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.

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.

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.

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.

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.

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

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.

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

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.

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...

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)

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.

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.)

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.

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.

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.

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...

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

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.

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

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

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.

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

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;

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

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.

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.

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.

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.

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.

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

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.

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

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.

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

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...

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.

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.

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.

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

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.

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.

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.

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.

Innovative Mechanism of Rural Organization Based on Self-Organization

Institute of Scientific and Technical Information of China (English)

2011-01-01

The paper analyzes the basic situation of the formation of innovative rural organizations with the form of self-organization;reveals the features of self-organization,including the four aspects of openness of rural organization,innovation of rural organization far away from equilibrium,the non-linear response mechanism of rural organization innovation and the random rise and fall of rural organization innovation.The evolution mechanism of rural organization innovation is revealed according to the growth stage,the ideal stage,the decline and the fall stage.The paper probes into the basic restriction mechanism of the self-organization evaluation of rural organization from three aspects,including target recognition,path dependence and knowledge sharing.The basic measures on cultivating the innovative mechanism of rural organization are put forward.Firstly,constructing the dissipative structure of rural organization innovation;secondly,cultivating the dynamic study capability of rural organization innovation system;thirdly,selecting the step-by-step evolution strategy of rural organization innovation system.

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.

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)

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)

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.

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

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...

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.

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....

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.

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

The Role of Malware in Reported Cyber Espionage: A Review of the Impact and Mechanism

OpenAIRE

Gaute Wangen

2015-01-01

This is the journal's PDF originally published in Information, http://dx.doi.org/10.3390/info6020183 The recent emergence of the targeted use of malware in cyber espionage versus industry requires a systematic review for better understanding of its impact and mechanism. This paper proposes a basic taxonomy to document major cyber espionage incidents, describing and comparing their impacts (geographic or political targets, origins and motivations) and their mechanisms (dropper, propagation,...

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.

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.

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.

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.

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....

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

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.

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

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.

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

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.

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.

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.

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

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.

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.

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

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.

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.

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.

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

A new electrospray method for targeted gene delivery.

Science.gov (United States)

Boehringer, Stephan; Ruzgys, Paulius; Tamò, Luca; Šatkauskas, Saulius; Geiser, Thomas; Gazdhar, Amiq; Hradetzky, David

2018-03-05

A challenge for gene therapy is absence of safe and efficient local delivery of therapeutic genetic material. An efficient and reproducible physical method of electrospray for localized and targeted gene delivery is presented. Electrospray works on the principle of coulombs repulsion, under influence of electric field the liquid carrying genetic material is dispersed into micro droplets and is accelerated towards the targeted tissue, acting as a counter electrode. The accelerated droplets penetrate the targeted cells thus facilitating the transfer of genetic material into the cell. The work described here presents the principle of electrospray for gene delivery, the basic instrument design, and the various optimized parameters to enhance gene transfer in vitro. We estimate a transfection efficiency of up to 60% was achieved. We describe an efficient gene transfer method and a potential electrospray-mediated gene transfer mechanism.

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.

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…

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)

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 [...

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.

The target landscape of clinical kinase drugs.

Science.gov (United States)

Klaeger, Susan; Heinzlmeir, Stephanie; Wilhelm, Mathias; Polzer, Harald; Vick, Binje; Koenig, Paul-Albert; Reinecke, Maria; Ruprecht, Benjamin; Petzoldt, Svenja; Meng, Chen; Zecha, Jana; Reiter, Katrin; Qiao, Huichao; Helm, Dominic; Koch, Heiner; Schoof, Melanie; Canevari, Giulia; Casale, Elena; Depaolini, Stefania Re; Feuchtinger, Annette; Wu, Zhixiang; Schmidt, Tobias; Rueckert, Lars; Becker, Wilhelm; Huenges, Jan; Garz, Anne-Kathrin; Gohlke, Bjoern-Oliver; Zolg, Daniel Paul; Kayser, Gian; Vooder, Tonu; Preissner, Robert; Hahne, Hannes; Tõnisson, Neeme; Kramer, Karl; Götze, Katharina; Bassermann, Florian; Schlegl, Judith; Ehrlich, Hans-Christian; Aiche, Stephan; Walch, Axel; Greif, Philipp A; Schneider, Sabine; Felder, Eduard Rudolf; Ruland, Juergen; Médard, Guillaume; Jeremias, Irmela; Spiekermann, Karsten; Kuster, Bernhard

2017-12-01

Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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.

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.

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

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.

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.

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

Heart failure—potential new targets for therapy

Science.gov (United States)

Nabeebaccus, Adam; Zheng, Sean; Shah, Ajay M.

2016-01-01

Abstract Introduction/background Heart failure is a major cause of cardiovascular morbidity and mortality. This review covers current heart failure treatment guidelines, emerging therapies that are undergoing clinical trial, and potential new therapeutic targets arising from basic science advances. Sources of data A non-systematic search of MEDLINE was carried out. International guidelines and relevant reviews were searched for additional articles. Areas of agreement Angiotensin-converting enzyme inhibitors and beta-blockers are first line treatments for chronic heart failure with reduced left ventricular function. Areas of controversy Treatment strategies to improve mortality in heart failure with preserved left ventricular function are unclear. Growing points Many novel therapies are being tested for clinical efficacy in heart failure, including those that target natriuretic peptides and myosin activators. A large number of completely novel targets are also emerging from laboratory-based research. Better understanding of pathophysiological mechanisms driving heart failure in different settings (e.g. hypertension, post-myocardial infarction, metabolic dysfunction) may allow for targeted therapies. Areas timely for developing research Therapeutic targets directed towards modifying the extracellular environment, angiogenesis, cell viability, contractile function and microRNA-based therapies. PMID:27365454

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.

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.

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.

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

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

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

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.

NK cell-based cancer immunotherapy: from basic biology to clinical application.

Science.gov (United States)

Li, Yang; Yin, Jie; Li, Ting; Huang, Shan; Yan, Han; Leavenworth, JianMei; Wang, Xi

2015-12-01

Natural killer (NK) cells, which recognize and kill target cells independent of antigen specificity and major histocompatibility complex (MHC) matching, play pivotal roles in immune defence against tumors. However, tumor cells often acquire the ability to escape NK cell-mediated immune surveillance. Thus, understanding mechanisms underlying regulation of NK cell phenotype and function within the tumor environment is instrumental for designing new approaches to improve the current cell-based immunotherapy. In this review, we elaborate the main biological features and molecular mechanisms of NK cells that pertain to regulation of NK cell-mediated anti-tumor activity. We further overview current clinical approaches regarding NK cell-based cancer therapy, including cytokine infusion, adoptive transfer of autologous or allogeneic NK cells, applications of chimeric antigen receptor (CAR)-expressing NK cells and adoptive transfer of memory-like NK cells. With these promising clinical outcomes and fuller understanding the basic questions raised in this review, we foresee that NK cell-based approaches may hold great potential for future cancer immunotherapy.

Basic design of parallel computational program for probabilistic structural analysis

International Nuclear Information System (INIS)

Kaji, Yoshiyuki; Arai, Taketoshi; Gu, Wenwei; Nakamura, Hitoshi

1999-06-01

In our laboratory, for 'development of damage evaluation method of structural brittle materials by microscopic fracture mechanics and probabilistic theory' (nuclear computational science cross-over research) we examine computational method related to super parallel computation system which is coupled with material strength theory based on microscopic fracture mechanics for latent cracks and continuum structural model to develop new structural reliability evaluation methods for ceramic structures. This technical report is the review results regarding probabilistic structural mechanics theory, basic terms of formula and program methods of parallel computation which are related to principal terms in basic design of computational mechanics program. (author)

Basic design of parallel computational program for probabilistic structural analysis

Energy Technology Data Exchange (ETDEWEB)

Kaji, Yoshiyuki; Arai, Taketoshi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Gu, Wenwei; Nakamura, Hitoshi

1999-06-01

In our laboratory, for `development of damage evaluation method of structural brittle materials by microscopic fracture mechanics and probabilistic theory` (nuclear computational science cross-over research) we examine computational method related to super parallel computation system which is coupled with material strength theory based on microscopic fracture mechanics for latent cracks and continuum structural model to develop new structural reliability evaluation methods for ceramic structures. This technical report is the review results regarding probabilistic structural mechanics theory, basic terms of formula and program methods of parallel computation which are related to principal terms in basic design of computational mechanics program. (author)

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.

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.

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

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.

The imperative for controlled mechanical stresses in unraveling cellular mechanisms of mechanotransduction

Directory of Open Access Journals (Sweden)

Sorkin Adam M

2006-05-01

Full Text Available Abstract Background In vitro mechanotransduction studies are designed to elucidate cell behavior in response to a well-defined mechanical signal that is imparted to cultured cells, e.g. through fluid flow. Typically, flow rates are calculated based on a parallel plate flow assumption, to achieve a targeted cellular shear stress. This study evaluates the performance of specific flow/perfusion chambers in imparting the targeted stress at the cellular level. Methods To evaluate how well actual flow chambers meet their target stresses (set for 1 and 10 dyn/cm2 for this study at a cellular level, computational models were developed to calculate flow velocity components and imparted shear stresses for a given pressure gradient. Computational predictions were validated with micro-particle image velocimetry (μPIV experiments. Results Based on these computational and experimental studies, as few as 66% of cells seeded along the midplane of commonly implemented flow/perfusion chambers are subjected to stresses within ±10% of the target stress. In addition, flow velocities and shear stresses imparted through fluid drag vary as a function of location within each chamber. Hence, not only a limited number of cells are exposed to target stress levels within each chamber, but also neighboring cells may experience different flow regimes. Finally, flow regimes are highly dependent on flow chamber geometry, resulting in significant variation in magnitudes and spatial distributions of stress between chambers. Conclusion The results of this study challenge the basic premise of in vitro mechanotransduction studies, i.e. that a controlled flow regime is applied to impart a defined mechanical stimulus to cells. These results also underscore the fact that data from studies in which different chambers are utilized can not be compared, even if the target stress regimes are comparable.

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...

Review on Molecular Mechanisms of Antifouling Compounds: An Update since 2012.

Science.gov (United States)

Chen, Lianguo; Qian, Pei-Yuan

2017-08-28

Better understanding of the mechanisms of antifouling compounds is recognized to be of high value in establishing sensitive biomarkers, allowing the targeted optimization of antifouling compounds and guaranteeing environmental safety. Despite vigorous efforts to find new antifouling compounds, information about the mechanisms of antifouling is still scarce. This review summarizes the progress into understanding the molecular mechanisms underlying antifouling activity since 2012. Non-toxic mechanisms aimed at specific targets, including inhibitors of transmembrane transport, quorum sensing inhibitors, neurotransmission blockers, adhesive production/release inhibitors and enzyme/protein inhibitors, are put forward for natural antifouling products or shelf-stable chemicals. Several molecular targets show good potential for use as biomarkers in future mechanistic screening, such as acetylcholine esterase for neurotransmission, phenoloxidase/tyrosinase for the formation of adhesive plaques, N -acyl homoserine lactone for quorum sensing and intracellular Ca 2+ levels as second messenger. The studies on overall responses to challenges by antifoulants can be categorized as general targets, including protein expression/metabolic activity regulators, oxidative stress inducers, neurotransmission blockers, surface modifiers, biofilm inhibitors, adhesive production/release inhibitors and toxic killing. Given the current situation and the knowledge gaps regarding the development of alternative antifoulants, a basic workflow is proposed that covers the indispensable steps, including preliminary mechanism- or bioassay-guided screening, evaluation of environmental risks, field antifouling performance, clarification of antifouling mechanisms and the establishment of sensitive biomarkers, which are combined to construct a positive feedback loop.

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.

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.

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.

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.

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...

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.

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 ...

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...

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.

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.

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)

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

Apoptosis and Molecular Targeting Therapy in Cancer

Science.gov (United States)

Hassan, Mohamed; Watari, Hidemichi; AbuAlmaaty, Ali; Ohba, Yusuke; Sakuragi, Noriaki

2014-01-01

Apoptosis is the programmed cell death which maintains the healthy survival/death balance in metazoan cells. Defect in apoptosis can cause cancer or autoimmunity, while enhanced apoptosis may cause degenerative diseases. The apoptotic signals contribute into safeguarding the genomic integrity while defective apoptosis may promote carcinogenesis. The apoptotic signals are complicated and they are regulated at several levels. The signals of carcinogenesis modulate the central control points of the apoptotic pathways, including inhibitor of apoptosis (IAP) proteins and FLICE-inhibitory protein (c-FLIP). The tumor cells may use some of several molecular mechanisms to suppress apoptosis and acquire resistance to apoptotic agents, for example, by the expression of antiapoptotic proteins such as Bcl-2 or by the downregulation or mutation of proapoptotic proteins such as BAX. In this review, we provide the main regulatory molecules that govern the main basic mechanisms, extrinsic and intrinsic, of apoptosis in normal cells. We discuss how carcinogenesis could be developed via defective apoptotic pathways or their convergence. We listed some molecules which could be targeted to stimulate apoptosis in different cancers. Together, we briefly discuss the development of some promising cancer treatment strategies which target apoptotic inhibitors including Bcl-2 family proteins, IAPs, and c-FLIP for apoptosis induction. PMID:25013758

Mechanistic insights into Mg2+-independent prenylation by CloQ from classical molecular mechanics and hybrid quantum mechanics/molecular mechanics molecular dynamics simulations.

Science.gov (United States)

Bayse, Craig A; Merz, Kenneth M

2014-08-05

Understanding the mechanism of prenyltransferases is important to the design of engineered proteins capable of synthesizing derivatives of naturally occurring therapeutic agents. CloQ is a Mg(2+)-independent aromatic prenyltransferase (APTase) that transfers a dimethylallyl group to 4-hydroxyphenylpyruvate in the biosynthetic pathway for clorobiocin. APTases consist of a common ABBA fold that defines a β-barrel containing the reaction cavity. Positively charged basic residues line the inside of the β-barrel of CloQ to activate the pyrophosphate leaving group to replace the function of the Mg(2+) cofactor in other APTases. Classical molecular dynamics simulations of CloQ, its E281G and F68S mutants, and the related NovQ were used to explore the binding of the 4-hydroxyphenylpyruvate (4HPP) and dimethylallyl diphosphate substrates in the reactive cavity and the role of various conserved residues. Hybrid quantum mechanics/molecular mechanics potential of mean force (PMF) calculations show that the effect of the replacement of the Mg(2+) cofactor with basic residues yields a similar activation barrier for prenylation to Mg(2+)-dependent APTases like NphB. The topology of the binding pocket for 4HPP is important for selective prenylation at the ortho position of the ring. Methylation at this position alters the conformation of the substrate for O-prenylation at the phenol group. Further, a two-dimensional PMF scan shows that a "reverse" prenylation product may be a possible target for protein engineering.

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.

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)

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.

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.

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.

[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

Targeted radionuclide therapy with astatine-211: Oxidative dehalogenation of astatobenzoate conjugates.

Science.gov (United States)

Teze, David; Sergentu, Dumitru-Claudiu; Kalichuk, Valentina; Barbet, Jacques; Deniaud, David; Galland, Nicolas; Maurice, Rémi; Montavon, Gilles

2017-05-31

211 At is a most promising radionuclide for targeted alpha therapy. However, its limited availability and poorly known basic chemistry hamper its use. Based on the analogy with iodine, labelling is performed via astatobenzoate conjugates, but in vivo deastatination occurs, particularly when the conjugates are internalized in cells. Actually, the chemical or biological mechanism responsible for deastatination is unknown. In this work, we show that the C-At "organometalloid" bond can be cleaved by oxidative dehalogenation induced by oxidants such as permanganates, peroxides or hydroxyl radicals. Quantum mechanical calculations demonstrate that astatobenzoates are more sensitive to oxidation than iodobenzoates, and the oxidative deastatination rate is estimated to be about 6 × 10 6 faster at 37 °C than the oxidative deiodination one. Therefore, we attribute the "internal" deastatination mechanism to oxidative dehalogenation in biological compartments, in particular lysosomes.

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

RELATIONS BETWEEN BASIC MOTOR ABILITIES AND SPECIFIC PRECISENESS OF FOOTBALLERS AGED 10-12

Directory of Open Access Journals (Sweden)

Miroslav Smajić

2007-05-01

Full Text Available According to the research on the sample of 256 footballers aged 10-12 and the battery including 20 tests for evaluation of the basic motor abilities and the battery of 24 tests for evaluation of specifi c preciseness, and as per canonic-correlation analysis, a general conclusion can be reached that the boys were rather different in their basic motor abilities. The differences were especially high in explosive strength, coordination, aerobic endurance and balance. One could also conclude that the sample treated in this manner (10-12 years of age is very heterogeneous with respect to basic motor abilities. The subjects showed the highest homogeneity in the tests of specifi c preciseness. They also achieved particularly good results in the tests of vertical target hitting by leg and head. Considering the relations of the basic motor abilities and specifi c preciseness, it was concluded that the structure-based basic motor-canonic factor might be interpreted as FACTOR OF SPEED ENDURANCE AND EXPLOSIVE STRENGTH, whereas structurebased canonic factor of specifi c preciseness might be interpreted as the FACTOR OF SPECIFIC PRECISENESS OF VERTICAL TARGET HITTING BY LEG AND HEAD. The structure of the relations of the fi rst pair of canonic factors indicates that footballers with lower speed endurance and lower explosive strength achieved poorer results in the tests of specifi c preciseness of vertical target hitting by leg and head, and vice versa. Structure of the relations of the second canonic factor indicates quite clearly that the footballers with lower repetitive strength achieved lower results in the tests of specifi c preciseness of horizontal and vertical target by leg and head in a newly created situation. Here of course, the opposite was true, i.e. footballers with higher repetitive strength were better in these tests too.

Identifying therapeutic targets in gastric cancer: the current status and future direction

Science.gov (United States)

Yu, Beiqin; Xie, Jingwu

2016-01-01

Gastric cancer is the third leading cause of cancer-related death worldwide. Our basic understanding of gastric cancer biology falls behind that of many other cancer types. Current standard treatment options for gastric cancer have not changed for the last 20 years. Thus, there is an urgent need to establish novel strategies to treat this deadly cancer. Successful clinical trials with Gleevec in CML and gastrointestinal stromal tumors have set up an example for targeted therapy of cancer. In this review, we will summarize major progress in classification, therapeutic options of gastric cancer. We will also discuss molecular mechanisms for drug resistance in gastric cancer. In addition, we will attempt to propose potential future directions in gastric cancer biology and drug targets. PMID:26373844

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.

What's hot, what's new in basic science: report from the American Transplant Congress 2015.

Science.gov (United States)

Heeger, P S

2015-11-01

Research reports presented at the American Transplant Congress 2015 provided an array of basic science findings of relevance to the transplant community. Among key themes is the concept that ischemia-reperfusion injury and early posttransplantation inflammation is linked to adaptive alloimmunity and transplant injury. Molecular and cellular mechanisms contributing to these interactions were highlighted. The relevance of understanding how blocking costimulation, including CD40/CD154 interactions, affects various aspects of the alloimmune response was enhanced by the description of preclinical studies demonstrating efficacy of a unique, blocking anti-CD40 monoclonal antibody that could potentially be used in humans. The identification of mechanisms underlying interactions among T cell subsets and B cells, including follicular helper T cells, regulatory T cells, effector B cells, and regulatory B cells, provides multiple previously unrecognized targets for future therapeutic interventions. Additional reports of interest include novel insights into effects of the gut microbiome on graft survival and the ability to differentiate insulin-secreting, islet-like cells from induced pluripotent stem cells. Overall, the reported basic science findings from American Transplant Congress 2015 add to the fundamental understanding of innate and adaptive alloimmunity and provide novel and testable hypotheses that have the potential to be translated into improved clinical care of transplant patients. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

A Cryogenic Infrared Calibration Target

Science.gov (United States)

Wollack, E. J.; Kinzer, R. E., Jr.; Rinehart, S. A.

2014-01-01

A compact cryogenic calibration target is presented that has a peak diffuse reflectance, R target. The resulting target assembly is lightweight, has a low-geometric profile, and has survived repeated thermal cycling from room temperature to approx.4 K. Basic design considerations, governing equations, and test data for realizing the structure described are provided. The optical properties of selected absorptive materials-Acktar Fractal Black, Aeroglaze Z306, and Stycast 2850 FT epoxy loaded with stainless steel powder-are characterized and presented

Survey report on smart-tribo-mechanics; Smart tribo mechanics

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-03-01

Survey results of smart-tribo-mechanics are described. For the smart-tribo-mechanics differing from the conventional tribology, an intelligent system is constructed by making full use of various science and technology ranging from basic to application, to solve problems. Self-diagnosis and self-remediation, active control, passive control, and smart-biotribo-mechanics are typical methods. Electronics, telecommunication, healthcare, and new biotechnology are new and advanced application areas. In these areas, tribology to control and act to the material surface in the atomic and molecular scale should be the key technology. In addition, the smart-tribo-mechanics is expected to be used for sustaining basic industry, such as material, transportation, and life industries. 101 refs., 67 figs., 14 tabs.

Argus target chamber

International Nuclear Information System (INIS)

Rienecker, F. Jr.; Glaros, S.S.; Kobierecki, M.

1975-01-01

A target chamber for application in the laser fusion program must satisfy some very basic requirements. (1) Provide a vacuum on the order of 10 -6 torr. (2) Support a microscopically small target in a fixed point in space and verify its location within 5 micrometers. (3) Contain an adjustable beam focusing system capable of delivering a number of laser beams onto the target simultaneously, both in time and space. (4) Provide access for diagnostics to evaluate the results of target irradiation. (5) Have flexibility to allow changes in targets, focusing optics and number of beams. The ARGUS laser which is now under construction at LLL will have a target chamber which meets these requirements in a simple economic manner. The chamber and auxiliary equipment are described, with reference to two double beam focusing systems; namely, lenses and ellipsoidal mirrors. Provision is made for future operation with four beams, using ellipsoidal mirrors for two-sided illumination and lens systems for tetragonal and tetrahedral irradiation

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.

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.

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

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

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)

Mechanisms for cytoplasmic organization: an overview.

Science.gov (United States)

Pagliaro, L

2000-01-01

One of the basic characteristics of life is the intrinsic organization of cytoplasm, yet we know surprisingly little about the manner in which cytoplasmic macromolecules are arranged. It is clear that cytoplasm is not the homogeneous "soup" it was once envisioned to be, but a comprehensive model for cytoplasmic organization is not available in modern cell biology. The premise of this volume is that phase separation in cytoplasm may play a role in organization at the subcellular level. Other mechanisms for non-membrane-bounded intracellular organization have previously been proposed. Some of these will be reviewed in this chapter. Multiple mechanisms, involving phase separation, specific intracellular targeting, formation of macromolecular complexes, and channeling, all could well contribute to cytoplasmic organization. Temporal and spatial organization, as well as composition, are likely to be important in defining the characteristics of cytoplasm.

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.

An Integrated Visualization and Basic Molecular Modeling Laboratory for First-Year Undergraduate Medicinal Chemistry

Science.gov (United States)

Hayes, Joseph M.

2014-01-01

A 3D model visualization and basic molecular modeling laboratory suitable for first-year undergraduates studying introductory medicinal chemistry is presented. The 2 h practical is embedded within a series of lectures on drug design, target-drug interactions, enzymes, receptors, nucleic acids, and basic pharmacokinetics. Serving as a teaching aid…

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.

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

Targeting mammalian organelles with internalizing phage (iPhage) libraries

Science.gov (United States)

Rangel, Roberto; Dobroff, Andrey S.; Guzman-Rojas, Liliana; Salmeron, Carolina C.; Gelovani, Juri G.; Sidman, Richard L.; Pasqualini, Renata; Arap, Wadih

2015-01-01

Techniques largely used for protein interaction studies and discovery of intracellular receptors, such as affinity capture complex purification and yeast two-hybrid, may produce inaccurate datasets due to protein insolubility, transient or weak protein interactions, or irrelevant intracellular context. A versatile tool to overcome these limitations as well as to potentially create vaccines and engineer peptides and antibodies as targeted diagnostic and therapeutic agents, is the phage display technique. We have recently developed a new technology for screening internalizing phage (iPhage) vectors and libraries utilizing a ligand/receptor-independent mechanism to penetrate eukaryotic cells. iPhage particles provide a unique discovery platform for combinatorial intracellular targeting of organelle ligands along with their corresponding receptors and to fingerprint functional protein domains in living cells. Here we explain the design, cloning, construction, and production of iPhage-based vectors and libraries, along with basic ligand-receptor identification and validation methodologies for organelle receptors. An iPhage library screening can be performed in ~8 weeks. PMID:24030441

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.

