A molecular rotor based ratiometric sensor for basic amino acids

NASA Astrophysics Data System (ADS)

Pettiwala, Aafrin M.; Singh, Prabhat K.

2018-01-01

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.

Developments on GM-Type Pulse Tube Cryorefrigerators with Large Cooling Power

NASA Astrophysics Data System (ADS)

Köttig, T.; Waldauf, A.; Thürk, M.; Seidel, P.

2004-06-01

Over the past several years the authors have participated in basic and prototype developments of four valve pulse tube refrigerators (FVPTR). Systematic studies have been carried out to characterize the basics of energy transport mechanisms, the flow distribution and loss mechanisms of this type of pulse tube refrigerator (PTR) with its active type of phase shifting. Based on the comprehension of these phenomena, several prototypes have been built and optimized for various applications. Recently a single-stage PTR in coaxial arrangement has been designed for maximum refrigeration power in the temperature range between 20 and 80 K limited by an available electrical input power of 7 kW. To reach this goal we used lead screens in the coldest part of the regenerator instead of spheres in order to decrease the pressure drop. The improvement of the regenerator prevents the reported fact that at higher temperatures the performance of a pulse tube with a regenerator partially filled with lead spheres can even be worse than a regenerator totally made of stainless steel. At the moment the cooler provides a cooling power of 120 W@74 K and 40 W@34 K. The minimum no-load temperature achieved is 18.6 K.

Polymers in Fluid Flows

NASA Astrophysics Data System (ADS)

Benzi, Roberto; Ching, Emily S. C.

2018-03-01

The interaction of flexible polymers with fluid flows leads to a number of intriguing phenomena observed in laboratory experiments, namely drag reduction, elastic turbulence, and heat transport modification in natural convection, and is one of the most challenging subjects in soft matter physics. In this review, we examine our present knowledge on the subject. Our present knowledge is mostly based on direct numerical simulations performed in the last twenty years, which have successfully explained, at least qualitatively, most of the experimental results. Our goal is to disentangle as much as possible the basic mechanisms acting in the system in order to capture the basic features underlying different theoretical approaches and explanations.

Theoretical investigation of crack formation in tungsten after heat loads

NASA Astrophysics Data System (ADS)

Arakcheev, A. S.; Huber, A.; Wirtz, M.; Sergienko, G.; Steudel, I.; Burdakov, A. V.; Coenen, J. W.; Kreter, A.; Linke, J.; Mertens, Ph.; Shoshin, A. A.; Unterberg, B.; Vasilyev, A. A.

2015-08-01

Transient events such as ELMs in large plasma devices lead to significant heat load on plasma-facing components (PFCs). ELMs cause mechanical damage of PFCs (e.g. cracks). The cracks appear due to stresses caused by thermal extension. Analytical calculations of the stresses are carried out for tungsten. The model only takes into account the basic features of solid body mechanics without material modifications (e.g. fatigue or recrystallization). The numerical results of the model demonstrate good agreement with experimental data obtained at the JUDITH-1, PSI-2 and GOL-3 facilities.

In vivo imaging of neuronal calcium during electrode implantation: Spatial and temporal mapping of damage and recovery.

PubMed

Eles, James R; Vazquez, Alberto L; Kozai, Takashi D Y; Cui, X Tracy

2018-08-01

Implantable electrode devices enable long-term electrophysiological recordings for brain-machine interfaces and basic neuroscience research. Implantation of these devices, however, leads to neuronal damage and progressive neural degeneration that can lead to device failure. The present study uses in vivo two-photon microscopy to study the calcium activity and morphology of neurons before, during, and one month after electrode implantation to determine how implantation trauma injures neurons. We show that implantation leads to prolonged, elevated calcium levels in neurons within 150 μm of the electrode interface. These neurons show signs of mechanical distortion and mechanoporation after implantation, suggesting that calcium influx is related to mechanical trauma. Further, calcium-laden neurites develop signs of axonal injury at 1-3 h post-insert. Over the first month after implantation, physiological neuronal calcium activity increases, suggesting that neurons may be recovering. By defining the mechanisms of neuron damage after electrode implantation, our results suggest new directions for therapies to improve electrode longevity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Tissue mechanics and fibrosis.

PubMed

Wells, Rebecca G

2013-07-01

Mechanical forces are essential to the development and progression of fibrosis, and are likely to be as important as soluble factors. These forces regulate the phenotype and proliferation of myofibroblasts and other cells in damaged tissues, the activation of growth factors, the structure and mechanics of the matrix, and, potentially, tissue patterning. Better understanding of the variety and magnitude of forces, the characteristics of those forces in biological tissues, and their impact on fibrosis in multiple tissues is needed and may lead to identification of important new therapeutic targets. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease. Copyright © 2013 Elsevier B.V. All rights reserved.

Advances in sepsis research derived from animal models.

PubMed

Männel, Daniela N

2007-09-01

Inflammation is the basic process by which tissues of the body respond to infection. Activation of the immune system normally leads to removal of microbial pathogens, and after resolution of the inflammation immune homeostasis is restored. This controlled process, however, can be disturbed resulting in disease. Therefore, many studies using infection models have investigated the participating immune mechanisms aiming at possible therapeutic interventions. Defined model substances such as bacterial lipopolysaccharide (endotoxin) have been used to mimic bacterial infections and analyze their immune stimulating functions. A complex network of molecular mechanisms involved in the recognition and activation processes of bacterial infections and their regulation has developed from these studies. More complex infection models will now help to interpret earlier observations leading to the design of relevant new infection models.

Basic Information about Lead in Drinking Water

MedlinePlus

... Water and Drinking Water Contact Us Share Basic Information about Lead in Drinking Water Have a question ... Related Information from Other Federal Government Agencies General Information about Lead in Drinking Water How Lead Gets ...

A molecular rotor based ratiometric sensor for basic amino acids.

PubMed

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.

The Nucleosome Remodeling and Deacetylase (NuRD) Complex in Development and Disease

PubMed Central

Basta, Jeannine; Rauchman, Michael

2014-01-01

The Nucleosome Remodeling and Deacetylase (NuRD) complex is one of the major chromatin remodeling complexes found in cells. It plays an important role in regulating gene transcription, genome integrity and cell cycle progression. Through its impact on these basic cellular processes, increasing evidence indicates that alterations in the activity of this macromolecular complex can lead to developmental defects, oncogenesis and accelerated ageing. Recent genetic and biochemical studies have elucidated the mechanisms of NuRD action in modifying the chromatin landscape. These advances have the potential to lead to new therapeutic approaches to birth defects and cancer. PMID:24880148

Mechanical Properties of Transcription

NASA Astrophysics Data System (ADS)

Sevier, Stuart A.; Levine, Herbert

2017-06-01

The mechanical properties of transcription have recently been shown to play a central role in gene expression. However, a full physical characterization of this central biological process is lacking. In this Letter, we introduce a simple description of the basic physical elements of transcription where RNA elongation, RNA polymerase rotation, and DNA supercoiling are coupled. The resulting framework describes the relative amount of RNA polymerase rotation and DNA supercoiling that occurs during RNA elongation. Asymptotic behavior is derived and can be used to experimentally extract unknown mechanical parameters of transcription. Mechanical limits to transcription are incorporated through the addition of a DNA supercoiling-dependent RNA polymerase velocity. This addition can lead to transcriptional stalling and resulting implications for gene expression, chromatin structure and genome organization are discussed.

Synergistic interactions of lipids and myelin basic protein

NASA Astrophysics Data System (ADS)

Hu, Yufang; Doudevski, Ivo; Wood, Denise; Moscarello, Mario; Husted, Cynthia; Genain, Claude; Zasadzinski, Joseph A.; Israelachvili, Jacob

2004-09-01

This report describes force measurements and atomic force microscope imaging of lipid-protein interactions that determine the structure of a model membrane system that closely mimics the myelin sheath. Our results suggest that noncovalent, mainly electrostatic and hydrophobic, interactions are responsible for the multilamellar structure and stability of myelin. We find that myelin basic protein acts as a lipid coupler between two apposed bilayers and as a lipid "hole-filler," effectively preventing defect holes from developing. From our protein-mediated-adhesion and force-distance measurements, we develop a simple quantitative model that gives a reasonably accurate picture of the molecular mechanism and adhesion of bilayer-bridging proteins by means of noncovalent interactions. The results and model indicate that optimum myelin adhesion and stability depend on the difference between, rather than the product of, the opposite charges on the lipid bilayers and myelin basic protein, as well as on the repulsive forces associated with membrane fluidity, and that small changes in any of these parameters away from the synergistically optimum values can lead to large changes in the adhesion or even its total elimination. Our results also show that the often-asked question of which membrane species, the lipids or the proteins, are the "important ones" may be misplaced. Both components work synergistically to provide the adhesion and overall structure. A better appreciation of the mechanism of this synergy may allow for a better understanding of stacked and especially myelin membrane structures and may lead to better treatments for demyelinating diseases such as multiple sclerosis. lipid-protein interactions | myelin membrane structure | membrane adhesion | membrane regeneration/healing | demyelinating diseases

Nonlinear growth dynamics and the origin of fluctuating asymmetry

USGS Publications Warehouse

Emlen, J.M.; Freeman, D.C.; Graham, J.H.

