basic cc circuit, Transistor and EET basic circuit, OP-Amp basic circuit, Digital basic circuit, Analog, digital circuit practice, digital circuit application and practice and ABM circuit application and practice.

  9. ESPlannerBASIC CANADA

    Directory of Open Access Journals (Sweden)

    Laurence Kotlikoff

    2015-02-01

    Full Text Available Traditional financial planning is based on a fundamental rule of thumb: Aim to save enough for retirement to replace 80 per cent of your pre-retirement income with income from pensions and assets. Millions of Canadians follow this formula. Yet, there is no guarantee this approach is consistent with a savings plan that will allow them to experience their optimal standard of living — given their income — throughout their working lives. Consumption smoothing happens when a consumer projects her income and her non-discretionary expenses (such as mortgage payments all the way up until the end of her life, and is able to determine her household discretionary spending power over time, to achieve the smoothest living standard path possible without going into debt. When consumption smoothing is calculated accurately, a person’s lifestyle should be roughly the same whether she is in her 30s with small children, in her 50s with kids in college, or in retirement, with adult children. Consumption smoothing allows that to happen. But while it is conceptually straightforward, consumption smoothing requires the use of advanced numerical techniques. Now, Canadian families have access to a powerful consumption-smoothing tool: ESPlannerBASIC Canada. This free, secure and confidential online tool will allow Canadian families to safely and securely enter their earnings and other financial resources and will calculate for them how much they can spend and how much they should save in order to maintain their lifestyle from now until they die, without going into debt. It will also calculate how much life insurance they should buy, to ensure that household living standards are not affected after a family member dies. Users can easily and instantly run “what-if” scenarios to see how retiring early (or later, changing jobs, adjusting retirement contributions, having children, moving homes, timing RRSP withdrawals, and other financial and lifestyle decisions would

  10. Cloud computing basics

    CERN Document Server

    Srinivasan, S

    2014-01-01

    Cloud Computing Basics covers the main aspects of this fast moving technology so that both practitioners and students will be able to understand cloud computing. The author highlights the key aspects of this technology that a potential user might want to investigate before deciding to adopt this service. This book explains how cloud services can be used to augment existing services such as storage, backup and recovery. Addressing the details on how cloud security works and what the users must be prepared for when they move their data to the cloud. Also this book discusses how businesses could prepare for compliance with the laws as well as industry standards such as the Payment Card Industry.

  11. Basic semiconductor physics

    CERN Document Server

    Hamaguchi, Chihiro

    2017-01-01

    This book presents a detailed description of basic semiconductor physics. The text covers a wide range of important phenomena in semiconductors, from the simple to the advanced. Four different methods of energy band calculations in the full band region are explained: local empirical pseudopotential, non-local pseudopotential, KP perturbation and tight-binding methods. The effective mass approximation and electron motion in a periodic potential, Boltzmann transport equation and deformation potentials used for analysis of transport properties are discussed. Further, the book examines experiments and theoretical analyses of cyclotron resonance in detail. Optical and transport properties, magneto-transport, two-dimensional electron gas transport (HEMT and MOSFET) and quantum transport are reviewed, while optical transition, electron-phonon interaction and electron mobility are also addressed. Energy and electronic structure of a quantum dot (artificial atom) are explained with the help of Slater determinants. The...

  12. Basic category theory

    CERN Document Server

    Leinster, Tom

    2014-01-01

    At the heart of this short introduction to category theory is the idea of a universal property, important throughout mathematics. After an introductory chapter giving the basic definitions, separate chapters explain three ways of expressing universal properties: via adjoint functors, representable functors, and limits. A final chapter ties all three together. The book is suitable for use in courses or for independent study. Assuming relatively little mathematical background, it is ideal for beginning graduate students or advanced undergraduates learning category theory for the first time. For each new categorical concept, a generous supply of examples is provided, taken from different parts of mathematics. At points where the leap in abstraction is particularly great (such as the Yoneda lemma), the reader will find careful and extensive explanations. Copious exercises are included.

  13. Energy the basics

    CERN Document Server

    Schobert, Harold

    2013-01-01

    People rarely stop to think about where the energy they use to power their everyday lives comes from and when they do it is often to ask a worried question: is mankind's energy usage killing the planet? How do we deal with nuclear waste? What happens when the oil runs out? Energy: The Basics answers these questions but it also does much more. In this engaging yet even-handed introduction, readers are introduced to: the concept of 'energy' and what it really means the ways energy is currently generated and the sources used new and emerging energy technologies such as solar power and biofuels the impacts of energy use on the environment including climate change Featuring explanatory diagrams, tables, a glossary and an extensive further reading list, this book is the ideal starting point for anyone interested in the impact and future of the world's energy supply.

  14. Basic ionizing physic radiation

    International Nuclear Information System (INIS)

    Abdul Nassir Ibrahim; Azali Muhammad; Ab. Razak Hamzah; Abd. Aziz Mohamed; Mohamad Pauzi Ismail

    2008-01-01

    To become an expert in this field, radiographer must first master in radiation physics. That why the second chapter discussed on radiation physic. The topic that must covered such as atom and molecule, atomic structure, proton, isotope, half life, types of radiation and some basic formula such as formula for shielding, half life, half value layer, tenth value layer and more. All of this must be mastered by radiographer if they want to know more detail on this technique because this technique was a combination of theory and practical. Once they failed the theory they cannot go further on this technique. And to master this technique, once cannot depend on theory only. So, for this technique theory and practical must walk together.