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.

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

Construction of irradiated material examination facility-basic design

International Nuclear Information System (INIS)

Ro, Seung Gy; Kim, Eun Ka; Hong, Gye Won; Herr, Young Hoi; Hong, Kwon Pyo; Lee, Myeong Han; Baik, Sang Youl; Choo, Yong Sun; Baik, Seung Je

1989-02-01

The basic design of the hot cell facility which has the main purpose of doing mechanical and physical property tests of irradiated materials, the examination process, and the annexed facility has been made. Also basic and detall designs for the underground excavation work have been performed. The project management and tasks required for the license application have been carried out in due course. The facility is expected to be completed by the end of 1992, if the budgetary support is sufficient. (Author)

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

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.

Bridging the gap between basic and applied biology: towards preclinical translation

Directory of Open Access Journals (Sweden)

Ross L. Cagan

2013-05-01

To better translate basic research findings into the clinic, we are moving away from the traditional one-gene–one-phenotype model towards the discovery of complex mechanisms. In this Editorial, the new Editor-in-Chief and Senior Editors of Disease Models & Mechanisms (DMM discuss the role that the journal will play in this transition. DMM will continue to provide a platform for studies that bridge basic and applied science, and, by demanding the rigorous assessment of animal models of disease, will help drive the establishment of robust standards of preclinical testing for drug development.

Accelerating complex for basic researches in the nuclear physics

NARCIS (Netherlands)

Dovbnya, A.N.; Guk, I.S.; Kononenko, S.G.; Peev, F.A.; Tarasenko, A.S.; Botman, J.I.M.

2009-01-01

In 2003 in NSC KIPT was begun the work on development the project of accelerator, base facility IHEPNP NSC KIPT electron recirculator SALO. The accelerator will be disposed in target hall of accelerator LU 2000 complex. It is projected first of all as facility for basic researches in the field of

Quantum mechanics in chemistry

CERN Document Server

Schatz, George C

2002-01-01

Intended for graduate and advanced undergraduate students, this text explores quantum mechanical techniques from the viewpoint of chemistry and materials science. Dynamics, symmetry, and formalism are emphasized. An initial review of basic concepts from introductory quantum mechanics is followed by chapters examining symmetry, rotations, and angular momentum addition. Chapter 4 introduces the basic formalism of time-dependent quantum mechanics, emphasizing time-dependent perturbation theory and Fermi's golden rule. Chapter 5 sees this formalism applied to the interaction of radiation and matt

Modelled basic parameters for semi-industrial irradiation plant design

International Nuclear Information System (INIS)

Mangussi, J.

2009-01-01

The basic parameters of an irradiation plant design are the total activity, the product uniformity ratio and the efficiency process. The target density, the minimum dose required and the throughput depends on the use to which the irradiator will be put at. In this work, a model for calculating the specific dose rate at several depths in an infinite homogeneous medium produced by a slab source irradiator is presented. The product minimum dose rate for a set of target thickness is obtained. The design method steps are detailed and an illustrative example is presented. (author)

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

Strong activation of bile acid-sensitive ion channel (BASIC) by ursodeoxycholic acid

Science.gov (United States)

Wiemuth, Dominik; Sahin, Hacer; Lefèvre, Cathérine M.T.; Wasmuth, Hermann E.; Gründer, Stefan

2013-01-01

Bile acid-sensitive ion channel (BASIC) is a member of the DEG/ENaC gene family of unknown function. Rat BASIC (rBASIC) is inactive at rest. We have recently shown that cholangiocytes, the epithelial cells lining the bile ducts, are the main site of BASIC expression in the liver and identified bile acids, in particular hyo- and chenodeoxycholic acid, as agonists of rBASIC. Moreover, it seems that extracellular divalent cations stabilize the resting state of rBASIC, because removal of extracellular divalent cations opens the channel. In this addendum, we demonstrate that removal of extracellular divalent cations potentiates the activation of rBASIC by bile acids, suggesting an allosteric mechanism. Furthermore, we show that rBASIC is strongly activated by the anticholestatic bile acid ursodeoxycholic acid (UDCA), suggesting that BASIC might mediate part of the therapeutic effects of UDCA. PMID:23064163

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.

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.

The Effectiveness of Learning Model of Basic Education with Character-Based at Universitas Muslim Indonesia

Science.gov (United States)

Rosmiati, Rosmiati; Mahmud, Alimuddin; Talib, Syamsul B.

2016-01-01

The purpose of this study was to determine the effectiveness of the basic education learning model with character-based through learning in the Universitas Muslim Indonesia. In addition, the research specifically examines the character of discipline, curiosity and responsibility. The specific target is to produce a basic education learning model…

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…

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.

Individualization of anticancer therapy; molecular targets of novel drugs in oncology

Directory of Open Access Journals (Sweden)

Katarzyna Regulska

2012-11-01

Full Text Available Deregulation of cellular signal transduction, caused by gene mutations, has been recognized as a basic factor of cancer initiation, promotion and progression. Thus, the ability to control the activity of overstimulated signal molecules by the use of appropriate inhibitors became the idea of targeted cancer therapy, which has provided an effective tool to normalize the molecular disorders in malignant cells and to treat certain types of cancer. The molecularly targeted drugs are divided into two major pharmaceutical classes: monoclonal antibodies and small-molecule kinase inhibitors. This review presents a summary of their characteristics, analyzing their chemical structures, specified molecular targets, mechanisms of action and indications for use. Also the molecules subjected to preclinical trials or phase I, II and III clinical trials evaluating their efficiency and safety are presented. Moreover, the article discusses further perspectives for development of targeted therapies focusing on three major directions: systematic searching and discovery of new targets that are oncogenic drivers, improving the pharmacological properties of currently known drugs, and developing strategies to overcome drug resistance. Finally, the role of proper pharmacodiagnostics as a key to rational anticancer therapy has been emphasized since the verification of reliable predictive biomarkers is a basis of individualized medicine in oncology. 

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

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.

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

The CERN polarized atomic hydrogen beam target project

International Nuclear Information System (INIS)

Kubischta, W.; Dick, L.

1990-01-01

The UA6-experiment at the CERN p bar p Colider is at present using an unpolarized hydrogen cluster target with a thickness up to 5.10 14 atoms/cm 2 . It is planned to replace this target by a polarized atomic hydrogen beam target with a thickness up to about 10 13 atoms/cm 2 . This paper discusses basic requirements and results of atom optical calculations

Theoretical aspects of inflation targeting

Directory of Open Access Journals (Sweden)

Obradović Jelena

2014-01-01

Full Text Available Inflation targeting is one of the possible strategies used by central banks during conducting monetary policy. The basic characteristics, advantages and disadvantages of inflation targeting will be presented in this paper. The focus is on the the presentation and interpretation of the understanding of this strategy from the perspective of monetarist and Keynesian theory, the theory of rational expectations, and methodological analysis of the strategy in light of the game theory using payoff matrix.

Polarized atomic beams for targets

International Nuclear Information System (INIS)

Grueebler, W.

1984-01-01

The basic principle of the production of polarized atomic hydrogen and deuterium beams are reviewed. The status of the present available polarization, density and intensity are presented. The improvement of atomic beam density by cooling the hydrogen atoms to low velocity is discussed. The possible use of polarized atomic beams as targets in storage rings is shown. It is proposed that polarized atomic beams can be used to produce polarized gas targets with high polarization and greatly improved density

THE METHOD OF MULTIPLE SPATIAL PLANNING BASIC MAP

OpenAIRE

Zhang, C.; Fang, C.

2018-01-01

The “Provincial Space Plan Pilot Program” issued in December 2016 pointed out that the existing space management and control information management platforms of various departments were integrated, and a spatial planning information management platform was established to integrate basic data, target indicators, space coordinates, and technical specifications. The planning and preparation will provide supportive decision support, digital monitoring and evaluation of the implementation of the p...

Children's identification of graphic symbols representing four basic emotions: comparison of Afrikaans-speaking and Sepedi-speaking children.

Science.gov (United States)

DeKlerk, Hester M; Dada, Shakila; Alant, Erna

2014-01-01

Speech language pathologists recommend graphic symbols for AAC users to facilitate communication, including labelling and expressing emotions. The purpose of the current study was to describe and compare how 5- to 6-year-old Afrikaans- and Sepedi-speaking children identify and choose graphic symbols to depict four basic emotions, specifically happy, sad, afraid, and angry. Ninety participants were asked to select the graphic symbol from a 16-matrix communication overlay that would represent the emotion in response to 24 vignettes. The results of the t-tests indicated that the differences between the two groups' selection of target symbols to represent the four emotions are statistically significant. The results of the study indicate that children from different language groups may not perceive graphic symbols in the same way. The Afrikaans-speaking participants more often choose target symbols to represent target basic emotions than did the Sepedi-speaking participants. The most preferred symbols per emotion were identified and these different symbols were analysed in terms of facial features that distinguish them. Readers of this article will (1) recognise the importance of expressing basic emotions for children, particularly those that use AAC, (2) identify the possible limitations of line drawings for expressing and labelling basic emotions in typically developing children and (3) recognise the importance of cultural influences on recognition of basic emotions. Copyright © 2014 Elsevier Inc. All rights reserved.

Basic Knowledge about Metal Stent Development

Directory of Open Access Journals (Sweden)

Seok Jeong

2016-03-01

Full Text Available Biliary self-expandable metal stents (SEMS, a group of non-vascular stents, have been used in the palliative management of biliary obstruction around the world. However, there are still unmet needs in the clinical application of biliary SEMS. Comprehensive understanding of the SEMS is required to resolve the drawbacks and difficulties of metal stent development. The basic structure of SEMS, including the materials and knitting methods of metal wires, covering materials, and radiopaque markers, are discussed in this review. What we know about the physical and mechanical properties of the SEMS is very important. With an understanding of the basic knowledge of metal stents, hurdles such as stent occlusion, migration, and kinking can be overcome to develop more ideal SEMS.

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.

Geoengineering: Basic science and ongoing research efforts in China

Directory of Open Access Journals (Sweden)

Long Cao

2015-09-01

Full Text Available Geoengineering (also called climate engineering, which refers to large-scale intervention in the Earth's climate system to counteract greenhouse gas-induced warming, has been one of the most rapidly growing areas of climate research as a potential option for tackling global warming. Here, we provide an overview of the scientific background and research progress of proposed geoengineering schemes. Geoengineering can be broadly divided into two categories: solar geoengineering (also called solar radiation management, or SRM, which aims to reflect more sunlight to space, and carbon dioxide removal (CDR, which aims to reduce the CO2 content in the atmosphere. First, we review different proposed geoengineering methods involved in the solar radiation management and carbon dioxide removal schemes. Then, we discuss the fundamental science underlying the climate response to the carbon dioxide removal and solar radiation management schemes. We focus on two basic issues: 1 climate response to the reduction in solar irradiance and 2 climate response to the reduction in atmospheric CO2. Next, we introduce an ongoing geoengineering research project in China that is supported by National Key Basic Research Program. This research project, being the first coordinated geoengineering research program in China, will systematically investigate the physical mechanisms, climate impacts, and risk and governance of a few targeted geoengineering schemes. It is expected that this research program will help us gain a deep understanding of the physical science underlying geoengineering schemes and the impacts of geoengineering on global climate, in particular, on the Asia monsoon region.

Ion-Exchange Chromatography: Basic Principles and Application.

Science.gov (United States)

Cummins, Philip M; Rochfort, Keith D; O'Connor, Brendan F

2017-01-01

Ion-Exchange Chromatography (IEC) allows for the separation of ionizable molecules on the basis of differences in charge properties. Its large sample-handling capacity, broad applicability (particularly to proteins and enzymes), moderate cost, powerful resolving ability, and ease of scale-up and automation have led to it becoming one of the most versatile and widely used of all liquid chromatography (LC) techniques. In this chapter, we review the basic principles of IEC, as well as the broader criteria for selecting IEC conditions. By way of further illustration, we outline basic laboratory protocols to partially purify a soluble serine peptidase from bovine whole brain tissue, covering crude tissue extract preparation through to partial purification of the target enzyme using anion-exchange chromatography. Protocols for assaying total protein and enzyme activity in both pre- and post-IEC fractions are also described.

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.

Variational analysis and generalized differentiation I basic theory

CERN Document Server

Mordukhovich, Boris S

2006-01-01

Contains a study of the basic concepts and principles of variational analysis and generalized differentiation in both finite-dimensional and infinite-dimensional spaces. This title presents many applications to problems in optimization, equilibria, stability and sensitivity, control theory, economics, mechanics, and more.

Frizzled Receptors as Potential Therapeutic Targets in Human Cancers

Directory of Open Access Journals (Sweden)

Chui-Mian Zeng

2018-05-01

Full Text Available Frizzled receptors (FZDs are a family of seven-span transmembrane receptors with hallmarks of G protein-coupled receptors (GPCRs that serve as receptors for secreted Wingless-type (WNT ligands in the WNT signaling pathway. Functionally, FZDs play crucial roles in regulating cell polarity, embryonic development, cell proliferation, formation of neural synapses, and many other processes in developing and adult organisms. In this review, we will introduce the basic structural features and review the biological function and mechanism of FZDs in the progression of human cancers, followed by an analysis of clinical relevance and therapeutic potential of FZDs. We will focus on the development of antibody-based and small molecule inhibitor-based therapeutic strategies by targeting FZDs for human cancers.

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)

Standardized Curriculum for Diesel Engine Mechanics.

Science.gov (United States)

Mississippi State Dept. of Education, Jackson. Office of Vocational, Technical and Adult Education.

Standardized curricula are provided for two courses for the secondary vocational education program in Mississippi: diesel engine mechanics I and II. The eight units in diesel engine mechanics I are as follows: orientation; shop safety; basic shop tools; fasteners; measurement; engine operating principles; engine components; and basic auxiliary…

Neonatal brain hemorrhage (NBH) of prematurity: translational mechanisms of the vascular-neural network.

Science.gov (United States)

Lekic, Tim; Klebe, Damon; Poblete, Roy; Krafft, Paul R; Rolland, William B; Tang, Jiping; Zhang, John H

2015-01-01

Neonatal brain hemorrhage (NBH) of prematurity is an unfortunate consequence of preterm birth. Complications result in shunt dependence and long-term structural changes such as posthemorrhagic hydrocephalus, periventricular leukomalacia, gliosis, and neurological dysfunction. Several animal models are available to study this condition, and many basic mechanisms, etiological factors, and outcome consequences, are becoming understood. NBH is an important clinical condition, of which treatment may potentially circumvent shunt complication, and improve functional recovery (cerebral palsy, and cognitive impairments). This review highlights key pathophysiological findings of the neonatal vascular-neural network in the context of molecular mechanisms targeting the posthemorrhagic hydrocephalus affecting this vulnerable infant population.

Neonatal Brain Hemorrhage (NBH) of Prematurity: Translational Mechanisms of the Vascular-Neural Network

Science.gov (United States)

Lekic, Tim; Klebe, Damon; Poblete, Roy; Krafft, Paul R.; Rolland, William B.; Tang, Jiping; Zhang, John H.

2015-01-01

Neonatal brain hemorrhage (NBH) of prematurity is an unfortunate consequence of preterm birth. Complications result in shunt dependence and long-term structural changes such as post-hemorrhagic hydrocephalus, periventricular leukomalacia, gliosis, and neurological dysfunction. Several animal models are available to study this condition, and many basic mechanisms, etiological factors, and outcome consequences, are becoming understood. NBH is an important clinical condition, of which treatment may potentially circumvent shunt complication, and improve functional recovery (cerebral palsy, and cognitive impairments). This review highlights key pathophysiological findings of the neonatal vascular-neural network in the context of molecular mechanisms targeting the post-hemorrhagic hydrocephalus affecting this vulnerable infant population. PMID:25620100

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 ...

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

Physics considerations in targeted anticancer drug delivery by magnetoelectric nanoparticles

Science.gov (United States)

Stimphil, Emmanuel; Nagesetti, Abhignyan; Guduru, Rakesh; Stewart, Tiffanie; Rodzinski, Alexandra; Liang, Ping; Khizroev, Sakhrat

2017-06-01

In regard to cancer therapy, magnetoelectric nanoparticles (MENs) have proven to be in a class of its own when compared to any other nanoparticle type. Like conventional magnetic nanoparticles, they can be used for externally controlled drug delivery via application of a magnetic field gradient and image-guided delivery. However, unlike conventional nanoparticles, due to the presence of a non-zero magnetoelectric effect, MENs provide a unique mix of important properties to address key challenges in modern cancer therapy: (i) a targeting mechanism driven by a physical force rather than antibody matching, (ii) a high-specificity delivery to enhance the cellular uptake of therapeutic drugs across the cancer cell membranes only, while sparing normal cells, (iii) an externally controlled mechanism to release drugs on demand, and (iv) a capability for image guided precision medicine. These properties separate MEN-based targeted delivery from traditional biotechnology approaches and lay a foundation for the complementary approach of technobiology. The biotechnology approach stems from the underlying biology and exploits bioinformatics to find the right therapy. In contrast, the technobiology approach is geared towards using the physics of molecular-level interactions between cells and nanoparticles to treat cancer at the most fundamental level and thus can be extended to all the cancers. This paper gives an overview of the current state of the art and presents an ab initio model to describe the underlying mechanisms of cancer treatment with MENs from the perspective of basic physics.

CIMAC: A Coordinated Introduction to Calculus and Mechanics

Science.gov (United States)

Fathe, Laurie; Quinn, Jennifer; McDonald, Michael A.

1997-04-01

CIMAC, new course incorporating Mechanics, Precalculus, and Calculus, targets the growing number of motivated but underprepared students who wish to pursue a major in science or mathematics. Team-taught by a Physicist and a Mathematician, CIMAC, a new course incorporating Mechanics, Precalculus, and Calculus, targets the growing number of motivated but underprepared students who wish to pursue a major in science or mathematics. Team-taught by a Physicist and a Mathematician, the class contains specific content while exploiting the substantial commonality of these subjects. CIMAC also addresses variety of non-content areas, including supplementing basic mathematics and communication skills, accommodating various learning styles, and building student confidence. Specific approaches include class formats; gateway exams; group assignments; emphasis on writing and reading; use of computers and graphing calculators for comprehension, data acquisition, analysis, and modeling; student-led help sessions; and use of the Web http://www.oxy.edu/ departments/math/cimac/ This talk highlights the development of the course and teaching insights and innovations which have arisen from it, and addresses benefits and difficulties of coordinating material and team teaching across disciplinary lines. Finally, it presents data on student success and retention.

Basic research in theoretical high energy physics. Progress report

International Nuclear Information System (INIS)

Adler, S.L.

1984-01-01

Activities in numerous areas of basic research in theoretical high energy physics are listed, and some highlights are given. Areas of research include statistical mechanics, quantum field theory, lattice gauge theories, and quantum gravity. 81 references

A molecular rotor based ratiometric sensor for basic amino acids.

Science.gov (United States)

Pettiwala, Aafrin M; Singh, Prabhat K

2018-01-05

The inevitable importance of basic amino acids, arginine and lysine, in human health and metabolism demands construction of efficient sensor systems for them. However, there are only limited reports on the 'ratiometric' detection of basic amino acids which is further restricted by the use of chemically complex sensor molecules, which impedes their prospect for practical applications. Herein, we report a ratiometric sensor system build on simple mechanism of disassociation of novel emissive Thioflavin-T H-aggregates from heparin surface, when subjected to interaction with basic amino acids. The strong and selective electrostatic and hydrogen bonding interaction of basic amino acids with heparin leads to large alteration in photophysical attributes of heparin bound Thioflavin-T, which forms a highly sensitive sensor platform for detection of basic amino acids in aqueous solution. These selective interactions between basic amino acids and heparin allow our sensor system to discriminate arginine and lysine from other amino acids. This unique mechanism of dissociation of Thioflavin-T aggregates from heparin surface provides ratiometric response on both fluorimetric and colorimetric outputs for detection of arginine and lysine, and thus it holds a significant advantage over other developed sensor systems which are restricted to single wavelength detection. Apart from the sensitivity and selectivity, our system also provides the advantage of simplicity, dual mode of sensing, and more importantly, it employs an inexpensive commercially available probe molecule, which is a significant advantage over other developed sensor systems that uses tedious synthesis protocol for the employed probe in the detection scheme, an impediment for practical applications. Additionally, our sensor system also shows response in complex biological media of serum samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Engineering mechanics

CERN Document Server

Gross, Dietmar; Schröder, Jörg; Wall, Wolfgang A; Rajapakse, Nimal

Statics is the first volume of a three-volume textbook on Engineering Mechanics. The authors, using a time-honoured straightforward and flexible approach, present the basic concepts and principles of mechanics in the clearest and simplest form possible to advanced undergraduate engineering students of various disciplines and different educational backgrounds. An important objective of this book is to develop problem solving skills in a systematic manner. Another aim of this volume is to provide engineering students as well as practising engineers with a solid foundation to help them bridge the gap between undergraduate studies on the one hand and advanced courses on mechanics and/or practical engineering problems on the other. The book contains numerous examples, along with their complete solutions. Emphasis is placed upon student participation in problem solving. The contents of the book correspond to the topics normally covered in courses on basic engineering mechanics at universities and colleges. Now in i...

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...

Mechanical design of machine components

CERN Document Server

Ugural, Ansel C

2015-01-01

Mechanical Design of Machine Components, Second Edition strikes a balance between theory and application, and prepares students for more advanced study or professional practice. It outlines the basic concepts in the design and analysis of machine elements using traditional methods, based on the principles of mechanics of materials. The text combines the theory needed to gain insight into mechanics with numerical methods in design. It presents real-world engineering applications, and reveals the link between basic mechanics and the specific design of machine components and machines. Divided into three parts, this revised text presents basic background topics, deals with failure prevention in a variety of machine elements and covers applications in design of machine components as well as entire machines. Optional sections treating special and advanced topics are also included.Key Features of the Second Edition:Incorporates material that has been completely updated with new chapters, problems, practical examples...

Basics of cutting and abrasive processes

CERN Document Server

Toenshoff, Hans Kurt

2013-01-01

Manufacturing is the basic industrial activity generating real value. Cutting and abrasive technologies are the backbone of precision production in machine, automotive and aircraft building as well as of production of consumer goods. We present the knowledge of modern manufacturing in these technologies on the basis of scientific research. The theory of cutting and abrasive processes and the knowledge about their application in industrial practice are a prerequisite for the studies of manufacturing science and an important part of the curriculum of the master study in German mechanical engineering. The basis of this book is our lecture “Basics of cutting and abrasive processes” (4 semester hours/3 credit hours) at the Leibniz University Hannover, which we offer to the diploma and master students specializing in manufacturing science.

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

Quantum mechanics in Hilbert space

CERN Document Server

Prugovecki, Eduard

1981-01-01

A critical presentation of the basic mathematics of nonrelativistic quantum mechanics, this text is suitable for courses in functional analysis at the advanced undergraduate and graduate levels. Its readable and self-contained form is accessible even to students without an extensive mathematical background. Applications of basic theorems to quantum mechanics make it of particular interest to mathematicians working in functional analysis and related areas.This text features the rigorous proofs of all the main functional-analytic statements encountered in books on quantum mechanics. It fills the

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

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.