1993-01-01

The nonlinear, complex nature of biosynthesis magnifies the impacts of small, random perturbations on organism growth, leading to distortions in adaptive allometries and, in particular, to fluctuating asymmetry. These distortions can be partly checked by cell-cell and inter-body part feedback during growth and development, though the latter mechanism also may lead to complex patterns in right-left asymmetry. Stress can be expected to increase the degree to which random growth perturbations are magnified and may also result in disruption of the check mechanisms, thus exaggerating fluctuating asymmetry.The processes described not only provide one explanation for the existence of fluctuating asymmetry and its augmentation under stress, but suggest additional effects of stress as well. Specifically, stress is predicted to lead to decreased fractal dimension of bone sutures and branching structures in animals, and in increased dimension of growth trace patterns such as those found in mollusc shells and fish otoliths and scales.A basic yet broad primer on fractals and chaos is provided as background for the theoretical development in this manuscript.

Unraveling hadron structure with generalized parton distributions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andrei Belitsky; Anatoly Radyushkin

2004-10-01

The recently introduced generalized parton distributions have emerged as a universal tool to describe hadrons in terms of quark and gluonic degrees of freedom. They combine the features of form factors, parton densities and distribution amplitudes - the functions used for a long time in studies of hadronic structure. Generalized parton distributions are analogous to the phase-space Wigner quasi-probability function of non-relativistic quantum mechanics which encodes full information on a quantum-mechanical system. We give an extensive review of main achievements in the development of this formalism. We discuss physical interpretation and basic properties of generalized parton distributions, their modeling andmore » QCD evolution in the leading and next-to-leading orders. We describe how these functions enter a wide class of exclusive reactions, such as electro- and photo-production of photons, lepton pairs, or mesons.« less

Biominerals- hierarchical nanocomposites: the example of bone

PubMed Central

Beniash, Elia

2010-01-01

Many organisms incorporate inorganic solids in their tissues to enhance their functional, primarily mechanical, properties. These mineralized tissues, also called biominerals, are unique organo-mineral nanocomposites, organized at several hierarchical levels, from nano- to macroscale. Unlike man made composite materials, which often are simple physical blends of their components, the organic and inorganic phases in biominerals interface at the molecular level. Although these tissues are made of relatively weak components at ambient conditions, their hierarchical structural organization and intimate interactions between different elements lead to superior mechanical properties. Understanding basic principles of formation, structure and functional properties of these tissues might lead to novel bioinspired strategies for material design and better treatments for diseases of the mineralized tissues. This review focuses on general principles of structural organization, formation and functional properties of biominerals on the example the bone tissues. PMID:20827739

Inclusion-body myositis and myopathies: different etiologies, possibly similar pathogenic mechanisms.

PubMed

Askanas, Valerie; Engel, W King

2002-10-01

Sporadic inclusion-body myositis (s-IBM) and hereditary inclusion body myopathies are progressive muscle diseases that lead to severe disability. We discuss recent advances in illuminating their pathogenic mechanism(s). We emphasize how different etiologies might lead to the strikingly similar pathology and possibly similar pathogenic cascade. Our basic hypothesis is that over-expression of amyloid-beta precursor protein within aging muscle fibers is an early upstream event causing the subsequent pathogenic cascade. On the basis of our research, several processes seem to be important in relation to the still speculative pathogenesis: (a) increased transcription and accumulation of amyloid-beta precursor protein, and accumulation of its proteolytic fragment Abeta; (b) accumulations of phosphorylated tau and other Alzheimer-related proteins; (c) accumulation of cholesterol and low-density lipoprotein receptors, the cholesterol accumulation possibly due to its abnormal trafficking; (d) oxidative stress; and (e) a milieu of muscle cellular aging in which these changes occur. We discuss unfolded and/or misfolded proteins as a possible mechanism in formation of the inclusion bodies and their consequences. The remarkable pathologic similarities between s-IBM muscle and Alzheimer disease brain are discussed. Unfolding knowledge of the various pathogenetic aspects of the s-IBMs and hereditary inclusion body myopathies may lead to new therapeutic avenues.

Basic principles of respiratory function monitoring in ventilated newborns: A review.

PubMed

Schmalisch, Gerd

2016-09-01

Respiratory monitoring during mechanical ventilation provides a real-time picture of patient-ventilator interaction and is a prerequisite for lung-protective ventilation. Nowadays, measurements of airflow, tidal volume and applied pressures are standard in neonatal ventilators. The measurement of lung volume during mechanical ventilation by tracer gas washout techniques is still under development. The clinical use of capnography, although well established in adults, has not been embraced by neonatologists because of technical and methodological problems in very small infants. While the ventilatory parameters are well defined, the calculation of other physiological parameters are based upon specific assumptions which are difficult to verify. Incomplete knowledge of the theoretical background of these calculations and their limitations can lead to incorrect interpretations with clinical consequences. Therefore, the aim of this review was to describe the basic principles and the underlying assumptions of currently used methods for respiratory function monitoring in ventilated newborns and to highlight methodological limitations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cell Therapy for Lung Diseases. Report from an NIH–NHLBI Workshop, November 13–14, 2012

PubMed Central

Matthay, Michael A.; Anversa, Piero; Bhattacharya, Jahar; Burnett, Bruce K.; Chapman, Harold A.; Hare, Joshua M.; Hei, Derek J.; Hoffman, Andrew M.; Kourembanas, Stella; McKenna, David H.; Ortiz, Luis A.; Ott, Harald C.; Tente, William; Thébaud, Bernard; Trapnell, Bruce C.; Weiss, Daniel J.; Yuan, Jason X.-J.

2013-01-01

The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health convened the Cell Therapy for Lung Disease Working Group on November 13–14, 2012, to review and formulate recommendations for future research directions. The workshop brought together investigators studying basic mechanisms and the roles of cell therapy in preclinical models of lung injury and pulmonary vascular disease, with clinical trial experts in cell therapy for cardiovascular diseases and experts from the NHLBI Production Assistance for Cell Therapy program. The purpose of the workshop was to discuss the current status of basic investigations in lung cell therapy, to identify some of the scientific gaps in current knowledge regarding the potential roles and mechanisms of cell therapy in the treatment of lung diseases, and to develop recommendations to the NHLBI and the research community on scientific priorities and practical steps that would lead to first-in-human trials of lung cell therapy. PMID:23713908

A simple polymeric model describes cell nuclear mechanical response

NASA Astrophysics Data System (ADS)

Banigan, Edward; Stephens, Andrew; Marko, John

The cell nucleus must continually resist inter- and intracellular mechanical forces, and proper mechanical response is essential to basic cell biological functions as diverse as migration, differentiation, and gene regulation. Experiments probing nuclear mechanics reveal that the nucleus stiffens under strain, leading to two characteristic regimes of force response. This behavior depends sensitively on the intermediate filament protein lamin A, which comprises the outer layer of the nucleus, and the properties of the chromatin interior. To understand these mechanics, we study a simulation model of a polymeric shell encapsulating a semiflexible polymer. This minimalistic model qualitatively captures the typical experimental nuclear force-extension relation and observed nuclear morphologies. Using a Flory-like theory, we explain the simulation results and mathematically estimate the force-extension relation. The model and experiments suggest that chromatin organization is a dominant contributor to nuclear mechanics, while the lamina protects cell nuclei from large deformations.