  15. 15. Basic economic indicators

    International Nuclear Information System (INIS)

    Carless, J.; Dow, B.; Farivari, R.; O'Connor, J.; Fox, T.; Tunstall, D.; Mentzingen, M.

    1992-01-01

    The clear value of economic data and analysis to decisionmakers has motivated them to mandate the creation of extensive global economic data sets. This chapter contains a set of these basic economic data, which provides the context for understanding the causes and the consequences of many of the decisions that affect the world's resources. Many traditional economic indicators fail to account for the depletion or deterioration of natural resources, the long-term consequences of such depletion, the equitable distribution of income within a country, or the sustainability of current economic practices. The type of measurement shown here, however, is still useful in showing the great differences between the wealthiest and the poorest countries. Tables are given on the following: Gross national product and official development assistance 1969-89; External debt indicators 1979-89; Central government expenditures; and World commodity indexes and prices 1975-89

  16. Chernobyl versus Basic Law

    Energy Technology Data Exchange (ETDEWEB)

    Sauer, G W

    1986-01-01

    The author discusses the terms 'remaining risk to be accepted' and 'remainder of the aggregate risk', and explains the line of action to be adopted in compliance with the Constitution in order to respond to the event at Chernobyl: The Constitution demands maximum acceptable limits to be defined as low as possible. The author discusses the various dose estimations and the contradictions to be observed in this context. He states that the Chernobyl accident has done most harm to our legal system, as the basic right of freedom from injury has been ploughed under with the radioactivity that covered the soil after the Chernobyl accident. But, he says, a positive effect is that the idea of abandoning nuclear power as too dangerous a technology has gained more widespread acceptance. (HSCH).

  17. Basic engineering mathematics

    CERN Document Server

    Bird, John

    2014-01-01

    Introductory mathematics written specifically for students new to engineering Now in its sixth edition, Basic Engineering Mathematics is an established textbook that has helped thousands of students to succeed in their exams. John Bird's approach is based on worked examples and interactive problems. This makes it ideal for students from a wide range of academic backgrounds as the student can work through the material at their own pace. Mathematical theories are explained in a straightforward manner, being supported by practical engineering examples and applications in order to ensure that readers can relate theory to practice. The extensive and thorough topic coverage makes this an ideal text for introductory level engineering courses. This title is supported by a companion website with resources for both students and lecturers, including lists of essential formulae, multiple choice tests, full solutions for all 1,600 further questions contained within the practice exercises, and biographical information on t...

  18. Chernobyl versus Basic Law?

    International Nuclear Information System (INIS)

    Sauer, G.W.

    1986-01-01

    The author discusses the terms 'remaining risk to be accepted' and 'remainder of the aggregate risk', and explains the line of action to be adopted in compliance with the Constitution in order to respond to the event at Chernobyl: The Constitution demands maximum acceptable limits to be defined as low as possible. The author discusses the various dose estimations and the contradictions to be observed in this context. He states that the Chernobyl accident has done most harm to our legal system, as the basic right of freedom from injury has been ploughed under with the radioactivity that covered the soil after the Chernobyl accident. But, he says, a positive effect is that the idea of abandoning nuclear power as too dangerous a technology has gained more widespread acceptance. (HSCH) [de

  19. Basic real analysis

    CERN Document Server

    Sohrab, Houshang H

    2014-01-01

    This expanded second edition presents the fundamentals and touchstone results of real analysis in full rigor, but in a style that requires little prior familiarity with proofs or mathematical language. The text is a comprehensive and largely self-contained introduction to the theory of real-valued functions of a real variable. The chapters on Lebesgue measure and integral have been rewritten entirely and greatly improved. They now contain Lebesgue’s differentiation theorem as well as his versions of the Fundamental Theorem(s) of Calculus. With expanded chapters, additional problems, and an expansive solutions manual, Basic Real Analysis, Second Edition, is ideal for senior undergraduates and first-year graduate students, both as a classroom text and a self-study guide. Reviews of first edition: The book is a clear and well-structured introduction to real analysis aimed at senior undergraduate and beginning graduate students. The prerequisites are few, but a certain mathematical sophistication is required. ....

  20. Magnetism basics and applications

    CERN Document Server

    Stefanita, Carmen-Gabriela

    2012-01-01

    This textbook is aimed at engineering students who are likely to come across magnetics applications in their professional practice. Whether designing lithography equipment containing ferromagnetic brushes, or detecting defects in aeronautics, some basic knowledge of 21st century magnetism is needed. From the magnetic tape on the pocket credit card to the read head in a personal computer, people run into magnetism in many products. Furthermore, in a variety of disciplines tools of the trade exploit magnetic principles, and many interdisciplinary laboratory research areas cross paths with magnetic phenomena that may seem mysterious to the untrained mind. Therefore, this course offers a broad coverage of magnetism topics encountered more often in this millenium, revealing key concepts on which many practical applications rest. Some traditional subjects in magnetism are discussed in the first half of the book, followed by areas likely to spark the curiosity of those more interested in today’s technological achi...