A bio-inspired swarm robot coordination algorithm for multiple target searching

Science.gov (United States)

Meng, Yan; Gan, Jing; Desai, Sachi

2008-04-01

The coordination of a multi-robot system searching for multi targets is challenging under dynamic environment since the multi-robot system demands group coherence (agents need to have the incentive to work together faithfully) and group competence (agents need to know how to work together well). In our previous proposed bio-inspired coordination method, Local Interaction through Virtual Stigmergy (LIVS), one problem is the considerable randomness of the robot movement during coordination, which may lead to more power consumption and longer searching time. To address these issues, an adaptive LIVS (ALIVS) method is proposed in this paper, which not only considers the travel cost and target weight, but also predicting the target/robot ratio and potential robot redundancy with respect to the detected targets. Furthermore, a dynamic weight adjustment is also applied to improve the searching performance. This new method a truly distributed method where each robot makes its own decision based on its local sensing information and the information from its neighbors. Basically, each robot only communicates with its neighbors through a virtual stigmergy mechanism and makes its local movement decision based on a Particle Swarm Optimization (PSO) algorithm. The proposed ALIVS algorithm has been implemented on the embodied robot simulator, Player/Stage, in a searching target. The simulation results demonstrate the efficiency and robustness in a power-efficient manner with the real-world constraints.

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.

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

Basic science behind the cardiovascular benefits of exercise.

Science.gov (United States)

Wilson, Mathew G; Ellison, Georgina M; Cable, N Tim

2016-01-01

Cardiorespiratory fitness is a strong predictor of cardiovascular (CV) disease and all-cause mortality, with increases in cardiorespiratory fitness associated with corresponding decreases in CV disease risk. The effects of exercise upon the myocardium and vascular system are dependent upon the frequency, intensity and duration of the exercise itself. Following a prolonged period (≥6 months) of regular intensive exercise in previously untrained individuals, resting and submaximal exercising heart rates are typically 5-20 beats lower, with an increase in stroke volume of ∼20% and enhanced myocardial contractility. Structurally, all four heart chambers increase in volume with mild increases in wall thickness, resulting in greater cardiac mass due to increased myocardial cell size. With this in mind, the present paper aims to review the basic science behind the CV benefits of exercise. Attention will be paid to understanding (1) the relationship between exercise and cardiac remodelling; (2) the cardiac cellular and molecular adaptations in response to exercise, including the examination of molecular mechanisms of physiological cardiac growth and applying these mechanisms to identify new therapeutic targets to prevent or reverse pathological remodelling and heart failure; and (3) vascular adaptations in response to exercise. Finally, this review will briefly examine how to optimise the CV benefits of exercise by considering how much and how intense exercise should be. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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.

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.

Results of the basic design of the European Pressurized Water Reactor (EPR) and further prospective

International Nuclear Information System (INIS)

Fischer, U.

1998-01-01

The EPR is an evolutionary design, with maximum consideration given to the experience accumulated by Framatome and Siemens with the existing designs of plants successfully operating.However, substantial improvements with regard to availability, safety and economy have been included. The main target of the basic design phase was a clear definition of technical features based on common technical codes that comply with economic targets and licensability requirements in France and Germany.The EPR basic design represents a new design for a nuclear power plant that complies with the latest laws and regulations, both in France and Germany as well as in most of the countries utilizing nuclear power. Cost estimates prove the design economically viable

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.

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.

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

Basic safety principles of KLT-40C reactor plants

International Nuclear Information System (INIS)

Beliaev, V.; Polunichev, V.

2000-01-01

The KLT-40 NSSS has been developed for a floating power block of a nuclear heat and power station on the basis of ice-breaker-type NSSS (Nuclear Steam Supply System) with application of shipbuilding technologies. Basic reactor plant components are pressurised water reactor, once-through coil-type steam generator, primary coolant pump, emergency protection rod drive mechanisms of compensate group-electromechanical type. Basic RP components are incorporated in a compact steam generating block which is arranged within metal-water shielding tank's caissons. Domestic regulatory documents on safety were used for the NSSS design. IAEA recommendations were also taken into account. Implementation of basic safety principles adopted presently for nuclear power allowed application of the KLT-40C plant for a floating power unit of a nuclear co-generation station. (author)

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.

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.

Lipossomas: a bala mágica acertou? Liposomes: has the magic bullet hit the target?

Directory of Open Access Journals (Sweden)

Nuno C. Santos

2002-12-01

Full Text Available Efficient drug delivery systems are as important as drug themselves. A powerful drug unable to reach the target cell is useless in practice. Ehrlich's Magic Bullet was the first carrier system to be proposed. The evolution in this domain has been quite slow as the natural mechanisms of mammals against foreign products are hard to overcome. However, lipid-based systems (liposomes and related vesicles have attained reasonable success. The basic preparations and structural features of liposomes and related vesicles as well as their applications are addressed from the chemist's and biochemist's point of view.

Abscisic-acid-dependent basic leucine zipper (bZIP) transcription factors in plant abiotic stress.

Science.gov (United States)

Banerjee, Aditya; Roychoudhury, Aryadeep

2017-01-01

One of the major causes of significant crop loss throughout the world is the myriad of environmental stresses including drought, salinity, cold, heavy metal toxicity, and ultraviolet-B (UV-B) rays. Plants as sessile organisms have evolved various effective mechanism which enable them to withstand this plethora of stresses. Most of such regulatory mechanisms usually follow the abscisic-acid (ABA)-dependent pathway. In this review, we have primarily focussed on the basic leucine zipper (bZIP) transcription factors (TFs) activated by the ABA-mediated signalosome. Upon perception of ABA by specialized receptors, the signal is transduced via various groups of Ser/Thr kinases, which phosphorylate the bZIP TFs. Following such post-translational modification of TFs, they are activated so that they bind to specific cis-acting sequences called abscisic-acid-responsive elements (ABREs) or GC-rich coupling elements (CE), thereby influencing the expression of their target downstream genes. Several in silico techniques have been adopted so far to predict the structural features, recognize the regulatory modification sites, undergo phylogenetic analyses, and facilitate genome-wide survey of TF under multiple stresses. Current investigations on the epigenetic regulation that controls greater accessibility of the inducible regions of DNA of the target gene to the bZIP TFs exclusively under stress situations, along with the evolved stress memory responses via genomic imprinting mechanism, have been highlighted. The potentiality of overexpression of bZIP TFs, either in a homologous or in a heterologous background, in generating transgenic plants tolerant to various abiotic stressors have also been addressed by various groups. The present review will provide a coherent documentation on the functional characterization and regulation of bZIP TFs under multiple environmental stresses, with the major goal of generating multiple-stress-tolerant plant cultivars in near future.

Mechanical engineers' handbook, materials and engineering mechanics

CERN Document Server

Kutz, Myer

2015-01-01

Full coverage of materials and mechanical design inengineering Mechanical Engineers' Handbook, Fourth Edition provides aquick guide to specialized areas you may encounter in your work,giving you access to the basics of each and pointing you towardtrusted resources for further reading, if needed. The accessibleinformation inside offers discussions, examples, and analyses ofthe topics covered. This first volume covers materials and mechanical design, givingyou accessible and in-depth access to the most common topics you'llencounter in the discipline: carbon and alloy steels, stainlesssteels, a

The Development of Basic Reading Skills in Children: A Cross-Language Perspective.

Science.gov (United States)

Geva, Esther; Wang, Min

2001-01-01

Reviews recent research evidence for universal and orthography- or language-specific processes in the development of basic reading skills in school-age children. The review focuses on three different aspects of reading--phonological processing, rapid naming, and morphosyntactic complexity--targeted in recent research on development of word…

Bayesian target tracking based on particle filter

Institute of Scientific and Technical Information of China (English)

无

2005-01-01

For being able to deal with the nonlinear or non-Gaussian problems, particle filters have been studied by many researchers. Based on particle filter, the extended Kalman filter (EKF) proposal function is applied to Bayesian target tracking. Markov chain Monte Carlo (MCMC) method, the resampling step, etc novel techniques are also introduced into Bayesian target tracking. And the simulation results confirm the improved particle filter with these techniques outperforms the basic one.

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.

Phospho switch triggers Brd4 chromatin binding and activator recruitment for gene-specific targeting.

Science.gov (United States)

Wu, Shwu-Yuan; Lee, A-Young; Lai, Hsien-Tsung; Zhang, Hong; Chiang, Cheng-Ming

2013-03-07

Bromodomain-containing protein 4 (Brd4) is an epigenetic reader and transcriptional regulator recently identified as a cancer therapeutic target for acute myeloid leukemia, multiple myeloma, and Burkitt's lymphoma. Although chromatin targeting is a crucial function of Brd4, there is little understanding of how bromodomains that bind acetylated histones are regulated, nor how the gene-specific activity of Brd4 is determined. Via interaction screen and domain mapping, we identified p53 as a functional partner of Brd4. Interestingly, Brd4 association with p53 is modulated by casein kinase II (CK2)-mediated phosphorylation of a conserved acidic region in Brd4 that selectively contacts either a juxtaposed bromodomain or an adjacent basic region to dictate the ability of Brd4 binding to chromatin and also the recruitment of p53 to regulated promoters. The unmasking of bromodomains and activator recruitment, concurrently triggered by the CK2 phospho switch, provide an intriguing mechanism for gene-specific targeting by a universal epigenetic reader. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

Sputtering. [as deposition technique in mechanical engineering

Science.gov (United States)

Spalvins, T.

1976-01-01

This paper primarily reviews the potential of using the sputtering process as a deposition technique; however, the manufacturing and sputter etching aspects are also discussed. Since sputtering is not regulated by classical thermodynamics, new multicomponent materials can be developed in any possible chemical composition. The basic mechanism for dc and rf sputtering is described. Sputter-deposition is described in terms of the unique advantageous features it offers such as versatility, momentum transfer, stoichiometry, sputter-etching, target geometry (coating complex surfaces), precise controls, flexibility, ecology, and sputtering rates. Sputtered film characteristics, such as strong adherence and coherence and film morphology, are briefly evaluated in terms of varying the sputtering parameters. Also described are some of the specific industrial areas which are turning to sputter-deposition techniques.

Amide proton transfer imaging in clinics: Basic concepts and current and future use in brain tumors and stoke

Energy Technology Data Exchange (ETDEWEB)

Park, Ji Eun [Dept. of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Jahng, Geon Ho [Dept. of Radiology, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul (Korea, Republic of); Jeong, Ha Kyu [Philips Korea, Seoul (Korea, Republic of)

2016-12-15

Amide proton transfer (APT) imaging is gaining attention as a relatively new in vivo molecular imaging technique that has higher sensitivity and spatial resolution than magnetic resonance spectroscopy imaging. APT imaging is a subset of the chemical exchange saturation transfer mechanism, which can offer unique image contrast by selectively saturating protons in target molecules that get exchanged with protons in bulk water. In this review, we describe the basic concepts of APT imaging, particularly with regard to the benefit in clinics from the current literature. Clinical applications of APT imaging are described from two perspectives: in the diagnosis and monitoring of the treatment response in brain glioma by reflecting endogenous mobile proteins and peptides, and in the potential for stroke imaging with respect to tissue acidity.

Learning basic programming using CLIS through gamification

Science.gov (United States)

Prabawa, H. W.; Sutarno, H.; Kusnendar, J.; Rahmah, F.

2018-05-01

The difficulty of understanding programming concept is a major problem in basic programming lessons. Based on the results of preliminary studies, 60% of students reveal the monotonous of learning process caused by the limited number of media. Children Learning in Science (CLIS) method was chosen as solution because CLIS has facilitated students’ initial knowledge to be optimized into conceptual knowledge. Technological involvement in CLIS (gamification) helped students to understand basic programming concept. This research developed a media using CLIS method with gamification elements to increase the excitement of learning process. This research declared that multimedia is considered good by students, especially regarding the mechanical aspects of multimedia, multimedia elements and aspects of multimedia information structure. Multimedia gamification learning with the CLIS model showed increased number of students’ concept understanding.

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 ...

Neutron performance analysis for ESS target proposal

International Nuclear Information System (INIS)

Magán, M.; Terrón, S.; Thomsen, K.; Sordo, F.; Perlado, J.M.; Bermejo, F.J.

2012-01-01

In the course of discussing different target types for their suitability in the European Spallation Source (ESS) one main focus was on neutronics' performance. Diverse concepts have been assessed baselining some preliminary engineering and geometrical details and including some optimization. With the restrictions and resulting uncertainty imposed by the lack of detailed designs optimizations at the time of compiling this paper, the conclusion drawn is basically that there is a little difference in the neutronic yield of the investigated targets. Other criteria like safety, environmental compatibility, reliability and cost will thus dominate the choice of an ESS target.

Basic theoretical physics a concise overview

CERN Document Server

Krey, Uwe

2007-01-01

This concise treatment embraces, in four parts, all the main aspects of theoretical physics (I . Mechanics and Basic Relativity, II. Electrodynamics and Aspects of Optics, III. Non-relativistic Quantum Mechanics, IV. Thermodynamics and Statistical Physics). It summarizes the material that every graduate student, physicist working in industry, or physics teacher should master during his or her degree course. It thus serves both as an excellent revision and preparation tool, and as a convenient reference source, covering the whole of theoretical physics. It may also be successfully employed to deepen its readers' insight and add new dimensions to their understanding of these fundamental concepts. Recent topics such as holography and quantum cryptography are included, thus making this a unique contribution to the learning material for theoretical physics.

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

Spatial Learning: Conditions and Basic Effects

Directory of Open Access Journals (Sweden)

Victoria D. Chamizo

2002-01-01

Full Text Available A growing body of evidence suggests that the spatial and the temporal domains seem to share the same or similar conditions, basic effects, and mechanisms. The blocking, unblocking and overshadowing experiments (and also those of latent inhibition and perceptual learning reviewed by Prados and Redhead in this issue show that to exclude associative learning as a basic mechanism responsible for spatial learning is quite inappropriate. All these results, especially those obtained with strictly spatial tasks, seem inconsistent with O’Keefe and Nadel’s account of true spatial learning or locale learning. Their theory claims that this kind of learning is fundamentally different and develops with total independence from other ways of learning (like classical and instrumental conditioning -taxon learning. In fact, the results reviewed can be explained appealing on to a sophisticated guidance system, like for example the one proposed by Leonard and McNaughton (1990; see also McNaughton and cols, 1996. Such a system would allow that an animal generates new space information: given the distance and address from of A to B and from A to C, being able to infer the distance and the address from B to C, even when C is invisible from B (see Chapuis and Varlet, 1987 -the contribution by McLaren in this issue constitutes a good example of a sophisticated guidance system.

Flat cladding and pellets in the design of an irradiation target

International Nuclear Information System (INIS)

Yorio, Daniel; Denis, Alicia C.; Soba, Alejandro; Beuter, Oscar; Marajofsky, Adolfo

2003-01-01

The design of an enriched uranium irradiation target made of flat pellets and cladding is proposed in order to improve the fission Mo 99 production. The variation range of each one of the parameters is studied and the basic design of the target is given

Quantum mechanics as applied mathematical statistics

International Nuclear Information System (INIS)

Skala, L.; Cizek, J.; Kapsa, V.

2011-01-01

Basic mathematical apparatus of quantum mechanics like the wave function, probability density, probability density current, coordinate and momentum operators, corresponding commutation relation, Schroedinger equation, kinetic energy, uncertainty relations and continuity equation is discussed from the point of view of mathematical statistics. It is shown that the basic structure of quantum mechanics can be understood as generalization of classical mechanics in which the statistical character of results of measurement of the coordinate and momentum is taken into account and the most important general properties of statistical theories are correctly respected.

Introduction to physics mechanics, hydrodynamics thermodynamics

CERN Document Server

Frauenfelder, P

2013-01-01

Introduction of Physics: Mechanics , Hydrodynamics, Thermodynamics covers the principles of matter and its motion through space and time, as well as the related concepts of energy and force. This book is composed of eleven chapters, and begins with an introduction to the basic principles of mechanics, hydrodynamics, and thermodynamics. The subsequent chapters deal with the statics of rigid bodies and the dynamics of particles and rigid bodies. These topics are followed by discussions on elasticity, mechanics of fluids, the basic concept of thermodynamic, kinetic theory, and crystal structure o

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.

Graphite target for the spiral project

International Nuclear Information System (INIS)

Putaux, J.C.; Ducourtieux, M.; Ferro, A.; Foury, P.; Kotfila, L.; Mueller, A.C.; Obert, J.; Pauwels, N.; Potier, J.C.; Proust, J.; Loiselet, M.

1996-01-01

A study of the thermal and physical properties of graphite targets for the SPIRAL project is presented. The main objective is to develop an optimized set-up both mechanically and thermally resistant, presenting good release properties (hot targets with thin slices). The results of irradiation tests concerning the mechanical and thermal resistance of the first prototype of SPIRAL target with conical geometry are presented. The micro-structural properties of the graphite target is also studied, in order to check that the release properties are not deteriorated by the irradiation. Finally, the results concerning the latest pilot target internally heated by an electrical current are shown. (author)

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

Stiffness analysis of spring mechanism for semi automatic gripper motion of tendon driven remote manipulator

International Nuclear Information System (INIS)

Yu, Seung Nam; Lee, Jong Kwang

2012-01-01

Remote handling manipulators are widely used for performing hazardous tasks, and it is essential to ensure the reliable performance of such systems. Toward this end, tendon driven mechanisms are adopted in such systems to reduce the weight of the distal parts of the manipulator while maintaining the handling performance. In this study, several approaches for the design of a gripper system for a tendon driven remote handling system are introduced. Basically, this gripper has an underactuated spring mechanism that is combined with a slave manipulator triggered by a master operator. Based on the requirements under the specified tendon driven mechanism, the connecting position of the spring system on the gripper mechanism and kinematic influence coefficient (KIC) analysis are performed. As a result, a suitable combination of components for the proper design of the target system is presented and verified

Basic characterization of normal multifocal electroretinogram

International Nuclear Information System (INIS)

Fernandez Cherkasova, Lilia; Rojas Rondon, Irene; Castro Perez, Pedro Daniel; Lopez Felipe, Daniel; Santiesteban Freixas, Rosaralis; Mendoza Santiesteban, Carlos E

2008-01-01

A scientific literature review was made on the novel multifocal electroretinogram technique, the involved cell mechanisms and some of the factors modifying its results together with the form of presentation. The basic characteristics of this electrophysiological record obtained from several regions of the retina of normal subjects is important in order to create at a small scale a comparative database to evaluate pathological eye tracing. All this will greatly help in early less invasive electrodiagnosis of localized retinal lesions. (Author)

Electricity demand and basic needs: Empirical evidence from China's households

International Nuclear Information System (INIS)

He, Xiaoping; Reiner, David

2016-01-01

An increasing block tariff (IBT) has been implemented nationwide in the residential sector in China since 2012. However, knowledge about IBT design is still limited, particularly how to determine the electricity volume for the first block of an IBT scheme. Assuming the first block should be set based on some measure of electricity poverty; we attempt to model household electricity demand such that the range of basic needs can be established. We show that in Chinese households there exists a threshold for electricity consumption with respect to income, which could be considered a measure of electricity poverty, and the threshold differs between rural and urban areas. For rural (urban) families, electricity consumption at the level of 7th (5th) income decile households can be considered the threshold for basic needs or a measure of electricity poverty since household electricity demand in rural (urban) areas does not respond to income changes until after 7th (5th) income decile. Accordingly, the first IBT block for some provinces (e.g., Beijing) appears to have been set at a level that is too high. Over time however, given continued rapid growth, the IBT will begin to better reflect actual basic needs. - Highlights: • Basic electricity needs of a household are investigated with survey data. • The Basic electricity needs differ between the rural and urban households. • The first block of the IBTs in China has proven too high and beyond the basic needs. • The initial policy targets of the IBTs in China will be difficult to achieve.

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.

Mathematical physics classical mechanics

CERN Document Server

Knauf, Andreas

2018-01-01

As a limit theory of quantum mechanics, classical dynamics comprises a large variety of phenomena, from computable (integrable) to chaotic (mixing) behavior. This book presents the KAM (Kolmogorov-Arnold-Moser) theory and asymptotic completeness in classical scattering. Including a wealth of fascinating examples in physics, it offers not only an excellent selection of basic topics, but also an introduction to a number of current areas of research in the field of classical mechanics. Thanks to the didactic structure and concise appendices, the presentation is self-contained and requires only knowledge of the basic courses in mathematics. The book addresses the needs of graduate and senior undergraduate students in mathematics and physics, and of researchers interested in approaching classical mechanics from a modern point of view.

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.

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

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 ...

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.

Adventures in Celestial Mechanics

CERN Document Server

Szebehely, Victor G

1998-01-01

A fascinating introduction to the basic principles of orbital mechanics. It has been three hundred years since Isaac Newton first formulated laws to explain the orbits of the Moon and the planets of our solar system. In so doing he laid the groundwork for modern science's understanding of the workings of the cosmos and helped pave the way to the age of space exploration. Adventures in Celestial Mechanics offers students an enjoyable way to become acquainted with the basic principles involved in the motions of natural and human-made bodies in space. Packed with examples in which these principle

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.

The Role of Epigenetic Mechanisms in the Regulation of Gene Expression in the Nervous System.

Science.gov (United States)

Cholewa-Waclaw, Justyna; Bird, Adrian; von Schimmelmann, Melanie; Schaefer, Anne; Yu, Huimei; Song, Hongjun; Madabhushi, Ram; Tsai, Li-Huei

2016-11-09

Neuroepigenetics is a newly emerging field in neurobiology that addresses the epigenetic mechanism of gene expression regulation in various postmitotic neurons, both over time and in response to environmental stimuli. In addition to its fundamental contribution to our understanding of basic neuronal physiology, alterations in these neuroepigenetic mechanisms have been recently linked to numerous neurodevelopmental, psychiatric, and neurodegenerative disorders. This article provides a selective review of the role of DNA and histone modifications in neuronal signal-induced gene expression regulation, plasticity, and survival and how targeting these mechanisms could advance the development of future therapies. In addition, we discuss a recent discovery on how double-strand breaks of genomic DNA mediate the rapid induction of activity-dependent gene expression in neurons. Copyright © 2016 the authors 0270-6474/16/3611427-08$15.00/0.

Drug-induced regulation of target expression

DEFF Research Database (Denmark)

Iskar, Murat; Campillos, Monica; Kuhn, Michael

2010-01-01

Drug perturbations of human cells lead to complex responses upon target binding. One of the known mechanisms is a (positive or negative) feedback loop that adjusts the expression level of the respective target protein. To quantify this mechanism systems-wide in an unbiased way, drug......-induced differential expression of drug target mRNA was examined in three cell lines using the Connectivity Map. To overcome various biases in this valuable resource, we have developed a computational normalization and scoring procedure that is applicable to gene expression recording upon heterogeneous drug treatments....... In 1290 drug-target relations, corresponding to 466 drugs acting on 167 drug targets studied, 8% of the targets are subject to regulation at the mRNA level. We confirmed systematically that in particular G-protein coupled receptors, when serving as known targets, are regulated upon drug treatment. We...

Handbook of compliant mechanisms

CERN Document Server

Howell, Larry L; Olsen, Brian M

2013-01-01

A fully illustrated reference book giving an easy-to-understand introduction to compliant mechanisms A broad compilation of compliant mechanisms to give inspiration and guidance to those interested in using compliant mechanisms in their designs, the Handbook of Compliant Mechanisms includes graphics and descriptions of many compliant mechanisms. It comprises an extensive categorization of devices that can be used to help readers identify compliant mechanisms related to their application. It also provides chapters on the basic background in compliant mechanisms, the categories o

The target laboratory of the Pelletron Accelerator's facilities

Energy Technology Data Exchange (ETDEWEB)

Ueta, Nobuko; Pereira Engel, Wanda Gabriel [Nuclear Physics Department - University of Sao Paulo (Brazil)

2013-05-06

A short report on the activities developed in the Target Laboratory, since 1970, will be presented. Basic target laboratory facilities were provided to produce the necessary nuclear targets as well as the ion beam stripper foils. Vacuum evaporation units, a roller, a press and an analytical balance were installed in the Oscar Sala building. A brief historical report will be presented in commemoration of the 40{sup th} year of the Pelletron Accelerator.

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

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.

Polarized proton and deuteron solid HD targets

International Nuclear Information System (INIS)

Honig, A.

1977-01-01

A decade has now elapsed since HD was proposed as a polarized proton and deuteron target with exceptionally desirable properties. These include a very high free proton proportion, independently polarizable proton and deuteron systems, and a ''frozen-spin'' mode of operation which allows separation of the functions of production and utilization of the highly polarized target. A discussion is given of what can be expected of the polarized HD system right now, without further research. The basic features of solid HD pertinent to its use as a ''frozen-spin'' target are outlined, then a summary is given of the particular experimental results which support the contention that the target will perform successfully, and finally, some feasible operating modes and the expected performances from them are presented

Landscape of Innovation for Cardiovascular Pharmaceuticals: From Basic Science to New Molecular Entities.