Self-Organization of Stem Cell Colonies and of Early Mammalian Embryos: Recent Experiments Shed New Light on the Role of Autonomy vs. External Instructions in Basic Body Plan Development

PubMed Central

Denker, Hans-Werner

2016-01-01

“Organoids”, i.e., complex structures that can develop when pluripotent or multipotent stem cells are maintained in three-dimensional cultures, have become a new area of interest in stem cell research. Hopes have grown that when focussing experimentally on the mechanisms behind this type of in vitro morphogenesis, research aiming at tissue and organ replacements can be boosted. Processes leading to the formation of organoids in vitro are now often addressed as self-organization, a term referring to the formation of complex tissue architecture in groups of cells without depending on specific instruction provided by other cells or tissues. The present article focuses on recent reports using the term self-organization in the context of studies on embryogenesis, specifically addressing pattern formation processes in human blastocysts attaching in vitro, or in colonies of pluripotent stem cells (“gastruloids”). These morphogenetic processes are of particular interest because, during development in vivo, they lead to basic body plan formation and individuation. Since improved methodologies like those employed by the cited authors became available, early embryonic pattern formation/self-organization appears to evolve now as a research topic of its own. This review discusses concepts concerning the involved mechanisms, focussing on autonomy of basic body plan development vs. dependence on external signals, as possibly provided by implantation in the uterus, and it addresses biological differences between an early mammalian embryo, e.g., a morula, and a cluster of pluripotent stem cells. It is concluded that, apart from being of considerable biological interest, the described type of research needs to be contemplated carefully with regard to ethical implications when performed with human cells. PMID:27792143

Self-Organization of Stem Cell Colonies and of Early Mammalian Embryos: Recent Experiments Shed New Light on the Role of Autonomy vs. External Instructions in Basic Body Plan Development.

PubMed

Denker, Hans-Werner

2016-10-25

" Organoids ", i.e., complex structures that can develop when pluripotent or multipotent stem cells are maintained in three-dimensional cultures, have become a new area of interest in stem cell research. Hopes have grown that when focussing experimentally on the mechanisms behind this type of in vitro morphogenesis, research aiming at tissue and organ replacements can be boosted. Processes leading to the formation of organoids in vitro are now often addressed as self-organization , a term referring to the formation of complex tissue architecture in groups of cells without depending on specific instruction provided by other cells or tissues. The present article focuses on recent reports using the term self-organization in the context of studies on embryogenesis , specifically addressing pattern formation processes in human blastocysts attaching in vitro, or in colonies of pluripotent stem cells (" gastruloids "). These morphogenetic processes are of particular interest because, during development in vivo, they lead to basic body plan formation and individuation. Since improved methodologies like those employed by the cited authors became available, early embryonic pattern formation/self-organization appears to evolve now as a research topic of its own. This review discusses concepts concerning the involved mechanisms, focussing on autonomy of basic body plan development vs. dependence on external signals, as possibly provided by implantation in the uterus, and it addresses biological differences between an early mammalian embryo, e.g., a morula, and a cluster of pluripotent stem cells. It is concluded that, apart from being of considerable biological interest, the described type of research needs to be contemplated carefully with regard to ethical implications when performed with human cells.

WEST ELEVATION OF USAIR MAINTENANCE HANGAR AT GREATER BUFFALO INTERNATIONAL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

WEST ELEVATION OF USAIR MAINTENANCE HANGAR AT GREATER BUFFALO INTERNATIONAL AIRPORT. A BOEING 737-200 HAS BEEN TOWED IN FOR AN OVERNIGHT (BALANCE) CHECK. THE TAIL DOCK STANDS ARE IN POSITION AT THE REAR OF THE AIRCRAFT TO FACILITATE INSPECTION. MAINTENANCE CREWS PERFORM NIGHTLY SERVICE ON UP TO 6 AIRCRAFT. THE NORMAL SEQUENCE OF 12 ROUTINE CHECKS COVERS SEVEN BASIC AREAS: INTERIOR, EXTERIOR, WINGS, LANDING GEAR, TAIL, AUXILIARY POWER UNIT (APU), AND ENGINES. THE WORK FORCE CONSISTS OF 5 INSPECTORS, 3 LEAD MECHANICS, AND 24 MECHANICS; NIGHTLY SCHEDULES ARE COORDINATED BY A PLANNER. - Greater Buffalo International Airport, Maintenance Hangar, Buffalo, Erie County, NY

CROI 2018: Advances in Basic Science Understanding of HIV.

PubMed

Stevenson, Mario

2018-05-01

The conference on Retroviruses and Opportunistic Infections represents the most important venue for the dissemination of research advances in HIV and AIDS. The 25th conference, held in Boston, featured presentations that provided insight into the mechanisms of HIV-1 spread in tissues as well as new information on mechanisms of HIV-1 persistence in individuals on effective antiretroviral treatment. The ability of the conference to convey research findings for a general audience is enhanced, to a large part, by preconference workshops. These workshops feature leading researchers who aim to present cutting edge research to a general audience. These sessions rank highly in terms of education and professional value.

Free radicals in the regulation of damage and cell death - basic mechanisms and prevention.

PubMed

Silva, J P; Coutinho, O P

2010-06-01

Reactive oxygen (ROS) and nitrogen (RNS) species are known to accumulate intracellularly due to both exogenous and/or endogenous factors. In normal physiological conditions, these reactive species are maintained in an equilibrium state by the cells' antioxidant defence systems. In addition, they are recognised to play important roles in several physiological functions. However, when an imbalance in the equilibrium between oxidants and antioxidants occurs in favour of the former, we come to a situation defined as oxidative stress. ROS/RNS can cause damage to all biomolecules (namely proteins, lipids and DNA) and ultimately participate in the regulation of mechanisms leading to cell death, being implicated in the etiology of several pathologies (like neurodegenerative and cardiovascular diseases). To cope with oxidative stress, cells possess effective enzymatic (e.g. superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic (e.g. glutathione, thioredoxin, coenzyme Q) antioxidant systems. In addition, several compounds present in plants and vegetables (e.g. vitamins C and E, polyphenols) have been described to react with free radicals. However, some drawbacks associated to these natural compounds are in part responsible for the undergoing development of novel synthetic compounds capable of acting as antioxidants and protect cells against oxidative stress-induced cell death. Here, we review the basic mechanisms of ROS/RNS formation, as well as their interaction with biomolecules and regulation of cell death, in order to identify possible drug targets. We also report the importance of natural antioxidant systems and the ongoing research leading to the development of more powerful and effective antioxidant drugs.

Pathophysiology of chest trauma.

PubMed

Calhoon, J H; Trinkle, J K

1997-05-01

Recent information indicates that there is a complex cellular and molecular generic response to injury that can lead to multi-organ failure. For many years, basic physiology and biochemistry were considered to be the systemic mechanisms to injury, but now it is known that subcellular and molecular events are the keys to unlocking the secrets of the body's response to trauma. The interaction of the endothelial cell with neutrophils and platelets to produce cytokines, free radicals, and upregulating adhesion molecules is especially significant.

Lead/acid battery development for heat engine/electric hybrid vehicles. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giner, J.; Taylor, A.H.; Goebel, F.

A program was undertaken to develop a lead/acid battery system for use in a hybrid heat engine/electric vehicle. The basic requirements are that the battery be capable of supplying high-rate power pulses and of accepting high-rate charge pulses, both of short duration. The feasibility of developing a bipolar lead/acid battery system which conforms to these specifications was investigated by using a modular approach to system design. In the preferred design, a vertical array of lead strips placed on either side of each substrate are connected with adjacent strips on the opposite side only over the top of the substrate tomore » provide electrical conduction through the substrate. The following topics are discussed concerning this system: study of electrochemical problem areas relevant to design of a high-power-density battery; corrosion of substrate materials; development and mechanical testing of structures; life testing; design and preliminary cost analysis.« less

Malassezia species and seborrheic dermatitis.

PubMed

Zisova, Lilia G

2009-01-01

Malassezia spp. are medically important dimorphic, lipophilic yeasts that form part of the normal cutaneous microflora of human. Seborrheic dermatitis is a multifactor disease that needs endogenous and exogenous predisposing factors for its development. Presence of these factors leads to reproduction of the saprophytic opportunistic pathogen Malassezia spp. and development of a disease. The inflammatory reaction against the yeast Malassezia is considered basic in the etiology of the seborrheic dermatitis. The pathogenesis and exact mechanisms via which these yeasts cause inflammation are still not fully elucidated. They are rather complex and subject of controversy in literature. Most probably Malassezia spp. cause seborrheic dermatitis by involving and combining both nonummune and immune mechanisms (nonspecific and specific). Which of these mechanisms will dominate in any single case depends on the number and virulence of the yeasts as well as on the microorganism reactivity. In the recent years a great interest have been aroused by the epidemiological investigations. Depending on the geographical place of the countries different Malassezia species in seborrheic dermatitis dominate in the different countries. In view of the etiology and pathogenesis of the seborrheic dermatitis comprehensive antifungal preparations have been recently introduced and are nowadays the basic therapeutic resource in the treatment of this disease.

Aspects of the mechanisms of smoke generation by burning materials

NASA Technical Reports Server (NTRS)

Bankston, C. P.; Zinn, B. T.; Browner, R. F.; Powell, E. A.

1981-01-01

An investigation of smoke generation during the burning of natural and synthetic solid materials (relevant to fire safety problems), under simulated fire conditions, is presented. Smoke formation mechanisms, including flaming and nonflaming combustion, are reviewed, and the complex physical, chemical, and electrical processes, important in smoke particulate production, are identified. With reference to the smoke formation mechanisms, measured experimental data are discussed, and include effects of ventilation gas temperature, dependence on material composition, and chemical analysis of smoke particulates. Significant differences in smoke characteristics are observed between flaming and nonflaming conditions, which is attributed to specific differences in controlling mechanisms and resultant ways leading to particulate formation. The effects of polymer substrate properties and effects of additives for a given substrate on smoke properties are also discussed in terms of basic processes. It is shown that many of the measured trends can be interpreted by considering postulated mechanisms of particulate formation.

Spectroscopic study of the degradation products in the holy water fonts in Santa Maria della Steccata Church in Parma (Italy).

PubMed

Bersani, D; Campani, E; Casoli, A; Lottici, P P; Marino, I-G

2008-03-03

Two holy water fonts (dated at the beginning of the XVII century) in the Santa Maria della Steccata Church in Parma (Italy) have recently been restored. Before the intervention, a detailed investigation on their degradation products was carried out to understand the mechanisms of alteration of the materials and to suggest appropriate restoration procedures. The analyses were performed by means of powder X-ray diffraction (XRD), micro-Fourier transform infrared (FTIR) and micro-Raman spectroscopies. Calcite, iron oxides, silicates and sodium chloride (from salted holy water) were found in the red coloured calcarenite. On and under the lead coverings, different lead oxides (mainly massicot), other lead salts (lead basic carbonate, cerussite, plumbonacrite Pb10O(OH)6(CO3)6 and lead-chlorine compounds as laurionite PbOHCl and phosgenite Pb2CO3Cl2) were identified by Raman spectroscopy and XRD. Haematite alpha-Fe2O3, goethite alpha-FeO(OH) and lepidocrocite gamma-FeO(OH) were found on and around the iron hinges. Lead compounds and sodium chloride, through crystallization and solubilization cycles, were responsible for the stone's degradation, whereas the iron corrosion materials on the hinges produced mechanical stress and cracks in the stone. Various suggestions have been given on how to restore these fonts and to remove the causes of damage.

Hot Corrosion at Air-Ports in Kraft Recovery Boilers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holcomb, Gordon R.; Covino, Bernard S., Jr.; Russell, James H.

2003-01-01

Hot corrosion can occur on the cold-side of airports in Kraft recovery boilers. The primary corrosion mechanism involves the migration of sodium hydroxide and potassium hydroxide vapors through leaks in the furnace wall at the airports and their subsequent condensation. It has been reported that stainless steel is attacked much faster than carbon steel in composite tubes, and that carbon steel tubing, when used with a low-chromium refractory, does not exhibit this type of corrosion. For hot corrosion fluxing of metal oxides, either acidic or basic fluxing takes place, with a solubility minimum at the basicity of transition between themore » two reactions. For stainless steel, if the basicity of the fused salt is between the iron and chromium oxide solubility minima, then a synergistic effect can occur that leads to rapid corrosion. The products of one reaction are the reactants of the other, which eliminates the need for rate-controlling diffusion. This effect can explain why stainless steel is attacked more readily than carbon steel.« less

Mechanism for longitudinal growth of rod-shaped bacteria

NASA Astrophysics Data System (ADS)

Taneja, Swadhin; Levitan, Ben; Rutenberg, Andrew

2013-03-01

The peptidoglycan (PG) cell wall along with MreB proteins are major determinants of shape in rod-shaped bacteria. However the mechanism guiding the growth of this elastic network of cross-linked PG (sacculus) that maintains the integrity and shape of the rod-shaped cell remains elusive. We propose that the known anisotropic elasticity and anisotropic loading, due to the shape and turgor pressure, of the sacculus is sufficient to direct small gaps in the sacculus to elongate around the cell, and that subsequent repair leads to longitudinal growth without radial growth. We computationally show in our anisotropically stressed anisotropic elasticity model small gaps can extend stably in the circumferential direction for the known elasticity of the sacculus. We suggest that MreB patches that normally propagate circumferentially, are associated with these gaps and are steered with this common mechanism. This basic picture is unchanged in Gram positive and Gram negative bacteria. We also show that small changes of elastic properties can in fact lead to bi-stable propagation of gaps, both longitudinal and circumferential, that can explain the bi-stability in patch movement observed in ΔmblΔmreb mutants.

Acidic ammonothermal growth of gallium nitride in a liner-free molybdenum alloy autoclave

NASA Astrophysics Data System (ADS)

Malkowski, Thomas F.; Pimputkar, Siddha; Speck, James S.; DenBaars, Steven P.; Nakamura, Shuji

2016-12-01

This paper discusses promising materials for use as internal, non-load bearing components as well as molybdenum-based alloys for autoclave structural components for an ammonothermal autoclave. An autoclave was constructed from the commercial titanium-zirconium-molybdenum (TZM) alloy and was found to be chemically inert and mechanically stable under acidic ammonothermal conditions. Preliminary seeded growth of GaN was demonstrated with negligible incorporation of transition metals (including molybdenum) into the grown material (<1017 cm-3). Molybdenum and TZM were exposed to a basic ammonothermal environment, leading to slight degradation through formation of molybdenum nitride powders on their surface at elevated temperatures (T>560 °C). The possibility of a 'universal', inexpensive, liner-free ammonothermal autoclave capable of exposure to basic and acidic chemistry is demonstrated.

What Protein Charging (and Supercharging) Reveal about the Mechanism of Electrospray Ionization

PubMed Central

Loo, Rachel R. Ogorzalek; Lakshmanan, Rajeswari

2014-01-01

Understanding the charging mechanism of electrospray ionization is central to overcoming shortcomings such as ion suppression or limited dynamic range and explaining phenomena such as supercharging. Towards that end, we explore what accumulated observations reveal about the mechanism of electrospray. We introduce the idea of an intermediate region for electrospray ionization (and other ionization methods) to account for the facts that solution charge state distributions (CSDs) do not correlate to those observed by ESI– MS (the latter bear more charge) and that gas phase reactions can reduce, but not increase the extent of charging. This region incorporates properties, e.g., basicities, intermediate between solution and gas phase. Assuming that droplet species polarize within the high electric field leads to equations describing ion emission resembling those from the equilibrium partitioning model. The equations predict many trends successfully, including CSD shifts to higher m/z for concentrated analytes and shifts to lower m/z for sprays employing smaller emitter opening diameters. From this view, a single mechanism can be formulated to explain how reagents that promote analyte charging (“supercharging”) such as m–NBA, sulfolane, and 3–nitrobenzonitrile increase analyte charge from “denaturing” and “native” solvent systems. It is suggested that additives’ Brønsted basicities are inversely correlated to their ability to shift CSDs to lower m/z in positive ESI, as are Brønsted acidities for negative ESI. Because supercharging agents reduce an analyte's solution ionization, excess spray charge is bestowed on evaporating ions carryingfewer opposing charges. Brønsted basicity (or acidity) determines how much ESI charge is lost to the agent (unavailable to evaporating analyte). PMID:25135609

Mechanisms of gender-linked ischemic brain injury

PubMed Central

Liu, Mingyue; Dziennis, Suzan; Hurn, Patricia D.; Alkayed, Nabil J.