Science.gov (United States)

Beierlein, Jennifer M; McNamee, Laura M; Walsh, Michael J; Kaitin, Kenneth I; DiMasi, Joseph A; Ledley, Fred D

2017-07-01

This study examines the complete timelines of translational science for new cardiovascular therapeutics from the initiation of basic research leading to identification of new drug targets through clinical development and US Food and Drug Administration (FDA) approval of new molecular entities (NMEs) based on this research. This work extends previous studies by examining the association between the growth of research on drug targets and approval of NMEs associated with these targets. Drawing on research on innovation in other technology sectors, where technological maturity is an important determinant in the success or failure of new product development, an analytical model was used to characterize the growth of research related to the known targets for all 168 approved cardiovascular therapeutics. Categorizing and mapping the technological maturity of cardiovascular therapeutics reveal that (1) there has been a distinct transition from phenotypic to targeted methods for drug discovery, (2) the durations of clinical and regulatory processes were significantly influenced by changes in FDA practice, and (3) the longest phase of the translational process was the time required for technology to advance from initiation of research to a statistically defined established point of technology maturation (mean, 30.8 years). This work reveals a normative association between metrics of research maturation and approval of new cardiovascular therapeutics and suggests strategies for advancing translational science by accelerating basic and applied research and improving the synchrony between the maturation of this research and drug development initiatives. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Investigation of mechanisms of production of argon, krypton and xenon isotopes formed in heavy targets by protons with an energy ranging from 0.15 to 24 GeV

International Nuclear Information System (INIS)

Sauvageon, Henri

1981-01-01

As experimental results of the investigation of interactions between high-energy protons and nucleus generally lead to the distinction between four types of reaction mechanisms (spallation, fission, fragmentation and isotope production), this research thesis reports the study of this mechanisms by using the so-called 'thick target - thick collector' experiment and by studying the production of various isotopes of rare gases (argon, krypton, xenon). These isotopes are produced by using platinum, gold, bismuth and thorium targets bombarded by protons with an energy ranging from 0.15 to 24 GeV. The author presents the experimental methods (target preparation and irradiation, rare gas analysis system), reports the analysis of thick target - thick-collector experiments (vector-based representation, path determination, path-curve energy, corrections of experimental data, excitation energy of the intermediate nucleus), presents the experimental results, and discusses their interpretation (two-stage model of high energy nuclear reactions, isotopes produced by spallation and by fission, isotopes produced by deep spallation, representations of mechanisms of fragmentation and deep spallation)

Tyrosine kinase inhibitors: Multi-targeted or single-targeted?

Science.gov (United States)

Broekman, Fleur; Giovannetti, Elisa; Peters, Godefridus J

2011-02-10

Since in most tumors multiple signaling pathways are involved, many of the inhibitors in clinical development are designed to affect a wide range of targeted kinases. The most important tyrosine kinase families in the development of tyrosine kinase inhibitors are the ABL, SCR, platelet derived growth factor, vascular endothelial growth factor receptor and epidermal growth factor receptor families. Both multi-kinase inhibitors and single-kinase inhibitors have advantages and disadvantages, which are related to potential resistance mechanisms, pharmacokinetics, selectivity and tumor environment. In different malignancies various tyrosine kinases are mutated or overexpressed and several resistance mechanisms exist. Pharmacokinetics is influenced by interindividual differences and differs for two single targeted inhibitors or between patients treated by the same tyrosine kinase inhibitor. Different tyrosine kinase inhibitors have various mechanisms to achieve selectivity, while differences in gene expression exist between tumor and stromal cells. Considering these aspects, one type of inhibitor can generally not be preferred above the other, but will depend on the specific genetic constitution of the patient and the tumor, allowing personalized therapy. The most effective way of cancer treatment by using tyrosine kinase inhibitors is to consider each patient/tumor individually and to determine the strategy that specifically targets the consequences of altered (epi)genetics of the tumor. This strategy might result in treatment by a single multi kinase inhibitor for one patient, but in treatment by a couple of single kinase inhibitors for other patients.

Recent advances in basic neurosciences and brain disease: from synapses to behavior

Directory of Open Access Journals (Sweden)

Salter Michael W

2006-12-01

Full Text Available Abstract Understanding basic neuronal mechanisms hold the hope for future treatment of brain disease. The 1st international conference on synapse, memory, drug addiction and pain was held in beautiful downtown Toronto, Canada on August 21–23, 2006. Unlike other traditional conferences, this new meeting focused on three major aims: (1 to promote new and cutting edge research in neuroscience; (2 to encourage international information exchange and scientific collaborations; and (3 to provide a platform for active scientists to discuss new findings. Up to 64 investigators presented their recent discoveries, from basic synaptic mechanisms to genes related to human brain disease. This meeting was in part sponsored by Molecular Pain, together with University of Toronto (Faculty of Medicine, Department of Physiology as well as Center for the Study of Pain. Our goal for this meeting is to promote future active scientific collaborations and improve human health through fundamental basic neuroscience researches. The second international meeting on Neurons and Brain Disease will be held in Toronto (August 29–31, 2007.

Search of unified theory of basic types of elementary particle interactions

International Nuclear Information System (INIS)

Anselm, A.

1981-01-01

Four types of forces are described (strong, weak, electromagnetic and gravitational) mediating the basic interactions of quarks and leptons, and attempts are reported of forming a unified theory of all basic interactions. The concepts are discussed, such as the theory symmetry (eg., invariance in relation to the Lorentz transformations) and isotopic symmetry (based on the interchangeability of particles in a given isotopic multiplet). Described are the gauge character of electromagnetic and gravitational interactions, the violation of the gauge symmetry and the mechanism of particle confinement. (H.S.)

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)

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.

Are ovarian cancer stem cells the target for innovative immunotherapy?

Directory of Open Access Journals (Sweden)

Wang L

2018-05-01

Full Text Available Liang Wang, Tianmin Xu, Manhua Cui Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin, People’s Republic of China Abstract: Cancer stem cells (CSCs, a subpopulation of cancer cells with the ability of self-renewal and differentiation, are believed to be responsible for tumor generation, progression, metastasis, and relapse. Ovarian cancer, the most malignant gynecological cancer, has consistent pathology behavior with CSC model, which suggests that therapies based on ovarian cancer stem cells (OCSCs can gain a more successful prognosis. Much evidence has proved that epigenetic mechanism played an important role in tumor formation and sustainment. Since CSCs are generally resistant to conventional therapies (chemotherapy and radiotherapy, immunotherapy is a more effective method that has been implemented in the clinic. Chimeric antigen receptor (CAR- T cell, an adoptive cellular immunotherapy, which results in apparent elimination of tumor in both hematologic and solid cancers, could be used for ovarian cancer. This review covers the basic conception of CSCs and OCSCs, the implication of epigenetic mechanism underlying cancer evolution considering CSC model, the immunotherapies reported for ovarian cancer targeting OCSCs currently, and the relationship between immune system and hierarchy cancer organized by CSCs. Particularly, the promising prospects and potential pitfalls of targeting OCSC surface markers to design CAR-T cellular immunotherapy are discussed here. Keywords: cancer stem cells, ovarian cancer, epigenetics, tumor cell surface marker, immunotherapy, CAR

The Newtonian form of wave mechanics

International Nuclear Information System (INIS)

Kapuscik, E.

1984-01-01

Following the general principles of both Newton's mechanics and quantum mechanics a new formulation of wave mechanics is proposed. The new basic equations do not contain physical parameters and admit a different interpretation of the Planck constant. (author)

Mechanisms of sintering

International Nuclear Information System (INIS)

Mohan, Ashok; Soni, N.C.; Moorthy, V.K.

1980-01-01

The basic mechanisms by which the material moves during sintering have not only held a strange fascination but are also very important in determining the properties of the end product. Kuczynski's exponent method has been subsequently refined by several schools to make it increasingly reliable. There is now a fairly good understanding of mechanisms in some of the materials. However in others the issue is complicated by their basic nature. The problems of ambiguity in criterion and that of more than one mechanism being simultaneously operative have been tackled with dexterity by Ashby for drawing sintering mechanism diagrams. The method has been modified to give Relative Contribution Diagrams (RCD). These yield additional information and have been used for analysis. The main criticism against this is that it uses a very large number of rate equations and material properties, which can communicate their inaccuracies to the diagram. A case study of UO 2 was undertaken and it has been shown quantitatively that inaccuracies in a smaller number of properties only affect the diagrams to any significant extent. (auth.)

Development of IFE target systems on the NIF

International Nuclear Information System (INIS)

Schultz, K.R.; Fagaly, R.L.; Bernat, T.; Meier, W.; Petzoldt, R.; Foreman, L.

1995-01-01

The Target Systems session of the Workshop on NIF Experiments for IFE developed a list of critical issues for inertial fusion energy (IFE) target systems, and considered the potential of the National Ignition Facility (NIF) to help in the resolution of these issues and in the development of IFE target systems. This paper describes the IFE Target System issues, categorized into target fabrication issues and target transport issues, describes potential NIF IFE target systems experiments, considers the impact of these experiments on the NIF and discusses the development required before these experiments could be done. Most target systems issues must be resolved by development in the laboratory, not in the NIF, and some must be resolved before the NIF can be successful. However, experiments done in the NIF could play a valuable role in developing target systems for IFE. These experiments should have modest impact on the basic design of the NIF, but could require several hundred dedicated, high yield shots

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…

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.

Modern concepts for basic radiobiological factors characterizing tumor tissue radiosensitivity

International Nuclear Information System (INIS)

Gocheva, L.; Sergieva, K.

2002-01-01

Traditionally radiotherapy is prescribed at doses consistent with the expected therapeutic response and tolerance of tumor and normal tissues without consideration to individual differences in radiosensitivity. However, the basic radiobiological knowledge and clinical experience along this line point to significant variations in the observed therapeutic results. It has been established that cells and tissues under experimental and clinical conditions manifest a wide spectrum of individual radiosensitivity. The aim of this survey is to outline the current concepts for the basic radiobiological factors influencing tumor radiosensitivity. A thorough discussion is done of the essence, mechanisms of action, methods of determination and measurement, and effect on the prognosis in patients with malignant diseases of a number of radiobiological factors, such as: tumor-cell proliferation, apoptosis, tumor hypoxia and neovascularization. Although the knowledge of the mechanisms of radiosensitivity is constantly expanding, its clinical implementation is still rather limited. The true role of radiosensitivity in predicting the therapeutic response should be more accurately defined. (authors)

The Role of Malware in Reported Cyber Espionage: A Review of the Impact and Mechanism

Directory of Open Access Journals (Sweden)

Gaute Wangen

2015-05-01

Full Text Available The recent emergence of the targeted use of malware in cyber espionage versus industry requires a systematic review for better understanding of its impact and mechanism. This paper proposes a basic taxonomy to document major cyber espionage incidents, describing and comparing their impacts (geographic or political targets, origins and motivations and their mechanisms (dropper, propagation, types of operating systems and infection rates. This taxonomy provides information on recent cyber espionage attacks that can aid in defense against cyber espionage by providing both scholars and experts a solid foundation of knowledge about the topic. The classification also provides a systematic way to document known and future attacks to facilitate research activities. Geopolitical and international relations researchers can focus on the impacts, and malware and security experts can focus on the mechanisms. We identify several dominant patterns (e.g., the prevalent use of remote access Trojan and social engineering. This article concludes that the research and professional community should collaborate to build an open data set to facilitate the geopolitical and/or technical analysis and synthesis of the role of malware in cyber espionage.

Basic natural circulation characteristics of SBWR

International Nuclear Information System (INIS)

Kuran, S.; Soekmen, C. N.

2001-01-01

Natural circulation is an important passive heat removal mechanism for both existing and next generation light water reactors. Simplified Boiling Water Reactor (SBWR) is one of the advanced light water reactors that rely on natural circulation for normal as well as emergency core cooling. In this study, basic natural circulation characteristics of this reactor are examined on a flow loop that simulates the operation of SBWR. On this model, effect of system operating parameters on the steady state natural circulation characteristics inside the loop is studied via solving the transcendental equation for loop flow rate

The priming of basic combinatory responses in MEG.

Science.gov (United States)

Blanco-Elorrieta, Esti; Ferreira, Victor S; Del Prato, Paul; Pylkkänen, Liina

2018-01-01

Priming has been a powerful tool for the study of human memory and especially the memory representations relevant for language. However, although it is well established that lexical access can be primed, we do not know exactly what types of computations can be primed above the word level. This work took a neurobiological approach and assessed the ways in which the complex representation of a minimal combinatory phrase, such as red boat, can be primed, as evidenced by the spatiotemporal profiles of magnetoencephalography (MEG) signals. Specifically, we built upon recent progress on the neural signatures of phrasal composition and tested whether the brain activities implicated for the basic combination of two words could be primed. In two experiments, MEG was recorded during a picture naming task where the prime trials were designed to replicate previously reported combinatory effects and the target trials to test whether those combinatory effects could be primed. The manipulation of the primes was successful in eliciting larger activity for adjective-noun combinations than single nouns in left anterior temporal and ventromedial prefrontal cortices, replicating prior MEG studies on parallel contrasts. Priming of similarly timed activity was observed during target trials in anterior temporal cortex, but only when the prime and target shared an adjective. No priming in temporal cortex was observed for single word repetition and two control tasks showed that the priming effect was not elicited if the prime pictures were simply viewed but not named. In sum, this work provides evidence that very basic combinatory operations can be primed, with the necessity for some lexical overlap between prime and target suggesting combinatory conceptual, as opposed to syntactic processing. Both our combinatory and priming effects were early, onsetting between 100 and 150ms after picture onset and thus are likely to reflect the very earliest planning stages of a combinatory message

Targeted Radionuclide Therapy

Directory of Open Access Journals (Sweden)

David Cheng

2011-10-01

Full Text Available Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. Several different radiopharmaceuticals are currently being used by various administration routes and targeting mechanisms. This article aims to briefly review the current status of targeted radiotherapy as well as to outline the advantages and disadvantages of radionuclides used for this purpose.

Targeted Radionuclide Therapy

Energy Technology Data Exchange (ETDEWEB)

Ersahin, Devrim, E-mail: devrimersahin@yahoo.com; Doddamane, Indukala; Cheng, David [Department of Diagnostic Radiology, School of Medicine, Yale University, 333 Cedar St., New Haven, CT 06520 (United States)

2011-10-11

Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. Several different radiopharmaceuticals are currently being used by various administration routes and targeting mechanisms. This article aims to briefly review the current status of targeted radiotherapy as well as to outline the advantages and disadvantages of radionuclides used for this purpose.

Targeted Radionuclide Therapy

International Nuclear Information System (INIS)

Ersahin, Devrim; Doddamane, Indukala; Cheng, David

2011-01-01

Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. Several different radiopharmaceuticals are currently being used by various administration routes and targeting mechanisms. This article aims to briefly review the current status of targeted radiotherapy as well as to outline the advantages and disadvantages of radionuclides used for this purpose

Producing the target seed: Seed collection, treatment, and storage

Science.gov (United States)

Robert P. Karrfalt

2011-01-01

The role of high quality seeds in producing target seedlings is reviewed. Basic seed handling and upgrading techniques are summarized. Current advances in seed science and technology as well as those on the horizon are discussed.

Basic Deformation Parameters of Solid Clay Bricks and Small Masonry Walls

Directory of Open Access Journals (Sweden)

P. Bouška

2000-01-01

Full Text Available The basic mechanical properties of clay brick masonry and its components were experimentally investigated in the laboratories of the Klokner Institute. The test specimens of masonry materials and the relevant mechanical properties have been identified in solid clay bricks and cement-lime mortar. The aim of the research activity was to study both the deformability of the prevailing type of clay masonry in the existing buildings, i.e. the masonry made from the solid clay units and the lime-cement mortar, and the most important mechanical properties of masonry components.

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.

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

Design of mechanical joints

CERN Document Server

Blake, Alexander

2018-01-01

A cornerstone publication that covers the basic principles and practical considerations of design methodology for joints held by rivets, bolts, weld seams, and adhesive materials, Design of Mechanical Joints gives engineers the practical results and formulas they need for the preliminary design of mechanical joints, combining the essential topics of joint mechanics...strength of materials...and fracture control to provide a complete treatment of problems pertinent to the field of mechanical connections.

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.

Targeted In-service Inspections Using Risk Insights

International Nuclear Information System (INIS)

Kulat, S.; Montgomery, B.; Robin Graybeal, M.

2012-01-01

This paper includes a discussion of the historical background and rationale for development of a targeted In-service Inspection (ISI) program using risk insights, known as Risk-Informed In-service Inspection (RI-ISI). RI-ISI programs are optimized inspection programs which target specific welds for inspection based upon potential degradation mechanisms and consequences of failure. Inspections are performed on those welds that are the highest contributors to plant risk. Additionally the inspections are tailored to detect the specific postulated degradation mechanisms. As a result, the numbers of inspections are reduced along with the associated cost and radiation exposure, while maintaining or improving the level of quality and safety. Provided in this paper are the basic principles of RI-ISI program development, and a summary of the impact of the implementation of such programs. For example, implementation of a Risk-Informed In-service Inspection program results in a reduction of both cost and radiation exposure. Cost savings are estimated at between USD 1,000,000 and USD 2,300,000 per unit per ten year interval for a Class 1 and2 RI-ISI application. Cost savings are estimated based on average cost per weld of USD 7600 for examination, including the following activities: erection and removal of scaffolding, removal and replacement of insulation, removal and replacement of interferences, weld preparation, examination, documentation, craft support. Reduction in radiation exposure is estimated at 75% to 90% for a Class 1 and2 RI-ISI application. Reduction in radiation exposure is due to the following factors: number of welds selected for examination decreases by 60% to 75%, surface examinations essentially eliminated, within a given risk category, welds can be selected for examination based on additional factors such as the minimization of radiation exposure.(author).

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.

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.

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

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)

Statistical mechanics

CERN Document Server

Schwabl, Franz

2006-01-01

The completely revised new edition of the classical book on Statistical Mechanics covers the basic concepts of equilibrium and non-equilibrium statistical physics. In addition to a deductive approach to equilibrium statistics and thermodynamics based on a single hypothesis - the form of the microcanonical density matrix - this book treats the most important elements of non-equilibrium phenomena. Intermediate calculations are presented in complete detail. Problems at the end of each chapter help students to consolidate their understanding of the material. Beyond the fundamentals, this text demonstrates the breadth of the field and its great variety of applications. Modern areas such as renormalization group theory, percolation, stochastic equations of motion and their applications to critical dynamics, kinetic theories, as well as fundamental considerations of irreversibility, are discussed. The text will be useful for advanced students of physics and other natural sciences; a basic knowledge of quantum mechan...

The generation of intense heat fluxes by electron bombardment to evaluate the use of swirl flow in the cooling of accelerator targets

International Nuclear Information System (INIS)

Genis, G.J.

1985-11-01

The thermal performance of isotope production targets for accelerators has been shown to be the limiting factor with regard to the cost of isotopes and the specific activity achievable. To allow the investigation of basic aspects of target cooling and the evaluation of certain target concepts off-line from accelerators, an electron bombardment system, including a radial electron accelerator (REA) in a diode configuration, was developed as heat source. Methods were developed to characterise the performance of the REA to supply a homogeneous heat flux to an axial target by which a technique for the construction of thermocouple placement holes in the body of the target can be evaluated from the measured temperatures. Having identified high velocity swirl flow as the most suitable technique to enhance the convective heat transfer in targets, experiments were conducted to determine the heat-transfer coefficient at high heat fluxes to high velocity swirl flow. The heat-transfer results substantiate the advantages of swirl flow for target cooling. Different correlations obtained indicate the importance of using the film properties instead of the bulk coolant properties in correlations and identify centrifugal convection as one of the most important heat transfer mechanisms in swirl flow

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.

Continuum mechanics of single-substance bodies

CERN Document Server

Eringen, A Cemal

1975-01-01

Continuum Physics, Volume II: Continuum Mechanics of Single-Substance Bodies discusses the continuum mechanics of bodies constituted by a single substance, providing a thorough and precise presentation of exact theories that have evolved during the past years. This book consists of three parts-basic principles, constitutive equations for simple materials, and methods of solution. Part I of this publication is devoted to a discussion of basic principles irrespective of material geometry and constitution that are valid for all kinds of substances, including composites. The geometrical notions, k

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.

What Are the Relative Macroeconomic Merits and Environmental Impacts of Direct Job Creation and Basic Income Guarantees?

Directory of Open Access Journals (Sweden)

Pavlina R. Tcherneva

2017-06-01

Full Text Available There is a body of literature that favors universal and unconditional public assurance policies over those that are targeted and means-tested. Two such proposals—the basic income proposal and job guarantees—are discussed here. The paper evaluates the impact of each program on macroeconomic stability, arguing that direct job creation has inherent stabilization features that are lacking in the basic income proposal. A discussion of modern finance and labor market dynamics renders the latter proposal inherently inflationary, and potentially stagflationary. After studying the macroeconomic viability of each program, the paper elaborates on their environmental merits. It is argued that the “green” consequences of the basic income proposal are likely to emerge, not from its modus operandi, but from the tax schemes that have been advanced for its financing. By contrast, the job guarantee proposal can serve as an institutional vehicle for achieving various environmental goals by explicitly targeting environmental rehabilitation, conservation, and sustainability. Finally, in the hope of consensus building, the paper advances a joint policy proposal that is economically viable, environmentally friendly, and socially just.

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.

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

Endoradiotherapy in cancer treatment--basic concepts and future trends.

Science.gov (United States)

Zoller, Frederic; Eisenhut, Michael; Haberkorn, Uwe; Mier, Walter

2009-12-25

Endoradiotherapy represents an alternative therapeutic method in cancer treatment with advantageous features compared to chemotherapy and radiation therapy. Intelligent dose delivery concepts using small drugs, peptides or antibodies as radionuclide carriers enable the verification of a selective accumulation in the tumour lesion and to reduce radiation toxicity for the peripheral organs. The development of endoradiotherapeutic agents, especially chelator-conjugated biomolecules, for example ibritumomab tiuxetan or DOTATOC, gains importance due to the stable complexation of versatile radiometals, such as (90)Y or (177)Lu. The rational design of novel target binding sides and their grafting into a drug scaffold is a highly promising strategy, which may promote further implication in endoradiotherapy. This review highlights the basic concepts of endoradiotherapy and discusses the potential of targeted therapy and the properties of energy-rich particles emitted by radionuclides for tumour therapy.

Exploding pusher targets for the SHIVA laser system

International Nuclear Information System (INIS)

Rosen, M.D.; Larsen, J.T.; Nuckolls, J.H.

1977-01-01

The first targets for the 20 TW SHIVA laser system were designed. They are simple glass micro-balloons, approximately 300 μm in diameter and 2 μm thick, filled with D-T gas. Using LASNEX, whose model physics was utilized successfully for ARGUS targets, we optimize for both gain and yield. The target behaves as an exploding pusher. Different simple analytic models for the physics of this mode are presented, and are tested by comparing their scaling predictions, at constant absorbed power, with those demonstrated by LASNEX. Emphasis is placed on successful prediction of the basic quantities of peak ion temperature and compression, rather than neutron yield or n tau

Wave mechanics applied to semiconductor heterostructures

International Nuclear Information System (INIS)

Bastard, G.

1990-01-01

This book examines the basic electronic and optical properties of two dimensional semiconductor heterostructures based on III-V and II-VI compounds. The book explores various consequences of one-dimensional size-quantization on the most basic physical properties of heterolayers. Beginning with basic quantum mechanical properties of idealized quantum wells and superlattices, the book discusses the occurrence of bound states when the heterostructure is imperfect or when it is shone with near bandgap light

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.

Mechanical vaccum pumps

CERN Document Server

Chew, A D

2007-01-01

This presentation gives an overview of the technology of contemporary primary and secondary mechanical vacuum pumps. For reference a brief history of vacuum and a summary of important and basic vacuum concepts are first presented.