2010-01-01

Biological sex is an important determinant of stroke risk and outcome. Women are protected from cerebrovascular disease relative to men, an observation commonly attributed to the protective effect of female sex hormones, estrogen and progesterone. However, sex differences in brain injury persist well beyond the menopause and can be found in the pediatric population, suggesting that the effects of reproductive steroids may not completely explain sexual dimorphism in stroke. We review recent advances in our understanding of sex steroids (estradiol, progesterone and testosterone) in the context of ischemic cell death and neuroprotection. Understanding the molecular and cell-based mechanisms underlying sex differences in ischemic brain injury will lead to a better understanding of basic mechanisms of brain cell death and is an important step toward designing more effective therapeutic interventions in stroke. PMID:19531872

Effects of biological sex on the pathophysiology of the heart

PubMed Central

Fazal, Loubina; Azibani, Feriel; Vodovar, Nicolas; Cohen Solal, Alain; Delcayre, Claude; Samuel, Jane-Lise

2014-01-01

Cardiovascular diseases are the leading causes of death in men and women in industrialized countries. While the effects of biological sex on cardiovascular pathophysiology have long been known, the sex-specific mechanisms mediating these processes have been further elucidated over recent years. This review aims at analysing the sex-based differences in cardiac structure and function in adult mammals, and the sex-based differences in the main molecular mechanisms involved in the response of the heart to pathological situations. It emerged from this review that the sex-based difference is a variable that should be dealt with, not only in basic science or clinical research, but also with regards to therapeutic approaches. PMID:23763376

Molecular insights into the enhanced rate of CO2 absorption to produce bicarbonate in aqueous 2-amino-2-methyl-1-propanol.

PubMed

Stowe, Haley M; Hwang, Gyeong S

2017-12-06

2-Amino-2-methyl-1-propanol (AMP), a sterically hindered amine, exhibits a much higher CO 2 absorption rate relative to tertiary amine diethylethanolamine (DEEA), while both yield bicarbonate as a major product in aqueous solution, despite their similar basicity. We present molecular mechanisms underlying the significant difference of CO 2 absorption rate based on ab initio molecular dynamics simulations combined with metadynamics. Our calculations predict the free energy barrier for base-catalyzed CO 2 hydration to be lower in aqueous AMP compared to DEEA. Further molecular analysis suggests that the difference in free energy barrier is largely attributed to entropic effects associated with reorganization of H 2 O molecules adjacent to the basic N site. Stronger hydrogen bonding of H 2 O with N of DEEA than AMP, in addition to the presence of bulky ethyl groups, suppresses the thermal rearrangement of adjacent H 2 O molecules, thereby leading to lower stability of the transition state involving OH - creation and CO 2 polarization. Moreover, the hindered reorganization of adjacent H 2 O molecules is found to facilitate migration of OH - (created via proton abstraction by DEEA) away from the N site while suppressing CO 2 approach. This leads us to speculate that catalyzed CO 2 hydration in aqueous DEEA may involve OH - migration through multiple hydrogen-bonded H 2 O molecules prior to reaction with CO 2 , whereas in aqueous AMP it seems to preferentially follow the one H 2 O-mediated mechanism. This study highlights the importance of entropic effects in determining both mechanisms and rates of CO 2 absorption into aqueous sterically hindered amines.

Center for Materials at Irradiation and Mechanical Extremes at LANL (A "Life at the Frontiers of Energy Research" contest entry from the 2011 Energy Frontier Research Centers (EFRCs) Summit and Forum)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nastasi, Michael

"Center for Materials at Irradiation and Mechanical Extremes (CMIME) at LANL" was submitted by CMIME to the "Life at the Frontiers of Energy Research" video contest at the 2011 Science for Our Nation's Energy Future: Energy Frontier Research Centers (EFRCs) Summit and Forum. Twenty-six EFRCs created short videos to highlight their mission and their work. CMIME, an EFRC directed by Michael Nastasi at Los Alamos National Laboratory is a partnership of scientists from four institutions: LANL (lead), Carnegie Mellon University, the University of Illinois at Urbana-Champaign, and the Massachusetts Institute of Technology. The Office of Basic Energy Sciences in themore » U.S. Department of Energy's Office of Science established the 46 Energy Frontier Research Centers (EFRCs) in 2009. These collaboratively-organized centers conduct fundamental research focused on 'grand challenges' and use-inspired 'basic research needs' recently identified in major strategic planning efforts by the scientific community. The overall purpose is to accelerate scientific progress toward meeting the nation's critical energy challenges.« less

Center for Materials at Irradiation and Mechanical Extremes at LANL (A "Life at the Frontiers of Energy Research" contest entry from the 2011 Energy Frontier Research Centers (EFRCs) Summit and Forum)

ScienceCinema

Michael Nastasi (Director, Center for Materials at Irradiation and Mechanical Extremes); CMIME Staff

2017-12-09

'Center for Materials at Irradiation and Mechanical Extremes (CMIME) at LANL' was submitted by CMIME to the 'Life at the Frontiers of Energy Research' video contest at the 2011 Science for Our Nation's Energy Future: Energy Frontier Research Centers (EFRCs) Summit and Forum. Twenty-six EFRCs created short videos to highlight their mission and their work. CMIME, an EFRC directed by Michael Nastasi at Los Alamos National Laboratory is a partnership of scientists from four institutions: LANL (lead), Carnegia Mellon University, the University of Illinois at Urbana Champaign, and the Massachusetts Institute of Technology. The Office of Basic Energy Sciences in the U.S. Department of Energy's Office of Science established the 46 Energy Frontier Research Centers (EFRCs) in 2009. These collaboratively-organized centers conduct fundamental research focused on 'grand challenges' and use-inspired 'basic research needs' recently identified in major strategic planning efforts by the scientific community. The overall purpose is to accelerate scientific progress toward meeting the nation's critical energy challenges.

Influence of various amount of diatomaceous earth used as cement substitute on mechanical properties of cement paste

NASA Astrophysics Data System (ADS)

Pokorný, Jaroslav; Pavlíková, Milena; Medved, Igor; Pavlík, Zbyšek; Zahálková, Jana; Rovnaníková, Pavla; Černý, Robert

2016-06-01

Active silica containing materials in the sub-micrometer size range are commonly used for modification of strength parameters and durability of cement based composites. In addition, these materials also assist to accelerate cement hydration. In this paper, two types of diatomaceous earths are used as partial cement replacement in composition of cement paste mixtures. For raw binders, basic physical and chemical properties are studied. The chemical composition of tested materials is determined using classical chemical analysis combined with XRD method that allowed assessment of SiO2 amorphous phase content. For all tested mixtures, initial and final setting times are measured. Basic physical and mechanical properties are measured on hardened paste samples cured 28 days in water. Here, bulk density, matrix density, total open porosity, compressive and flexural strength, are measured. Relationship between compressive strength and total open porosity is studied using several empirical models. The obtained results give evidence of high pozzolanic activity of tested diatomite earths. Their application leads to the increase of both initial and final setting times, decrease of compressive strength, and increase of flexural strength.

Self-Regulation and Mechanisms of Action in Psychotherapy: A Theory-Based Translational Perspective

PubMed Central

Strauman, Timothy J.; Goetz, Elena L.; Detloff, Allison M.; MacDuffie, Katherine E.; Zaunmüller, Luisa; Lutz, Wolfgang

2012-01-01

Psychotherapy is a complex, multi-layered process with the potential to bring about changes at multiple levels of functioning, from the neurobiology of the brain to the individual’s role in the social world. Although studies of the mechanisms by which psychotherapy leads to change continue to appear, there remains much to be learned about how psychological interventions work. To guide explorations of how and for whom particular treatment approaches lead to change, researchers can rely on theory to identify potential loci for change and on translational research methods to integrate basic behavioral science and neuroscience with clinical science. In this article, we describe research linking individual differences in the self-regulation of personal goal pursuit with the etiology and treatment of mood disorders. The research draws upon regulatory focus theory as a model of self-regulation and on microintervention designs – controlled laboratory investigations of a specific therapeutic technique – to generate and test hypotheses about how psychological interventions can help to reverse maladaptive self-regulatory processes. PMID:23072383

Geography, assortative mating, and the effects of sexual selection on speciation with gene flow.

PubMed

Servedio, Maria R

2016-01-01

Theoretical and empirical research on the evolution of reproductive isolation have both indicated that the effects of sexual selection on speciation with gene flow are quite complex. As part of this special issue on the contributions of women to basic and applied evolutionary biology, I discuss my work on this question in the context of a broader assessment of the patterns of sexual selection that lead to, versus inhibit, the speciation process, as derived from theoretical research. In particular, I focus on how two factors, the geographic context of speciation and the mechanism leading to assortative mating, interact to alter the effect that sexual selection through mate choice has on speciation. I concentrate on two geographic contexts: sympatry and secondary contact between two geographically separated populations that are exchanging migrants and two mechanisms of assortative mating: phenotype matching and separate preferences and traits. I show that both of these factors must be considered for the effects of sexual selection on speciation to be inferred.

Metallothionein as a Scavenger of Free Radicals - New Cardioprotective Therapeutic Agent or Initiator of Tumor Chemoresistance?

PubMed

Heger, Zbynek; Rodrigo, Miguel Angel Merlos; Krizkova, Sona; Ruttkay-Nedecky, Branislav; Zalewska, Marta; Del Pozo, Elena Maria Planells; Pelfrene, Aurelie; Pourrut, Bertrand; Stiborova, Marie; Eckschlager, Tomas; Emri, Gabriella; Kizek, Rene; Adam, Vojtech

2016-01-01

Cardiotoxicity is a serious complication of anticancer therapy by anthracycline antibiotics. Except for intercalation into DNA/RNA structure, inhibition of DNA-topoisomerase and histone eviction from chromatin, the main mechanism of their action is iron-mediated formation of various forms of free radicals, which leads to irreversible damage to cancer cells. The most serious adverse effect of anthracyclines is, thus, cardiomyopathy leading to congestive heart failure, which is caused by the same mechanisms. Here, we briefly summarize the basic types of free radicals formed by anthracyclines and the main processes how to scavenge them. From these, the main attention is paid to metallothioneins. These low-molecular cysteine-rich proteins are introduced and their functions and properties are reviewed. Further, their role in detoxification of metals and drugs is discussed. Based on these beneficial roles, their use as a new therapeutic agent against oxidative stress and for cardioprotection is critically evaluated with respect to their ability to increase chemoresistance against some types of commonly used cytostatics.

Biology of portal hypertension.

PubMed

McConnell, Matthew; Iwakiri, Yasuko

2018-02-01

Portal hypertension develops as a result of increased intrahepatic vascular resistance often caused by chronic liver disease that leads to structural distortion by fibrosis, microvascular thrombosis, dysfunction of liver sinusoidal endothelial cells (LSECs), and hepatic stellate cell (HSC) activation. While the basic mechanisms of LSEC and HSC dysregulation have been extensively studied, the role of microvascular thrombosis and platelet function in the pathogenesis of portal hypertension remains to be clearly characterized. As a secondary event, portal hypertension results in splanchnic and systemic arterial vasodilation, leading to the development of a hyperdynamic circulatory syndrome and subsequently to clinically devastating complications including gastroesophageal varices and variceal hemorrhage, hepatic encephalopathy from the formation of portosystemic shunts, ascites, and renal failure due to the hepatorenal syndrome. This review article discusses: (1) mechanisms of sinusoidal portal hypertension, focusing on HSC and LSEC biology, pathological angiogenesis, and the role of microvascular thrombosis and platelets, (2) the mesenteric vasculature in portal hypertension, and (3) future directions for vascular biology research in portal hypertension.

Enhancement of human cognitive performance using transcranial magnetic stimulation (TMS)

PubMed Central

Luber, Bruce; Lisanby, and Sarah H.

2014-01-01

Here we review the usefulness of transcranial magnetic stimulation (TMS) in modulating cortical networks in ways that might produce performance enhancements in healthy human subjects. To date over sixty studies have reported significant improvements in speed and accuracy in a variety of tasks involving perceptual, motor, and executive processing. Two basic categories of enhancement mechanisms are suggested by this literature: direct modulation of a cortical region or network that leads to more efficient processing, and addition-by-subtraction, which is disruption of processing which competes or distracts from task performance. Potential applications of TMS cognitive enhancement, including research into cortical function, rehabilitation therapy in neurological and psychiatric illness, and accelerated skill acquisition in healthy individuals are discussed, as are methods of optimizing the magnitude and duration of TMS-induced performance enhancement, such as improvement of targeting through further integration of brain imaging with TMS. One technique, combining multiple sessions of TMS with concurrent TMS/task performance to induce Hebbian-like learning, appears to be promising for prolonging enhancement effects. While further refinements in the application of TMS to cognitive enhancement can still be made, and questions remain regarding the mechanisms underlying the observed effects, this appears to be a fruitful area of investigation that may shed light on the basic mechanisms of cognitive function and their therapeutic modulation. PMID:23770409

The status and future of acupuncture mechanism research.

PubMed

Napadow, Vitaly; Ahn, Andrew; Longhurst, John; Lao, Lixing; Stener-Victorin, Elisabet; Harris, Richard; Langevin, Helene M

2008-09-01

On November 8-9, 2007, the Society for Acupuncture Research (SAR) hosted an international conference to mark the tenth anniversary of the landmark NIH [National Institutes of Health] Consensus Development Conference on Acupuncture. More than 300 acupuncture researchers, practitioners, students, funding agency personnel, and health policy analysts from 20 countries attended the SAR meeting held at the University of Maryland School of Medicine, Baltimore, MD. This paper summarizes important invited lectures in the area of basic and translational acupuncture research. Specific areas include the scientific assessment of acupuncture points and meridians, the neural mechanisms of cardiovascular regulation by acupuncture, mechanisms for electroacupuncture applied to persistent inflammation and pain, basic and translational research on acupuncture in gynecologic applications, the application of functional neuroimaging to acupuncture research with specific application to carpal-tunnel syndrome and fibromyalgia, and the association of the connective tissue system to acupuncture research. In summary, mechanistic models for acupuncture effects that have been investigated experimentally have focused on the effects of acupuncture needle stimulation on the nervous system, muscles, and connective tissue. These mechanistic models are not mutually exclusive. Iterative testing, expanding, and perhaps merging of such models will potentially lead to an incremental understanding of the effects of manual and electrical stimulation of acupuncture needles that is solidly rooted in physiology.

DNP-enhanced ultrawideline 207Pb solid-state NMR spectroscopy: an application to cultural heritage science

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kobayashi, Takeshi; Perras, Frederic A.; Murphy, Anna

Dynamic nuclear polarization (DNP) is used to enhance the (ultra)wideline 207Pb solid-state NMR spectra of lead compounds of relevance in the preservation of cultural heritage objects. The DNP SSNMR experiments enabled, for the first time, the detection of the basic lead carbonate phase of the lead white pigment by 207Pb SSNMR spectroscopy. Variable-temperature experiments revealed that the short T'2 relaxation time of the basic lead carbonate phase hinders the acquisition of the NMR signal at room temperature. We additionally observe that the DNP enhancement is twice as large for lead palmitate (a lead soap, which is a degradation product implicatedmore » in the visible deterioration of lead-based oil paintings), than it is for the basic lead carbonate. As a result, this enhancement has allowed us to detect the formation of a lead soap in an aged paint film by 207Pb SSNMR spectroscopy; which may aid in the detection of deterioration products in smaller samples removed from works of art.« less

DNP-enhanced ultrawideline 207Pb solid-state NMR spectroscopy: an application to cultural heritage science

DOE PAGES

Kobayashi, Takeshi; Perras, Frederic A.; Murphy, Anna; ...