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

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.

The dynamic stability of OPEC's oil price mechanism

International Nuclear Information System (INIS)

Hammoudeh, S.; Madan, V.

1992-01-01

This paper examines OPEC's long-lived mechanism which targets the oil price and adjusts the quality ceiling to meet the target. The stability of this controversial mechanism is compared to that of two alternatives: one requires quantity control without any price targeting and the other is a synthesis of quantity control and the OPEC mechanisms. All three mechanisms passed the stability test and the two alternatives give rise to some interesting policy implications. Practicality considerations which involve the availability of specific information make OPEC's mechanism the most appropriate in terms of achieved targeted revenues. The paper also offers a convergence strategy that speeds up the achievement of targeted revenues under OPEC's current mechanism. (author)

Mechanical Material Engineering

International Nuclear Information System (INIS)

Kim, Mun Il

1993-01-01

This book introduced mechanical material with introduction, basic problems about metal ingredient of machine of metal and alloy, property of metal material mechanical metal material such as categorization of metal material and high tensile structure steel, mechanic design and steel material with three important points on using of steel materials, selection and directions machine structural steel, selection and directions of steel for tool, selection and instruction of special steel like stainless steel and spring steel, nonferrous metal materials and plastic.

Fusion-relevant basic radiation effects: theory and experiment

International Nuclear Information System (INIS)

Mansur, L.K.; Coghlan, W.A.; Farrell, K.; Horton, L.L.; Lee, E.H.; Lewis, M.B.; Packan, N.H.

1983-01-01

A summary is given of results of the basic radiation effects program at Oak Ridge National Laboratory, which are relevant to fusion reactor materials applications. The basic radiation effects program at ORNL is a large effort with the dual objectives of understanding the atomic and microstructural defect mechanisms underlying radiation effects and of determining principles for the design of radiation resistant materials. A strength of this effort is the parallel and integrated experimental and theoretical approaches in each major research area. The experimental effort is active in electron microscopy, ion irradiations and ion-beam techniques, neutron irradiations, surface analysis and in other areas. The theoretical effort is active in developing the theory of radiation effects for a broad range of phenomena and in applying it to the design and interpretation of experiments and to alloy design

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....

Basic dynamics at a multiple resonance

International Nuclear Information System (INIS)

Ferraz-Mello, S.; Yokoyama, T.

The problem of multiple resonance is dealt with as it occurs in Celestial Mechanics and in non-linear Mechanics. In perturbation theory small divisors occur as a consequence of the fact that the flows in the phase space of the real system and the flows in the phase space of the so-called undisturbed system are not homeomorphic at all. Whatever the perturbation technique we adopt, the first step is to correct the topology of the undisturbed flows. It is shown that at a multiple resonance we are led to dynamical systems that are generally non-integrable. The basic representatives of these systems are the n-pendulums theta sup(:) sub(k) = σ sub(j)A sub(jk) sin theta sub(j). Multiple resonances are classified as syndetic or asyndetic following the eigenvalues of a quadratic form. Some degenerate cases are also presented. (Author) [pt

Mars 2020 Rover SHERLOC Calibration Target

Science.gov (United States)

Graff, Trevor; Fries, Marc; Burton, Aaron; Ross, Amy; Larson, Kristine; Garrison, Dan; Calaway, Mike; Tran, Vinh; Bhartia, Roh; Beegle, Luther

2016-01-01

The Scanning Habitable Environments with Raman & Luminescence for Organics & Chemicals (SHERLOC) instrument is a deep ultraviolet (UV) Raman Fluorescence instrument selected as part of the Mars 2020 rover instrument suite. SHERLOC will be mounted on the rover arm and its primary role is to identify carbonaceous species in martian samples. The SHERLOC instrument requires a calibration target which is being designed and fabricated at JSC as part of our continued science participation in Mars robotic missions. The SHERLOC calibration target will address a wide range of NASA goals to include basic science of interest to both the Science Mission Directorate and Human Exploration and Operations Mission Directorate.

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

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

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

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.

Geographical and temporal distribution of basic research experiments in homeopathy.

Science.gov (United States)

Clausen, Jürgen; van Wijk, Roeland; Albrecht, Henning

2014-07-01

The database HomBRex (Homeopathy Basic Research experiments) was established in 2002 to provide an overview of the basic research already done on homeopathy (http://www.carstens-stiftung.de/hombrex). By this means, it facilitates the exploration of the Similia Principle and the working mechanism of homeopathy. Since 2002, the total number of experiments listed has almost doubled. The current review reports the history of basic research in homeopathy as evidenced by publication dates and origin of publications. In July 2013, the database held 1868 entries. Most publications were reported from France (n = 267), followed by Germany (n = 246) and India (n = 237). In the last ten years, the number of publications from Brazil dramatically increased from n = 13 (before 2004) to n = 164 (compared to n = 251 published in France before 2004, and n = 16 between 2004 and 2013). The oldest database entry was from Germany (1832). Copyright © 2014 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

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.

Research and development of the industrial basic technologies of the next generation, 'composite materials (metal-based)'. Evaluation of the first phase research and development; Jisedai sangyo kiban gijutsu kenkyu kaihatsu 'fukugo zairyo (kinzokukei)'. Daiikki kenkyu kaihatsu hyoka

Energy Technology Data Exchange (ETDEWEB)

NONE

1983-03-31

The results of the first phase research and development project for developing the metal-based composite materials as the basic technologies of the next generation are evaluated. For development of highly functional materials, the efforts are directed to understanding the basic characteristics regarding wettability and reactivity of PAN-based carbon fibers and PCS-based silicon carbide fibers with metals, in which aluminum-based matrices are considered; preliminary tests for various composting methods; and development of wire preforms as the intermediate materials. Bright prospects have been obtained for improving problems involved in each technique. For development of molding/processing techniques, basic researches have been conducted for hot pressing/rolling, extrusion/withdrawal, powder molding and melt molding, using various reinforcing fibers. Bright prospects have been also obtained for combinations of adequate molding processes for individual materials. For development of design techniques, the basic data regarding mechanical characteristics of FRMs, both domestic and foreign, are collected, and analyzed by the trace tests with specimens, to set up the targets for FRM function improvements, viewed from the designs. (NEDO)

TISCON, a BASIC computer program for the calculation of the biodistribution of radionuclide-labelled drugs in rats and mice

International Nuclear Information System (INIS)

Maddalena, D.J.

1983-09-01

Animal biodistribution studies on radionuclide-labelled drugs are labour-intensive and time-consuming. A method for rapidly carrying out these studies on rats and mice is presented. An interactive computer program, written in BASIC, is used to calculate parameters of interest, such as per cent injected dose (%ID),%ID per gram and target to non-target ratios

Standardized Curriculum for Automotive Mechanics.

Science.gov (United States)

Mississippi State Dept. of Education, Jackson. Office of Vocational, Technical and Adult Education.

Standardized curricula are provided for two courses for the secondary vocational education program in Mississippi: automotive mechanics I and II. The six units in automotive mechanics I are as follows: orientation and safety; tools, equipment, and manuals; measurement; automotive engines; basic electrical systems; and fuel systems. Automotive…

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

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

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 ...

From basic survival analytic theory to a non-standard application

CERN Document Server

Zimmermann, Georg

2017-01-01

Georg Zimmermann provides a mathematically rigorous treatment of basic survival analytic methods. His emphasis is also placed on various questions and problems, especially with regard to life expectancy calculations arising from a particular real-life dataset on patients with epilepsy. The author shows both the step-by-step analyses of that dataset and the theory the analyses are based on. He demonstrates that one may face serious and sometimes unexpected problems, even when conducting very basic analyses. Moreover, the reader learns that a practically relevant research question may look rather simple at first sight. Nevertheless, compared to standard textbooks, a more detailed account of the theory underlying life expectancy calculations is needed in order to provide a mathematically rigorous framework. Contents Regression Models for Survival Data Model Checking Procedures Life Expectancy Target Groups Researchers, lecturers, and students in the fields of mathematics and statistics Academics and experts work...

Basic and Applied Research at the Los Alamos Neutron Science Center

International Nuclear Information System (INIS)

Lisowski, P.W.

2003-01-01

The Los Alamos Neutron Science Center, or LANSCE, is an accelerator-based national user facility for research in basic and applied science. At present LANSCE has two experimental areas primarily using neutrons generated by 800-MeV protons striking tungsten target systems. A third area uses the proton beam for radiography. This paper describes the three LANSCE experimental areas, gives highlights of the past operating period, and discusses plans for the future

Tradeoffs between hydraulic and mechanical stress responses of mature Norway spruce trunk wood.

Science.gov (United States)

Rosner, Sabine; Klein, Andrea; Müller, Ulrich; Karlsson, Bo

2008-08-01

We tested the effects of growth characteristics and basic density on hydraulic and mechanical properties of mature Norway spruce (Picea abies (L.) Karst.) wood from six 24-year-old clones, grown on two sites in southern Sweden differing in water availability. Hydraulic parameters assessed were specific hydraulic conductivity at full saturation (ks100) and vulnerability to cavitation (Psi50), mechanical parameters included bending strength (sigma b), modulus of elasticity (MOE), compression strength (sigma a) and Young's modulus (E). Basic density, diameter at breast height, tree height, and hydraulic and mechanical parameters varied considerably among clones. Clonal means of hydraulic and mechanical properties were strongly related to basic density and to growth parameters across sites, especially to diameter at breast height. Compared with stem wood of slower growing clones, stem wood of rapidly growing clones had significantly lower basic density, lower sigma b, MOE, sigma a and E, was more vulnerable to cavitation, but had higher ks100. Basic density was negatively correlated to Psi50 and ks100. We therefore found a tradeoff between Psi50 and ks100. Clones with high basic density had significantly lower hydraulic vulnerability, but also lower hydraulic conductivity at full saturation and thus less rapid growth than clones with low basic density. This tradeoff involved a negative relationship between Psi50 and sigma b as well as MOE, and between ks100 and sigma b, MOE and sigma a. Basic density and Psi50 showed no site-specific differences, but tree height, diameter at breast height, ks100 and mechanical strength and stiffness were significantly lower at the drier site. Basic density had no influence on the site-dependent differences in hydraulic and mechanical properties, but was strongly negatively related to diameter at breast height. Selecting for growth may thus lead not only to a reduction in mechanical strength and stiffness but also to a reduction in

A cryogenic infrared calibration target

Science.gov (United States)

Wollack, E. J.; Kinzer, R. E.; Rinehart, S. A.

2014-04-01

A compact cryogenic calibration target is presented that has a peak diffuse reflectance, R ⩽ 0.003, from 800 to 4800 cm-1 (12 - 2 μm). Upon expanding the spectral range under consideration to 400-10 000 cm-1 (25 - 1 μm) the observed performance gracefully degrades to R ⩽ 0.02 at the band edges. In the implementation described, a high-thermal-conductivity metallic substrate is textured with a pyramidal tiling and subsequently coated with a thin lossy dielectric coating that enables high absorption and thermal uniformity across the target. The resulting target assembly is lightweight, has a low-geometric profile, and has survived repeated thermal cycling from room temperature to ˜4 K. Basic design considerations, governing equations, and test data for realizing the structure described are provided. The optical properties of selected absorptive materials—Acktar Fractal Black, Aeroglaze Z306, and Stycast 2850 FT epoxy loaded with stainless steel powder—are characterized and presented.

Mechanics and Physics of Precise Vacuum Mechanisms

CERN Document Server

Deulin, E. A; Panfilov, Yu V; Nevshupa, R. A

2010-01-01

In this book the Russian expertise in the field of the design of precise vacuum mechanics is summarized. A wide range of physical applications of mechanism design in electronic, optical-electronic, chemical, and aerospace industries is presented in a comprehensible way. Topics treated include the method of microparticles flow regulation and its determination in vacuum equipment and mechanisms of electronics; precise mechanisms of nanoscale precision based on magnetic and electric rheology; precise harmonic rotary and not-coaxial nut-screw linear motion vacuum feedthroughs with technical parameters considered the best in the world; elastically deformed vacuum motion feedthroughs without friction couples usage; the computer system of vacuum mechanisms failure predicting. This English edition incorporates a number of features which should improve its usefulness as a textbook without changing the basic organization or the general philosophy of presentation of the subject matter of the original Russian work. Exper...

Soil Mechanics

OpenAIRE

Verruijt, A.

2010-01-01

This book is the text for the introductory course of Soil Mechanics in the Department of Civil Engineering of the Delft University of Technology, as I have given from 1980 until my retirement in 2002. It contains an introduction into the major principles and methods of soil mechanics, such as the analysis of stresses, deformations, and stability. The most important methods of determining soil parameters, in the laboratory and in situ, are also described. Some basic principles of applied mecha...

The Method of Multiple Spatial Planning Basic Map

Science.gov (United States)

Zhang, C.; Fang, C.

2018-04-01

The "Provincial Space Plan Pilot Program" issued in December 2016 pointed out that the existing space management and control information management platforms of various departments were integrated, and a spatial planning information management platform was established to integrate basic data, target indicators, space coordinates, and technical specifications. The planning and preparation will provide supportive decision support, digital monitoring and evaluation of the implementation of the plan, implementation of various types of investment projects and space management and control departments involved in military construction projects in parallel to approve and approve, and improve the efficiency of administrative approval. The space planning system should be set up to delimit the control limits for the development of production, life and ecological space, and the control of use is implemented. On the one hand, it is necessary to clarify the functional orientation between various kinds of planning space. On the other hand, it is necessary to achieve "multi-compliance" of various space planning. Multiple spatial planning intergration need unified and standard basic map(geographic database and technical specificaton) to division of urban, agricultural, ecological three types of space and provide technical support for the refinement of the space control zoning for the relevant planning. The article analysis the main space datum, the land use classification standards, base map planning, planning basic platform main technical problems. Based on the geographic conditions, the results of the census preparation of spatial planning map, and Heilongjiang, Hainan many rules combined with a pilot application.

Basics of Antibody Phage Display Technology.

Science.gov (United States)

Ledsgaard, Line; Kilstrup, Mogens; Karatt-Vellatt, Aneesh; McCafferty, John; Laustsen, Andreas H

2018-06-09

Antibody discovery has become increasingly important in almost all areas of modern medicine. Different antibody discovery approaches exist, but one that has gained increasing interest in the field of toxinology and antivenom research is phage display technology. In this review, the lifecycle of the M13 phage and the basics of phage display technology are presented together with important factors influencing the success rates of phage display experiments. Moreover, the pros and cons of different antigen display methods and the use of naïve versus immunized phage display antibody libraries is discussed, and selected examples from the field of antivenom research are highlighted. This review thus provides in-depth knowledge on the principles and use of phage display technology with a special focus on discovery of antibodies that target animal toxins.

Thin film production of ceramic high-Tc-superconductors (targets)

International Nuclear Information System (INIS)

1992-01-01

Presently high-quality thin superconducting films having high T c 's may prepared by the sputtering technique. However, a large-area coating is required for an industrial application. One requirement is the availability of sputter targets with controlled and reproducible properties. By means of basic experiments with respect to powder processing, shaping and the densification process superconducting targets up to 200 mm in diameter were prepared in the Y-Ba-Cu-O- system. Additionally, targets from other systems with different geometries (e.g. ring targets) were prepared. These targets were submitted to the project partners as well as to other institutes and companies. During the course of this project the foundations for an industrial-type coating of large-area substrates were elaborated. (orig.). 9 refs., 5 tabs., 15 figs [de

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

Single-Molecule View of Small RNA-Guided Target Search and Recognition.

Science.gov (United States)

Globyte, Viktorija; Kim, Sung Hyun; Joo, Chirlmin

2018-05-20

Most everyday processes in life involve a necessity for an entity to locate its target. On a cellular level, many proteins have to find their target to perform their function. From gene-expression regulation to DNA repair to host defense, numerous nucleic acid-interacting proteins use distinct target search mechanisms. Several proteins achieve that with the help of short RNA strands known as guides. This review focuses on single-molecule advances studying the target search and recognition mechanism of Argonaute and CRISPR (clustered regularly interspaced short palindromic repeats) systems. We discuss different steps involved in search and recognition, from the initial complex prearrangement into the target-search competent state to the final proofreading steps. We focus on target search mechanisms that range from weak interactions, to one- and three-dimensional diffusion, to conformational proofreading. We compare the mechanisms of Argonaute and CRISPR with a well-studied target search system, RecA.

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...

Mechanics of Failure Mechanisms in Structures

CERN Document Server

Carlson, R L; Craig, J I

2012-01-01

This book focuses on the mechanisms and underlying mechanics of failure in various classes of materials such as metallic, ceramic, polymeric, composite and bio-material.  Topics include tensile and compressive fracture, crack initiation and growth, fatigue and creep rupture in metallic materials, matrix cracking and delamination and environmental degradation in polymeric composites, failure of bio-materials such as prosthetic heart valves and prosthetic hip joints, failure of ceramics and ceramic matrix composites, failure of metallic matrix composites, static and dynamic buckling failure, dynamic excitations and creep buckling failure in structural systems. Chapters are devoted to failure mechanisms that are characteristic of each of the materials.  The work also provides the basic elements of fracture mechanics and studies in detail several niche topics such as the effects of toughness gradients, variable amplitude loading effects in fatigue, small fatigue cracks, and creep induced brittleness. Furthe...

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).

Disaster Relief and Emergency Medical Services Project (DREAMS TM): Clinical and Basic Science Projects

National Research Council Canada - National Science Library

Casscells, Ward

1999-01-01

DREAMS clinical and basic science projects complement the digital EMS effort by investigating the mechanisms of tissue injury in order to minimize the mortality and mortality of trauma and "natural...

Cell targeting peptides as smart ligands for targeting of therapeutic or diagnostic agents: a systematic review.

Science.gov (United States)

Mousavizadeh, Ali; Jabbari, Ali; Akrami, Mohammad; Bardania, Hassan

2017-10-01

Cell targeting peptides (CTP) are small peptides which have high affinity and specificity to a cell or tissue targets. They are typically identified by using phage display and chemical synthetic peptide library methods. CTPs have attracted considerable attention as a new class of ligands to delivery specifically therapeutic and diagnostic agents, because of the fact they have several advantages including easy synthesis, smaller physical sizes, lower immunogenicity and cytotoxicity and their simple and better conjugation to nano-carriers and therapeutic or diagnostic agents compared to conventional antibodies. In this systematic review, we will focus on the basic concepts concerning the use of cell-targeting peptides (CTPs), following the approaches of selecting them from peptide libraries. We discuss several developed strategies for cell-specific delivery of different cargos by CTPs, which are designed for drug delivery and diagnostic applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Conceptual design of the handling and storage system for spent target vessel

Energy Technology Data Exchange (ETDEWEB)

Adachi, Junichi; Sasaki, Shinobu; Kaminaga, Masanori; Hino, Ryutaro [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

2001-03-01

A conceptual design of a handling and storage system for spent target vessels has been carried out, in order to establish spent target technology for the neutron scattering facility. The spent target vessels must be treated remotely with high reliability and safety, since they are highly activated and contain the poisonous mercury. The system is composed of a target exchange trolley to exchange the target vessel, remote handling equipment such as manipulators, airtight casks for the spent target vessel, storage pits and so on. This report presents the results of conceptual design study on a basic plan, a handling procedure, main devices and their arrangement of a handling and storage system for the spent target vessels. (author)

Basic research on flue gas smoke treatment by electron beam

International Nuclear Information System (INIS)

Namba, Hideki

1995-01-01

Recently, accompanying the increase of the use of fossil fuel, the environment destruction due to the sulfur oxides and nitrogen oxides contained in combustion smoke has become a serious problem. The development of flue gas smoke treatment technology by using electron beam was started in Japan, and attention has been paid worldwide as the promising dry type simultaneous desulfurizing and denitrating process. In this process, by adding ammonia to smoke, and irradiating electron beam on it, ammonium nitrate and ammonium sulfate are formed. As to the reaction mechanism of denitration and desulfurization, radical formation, radical reaction, denitration mechanism, desulfurization mechanism, the particle size distribution of the formed aerosol, the amounts of denitration and desulfurization by electron beam smoke treatment process, the improvement of the denitration efficiency by multi-stage irradiation method and the improvement of the desulfurization rate by low temperature irradiation, and the basic test toward the pilot test are explained. The basic research for putting this system to practical use was carried out jointly by Japan Atomic Energy Research Institute, Chubu Electric Power Co., Inc., and Ebara Seisakusho for standard coal burning smoke in Japan. The verifying test at the pilot plant in Shinnagoya Thermal Power Station was carried out, and it was verified that this process can be used practically for treating coal-burning smoke. (K.I.)

A textbook of quantum mechanics

International Nuclear Information System (INIS)

Mathews, P.M.; Venkatesan, K.

1977-01-01

After briefly surveying the inadequacy of the classical ideas and elementary older quantum theory, the ideas of wave mechanics, the postulates of quantum mechanics, exactly soluble problems, approximation techniques, scattering theory, angular momentum, time dependent problems and the basic ideas of relativistic quantum mechanics are discussed. The book is meant for the Master of Science degree course students of Indian Universities. (M.G.B.)

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

Basic infrastructure for a nuclear power project

International Nuclear Information System (INIS)

2006-06-01

There are several stages in the process of introducing nuclear power in a country. These include development of nuclear policies and regulations, feasibility studies, public consultations, technology evaluation, requests for proposals and evaluations, contracts and financing, supply, construction, commissioning, operation and finally decommissioning. This publication addresses the 'basic' infrastructure needs, which are adequate until the issue of the construction license. It is obvious that a fully developed nuclear infrastructure will be required for the further implementation stages of a nuclear power reactor. The officials and experts in each country will undertake the transition from a basic infrastructure to a fully developed infrastructure that covers the stages of construction, commissioning, operation and decommissioning. The publication is directed to provide guidance for assessing the basic infrastructure necessary for: - A host country to consider when engaging in the implementation of nuclear power, and - A supplier country to consider when assessing whether the recipient country is in an acceptable condition to begin the implementation of a nuclear power project. The target users are decision makers, advisers and senior managers in the governmental organizations, utilities, industrial organizations and regulatory bodies in the countries adopting nuclear power programmes or exporting supplies for these programmes. The governmental organizations that may find this publication useful include: Ministries of Economy, Energy, Foreign Affairs, Finance, Mining, Internal Affairs, Academic Institutions, Nuclear Energy Agencies and Environmental Agencies. This publication was produced within the IAEA programme directed to increase the capability of Member States to plan and implement nuclear power programmes and to establish and enhance national nuclear infrastructure. This publication should be used in conjunction with the IAEA Safety Standards Series and other

Type I-E CRISPR-Cas Systems Discriminate Target from Non-Target DNA through Base Pairing-Independent PAM Recognition

Science.gov (United States)

Datsenko, Kirill A.; Jackson, Ryan N.; Wiedenheft, Blake; Severinov, Konstantin; Brouns, Stan J. J.

2013-01-01

Discriminating self and non-self is a universal requirement of immune systems. Adaptive immune systems in prokaryotes are centered around repetitive loci called CRISPRs (clustered regularly interspaced short palindromic repeat), into which invader DNA fragments are incorporated. CRISPR transcripts are processed into small RNAs that guide CRISPR-associated (Cas) proteins to invading nucleic acids by complementary base pairing. However, to avoid autoimmunity it is essential that these RNA-guides exclusively target invading DNA and not complementary DNA sequences (i.e., self-sequences) located in the host's own CRISPR locus. Previous work on the Type III-A CRISPR system from Staphylococcus epidermidis has demonstrated that a portion of the CRISPR RNA-guide sequence is involved in self versus non-self discrimination. This self-avoidance mechanism relies on sensing base pairing between the RNA-guide and sequences flanking the target DNA. To determine if the RNA-guide participates in self versus non-self discrimination in the Type I-E system from Escherichia coli we altered base pairing potential between the RNA-guide and the flanks of DNA targets. Here we demonstrate that Type I-E systems discriminate self from non-self through a base pairing-independent mechanism that strictly relies on the recognition of four unchangeable PAM sequences. In addition, this work reveals that the first base pair between the guide RNA and the PAM nucleotide immediately flanking the target sequence can be disrupted without affecting the interference phenotype. Remarkably, this indicates that base pairing at this position is not involved in foreign DNA recognition. Results in this paper reveal that the Type I-E mechanism of avoiding self sequences and preventing autoimmunity is fundamentally different from that employed by Type III-A systems. We propose the exclusive targeting of PAM-flanked sequences to be termed a target versus non-target discrimination mechanism. PMID:24039596

Targeted Phototherapy (newer phototherapy

Directory of Open Access Journals (Sweden)

Zonunsanga

2015-04-01

Full Text Available Conventional phototherapy uses a whole body cabinet or body part machine such as hand, foot or scalp machines. They have many disadvantages due to which new phototherapy technique was then developed to overcome this situation. This new technique is called targeted phototherapy which includes excimer laser, intense pulse light system (IPL, photodynamic therapy and ultraviolet (UV light source with a sophisticated delivery system which is easy to be operated by hands. The mechanisms of action of targeted phototherapy systems are similar to those in conventional UVB/UVA therapy. They have many advantages like less chances of side effects, avoidance of exposure of unnecessary sites, faster response, shortening of the duration of treatments. But they have disadvantages like high costs and inability to use for extensive areas. This review article discusses targeted phototherapy in considerable to the mechanism of actions and advantages and disadvantages in comparison to the conventional phototherapy.