2017-02-17

Dynamic nuclear polarization (DNP) is used to enhance the (ultra)wideline 207Pb solid-state NMR spectra of lead compounds of relevance in the preservation of cultural heritage objects. The DNP SSNMR experiments enabled, for the first time, the detection of the basic lead carbonate phase of the lead white pigment by 207Pb SSNMR spectroscopy. Variable-temperature experiments revealed that the short T'2 relaxation time of the basic lead carbonate phase hinders the acquisition of the NMR signal at room temperature. We additionally observe that the DNP enhancement is twice as large for lead palmitate (a lead soap, which is a degradation product implicatedmore » in the visible deterioration of lead-based oil paintings), than it is for the basic lead carbonate. As a result, this enhancement has allowed us to detect the formation of a lead soap in an aged paint film by 207Pb SSNMR spectroscopy; which may aid in the detection of deterioration products in smaller samples removed from works of art.« less

Improving the particle distribution and mechanical properties of friction-stir-welded composites by using a smooth pin tool

NASA Astrophysics Data System (ADS)

Liu, Huijie; Hu, Yanying; Zhao, Yunqiang; Fujii, Hidetoshi

2017-09-01

Friction stir welding (FSW) is a very promising technique for joining particle-reinforced aluminum-matrix composites (PRAMCs), but with increase in the volume fraction of reinforcing particles, their distribution in welds becomes inhomogeneous. This leads to an inconsistent deformation of welds and their destruction at low stresses. In order to improve the weld microstructure, a smooth pin tool was used for the friction stir welding of AC4A + 30 vol.% SiC particle-reinforced aluminum-matrix composites. The present work describes the effect of welding parameters on the characteristics of particle distribution and the mechanical properties of welds. The ultimate strength of weld reached, 309 MPa, was almost 190% of that of the basic material. The mechanism of SiC particle conglomeration is clearly illustrated by means of schematic illustrations.

Mass action at the single-molecule level.

PubMed

Shon, Min Ju; Cohen, Adam E

2012-09-05

We developed a system to reversibly encapsulate small numbers of molecules in an array of nanofabricated "dimples". This system enables highly parallel, long-term, and attachment-free studies of molecular dynamics via single-molecule fluorescence. In studies of bimolecular reactions of small numbers of confined molecules, we see phenomena that, while expected from basic statistical mechanics, are not observed in bulk chemistry. Statistical fluctuations in the occupancy of sealed reaction chambers lead to steady-state fluctuations in reaction equilibria and rates. These phenomena are likely to be important whenever reactions happen in confined geometries.

Behavioral epigenetics

PubMed Central

Lester, Barry M.; Tronick, Edward; Nestler, Eric; Abel, Ted; Kosofsky, Barry; Kuzawa, Christopher W.; Marsit, Carmen J.; Maze, Ian; Meaney, Michael J.; Monteggia, Lisa M.; Reul, Johannes M. H. M.; Skuse, David H.; Sweatt, J. David; Wood, Marcelo A.

2013-01-01

Sponsored by the New York Academy of Sciences, the Warren Alpert Medical School of Brown University and the University of Massachusetts Boston, “Behavioral Epigenetics” was held on October 29–30, 2010 at the University of Massachusetts Boston Campus Center, Boston, Massachusetts. This meeting featured speakers and panel discussions exploring the emerging field of behavioral epigenetics, from basic biochemical and cellular mechanisms to the epigenetic modulation of normative development, developmental disorders, and psychopathology. This report provides an overview of the research presented by leading scientists and lively discussion about the future of investigation at the behavioral epigenetic level. PMID:21615751

Olfactory Cued Learning Paradigm.

PubMed

Liu, Gary; McClard, Cynthia K; Tepe, Burak; Swanson, Jessica; Pekarek, Brandon; Panneerselvam, Sugi; Arenkiel, Benjamin R

2017-05-05

Sensory stimulation leads to structural changes within the CNS (Central Nervous System), thus providing the fundamental mechanism for learning and memory. The olfactory circuit offers a unique model for studying experience-dependent plasticity, partly due to a continuous supply of integrating adult born neurons. Our lab has recently implemented an olfactory cued learning paradigm in which specific odor pairs are coupled to either a reward or punishment to study downstream circuit changes. The following protocol outlines the basic set up for our learning paradigm. Here, we describe the equipment setup, programming of software, and method of behavioral training.

The development of a successful physician compensation plan.

PubMed

Berkowitz, Steven M

2002-10-01

Physician compensation plans are critical to the success of a physician group or may lead to the demise of the group. Essential components of the development and implementation of a successful physician compensation plan include: strategic planning, physician understanding and buy-in, appropriate incentives, objective performance measurement, and a specific funding source or mechanism. There are two basic philosophies to consider for use: the market-based model and the net economic contribution model. Advantages and disadvantages of each are discussed. Methods of incorporating these multiple aspects into a single plan are described.

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

NASA Astrophysics Data System (ADS)

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

2018-05-01

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

Different immunological mechanisms govern protection from experimental stroke in young and older mice with recombinant TCR ligand therapy

PubMed Central

Dotson, Abby L.; Zhu, Wenbin; Libal, Nicole; Alkayed, Nabil J.; Offner, Halina

2014-01-01

Stroke is a leading cause of death and disability in the United States. The lack of clinical success in stroke therapies can be attributed, in part, to inadequate basic research on aging rodents. The current study demonstrates that recombinant TCR ligand therapy uses different immunological mechanisms to protect young and older mice from experimental stroke. In young mice, RTL1000 therapy inhibited splenocyte efflux while reducing frequency of T cells and macrophages in the spleen. Older mice treated with RTL1000 exhibited a significant reduction in inflammatory cells in the brain and inhibition of splenic atrophy. Our data suggest age specific differences in immune response to stroke that allow unique targeting of stroke immunotherapies. PMID:25309326

Effects of biological sex on the pathophysiology of the heart.

PubMed

Fazal, Loubina; Azibani, Feriel; Vodovar, Nicolas; Cohen Solal, Alain; Delcayre, Claude; Samuel, Jane-Lise

2014-02-01

Cardiovascular diseases are the leading causes of death in men and women in industrialized countries. While the effects of biological sex on cardiovascular pathophysiology have long been known, the sex-specific mechanisms mediating these processes have been further elucidated over recent years. This review aims at analysing the sex-based differences in cardiac structure and function in adult mammals, and the sex-based differences in the main molecular mechanisms involved in the response of the heart to pathological situations. It emerged from this review that the sex-based difference is a variable that should be dealt with, not only in basic science or clinical research, but also with regards to therapeutic approaches. © 2013 The British Pharmacological Society.

Carbon nanostructure based mechano-nanofluidics

NASA Astrophysics Data System (ADS)

Cao, Wei; Wang, Jin; Ma, Ming

2018-03-01

Fast transport of water inside carbon nanostructures, such as carbon nanotubes and graphene-based nanomaterials, has addressed persistent challenges in nanofluidics. Recently reported new mechanisms show that the coupling between phonons in these materials and fluids under-confinement could lead to the enhancement of the diffusion coefficient. These developments have led to the emerging field of mechano-nanofluidics, which studies the effects of mechanical actuations on the properties of nanofluidics. In this tutorial review, we provide the basic concepts and development of mechano-nanofluidics. We also summarize the current status of experimental observations of fluids flow in individual nanochannels and theoretical interpretations. Finally, we briefly discuss the challenges and opportunities for the utilization of mechano-nanofluidics, such as controlling the fluid flow through regulating the coupling between materials and fluids.

Mitral valve disease—morphology and mechanisms

PubMed Central

Levine, Robert A.; Hagége, Albert A.; Judge, Daniel P.; Padala, Muralidhar; Dal-Bianco, Jacob P.; Aikawa, Elena; Beaudoin, Jonathan; Bischoff, Joyce; Bouatia-Naji, Nabila; Bruneval, Patrick; Butcher, Jonathan T.; Carpentier, Alain; Chaput, Miguel; Chester, Adrian H.; Clusel, Catherine; Delling, Francesca N.; Dietz, Harry C.; Dina, Christian; Durst, Ronen; Fernandez-Friera, Leticia; Handschumacher, Mark D.; Jensen, Morten O.; Jeunemaitre, Xavier P.; Le Marec, Hervé; Le Tourneau, Thierry; Markwald, Roger R.; Mérot, Jean; Messas, Emmanuel; Milan, David P.; Neri, Tui; Norris, Russell A.; Peal, David; Perrocheau, Maelle; Probst, Vincent; Pucéat, Michael; Rosenthal, Nadia; Solis, Jorge; Schott, Jean-Jacques; Schwammenthal, Ehud; Slaugenhaupt, Susan A.; Song, Jae-Kwan; Yacoub, Magdi H.