Science Academies' Refresher Course in Quantum Mechanics

Indian Academy of Sciences (India)

IAS Admin

2013-02-28

Feb 28, 2013 ... A Refresher Course in Quantum Mechanics for college/university teachers ... The Course will cover the basic and advanced topics of Quantum ... Module 1:- Principles of Quantum Mechanics (with associated mathematics), ...

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);…

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

Targets of curcumin

Science.gov (United States)

Zhou, Hongyu; Beevers, Christopher S.; Huang, Shile

2010-01-01

Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-κB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer’s disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here. PMID:20955148

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…

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 ...

Immunological mechanisms of sublingual allergen-specific immunotherapy.

Science.gov (United States)

Novak, Natalija; Bieber, T; Allam, J-P

2011-06-01

Within the last 100 years of allergen-specific immunotherapy, many clinical and scientific efforts have been made to establish alternative noninvasive allergen application strategies. Thus, intra-oral allergen delivery to the sublingual mucosa has been proven to be safe and effective. As a consequence, to date, sublingual immunotherapy (SLIT) is widely accepted by most allergists as an alternative to conventional subcutaneous immunotherapy. Although immunological mechanisms remain to be elucidated in detail, several studies in mice and humans within recent years provided deeper insights into local as well as systemic immunological features in response to SLIT. First of all, it was shown that the target organ, the oral mucosa, harbours a sophisticated immunological network as an important prerequisite for SLIT, which contains among other cells, local antigen-presenting cells (APC), such as dendritic cells (DCs), with a constitutive disposition to enforce tolerogenic mechanisms. Further on, basic research on local DCs within the oral mucosa gave rise to possible alternative strategies to deliver the allergens to other mucosal regions than sublingual tissue, such as the vestibulum oris. Moreover, characterization of oral DCs led to the identification of target structures for both allergens as well as adjuvants, which could be applied during SLIT. Altogether, SLIT came a long way since its very beginning in the last century and some, but not all questions about SLIT could be answered so far. However, recent research efforts as well as clinical approaches paved the way for another exciting 100 years of SLIT. © 2011 John Wiley & Sons A/S.

Polymeric micelles as a drug carrier for tumor targeting

Directory of Open Access Journals (Sweden)

Neha M Dand

2013-01-01

Full Text Available Polymeric micelle can be targeted to tumor site by passive and active mechanism. Some inherent properties of polymeric micelle such as size in nanorange, stability in plasma, longevity in vivo, and pathological characteristics of tumor make polymeric micelles to be targeted at the tumor site by passive mechanism called enhanced permeability and retention effect. Polymeric micelle formed from the amphiphilic block copolymer is suitable for encapsulation of poorly water soluble, hydrophobic anticancer drugs. Other characteristics of polymeric micelles such as separated functionality at the outer shell are useful for targeting the anticancer drug to tumor by active mechanisms. Polymeric micelles can be conjugated with many ligands such as antibodies fragments, epidermal growth factors, α2 -glycoprotein, transferrine, and folate to target micelles to cancer cells. Application of heat and ultrasound are the alternative methods to enhance drug accumulation in tumoral cells. Targeting using micelles can also be done to tumor angiogenesis which is the potentially promising target for anticancer drugs. This review summarizes about recently available information regarding targeting the anticancer drug to the tumor site using polymeric micelles.

The Neural Basis of Recollection Rejection: Increases in Hippocampal-Prefrontal Connectivity in the Absence of a Shared Recall-to-Reject and Target Recollection Network.

Science.gov (United States)

Bowman, Caitlin R; Dennis, Nancy A

2016-08-01

Recollection rejection or "recall-to-reject" is a mechanism that has been posited to help maintain accurate memory by preventing the occurrence of false memories. Recollection rejection occurs when the presentation of a new item during recognition triggers recall of an associated target, a mismatch in features between the new and old items is registered, and the lure is correctly rejected. Critically, this characterization of recollection rejection involves a recall signal that is conceptually similar to recollection as elicited by a target. However, previous neuroimaging studies have not evaluated the extent to which recollection rejection and target recollection rely on a common neural signal but have instead focused on recollection rejection as a postretrieval monitoring process. This study utilized a false memory paradigm in conjunction with an adapted remember-know-new response paradigm that separated "new" responses based on recollection rejection from those that were based on a lack of familiarity with the item. This procedure allowed for parallel recollection rejection and target recollection contrasts to be computed. Results revealed that, contrary to predictions from theoretical and behavioral literature, there was virtually no evidence of a common retrieval mechanism supporting recollection rejection and target recollection. Instead of the typical target recollection network, recollection rejection recruited a network of lateral prefrontal and bilateral parietal regions that is consistent with the retrieval monitoring network identified in previous neuroimaging studies of recollection rejection. However, a functional connectivity analysis revealed a component of the frontoparietal rejection network that showed increased coupling with the right hippocampus during recollection rejection responses. As such, we demonstrate a possible link between PFC monitoring network and basic retrieval mechanisms within the hippocampus that was not revealed with

Fundamentals of Quantum Mechanics

Science.gov (United States)

Tang, C. L.

2005-06-01

Quantum mechanics has evolved from a subject of study in pure physics to one with a wide range of applications in many diverse fields. The basic concepts of quantum mechanics are explained in this book in a concise and easy-to-read manner emphasising applications in solid state electronics and modern optics. Following a logical sequence, the book is focused on the key ideas and is conceptually and mathematically self-contained. The fundamental principles of quantum mechanics are illustrated by showing their application to systems such as the hydrogen atom, multi-electron ions and atoms, the formation of simple organic molecules and crystalline solids of practical importance. It leads on from these basic concepts to discuss some of the most important applications in modern semiconductor electronics and optics. Containing many homework problems and worked examples, the book is suitable for senior-level undergraduate and graduate level students in electrical engineering, materials science and applied physics. Clear exposition of quantum mechanics written in a concise and accessible style Precise physical interpretation of the mathematical foundations of quantum mechanics Illustrates the important concepts and results by reference to real-world examples in electronics and optoelectronics Contains homeworks and worked examples, with solutions available for instructors

Centro de Biologia Molecular "Severo Ochoa": a center for basic research into Alzheimer's disease.

Science.gov (United States)

Avila, Jesus; Hernandez, Felix; Wandosell, Francisco; Lucas, Jose J; Esteban, Jose A; Ledesma, M Dolores; Bullido, Maria J

2010-01-01

One important aspect of studies carried out at the Center for Molecular Biology "Severo Ochoa" is focused on basic aspects of Alzheimer's disease, mainly the search for suitable therapeutic targets for this disorder. Several groups at the Center are involved in these studies, and, in this spotlight, the work they are carrying out will be described.

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

The mirror mechanism in the parietal lobe.

Science.gov (United States)

Rizzolatti, Giacomo; Rozzi, Stefano

2018-01-01

The mirror mechanism is a basic mechanism that transforms sensory representations of others' actions into motor representations of the same actions in the brain of the observer. The mirror mechanism plays an important role in understanding actions of others. In the present chapter we discuss first the basic organization of the posterior parietal lobe in the monkey, stressing that it is best characterized as a motor scaffold, on the top of which sensory information is organized. We then describe the location of the mirror mechanism in the posterior parietal cortex of the monkey, and its functional role in areas PFG, and anterior, ventral, and lateral intraparietal areas. We will then present evidence that a similar functional organization is present in humans. We will conclude by discussing the role of the mirror mechanism in the recognition of action performed with tools. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

Effective source of bremsstrahlung with multiple crossing of a thin target by an electron beam

International Nuclear Information System (INIS)

Grishin, V.K.; Ishkhanov, B.S.; Shvedunov, V.I.

1996-01-01

A basically new scheme of electron beam discharge to the target for x ray and gamma radiation generation is proposed. In this case an accelerated electron beam crosses a thin braking target many times, which substantially increases the integral radiation yield. 3 refs.; 2 figs

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.

Rheology and Fracture Mechanics of Foods

NARCIS (Netherlands)

Vliet, van T.

2013-01-01

The mechanical properties of food play an important role during manufacturing, storage, handling, and last but not least, during consumption. For an adequate understanding of the mechanical properties of liquid, liquid-like, soft solid, and solid foods, a basic understanding of relevant aspects of

Effects of preschool education in mixed and targeted classrooms

NARCIS (Netherlands)

de Haan, A.K.E.

2015-01-01

One of the remaining questions in the field of early childhood education is whether efforts aiming to promote the school readiness skills of young learners should be targeted specifically at children at risk for delays in these basic skills or whether efforts should be aimed at all young children

Setting reference targets

International Nuclear Information System (INIS)

Ruland, R.E.

1997-04-01

Reference Targets are used to represent virtual quantities like the magnetic axis of a magnet or the definition of a coordinate system. To explain the function of reference targets in the sequence of the alignment process, this paper will first briefly discuss the geometry of the trajectory design space and of the surveying space, then continue with an overview of a typical alignment process. This is followed by a discussion on magnet fiducialization. While the magnetic measurement methods to determine the magnetic centerline are only listed (they will be discussed in detail in a subsequent talk), emphasis is given to the optical/mechanical methods and to the task of transferring the centerline position to reference targets

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

Target and collection optimization for muon colliders

International Nuclear Information System (INIS)

Mokhov, N.V.; Noble, R.J.; Van Ginneken, A.

1996-01-01

To achieve adequate luminosity in a muon collider it is necessary to produce and collect large numbers of muons. The basic method used in this paper follows closely a proposed scheme which starts with a proton beam impinging on a thick target (∼ one interaction length) followed by a long solenoid which collects muons resulting mainly from pion decay. Production and collection of pions and their decay muons must be optimized while keeping in mind limitations of target integrity and of the technology of magnets and cavities. Results of extensive simulations for 8 GeV protons on various targets and with various collection schemes are reported. Besides muon yields results include-energy deposition in target and solenoid to address cooling requirements for these systems. Target composition, diameter, and length are varied in this study as well as the configuration and field strengths of the solenoid channel. A curved solenoid field is introduced to separate positive and negative pions within a few meters of the target. This permits each to be placed in separate RF buckets for acceleration which effectively doubles the number of muons per bunch available for collisions and increases the luminosity fourfold

THE METHOD OF MULTIPLE SPATIAL PLANNING BASIC MAP

Directory of Open Access Journals (Sweden)

C. Zhang

2018-04-01

Full Text Available The “Provincial Space Plan Pilot Program” issued in December 2016 pointed out that the existing space management and control information management platforms of various departments were integrated, and a spatial planning information management platform was established to integrate basic data, target indicators, space coordinates, and technical specifications. The planning and preparation will provide supportive decision support, digital monitoring and evaluation of the implementation of the plan, implementation of various types of investment projects and space management and control departments involved in military construction projects in parallel to approve and approve, and improve the efficiency of administrative approval. The space planning system should be set up to delimit the control limits for the development of production, life and ecological space, and the control of use is implemented. On the one hand, it is necessary to clarify the functional orientation between various kinds of planning space. On the other hand, it is necessary to achieve “multi-compliance” of various space planning. Multiple spatial planning intergration need unified and standard basic map(geographic database and technical specificaton to division of urban, agricultural, ecological three types of space and provide technical support for the refinement of the space control zoning for the relevant planning. The article analysis the main space datum, the land use classification standards, base map planning, planning basic platform main technical problems. Based on the geographic conditions, the results of the census preparation of spatial planning map, and Heilongjiang, Hainan many rules combined with a pilot application.

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.

Combinatorial microRNA target predictions

DEFF Research Database (Denmark)

Krek, Azra; Grün, Dominic; Poy, Matthew N.

2005-01-01

MicroRNAs are small noncoding RNAs that recognize and bind to partially complementary sites in the 3' untranslated regions of target genes in animals and, by unknown mechanisms, regulate protein production of the target transcript1, 2, 3. Different combinations of microRNAs are expressed...... in different cell types and may coordinately regulate cell-specific target genes. Here, we present PicTar, a computational method for identifying common targets of microRNAs. Statistical tests using genome-wide alignments of eight vertebrate genomes, PicTar's ability to specifically recover published micro......RNA targets, and experimental validation of seven predicted targets suggest that PicTar has an excellent success rate in predicting targets for single microRNAs and for combinations of microRNAs. We find that vertebrate microRNAs target, on average, roughly 200 transcripts each. Furthermore, our results...

Molecular medicine of fragile X syndrome: based on known molecular mechanisms.

Science.gov (United States)

Luo, Shi-Yu; Wu, Ling-Qian; Duan, Ran-Hui

2016-02-01

Extensive research on fragile X mental retardation gene knockout mice and mutant Drosophila models has largely expanded our knowledge on mechanism-based treatment of fragile X syndrome (FXS). In light of these findings, several clinical trials are now underway for therapeutic translation to humans. Electronic literature searches were conducted using the PubMed database and ClinicalTrials.gov. The search terms included "fragile X syndrome", "FXS and medication", "FXS and therapeutics" and "FXS and treatment". Based on the publications identified in this search, we reviewed the neuroanatomical abnormalities in FXS patients and the potential pathogenic mechanisms to monitor the progress of FXS research, from basic studies to clinical trials. The pathological mechanisms of FXS were categorized on the basis of neuroanatomy, synaptic structure, synaptic transmission and fragile X mental retardation protein (FMRP) loss of function. The neuroanatomical abnormalities in FXS were described to motivate extensive research into the region-specific pathologies in the brain responsible for FXS behavioural manifestations. Mechanism-directed molecular medicines were classified according to their target pathological mechanisms, and the most recent progress in clinical trials was discussed. Current mechanism-based studies and clinical trials have greatly contributed to the development of FXS pharmacological therapeutics. Research examining the extent to which these treatments provided a rescue effect or FMRP compensation for the developmental impairments in FXS patients may help to improve the efficacy of treatments.

Fundamentals of Counting Statistics in Digital PCR: I Just Measured Two Target Copies-What Does It Mean?

Science.gov (United States)

Tzonev, Svilen

2018-01-01

Current commercially available digital PCR (dPCR) systems and assays are capable of detecting individual target molecules with considerable reliability. As tests are developed and validated for use on clinical samples, the need to understand and develop robust statistical analysis routines increases. This chapter covers the fundamental processes and limitations of detecting and reporting on single molecule detection. We cover the basics of quantification of targets and sources of imprecision. We describe the basic test concepts: sensitivity, specificity, limit of blank, limit of detection, and limit of quantification in the context of dPCR. We provide basic guidelines how to determine those, how to choose and interpret the operating point, and what factors may influence overall test performance in practice.

Fractional vector calculus and fluid mechanics

Science.gov (United States)

Lazopoulos, Konstantinos A.; Lazopoulos, Anastasios K.

2017-04-01

Basic fluid mechanics equations are studied and revised under the prism of fractional continuum mechanics (FCM), a very promising research field that satisfies both experimental and theoretical demands. The geometry of the fractional differential has been clarified corrected and the geometry of the fractional tangent spaces of a manifold has been studied in Lazopoulos and Lazopoulos (Lazopoulos KA, Lazopoulos AK. Progr. Fract. Differ. Appl. 2016, 2, 85-104), providing the bases of the missing fractional differential geometry. Therefore, a lot can be contributed to fractional hydrodynamics: the basic fractional fluid equations (Navier Stokes, Euler and Bernoulli) are derived and fractional Darcy's flow in porous media is studied.

Population-level associations between preschool vulnerability and grade-four basic skills.

Directory of Open Access Journals (Sweden)

Amedeo D'Angiulli

2009-11-01

Full Text Available This is a predictive validity study examining the extent to which developmental vulnerability at kindergarten entry (as measured by the Early Development Instrument, EDI is associated with children's basic skills in 4th grade (as measured by the Foundation Skills Assessment, FSA.Relative risk analysis was performed on a large database linking individual-level EDI ratings to the scores the same children obtained on a provincial assessment of academic skills (FSA--Foundation Skills Assessment four years later. We found that early vulnerability in kindergarten is associated with the basic skills that underlie populations of children's academic achievement in reading, writing and math, indicating that the Early Development Instrument permits to predict achievement-related skills four years in advance.The EDI can be used to predict children's educational trends at the population level and can help select early prevention and intervention programs targeting pre-school populations at minimum cost.

Computational mechanics research at ONR

International Nuclear Information System (INIS)

Kushner, A.S.

1986-01-01

Computational mechanics is not an identified program at the Office of Naval Research (ONR), but rather plays a key role in the Solid Mechanics, Fluid Mechanics, Energy Conversion, and Materials Science programs. The basic philosophy of the Mechanics Division at ONR is to support fundamental research which expands the basis for understanding, predicting, and controlling the behavior of solid and fluid materials and systems at the physical and geometric scales appropriate to the phenomena of interest. It is shown in this paper that a strong commonalty of computational mechanics drivers exists for the forefront research areas in both solid and fluid mechanics

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...

Adolescents' Use of Basic, Intermediate, and Advanced Device Types for Vaping.

Science.gov (United States)

Pepper, Jessica K; MacMonegle, Anna J; Nonnemaker, James M

2017-12-23

Advanced models of electronic vaping products (EVPs) likely pose a greater risk to adolescent health than basic or intermediate models because advanced models deliver nicotine more effectively and heat e-liquid to higher temperatures, producing more harmful chemical emissions. However, little is known about adolescents' risk factors for using different device types. We used social media to recruit an online sample of 1,508 U.S. adolescents aged 15-17 who reported past 30-day use of e-cigarettes. We assessed tobacco use, beliefs and knowledge about EVPs, and EVP use behavior, including the device type participants use most frequently. We used multinomial logistic regression to examine differences between adolescents who usually use intermediate versus basic and advanced versus basic devices. Most respondents usually used modifiable advanced devices (56.8%) rather than basic "cigalike" (14.5%) or pen-style intermediate (28.7%) devices. Use of multiple device types was common, particularly among those who primarily used basic devices. Younger age and less frequent vaping were associated with mainly using basic devices. Adolescents who were older, male, personally bought their main device, and had ever mixed e-liquids were at elevated risk for usually using advanced devices. Adolescents who primarily use basic devices may be newer users who are experimenting with multiple devices. Future research should examine which adolescents are most likely to transition to advanced devices in order to develop targeted interventions. Regulators should consider strategies to reduce access to all types of EVPs, such as better enforcement of the current ban on sales to minors. This research addresses two gaps in research on adolescent electronic vaping product use: (1) characterizing use of advanced devices as distinct from intermediate devices rather than grouping them together and (2) examining factors associated with use of specific device types. This study suggests that there

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...

Mechanics, Waves and Thermodynamics

Science.gov (United States)

Ranjan Jain, Sudhir

2016-05-01

Figures; Preface; Acknowledgement; 1. Energy, mass, momentum; 2. Kinematics, Newton's laws of motion; 3. Circular motion; 4. The principle of least action; 5. Work and energy; 6. Mechanics of a system of particles; 7. Friction; 8. Impulse and collisions; 9. Central forces; 10. Dimensional analysis; 11. Oscillations; 12. Waves; 13. Sound of music; 14. Fluid mechanics; 15. Water waves; 16. The kinetic theory of gases; 17. Concepts and laws of thermodynamics; 18. Some applications of thermodynamics; 19. Basic ideas of statistical mechanics; Bibliography; Index.

Use of antimicrobials in veterinary medicine and mechanisms of resistance.

Science.gov (United States)

Schwarz, S; Chaslus-Dancla, E

2001-01-01

This review deals with the application of antimicrobial agents in veterinary medicine and food animal production and the possible consequences arising from the widespread and multipurpose use of antimicrobials. The various mechanisms that bacteria have developed to escape the inhibitory effects of the antimicrobials most frequently used in the veterinary field are reported in detail. Resistance of bacteria to tetracyclines, macrolide-lincosamide-streptogramin antibiotics, beta-lactam antibiotics, aminoglycosides, sulfonamides, trimethoprim, fluoroquinolones and chloramphenicol/florfenicol is described with regard to enzymatic inactivation, decreased intracellular drug accumulation and modification/protection/replacement of the target sites. In addition, basic information is given about mobile genetic elements which carry the respective resistance genes, such as plasmids, transposons, and gene cassettes/integrons, and their ways of spreading via conjugation, mobilisation, transduction, and transformation.

Management of basic education for ethnic groups in highland and border regions of Thailand

Directory of Open Access Journals (Sweden)

Phathombut Keawsomnuk

2017-05-01

The research findings revealed that the actors for advocacy policy in basic education for ethnic groups consist of: 1 the primary education service area, 2 community, 3 NGOs, 4 scholars, and 5 schools. This study indicated that the provision of basic education policy for ethnic groups must consist of knowledge from communities such as ethnic life styles integrated in the curriculum, and a special education mechanism and process for Thai ethnic groups, including facilitation of ethnic group participation in the abovementioned actors by various means.

Macromolecular target prediction by self-organizing feature maps.

Science.gov (United States)

Schneider, Gisbert; Schneider, Petra

2017-03-01

Rational drug discovery would greatly benefit from a more nuanced appreciation of the activity of pharmacologically active compounds against a diverse panel of macromolecular targets. Already, computational target-prediction models assist medicinal chemists in library screening, de novo molecular design, optimization of active chemical agents, drug re-purposing, in the spotting of potential undesired off-target activities, and in the 'de-orphaning' of phenotypic screening hits. The self-organizing map (SOM) algorithm has been employed successfully for these and other purposes. Areas covered: The authors recapitulate contemporary artificial neural network methods for macromolecular target prediction, and present the basic SOM algorithm at a conceptual level. Specifically, they highlight consensus target-scoring by the employment of multiple SOMs, and discuss the opportunities and limitations of this technique. Expert opinion: Self-organizing feature maps represent a straightforward approach to ligand clustering and classification. Some of the appeal lies in their conceptual simplicity and broad applicability domain. Despite known algorithmic shortcomings, this computational target prediction concept has been proven to work in prospective settings with high success rates. It represents a prototypic technique for future advances in the in silico identification of the modes of action and macromolecular targets of bioactive molecules.

Statistical mechanics in a nutshell

CERN Document Server

Peliti, Luca

2011-01-01

Statistical mechanics is one of the most exciting areas of physics today, and it also has applications to subjects as diverse as economics, social behavior, algorithmic theory, and evolutionary biology. Statistical Mechanics in a Nutshell offers the most concise, self-contained introduction to this rapidly developing field. Requiring only a background in elementary calculus and elementary mechanics, this book starts with the basics, introduces the most important developments in classical statistical mechanics over the last thirty years, and guides readers to the very threshold of today

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.

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

[Basic research in ophthalmology in Germany and its international context].

Science.gov (United States)

Schlötzer-Schrehardt, U; Cursiefen, C

2017-09-01

Experimental basic research provides the foundations for the elucidation of pathophysiological mechanisms of diseases and the development of novel diagnostic and therapeutic strategies for ophthalmological diseases. The objective of this contribution is to provide an overview of the international interconnection of basic research in ophthalmology in Germany. The international context of ophthalmological research conducted in Germany is presented by means of personal experiences and data published by the German Ophthalmological Society (DOG), the German Research Foundation (DFG) and the European Union (EU). Due to the lack of organized databases this article lays no claim to completeness. Basic research in ophthalmology in Germany is mainly conducted in university eye departments and is mainly related to the etiology, pathophysiology and therapy development for various ophthalmic diseases. It is primarily funded by the DFG, the Federal Ministry of Education and Research (BMBF) and the EU plays an increasingly important role. Thus, ophthalmological research is integrated into numerous European research networks and beyond that into many international interconnections and relationships. In Germany, both clinical and basic research in ophthalmology is integrated into many international networks and is only functionally viable in an international context; however, given the increasing impact of ophthalmological research in Asian countries, future strategies require a continued focus on career development, research infrastructure, working environment and international cooperation.

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)

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)

Research on infrared small-target tracking technology under complex background

Science.gov (United States)

Liu, Lei; Wang, Xin; Chen, Jilu; Pan, Tao

2012-10-01

In this paper, some basic principles and the implementing flow charts of a series of algorithms for target tracking are described. On the foundation of above works, a moving target tracking software base on the OpenCV is developed by the software developing platform MFC. Three kinds of tracking algorithms are integrated in this software. These two tracking algorithms are Kalman Filter tracking method and Camshift tracking method. In order to explain the software clearly, the framework and the function are described in this paper. At last, the implementing processes and results are analyzed, and those algorithms for tracking targets are evaluated from the two aspects of subjective and objective. This paper is very significant in the application of the infrared target tracking technology.

Conceptual design of the handling and storage system of the spent target vessel for neutron scattering facility 2

International Nuclear Information System (INIS)

Adachi, Junichi; Kaminaga, Masanori; Sasaki, Shinobu; Haga, Katsuhiro; Aso, Tomokazu; Kinoshita, Hidetaka; Hino, Ryutaro

2002-01-01

In designing the neutron scattering facility, a spent target vessel should be replaced with remote handling devices in order to protect radioactive exposure, since it would be highly activated through the high energy neutron irradiation caused by the spallation reaction between mercury of the target material and the MW-class proton beam. In the storage of the spent target vessel, it is necessary to consider decay heat of the target vessel and mercury contamination caused by vaporization of the residual mercury in the vessel. A conceptual design has been carried out to establish basic concept and to clarify its specification of main equipments on handling and storage systems for the spent target vessel. This report presents the basic concept and a system plot plan based on latest design works of remote handling devices such as a spent target vessel storage cask and a target vessel exchange trolley, which aim at reasonability and simplification. In addition, storage systems for the spent moderator vessel, the spent proton beam window and the spent reflector vessel are also investigated based on the plot plan. (author)

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

Statistical mechanics rigorous results

CERN Document Server

Ruelle, David

1999-01-01

This classic book marks the beginning of an era of vigorous mathematical progress in equilibrium statistical mechanics. Its treatment of the infinite system limit has not been superseded, and the discussion of thermodynamic functions and states remains basic for more recent work. The conceptual foundation provided by the Rigorous Results remains invaluable for the study of the spectacular developments of statistical mechanics in the second half of the 20th century.

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.

Foundations of mechanics

International Nuclear Information System (INIS)

Zorski, Henryk; Bazanski, Stanislaw; Gutowski, Roman; Slawianowski, Jan; Wilmanski, Krysztof; Wozniak, Czeslaw

1992-01-01

In the last 3 decades the field of mechanics has seen spectacular progress due to the demand for applications in problems of cosmology, thermonuclear fusion, metallurgy, etc. This book provides a broad and thorough overview on the foundations of mechanics. It discusses theoretical mechanics and continuum mechanics, as well as phenomenological thermodynamics, quantum mechanics and relativistic mechanics. Each chapter presents the basic physical facts of interest without going into details and derivations and without using advanced mathematical formalism. The first part constitutes a classical exposition of Lagrange's and Hamiltonian's analytical mechanics on which most of the continuum theory is based. The section on continuum mechanics focuses mainly on the axiomatic foundations, with many pointers for further research in this area. Special attention is given to modern continuum thermodynamics, both for the foundations and applications. A section on quantum mechanics is also included, since the phenomenological description of various quantum phenomena is becoming of increasing importance. refs.; figs.; tabs

Tracking Maneuvering Group Target with Extension Predicted and Best Model Augmentation Method Adapted

Directory of Open Access Journals (Sweden)

Linhai Gan

2017-01-01

Full Text Available The random matrix (RM method is widely applied for group target tracking. The assumption that the group extension keeps invariant in conventional RM method is not yet valid, as the orientation of the group varies rapidly while it is maneuvering; thus, a new approach with group extension predicted is derived here. To match the group maneuvering, a best model augmentation (BMA method is introduced. The existing BMA method uses a fixed basic model set, which may lead to a poor performance when it could not ensure basic coverage of true motion modes. Here, a maneuvering group target tracking algorithm is proposed, where the group extension prediction and the BMA adaption are exploited. The performance of the proposed algorithm will be illustrated by simulation.

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.

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

Recent advances in basic and clinical nanomedicine.

Science.gov (United States)

Morrow, K John; Bawa, Raj; Wei, Chiming

2007-09-01

Nanomedicine is a global business enterprise. Industry and governments clearly are beginning to envision nanomedicine's enormous potential. A clear definition of nanotechnology is an issue that requires urgent attention. This problem exists because nanotechnology represents a cluster of technologies, each of which may have different characteristics and applications. Although numerous novel nanomedicine-related applications are under development or nearing commercialization, the process of converting basic research in nanomedicine into commercially viable products will be long and difficult. Although realization of the full potential of nanomedicine may be years or decades away, recent advances in nanotechnology-related drug delivery, diagnosis, and drug development are beginning to change the landscape of medicine. Site-specific targeted drug delivery and personalized medicine are just a few concepts that are on the horizon.

THE STRUCTURAL AND MECHANICAL PROPERTIES OF THE BONE

Directory of Open Access Journals (Sweden)

Robert Karpiński

2017-06-01

Full Text Available The work contains basic information on the anatomy and physiology of bone tissue. Basic concepts related to the structure of bone tissue are presented. General issues related to bone reconstruction processes and biomechanical structural adaptations processes were described. Mechanical parameters of bone tissue were presented.

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

Mechanical design of deformation compensated flexural pivots structured for linear nanopositioning stages

Science.gov (United States)

Shu, Deming; Kearney, Steven P.; Preissner, Curt A.

2015-02-17

A method and deformation compensated flexural pivots structured for precision linear nanopositioning stages are provided. A deformation-compensated flexural linear guiding mechanism includes a basic parallel mechanism including a U-shaped member and a pair of parallel bars linked to respective pairs of I-link bars and each of the I-bars coupled by a respective pair of flexural pivots. The basic parallel mechanism includes substantially evenly distributed flexural pivots minimizing center shift dynamic errors.

Cannabinoids and Vanilloids in Schizophrenia: Neurophysiological Evidence and Directions for Basic Research

Directory of Open Access Journals (Sweden)

Rafael N. Ruggiero

2017-06-01

Full Text Available Much of our knowledge of the endocannabinoid system in schizophrenia comes from behavioral measures in rodents, like prepulse inhibition of the acoustic startle and open-field locomotion, which are commonly used along with neurochemical approaches or drug challenge designs. Such methods continue to map fundamental mechanisms of sensorimotor gating, hyperlocomotion, social interaction, and underlying monoaminergic, glutamatergic, and GABAergic disturbances. These strategies will require, however, a greater use of neurophysiological tools to better inform clinical research. In this sense, electrophysiology and viral vector-based circuit dissection, like optogenetics, can further elucidate how exogenous cannabinoids worsen (e.g., tetrahydrocannabinol, THC or ameliorate (e.g., cannabidiol, CBD schizophrenia symptoms, like hallucinations, delusions, and cognitive deficits. Also, recent studies point to a complex endocannabinoid-endovanilloid interplay, including the influence of anandamide (endogenous CB1 and TRPV1 agonist on cognitive variables, such as aversive memory extinction. In fact, growing interest has been devoted to TRPV1 receptors as promising therapeutic targets. Here, these issues are reviewed with an emphasis on the neurophysiological evidence. First, we contextualize imaging and electrographic findings in humans. Then, we present a comprehensive review on rodent electrophysiology. Finally, we discuss how basic research will benefit from further combining psychopharmacological and neurophysiological tools.

Availability of enriched isotopic material for accelerator targets

International Nuclear Information System (INIS)

Newman, E.

1982-01-01

The electromagnetic isotope enrichment facility at ORNL provides a broad spectrum of highly enriched stable isotopes to the worldwide scientific community. The continued timely availability of these materials is of vital importance in many areas of basic research and, in particular, as source material for the fabrication of accelerator targets. A brief description of the facility and its capabilities and limitations is presented

Responses to Error: Sentence-Level Error and the Teacher of Basic Writing

Science.gov (United States)

Foltz-Gray, Dan

2012-01-01

In this article, the author talks about sentence-level error, error in grammar, mechanics, punctuation, usage, and the teacher of basic writing. He states that communities are crawling with teachers and administrators and parents and state legislators and school board members who are engaged in sometimes rancorous debate over what to do about…

Basic science right, not basic science lite: medical education at a crossroad.

Science.gov (United States)

Fincher, Ruth-Marie E; Wallach, Paul M; Richardson, W Scott

2009-11-01

This perspective is a counterpoint to Dr. Brass' article, Basic biomedical sciences and the future of medical education: implications for internal medicine. The authors review development of the US medical education system as an introduction to a discussion of Dr. Brass' perspectives. The authors agree that sound scientific foundations and skill in critical thinking are important and that effective educational strategies to improve foundational science education should be implemented. Unfortunately, many students do not perceive the relevance of basic science education to clinical practice.The authors cite areas of disagreement. They believe it is unlikely that the importance of basic sciences will be diminished by contemporary directions in medical education and planned modifications of USMLE. Graduates' diminished interest in internal medicine is unlikely from changes in basic science education.Thoughtful changes in education provide the opportunity to improve understanding of fundamental sciences, the process of scientific inquiry, and translation of that knowledge to clinical practice.

Wheat grain mechanical vulnerability to mechanical damage in light of the recent agrophysical research

International Nuclear Information System (INIS)

Grundas, S.

1995-01-01

The paper contains basic information on mechanical damage to wheat grains. The most important causes of mechanical damage and some of its effects in manufacturing are discussed. Grain material included 5 varieties of winter wheat and 2 varieties of spring wheat. Internal mechanical damage was examined by X-ray technique; external damage was examined with the colorimeter method. The results obtained were compared with the estimation results of more important processing features of the grain: gluten quantity and quality and grain hardness. (author)

The biology of Mur ligases as an antibacterial target.

Science.gov (United States)

Kouidmi, Imène; Levesque, Roger C; Paradis-Bleau, Catherine

2014-10-01

With antibiotic resistance mechanisms increasing in diversity and spreading among bacterial pathogens, the development of new classes of antibacterial agents against judiciously chosen targets is a high-priority task. The biochemical pathway for peptidoglycan biosynthesis is one of the best sources of antibacterial targets. Within this pathway are the Mur ligases, described in this review as highly suitable targets for the development of new classes of antibacterial agents. The amide ligases MurC, MurD, MurE and MurF function with the same catalytic mechanism and share conserved amino acid regions and structural features that can conceivably be exploited for the design of inhibitors that simultaneously target more than one enzyme. This would provide multi-target antibacterial weapons with minimized likelihood of target-mediated resistance development. © 2014 John Wiley & Sons Ltd.

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.

Mechanical ventilation in neurosurgical patients

Directory of Open Access Journals (Sweden)

Keshav Goyal

2013-01-01

Full Text Available Mechanical ventilation significantly affects cerebral oxygenation and cerebral blood flow through changes in arterial carbon dioxide levels. Neurosurgical patients might require mechanical ventilation for correction and maintenance of changes in the pulmonary system that occur either due to neurosurgical pathology or following surgery during the acute phase. This review discusses the basics of mechanical ventilation relevant to the neurosurgeon in the day-to-day management of neurosurgical patient requiring artificial support of the respiration.

Developments in numerical simulation of IFE target and chamber physics

International Nuclear Information System (INIS)

Velarde, G.; Minguez, E.; Alonso, E.; Gil, J.M.; Malerba, L.; Marian, J.; Martel, P.; Martinez-Val, J.M.; Munoz, R.; Ogando, F.; Perlado, J.M.; Piera, M.; Reyes, S.; Rubiano, J.G.; Sanz, J.; Sauvan, P.; Velarde, M.; Velarde, P.

2000-01-01

The work presented outlines the global frame given at the Institute of Nuclear Fusion (DENIM) for having an integral perspective of the different research areas with the development of Inertial Fusion for energy generation. The coupling of a new radiation transport (RT) solver with an existing multi-material fluid dynamics code using Adaptive Mesh Refinement (ARM) is presented in Section 2, including improvements and additional information about the solver precision. In Section 3, new developments in the atomic physics codes under target conditions, to determine populations, opacity data and emissivities have been performed. Exotic and innovative ideas about Inertial Fusion Energy (IFE), as catalytic fuels and Z-pinches have been explored, and they are explained in Section 4. Numerical simulations demonstrate important reductions in the tritium inventory. Section 5 is devoted to safety and environment of the IFE. Uncertainties analysis in activation calculations have been included in the ACAB activation code, and also calculations on pulse activation in IFE reactors and on the activation of target debris in NIF are presented. A comparison of the accidental releases of tritium from some IFE reactors computed using MACCS2 code is explained. Finally, Section 6 contains the research on the basic mechanisms of neutron damage in SiC (low-activation material) and FeCu alloy using the DENIM/LLNL molecular dynamics code MDCASK. (authors)

Introduction to quantum statistical mechanics

International Nuclear Information System (INIS)

Bogolyubov, N.N.; Bogolyubov, N.N.

1980-01-01

In a set of lectures, which has been delivered at the Physical Department of Moscow State University as a special course for students represented are some basic ideas of quantum statistical mechanics. Considered are in particular, the Liouville equations in classical and quantum mechanics, canonical distribution and thermodynamical functions, two-time correlation functions and Green's functions in the theory of thermal equilibrium

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.

Analytical mechanics

CERN Document Server

Lemos, Nivaldo A

2018-01-01

Analytical mechanics is the foundation of many areas of theoretical physics including quantum theory and statistical mechanics, and has wide-ranging applications in engineering and celestial mechanics. This introduction to the basic principles and methods of analytical mechanics covers Lagrangian and Hamiltonian dynamics, rigid bodies, small oscillations, canonical transformations and Hamilton–Jacobi theory. This fully up-to-date textbook includes detailed mathematical appendices and addresses a number of advanced topics, some of them of a geometric or topological character. These include Bertrand's theorem, proof that action is least, spontaneous symmetry breakdown, constrained Hamiltonian systems, non-integrability criteria, KAM theory, classical field theory, Lyapunov functions, geometric phases and Poisson manifolds. Providing worked examples, end-of-chapter problems, and discussion of ongoing research in the field, it is suitable for advanced undergraduate students and graduate students studying analyt...

Magnetic biosensor system to detect biological targets

KAUST Repository

Li, Fuquan; Gooneratne, Chinthaka Pasan; Kosel, Jü rgen

2012-01-01

magnetic concentration, magnetic as well as mechanical trapping and magnetic sensing. Target detection is based on the size difference between bare magnetic beads and magnetic beads with targets attached. This method remedies the need for a coating layer

Experimental study of hydrodynamics of target system construction with liquid metallic coolant on water models

International Nuclear Information System (INIS)

Beznosov, A.; Davidov, D.; Khokhlov, D.

2001-01-01

This paper is about experimental study of hydrodynamics of target system construction with a spherical beam window (membrane). The visualization of current and current velocity fields in energy release area was considered. The findings are used to optimize the geometrical characteristics of target system. Also report contains the information about functioning accelerator-driven system, description it principle circuit and description of basic requirements what the target design should satisfy. (authors)

Treating rheumatoid arthritis to target: Revision of the 2014 International Expert Group Recommendations

Directory of Open Access Journals (Sweden)

N. T. Vatutin

2016-01-01

Full Text Available The paper presents a new edition (2014 of basic approaches to therapy of rheumatoid arthritis (RA based on the principle of «Treat to target », which has been elaborated by the experts of the European League Against Rheumatism (EULAR and the American College of Rheumatology (ACR. The revised recommendations consider the results of numerous randomized controlled and cohort studies, as well as the data of an extensive systematic review of the literature. The new 2014 version contains 4 basic principles and 10 recommendations for the management of patients with RA. When making the updated recommendations, the experts took into account particularly issues, such as criteria for defining a remission, the need to minimize comorbidities in patients with RA and to individualize its therapy, as well as their working ability. The basic principles in the management of patients with RA, by using a treat-to-target strategy, are discussed in detail and the rewording of the main points of the 2010 recommendations and their new edition are substantiated.

Visual Basic 2012 programmer's reference

CERN Document Server

Stephens, Rod

2012-01-01

The comprehensive guide to Visual Basic 2012 Microsoft Visual Basic (VB) is the most popular programming language in the world, with millions of lines of code used in businesses and applications of all types and sizes. In this edition of the bestselling Wrox guide, Visual Basic expert Rod Stephens offers novice and experienced developers a comprehensive tutorial and reference to Visual Basic 2012. This latest edition introduces major changes to the Visual Studio development platform, including support for developing mobile applications that can take advantage of the Windows 8 operating system

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

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.)

Auger radiation targeted into DNA: a therapy perspective

Energy Technology Data Exchange (ETDEWEB)

Buchegger, Franz [University Hospital of Lausanne CHUV, Service of Nuclear Medicine, Lausanne (Switzerland); University Hospital of Lausanne, Service of Nuclear Medicine, Lausanne (Switzerland); Perillo-Adamer, Florence; Bischof Delaloye, Angelika [University Hospital of Lausanne CHUV, Service of Nuclear Medicine, Lausanne (Switzerland); Dupertuis, Yves M. [University Hospital of Geneva, Service of Nutrition, Geneva (Switzerland)

2006-11-15

Auger electron emitters that can be targeted into DNA of tumour cells represent an attractive systemic radiation therapy goal. In the situation of DNA-associated decay, the high linear energy transfer (LET) of Auger electrons gives a high relative biological efficacy similar to that of {alpha} particles. In contrast to {alpha} radiation, however, Auger radiation is of low toxicity when decaying outside the cell nucleus, as in cytoplasm or outside cells during blood transport. The challenge for such therapies is the requirement to target a high percentage of all cancer cells. An overview of Auger radiation therapy approaches of the past decade shows several research directions and various targeting vehicles. The latter include hormones, peptides, halogenated nucleotides, oligonucleotides and internalising antibodies. Here, we will discuss the basic principles of Auger electron therapy as compared with vector-guided {alpha} and {beta} radiation. We also review some radioprotection issues and briefly present the main advantages and disadvantages of the different targeting modalities that are under investigation. (orig.)

Auger radiation targeted into DNA: a therapy perspective

International Nuclear Information System (INIS)

Buchegger, Franz; Perillo-Adamer, Florence; Bischof Delaloye, Angelika; Dupertuis, Yves M.

2006-01-01

Auger electron emitters that can be targeted into DNA of tumour cells represent an attractive systemic radiation therapy goal. In the situation of DNA-associated decay, the high linear energy transfer (LET) of Auger electrons gives a high relative biological efficacy similar to that of α particles. In contrast to α radiation, however, Auger radiation is of low toxicity when decaying outside the cell nucleus, as in cytoplasm or outside cells during blood transport. The challenge for such therapies is the requirement to target a high percentage of all cancer cells. An overview of Auger radiation therapy approaches of the past decade shows several research directions and various targeting vehicles. The latter include hormones, peptides, halogenated nucleotides, oligonucleotides and internalising antibodies. Here, we will discuss the basic principles of Auger electron therapy as compared with vector-guided α and β radiation. We also review some radioprotection issues and briefly present the main advantages and disadvantages of the different targeting modalities that are under investigation. (orig.)

Fracture Mechanics

CERN Document Server

Zehnder, Alan T

2012-01-01

Fracture mechanics is a vast and growing field. This book develops the basic elements needed for both fracture research and engineering practice. The emphasis is on continuum mechanics models for energy flows and crack-tip stress- and deformation fields in elastic and elastic-plastic materials. In addition to a brief discussion of computational fracture methods, the text includes practical sections on fracture criteria, fracture toughness testing, and methods for measuring stress intensity factors and energy release rates. Class-tested at Cornell, this book is designed for students, researchers and practitioners interested in understanding and contributing to a diverse and vital field of knowledge. Alan Zehnder joined the faculty at Cornell University in 1988. Since then he has served in a number of leadership roles including Chair of the Department of Theoretical and Applied Mechanics, and Director of the Sibley School of Mechanical and Aerospace Engineering.  He teaches applied mechanics and his research t...

Distributions of hit-numbers in single targets

Energy Technology Data Exchange (ETDEWEB)

Fowler, J F [Postgraduate Medical School, Hammersmith Hospital, London (United Kingdom)

1966-07-01

Very general models can be proposed for relating the surviving proportion of an irradiated population of cells or bacteria to the absorbed dose, but if the number of free parameters is large the model can never be tested experimentally (Zimmer; Zirkie; Tobias). A relatively simple model is therefore proposed here, based on the physical facts of energy deposition in small volumes which are currently under active investigation (Rossi), and on cell-survival experiments over a wide range of LET (e.g. Barendsen et al.; Barendsen). It is not suggested that the model is correct or final, but only that its shortcomings should be demonstrated by comparison with experimental results before more complicated models are worth pursuing. It is basically a multihit model applied first to a single target volume, but also applicable to the situation where only one out of many potential target volumes has to be inactivated to kill the organism. It can be extended to two or more target volumes if necessary. Emphasis is placed upon the amount of energy locally deposited in certain sensitive volumes called 'target volumes'.

Relativistic Quantum Mechanics

International Nuclear Information System (INIS)

Antoine, J-P

2004-01-01

The aim of relativistic quantum mechanics is to describe the finer details of the structure of atoms and molecules, where relativistic effects become nonnegligible. It is a sort of intermediate realm, between the familiar nonrelativistic quantum mechanics and fully relativistic quantum field theory, and thus it lacks the simplicity and elegance of both. Yet it is a necessary tool, mostly for quantum chemists. Pilkuhn's book offers to this audience an up-to-date survey of these methods, which is quite welcome since most previous textbooks are at least ten years old. The point of view of the author is to start immediately in the relativistic domain, following the lead of Maxwell's equations rather than classical mechanics, and thus to treat the nonrelativistic version as an approximation. Thus Chapter 1 takes off from Maxwell's equations (in the noncovariant Coulomb gauge) and gradually derives the basic aspects of Quantum Mechanics in a rather pedestrian way (states and observables, Hilbert space, operators, quantum measurement, scattering,. Chapter 2 starts with the Lorentz transformations, then continues with the Pauli spin equation and the Dirac equation and some of their applications (notably the hydrogen atom). Chapter 3 is entitled 'Quantum fields and particles', but falls short of treating quantum field theory properly: only creation/annihilation operators are considered, for a particle in a box. The emphasis is on two-electron states (the Pauli principle, the Foldy--Wouthuysen elimination of small components of Dirac spinors, Breit projection operators. Chapter 4 is devoted to scattering theory and the description of relativistic bound states. Chapter 5, finally, covers hyperfine interactions and radiative corrections. As we said above, relativistic quantum mechanics is by nature limited in scope and rather inelegant and Pilkuhn's book is no exception. The notation is often heavy (mostly noncovariant) and the mathematical level rather low. The central topic

Criteria for selection of target materials and design of high-efficiency-release targets for radioactive ion beam generation

CERN Document Server

Alton, G D; Liu, Y

1999-01-01

In this report, we define criteria for choosing target materials and for designing, mechanically stable, short-diffusion-length, highly permeable targets for generation of high-intensity radioactive ion beams (RIBs) for use at nuclear physics and astrophysics research facilities based on the ISOL principle. In addition, lists of refractory target materials are provided and examples are given of a number of successful targets, based on these criteria, that have been fabricated and tested for use at the Holifield Radioactive Ion Beam Facility (HRIBF).

Mechanisms of Cancer - Annual Plan

Science.gov (United States)

NCI works to understand the mechanisms of cancer cell growth, survival, and metastasis. Get more information on how NCI supports basic scientific research that will lead to new ways to prevent, detect, and treat cancer.

The targets of curcumin.

Science.gov (United States)

Zhou, Hongyu; Beevers, Christopher S; Huang, Shile

2011-03-01

Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-kB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer's disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here.

Nuclear and nucleolar localization signals and their targeting function in phosphatidylinositol 4-kinase PI4K230

International Nuclear Information System (INIS)

Kakuk, Annamaria; Friedlaender, Elza; Vereb, Gyoergy; Lisboa, Duarte; Bagossi, Peter; Toth, Gabor; Gergely, Pal; Vereb, Gyoergy

2008-01-01

PI4K230, an isoform of phosphatidylinositol 4-kinase, known primarily as a cytoplasmic membrane-bound enzyme, was detected recently also in the nucleolus of several cells. Here we provide mechanistic insight on the targeting function of its putative nuclear localization signal (NLS) sequences using molecular modeling, digitonin-permeabilized HeLa cells and binding to various importins. The synthetic sequence 916 NFNHIHKRIRRVADKYLSG 934 comprising a putative monopartite NLS (NLS1), targeted covalently bound fluorescent BSA to the nucleoplasm via classical importin α/β mechanism employing importins α1 and α3 but not α5. This transport was inhibited by wheat germ agglutinin and GTPγS. The sequence 1414 SKKTNRGSQLHKYYMKRRTL 1433 , a putative bipartite NLS (NLS2) proved ineffective in nuclear targeting if conjugated to fluorescently labeled BSA. Nonetheless, NLS2 or either of its basic clusters directed to the nucleolus soybean trypsin inhibitor that can pass the nuclear pore complex passively; moreover, an expressed 58 kDa fragment of PI4K230 (AA1166-1667) comprising NLS2 was also imported into the nucleus by import factors of reticulocyte lysate or by importin α1/β or α3/β complexes and localized to the nucleolus. We conclude that the putative bipartite NLS itself is a nucleolar targeting signal, and for nuclear import PI4K230 requires a larger sequence around it or, alternatively, the monopartite NLS

Caenorhabditis elegans as a Model to Study the Molecular and Genetic Mechanisms of Drug Addiction

Science.gov (United States)

Engleman, Eric A.; Katner, Simon N.; Neal-Beliveau, Bethany S.

2016-01-01

Drug addiction takes a massive toll on society. Novel animal models are needed to test new treatments and understand the basic mechanisms underlying addiction. Rodent models have identified the neurocircuitry involved in addictive behavior and indicate that rodents possess some of the same neurobiologic mechanisms that mediate addiction in humans. Recent studies indicate that addiction is mechanistically and phylogenetically ancient and many mechanisms that underlie human addiction are also present in invertebrates. The nematode Caenorhabditis elegans has conserved neurobiologic systems with powerful molecular and genetic tools and a rapid rate of development that enables cost-effective translational discovery. Emerging evidence suggests that C. elegans is an excellent model to identify molecular mechanisms that mediate drug-induced behavior and potential targets for medications development for various addictive compounds. C. elegans emit many behaviors that can be easily quantitated including some that involve interactions with the environment. Ethanol (EtOH) is the best-studied drug-of-abuse in C. elegans and at least 50 different genes/targets have been identified as mediating EtOH’s effects and polymorphisms in some orthologs in humans are associated with alcohol use disorders. C. elegans has also been shown to display dopamine and cholinergic system–dependent attraction to nicotine and demonstrate preference for cues previously associated with nicotine. Cocaine and methamphetamine have been found to produce dopamine-dependent reward-like behaviors in C. elegans. These behavioral tests in combination with genetic/molecular manipulations have led to the identification of dozens of target genes/systems in C. elegans that mediate drug effects. The one target/gene identified as essential for drug-induced behavioral responses across all drugs of abuse was the cat-2 gene coding for tyrosine hydroxylase, which is consistent with the role of dopamine

Caenorhabditis elegans as a Model to Study the Molecular and Genetic Mechanisms of Drug Addiction.

Science.gov (United States)

Engleman, Eric A; Katner, Simon N; Neal-Beliveau, Bethany S

2016-01-01

Drug addiction takes a massive toll on society. Novel animal models are needed to test new treatments and understand the basic mechanisms underlying addiction. Rodent models have identified the neurocircuitry involved in addictive behavior and indicate that rodents possess some of the same neurobiologic mechanisms that mediate addiction in humans. Recent studies indicate that addiction is mechanistically and phylogenetically ancient and many mechanisms that underlie human addiction are also present in invertebrates. The nematode Caenorhabditis elegans has conserved neurobiologic systems with powerful molecular and genetic tools and a rapid rate of development that enables cost-effective translational discovery. Emerging evidence suggests that C. elegans is an excellent model to identify molecular mechanisms that mediate drug-induced behavior and potential targets for medications development for various addictive compounds. C. elegans emit many behaviors that can be easily quantitated including some that involve interactions with the environment. Ethanol (EtOH) is the best-studied drug-of-abuse in C. elegans and at least 50 different genes/targets have been identified as mediating EtOH's effects and polymorphisms in some orthologs in humans are associated with alcohol use disorders. C. elegans has also been shown to display dopamine and cholinergic system-dependent attraction to nicotine and demonstrate preference for cues previously associated with nicotine. Cocaine and methamphetamine have been found to produce dopamine-dependent reward-like behaviors in C. elegans. These behavioral tests in combination with genetic/molecular manipulations have led to the identification of dozens of target genes/systems in C. elegans that mediate drug effects. The one target/gene identified as essential for drug-induced behavioral responses across all drugs of abuse was the cat-2 gene coding for tyrosine hydroxylase, which is consistent with the role of dopamine neurotransmission

Molecular Targets for Targeted Radionuclide Therapy

International Nuclear Information System (INIS)

Mather, S.J.

2009-01-01

Molecular targeted radionuclide cancer therapy is becoming of increasing importance, especially for disseminated diseases. Systemic chemotherapies often lack selectivity while targeted radionuclide therapy has important advantages as the radioactive cytotoxic unit of the targeting vector is specifically directed to the cancer, sparing normal tissues. The principle strategy to improve cancer selectivity is to couple therapeutic agents to tumour-targeting vectors. In targeted radionuclide therapy (TRT), the cytotoxic portion of the conjugates normally contains a therapeutic radiometal immobilised by a bifunctional chelator. The aim is therefore to use as ligand-targeted therapeutics vectors coupled to Auger-, alpha- and/or beta-emitting radionuclides. An advantage of using radiation instead of chemotherapeutics as the cytotoxic agent is the so called 'crossfire effect'. This allows sterilisation of tumour cells that are not directly targeted due to heterogeneity in target molecule expression or inhomogeneous vector delivery. However, before the targeting ligands can be selected, the target molecule on the tumour has to be selected. It should be uniquely expressed, or at least highly overexpressed, on or in the target cells relative to normal tissues. The target should be easily accessible for ligand delivery and should not be shed or down- regulated after ligand binding. An important property of a receptor (or antigen) is its potential to be internalized upon binding of the ligand. This provides an active uptake mechanism and allows the therapeutic agent to be trapped within the tumour cells. Molecular targets of current interest include: Receptors: G-protein coupled receptors are overexpressed on many major human tumours. The prototype of these receptors are somatostatin receptors which show very high density in neuroendocrine tumours, but there are many other most interesting receptors to be applied for TRT. The targeting ligands for these receptors are

Preparation of thin nuclear targets

International Nuclear Information System (INIS)

Muggleton, A.H.F.

1979-03-01

Thin film backings, sources and targets are needed for many applications in low energy nuclear physics and nuclear chemistry experiments. A survey of techniques used in the preparation of nuclear targets is first briefly discussed. These are classified as chemical, mechanical and physical preparations. Vacuum evaporation, being the most generally used technique, is discussed in detail. It is highly desirable to monitor the film thickness and control the deposition rate during evaporation and to measure the final target thickness after deposition has concluded. The relative merits of various thickness measuring techniques are described. Stages in the fabrication and mounting of self-supporting foils are described in detail, with emphasis given to the preparation of thin self-supporting carbon foils used as target backings and stripper foils. Various target backings, and the merits of the more generally used release agents are described in detail. The preparations of more difficult elemental targets are discussed, and a comprehensive list of the common targets is presented

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.

Tumor target amplification: Implications for nano drug delivery systems.

Science.gov (United States)

Seidi, Khaled; Neubauer, Heidi A; Moriggl, Richard; Jahanban-Esfahlan, Rana; Javaheri, Tahereh

2018-04-10

Tumor cells overexpress surface markers which are absent from normal cells. These tumor-restricted antigenic signatures are a fundamental basis for distinguishing on-target from off-target cells for ligand-directed targeting of cancer cells. Unfortunately, tumor heterogeneity impedes the establishment of a solid expression pattern for a given target marker, leading to drastic changes in quality (availability) and quantity (number) of the target. Consequently, a subset of cancer cells remains untargeted during the course of treatment, which subsequently promotes drug-resistance and cancer relapse. Since target inefficiency is only problematic for cancer treatment and not for treatment of other pathological conditions such as viral/bacterial infections, target amplification or the generation of novel targets is key to providing eligible antigenic markers for effective targeted therapy. This review summarizes the limitations of current ligand-directed targeting strategies and provides a comprehensive overview of tumor target amplification strategies, including self-amplifying systems, dual targeting, artificial markers and peptide modification. We also discuss the therapeutic and diagnostic potential of these approaches, the underlying mechanism(s) and established methodologies, mostly in the context of different nanodelivery systems, to facilitate more effective ligand-directed cancer cell monitoring and targeting. Copyright © 2018 Elsevier B.V. All rights reserved.

Mechanical engineering

International Nuclear Information System (INIS)

1988-01-01

The Mechanical Engineering Division provides the other NAC divisions with design and construction services. Items of special mechanical significance are discussed here. The projects which received major design attention during the past year were: a coupling capacitor for SPC2; a bending magnet and solenoid for ECR ion source; a scanner for outer orbits of the SSC; a scattering chamber for an experimental beamline; a beam swinger; a rotary target magazine for isotope production; a robot arm for isotope production; an isotope transport system and a target cooling system for isotope production. The major projects that were under construction are: a magnetic spectrometer; a second injector cyclotron (SPC2) and extensions to the high-energy beamlines. 4 figs

Sensitivity, uncertainty assessment, and target accuracies related to radiotoxicity evaluation

International Nuclear Information System (INIS)

Palmiotti, G.; Salvatores, M.; Hill, R.N.

1994-01-01

Time-dependent sensitivity techniques, which have been used in the past for standard reactor applications, are adapted to calculate the impact of data uncertainties and to estimate target data accuracies in radiotoxicity evaluations. The methodology is applied to different strategies of radioactive waste management connected with the European Fast Reactor and the Integral Fast Reactor fuel cycles. Results are provided in terms of sensitivity coefficients of basic data (cross sections and decay constants), uncertainties of global radiotoxicity at different times of storing after discharge, and target data accuracies needed to satisfy maximum uncertainty limits

Engineering quantum mechanics

CERN Document Server

Ahn, Doyeol

2011-01-01

A clear introduction to quantum mechanics concepts Quantum mechanics has become an essential tool for modern engineering, particularly due to the recent developments in quantum computing as well as the rapid progress in optoelectronic devices. Engineering Quantum Mechanics explains the fundamentals of this exciting field, providing broad coverage of both traditional areas such as semiconductor and laser physics as well as relatively new yet fast-growing areas such as quantum computation and quantum information technology. The book begins with basic quantum mechanics, reviewing measurements and probability, Dirac formulation, the uncertainty principle, harmonic oscillator, angular momentum eigenstates, and perturbation theory. Then, quantum statistical mechanics is explored, from second quantization and density operators to coherent and squeezed states, coherent interactions between atoms and fields, and the Jaynes-Cummings model. From there, the book moves into elementary and modern applications, discussing s...

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.

Translating basic research in cancer patient care

Directory of Open Access Journals (Sweden)

Marcello Maugeri-Saccà

2011-01-01

Full Text Available With the advent of molecular targeted therapies and the development of high-throughput biotechnologies, it has become evident that progress in cancer research is largely due to the creation of multidisciplinary teams able to plan clinical trials supported by appropriate molecular hypotheses. These efforts have culminated in the identification and validation of biomarkers predictive of response, as well as in the generation of more accurate prognostic tools. The identification of cancer stem cells has provided further insights into mechanisms of cancer, and many studies have tried to translate this biological notion into prognostic and predictive information. In this regard, new agents targeting key stemness-related pathways have entered the clinical development, and preliminary data suggested an encouraging antitumor activity.

Tracking considerations for fixed target B experiments at SSC and LHC

International Nuclear Information System (INIS)

McManus, A.P.; Conetti, S.; Corti, G.; Cox, B.; Dukes, E.C.; Lawry, T.; Nelson, K.; Tzamouranis, I.

1993-01-01

Fixed target beauty (B) experiments proposed at the SSC or LHC come in two basic types. Extracted beam experiments use a bent crystal of silicon or some other method to extract a beam of protons parasitically from the circulating beam as the collider experiments are taking data. The two chief extracted beam experiments are the LHB collaboration at the LHC and the SFT collaboration at the SSC. The second type of fixed target experiment places the detector around the circulating beam using a gas jet or thin wire(s) as a target. The (GAJET) experiment proposed at CERN for LHC and the Hera-B experiment at DESY are of this type

[Resistance to target-based therapy and its circumvention].

Science.gov (United States)

Nishio, Kazuto

2004-07-01

Intrinsic and acquired resistance to molecular target therapy critically limits the outcome of cancer treatments. Target levels including quantitative and gene alteration should be determinants for the resistance. Downstream of the target molecules, drug metabolism, and drug transport influences the tumor sensitivity to molecular target therapy. The mechanisms of resistance to antibody therapy have not been fully clarified. Correlative clinical studies using these biomarkers of resistance are extremely important for circumvention of clinical resistance to target based therapy.

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

Understanding the molecular mechanisms of reprogramming

Energy Technology Data Exchange (ETDEWEB)

Krause, Marie N. [Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla 92037, CA (United States); University Hospital of Würzburg, Department of Pediatrics, 2 Josef-Schneiderstrasse, 97080 Würzburg (Germany); Sancho-Martinez, Ignacio [Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla 92037, CA (United States); Centre for Stem Cells and Regenerative Medicine, King' s College London, 28th Floor, Tower Wing, Guy' s Hospital, Great Maze Pond, London (United Kingdom); Izpisua Belmonte, Juan Carlos, E-mail: belmonte@salk.edu [Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla 92037, CA (United States)

2016-05-06

Despite the profound and rapid advancements in reprogramming technologies since the generation of the first induced pluripotent stem cells (iPSCs) in 2006[1], the molecular basics of the process and its implications are still not fully understood. Recent work has suggested that a subset of TFs, so called “Pioneer TFs”, play an important role during the stochastic phase of iPSC reprogramming [2–6]. Pioneer TFs activities differ from conventional transcription factors in their mechanism of action. They bind directly to condensed chromatin and elicit a series of chromatin remodeling events that lead to opening of the chromatin. Chromatin decondensation by pioneer factors progressively occurs during cell division and in turn exposes specific gene promoters in the DNA to which TFs can now directly bind to promoters that are readily accessible[2, 6]. Here, we will summarize recent advancements on our understanding of the molecular mechanisms underlying reprogramming to iPSC as well as the implications that pioneer Transcription Factor activities might play during different lineage conversion processes. - Highlights: • Pioneer transcription factor activity underlies the initial steps of iPSC generation. • Reprogramming can occur by cis- and/or trans- reprogramming events. • Cis-reprogramming implies remodeling of the chromatin for enabling TF accessibility. • Trans-reprogramming encompasses direct binding of Tfs to their target gene promoters.

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''.

Disease-Associated Particulates and Joint Inflammation; Mechanistic Insights and Potential Therapeutic Targets

Directory of Open Access Journals (Sweden)

Olwyn R. Mahon

2018-05-01

Full Text Available It is now well established that intra-articular deposition of endogenous particulates, such as osteoarthritis-associated basic calcium phosphate crystals, gout-associated monosodium urate crystals, and calcium deposition disease-associated calcium pyrophosphate crystals, contributes to joint destruction through the production of cartilage-degrading enzymes and pro-inflammatory cytokines. Furthermore, exogenous wear-debris particles, generated from prosthetic implants, drive periprosthetic osteolysis which impacts on the longevity of total joint replacements. Over the last few years, significant insight has been gained into the mechanisms through which these particulates exert their effects. Not only has this increased our understanding of the pathological processes associated with crystal deposition but it has also led to the identification of a number of therapeutic targets to treat particulate-associated disease. In this review, we discuss recent developments regarding the cellular events triggered by joint-associated particulates, as well as future directions in therapy for particulate-related arthropathies.

Quantum mechanics I the fundamentals

CERN Document Server

Rajasekar, S

2015-01-01

Quantum Mechanics I: The Fundamentals provides a graduate-level account of the behavior of matter and energy at the molecular, atomic, nuclear, and sub-nuclear levels. It covers basic concepts, mathematical formalism, and applications to physically important systems.

The Molecular and Cellular Mechanisms of Axon Guidance in Mossy Fiber Sprouting

Directory of Open Access Journals (Sweden)

Ryuta Koyama

2018-05-01

Full Text Available The question of whether mossy fiber sprouting is epileptogenic has not been resolved; both sprouting-induced recurrent excitatory and inhibitory circuit hypotheses have been experimentally (but not fully supported. Therefore, whether mossy fiber sprouting is a potential therapeutic target for epilepsy remains under debate. Moreover, the axon guidance mechanisms of mossy fiber sprouting have attracted the interest of neuroscientists. Sprouting of mossy fibers exhibits several uncommon axonal growth features in the basically non-plastic adult brain. For example, robust branching of axonal collaterals arises from pre-existing primary mossy fiber axons. Understanding the branching mechanisms in adulthood may contribute to axonal regeneration therapies in neuroregenerative medicine in which robust axonal re-growth is essential. Additionally, because granule cells are produced throughout life in the neurogenic dentate gyrus, it is interesting to examine whether the mossy fibers of newly generated granule cells follow the pre-existing trajectories of sprouted mossy fibers in the epileptic brain. Understanding these axon guidance mechanisms may contribute to neuron transplantation therapies, for which the incorporation of transplanted neurons into pre-existing neural circuits is essential. Thus, clarifying the axon guidance mechanisms of mossy fiber sprouting could lead to an understanding of central nervous system (CNS network reorganization and plasticity. Here, we review the molecular and cellular mechanisms of axon guidance in mossy fiber sprouting by discussing mainly in vitro studies.

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

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

Evaluation of the effect of prepulses on HF laser-target interactions

International Nuclear Information System (INIS)

Matzen, M.K.

1979-06-01

We have assessed the effect of multinanosecond, low-power-density prepulses on the interaction of multinanosecond, 10 14 W/cm 2 , approx. 3 -μm HF laser pulses with slab targets. The emphasis is on analyzing absorption and x-ray conversion efficiency. A survey of previous experiments gives no evidence that these prepulses will affect the total absorption. However, prepulses have been observed to cause qualitative changes in both the x-ray spectrum and conversion efficiency. Numerical simulations indicate that the laser-target interaction is effectively insensitive to low-power-density prepulses. These studies imply that basic laser-target experiments with multiplexed, HF laser pulses will provide an important characterization of the interaction of long pulse, multi-line, approx. 3 μm radiation with targets. Future wavelength comparison experiments will require prepulse suppression or target isolation

Risk-targeted maps for Romania

Science.gov (United States)

Vacareanu, Radu; Pavel, Florin; Craciun, Ionut; Coliba, Veronica; Arion, Cristian; Aldea, Alexandru; Neagu, Cristian

2018-03-01

Romania has one of the highest seismic hazard levels in Europe. The seismic hazard is due to a combination of local crustal seismic sources, situated mainly in the western part of the country and the Vrancea intermediate-depth seismic source, which can be found at the bend of the Carpathian Mountains. Recent seismic hazard studies have shown that there are consistent differences between the slopes of the seismic hazard curves for sites situated in the fore-arc and back-arc of the Carpathian Mountains. Consequently, in this study we extend this finding to the evaluation of the probability of collapse of buildings and finally to the development of uniform risk-targeted maps. The main advantage of uniform risk approach is that the target probability of collapse will be uniform throughout the country. Finally, the results obtained are discussed in the light of a recent study with the same focus performed at European level using the hazard data from SHARE project. The analyses performed in this study have pointed out to a dominant influence of the quantile of peak ground acceleration used for anchoring the fragility function. This parameter basically alters the shape of the risk-targeted maps shifting the areas which have higher collapse probabilities from eastern Romania to western Romania, as its exceedance probability increases. Consequently, a uniform procedure for deriving risk-targeted maps appears as more than necessary.

Rapid Deterioration of Basic Life Support Skills in Dentists With Basic Life Support Healthcare Provider.

Science.gov (United States)

Nogami, Kentaro; Taniguchi, Shogo; Ichiyama, Tomoko

2016-01-01

The aim of this study was to investigate the correlation between basic life support skills in dentists who had completed the American Heart Association's Basic Life Support (BLS) Healthcare Provider qualification and time since course completion. Thirty-six dentists who had completed the 2005 BLS Healthcare Provider course participated in the study. We asked participants to perform 2 cycles of cardiopulmonary resuscitation on a mannequin and evaluated basic life support skills. Dentists who had previously completed the BLS Healthcare Provider course displayed both prolonged reaction times, and the quality of their basic life support skills deteriorated rapidly. There were no correlations between basic life support skills and time since course completion. Our results suggest that basic life support skills deteriorate rapidly for dentists who have completed the BLS Healthcare Provider. Newer guidelines stressing chest compressions over ventilation may help improve performance over time, allowing better cardiopulmonary resuscitation in dental office emergencies. Moreover, it may be effective to provide a more specialized version of the life support course to train the dentists, stressing issues that may be more likely to occur in the dental office.

Mechanics and thermodynamics

CERN Document Server

Demtröder, Wolfgang

2017-01-01

This introduction to classical mechanics and thermodynamics provides an accessible and clear treatment of the fundamentals. Starting with particle mechanics and an early introduction to special relativity this textbooks enables the reader to understand the basics in mechanics. The text is written from the experimental physics point of view, giving numerous real life examples and applications of classical mechanics in technology. This highly motivating presentation deepens the knowledge in a very accessible way. The second part of the text gives a concise introduction to rotational motion, an expansion to rigid bodies, fluids and gases. Finally, an extensive chapter on thermodynamics and a short introduction to nonlinear dynamics with some instructive examples intensify the knowledge of more advanced topics. Numerous problems with detailed solutions are perfect for self study.

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.

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 ...

Eye tracking a self-moved target with complex hand-target dynamics

Science.gov (United States)

Landelle, Caroline; Montagnini, Anna; Madelain, Laurent

2016-01-01

Previous work has shown that the ability to track with the eye a moving target is substantially improved when the target is self-moved by the subject's hand compared with when being externally moved. Here, we explored a situation in which the mapping between hand movement and target motion was perturbed by simulating an elastic relationship between the hand and target. Our objective was to determine whether the predictive mechanisms driving eye-hand coordination could be updated to accommodate this complex hand-target dynamics. To fully appreciate the behavioral effects of this perturbation, we compared eye tracking performance when self-moving a target with a rigid mapping (simple) and a spring mapping as well as when the subject tracked target trajectories that he/she had previously generated when using the rigid or spring mapping. Concerning the rigid mapping, our results confirmed that smooth pursuit was more accurate when the target was self-moved than externally moved. In contrast, with the spring mapping, eye tracking had initially similar low spatial accuracy (though shorter temporal lag) in the self versus externally moved conditions. However, within ∼5 min of practice, smooth pursuit improved in the self-moved spring condition, up to a level similar to the self-moved rigid condition. Subsequently, when the mapping unexpectedly switched from spring to rigid, the eye initially followed the expected target trajectory and not the real one, thereby suggesting that subjects used an internal representation of the new hand-target dynamics. Overall, these results emphasize the stunning adaptability of smooth pursuit when self-maneuvering objects with complex dynamics. PMID:27466129

Neural processing of basic tastes in healthy young and older adults - an fMRI study