2016-01-01

Mitral valve disease is a frequent cause of heart failure and death. Emerging evidence indicates that the mitral valve is not a passive structure, but—even in adult life—remains dynamic and accessible for treatment. This concept motivates efforts to reduce the clinical progression of mitral valve disease through early detection and modification of underlying mechanisms. Discoveries of genetic mutations causing mitral valve elongation and prolapse have revealed that growth factor signalling and cell migration pathways are regulated by structural molecules in ways that can be modified to limit progression from developmental defects to valve degeneration with clinical complications. Mitral valve enlargement can determine left ventricular outflow tract obstruction in hypertrophic cardiomyopathy, and might be stimulated by potentially modifiable biological valvular–ventricular interactions. Mitral valve plasticity also allows adaptive growth in response to ventricular remodelling. However, adverse cellular and mechanobiological processes create relative leaflet deficiency in the ischaemic setting, leading to mitral regurgitation with increased heart failure and mortality. Our approach, which bridges clinicians and basic scientists, enables the correlation of observed disease with cellular and molecular mechanisms, leading to the discovery of new opportunities for improving the natural history of mitral valve disease. PMID:26483167

Achievement Test Program.

ERIC Educational Resources Information Center

Ohio State Dept. of Education, Columbus. Trade and Industrial Education Service.

The Ohio Trade and Industrial Education Achievement Test battery is comprised of seven basic achievement tests: Machine Trades, Automotive Mechanics, Basic Electricity, Basic Electronics, Mechanical Drafting, Printing, and Sheet Metal. The tests were developed by subject matter committees and specialists in testing and research. The Ohio Trade and…

Molecular recognition of the environment and mechanisms of the origin of species in quantum-like modeling of evolution.

PubMed

Melkikh, Alexey V; Khrennikov, Andrei

2017-11-01

A review of the mechanisms of speciation is performed. The mechanisms of the evolution of species, taking into account the feedback of the state of the environment and mechanisms of the emergence of complexity, are considered. It is shown that these mechanisms, at the molecular level, cannot work steadily in terms of classical mechanics. Quantum mechanisms of changes in the genome, based on the long-range interaction potential between biologically important molecules, are proposed as one of possible explanation. Different variants of interactions of the organism and environment based on molecular recognition and leading to new species origins are considered. Experiments to verify the model are proposed. This bio-physical study is completed by the general operational model of based on quantum information theory. The latter is applied to model of epigenetic evolution. We briefly present the basics of the quantum-like approach to modeling of bio-informational processes. This approach is illustrated by the quantum-like model of epigenetic evolution. Copyright © 2017 Elsevier Ltd. All rights reserved.

Attacking the Multi-tiered Proteolytic Pathology of COPD: New Insights from Basic and Translational Studies

PubMed Central

Djekic, Uros V; Gaggar, Amit; Weathington, Nathaniel M

2015-01-01

Protease activity in inflammation is complex. Proteases released by cells in response to infection, cytokines, or environmental triggers like cigarette smoking cause breakdown of the extracellular matrix (ECM). In chronic inflammatory diseases like chronic obstructive pulmonary disease (COPD), current findings indicate that pathology and morbidity are driven by dysregulation of protease activity, either through hyperactivity of proteases or deficiency or dysfunction their antiprotease regulators. Animal studies demonstrate the accuracy of this hypothesis through genetic and pharmacologic tools. New work shows that ECM destruction generates peptide fragments active on leukocytes via neutrophil or macrophage chemotaxis towards collagen and elastin derived peptides respectively. Such fragments now have been isolated and characterized in vivo in each case. Collectively, this describes a biochemical circuit in which protease activity leads to activation of local immunocytes, which in turn release cytokines and more proteases, leading to further leukocyte infiltration and cyclical disease progression that is chronic. This circuit concept is well known, and is intrinsic to the protease-antiprotease hypothesis; recently analytic techniques have become sensitive enough to establish fundamental mechanisms of this hypothesis, and basic and clinical data now implicate protease activity and peptide signaling as pathologically significant pharmacologic targets. This review discusses targeting protease activity for chronic inflammatory disease with special attention to COPD, covering important basic and clinical findings in the field; novel therapeutic strategies in animal or human studies; and a perspective on the successes and failures of agents with a focus on clinical potential in human disease. PMID:19026684

Testosterone and Erectile Function: From Basic Research to a New Clinical Paradigm for Managing Men with Androgen Insufficiency and Erectile Dysfunction

PubMed Central

Traish, Abdulmaged M.; Goldstein, Irwin; Kim, Noel N.

2007-01-01

Objectives Androgens are essential for the development and growth of the penis, and they regulate erectile physiology by multiple mechanisms. Our goal is to provide a concise overview of the basic research and how this knowledge can be translated into a new clinical paradigm for patient management. In addition, this new paradigm may serve as a basis for stimulating constructive debate regarding the use of testosterone in men, and to promote new, innovative basic and clinical research to further understand the underlying mechanisms of androgen action in restoring erectile physiology. Methods A literature review was performed utilizing the US National Library of Medicine's PubMed database. Results On the basis of evidence derived from laboratory animal studies and clinical data, we postulate that androgen insufficiency disrupts cellular-signaling pathways and produces pathologic alterations in penile tissues, leading to erectile dysfunction. In this review, we discuss androgen-dependent cellular, molecular, and physiologic mechanisms modulating erectile function in the animal model, and the implication of this knowledge in testosterone use in the clinical setting to treat erectile dysfunction. The new clinical paradigm incorporates many of the consensed points of view discussed in traditional consensed algorithms exclusively designed for men with androgen insufficiency. There are, however, novel and innovative differences with this new clinical paradigm. This paradigm represents a fresh effort to provide mandatory and optional management strategies for men with both androgen insufficiency and erectile dysfunction. Conclusions The new clinical paradigm is evidence-based and represents one of the first attempts to address a logical management plan for men with concomitant hormonal and sexual health concerns. PMID:17329016

Tackling overweight and obesity: does the public health message match the science?

PubMed

Hafekost, Katherine; Lawrence, David; Mitrou, Francis; O'Sullivan, Therese A; Zubrick, Stephen R

2013-02-18

Despite the increasing understanding of the mechanisms relating to weight loss and maintenance, there are currently no validated public health interventions that are able to achieve sustained long-term weight loss or to stem the increasing prevalence of obesity in the population. We aimed to examine the models of energy balance underpinning current research about weight-loss intervention from the field of public health, and to determine whether they are consistent with the model provided by basic science. EMBASE was searched for papers published in 2011 on weight-loss interventions. We extracted details of the population, nature of the intervention, and key findings for 27 articles. Most public health interventions identified were based on a simple model of energy balance, and thus attempted to reduce caloric consumption and/or increase physical activity in order to create a negative energy balance. There appeared to be little consideration of homeostatic feedback mechanisms and their effect on weight-loss success. It seems that there has been a lack of translation between recent advances in understanding of the basic science behind weight loss, and the concepts underpinning the increasingly urgent efforts to reduce excess weight in the population. Public health weight-loss interventions seem to be based on an outdated understanding of the science. Their continued failure to achieve any meaningful, long-term results reflects the need to develop intervention science that is integrated with knowledge from basic science. Instead of asking why people persist in eating too much and exercising too little, the key questions of obesity research should address those factors (environmental, behavioral or otherwise) that lead to dysregulation of the homeostatic mechanism of energy regulation. There is a need for a multidisciplinary approach in the design of future weight-loss interventions in order to improve long-term weight-loss success.

The Development of Eating Behavior - Biology and Context

PubMed Central

Gahagan, Sheila

2012-01-01

Eating is necessary for survival, gives great pleasure and can be perturbed leading to undernutrition, overnutrition and eating disorders. The development of feeding in humans relies on complex interplay between homeostatic mechanisms; neural reward systems; and child motor, sensory and socio-emotional capability. Furthermore, parenting, social influences and the food environment influence the development of eating behavior. The rapid expansion of new knowledge in this field, from basic science to clinical and community-based research, is expected to lead to urgently needed research in support of effective, evidence-based prevention and treatment strategies for undernutrition, overnutrition and eating disorders in early childhood. Using a biopsychosocial approach, this review covers current knowledge of the development of eating behavior from the brain to the individual child, taking into account important contextual influences. PMID:22472944

Fractional Klein-Gordon equation composed of Jumarie fractional derivative and its interpretation by a smoothness parameter

NASA Astrophysics Data System (ADS)

Ghosh, Uttam; Banerjee, Joydip; Sarkar, Susmita; Das, Shantanu

2018-06-01

Klein-Gordon equation is one of the basic steps towards relativistic quantum mechanics. In this paper, we have formulated fractional Klein-Gordon equation via Jumarie fractional derivative and found two types of solutions. Zero-mass solution satisfies photon criteria and non-zero mass satisfies general theory of relativity. Further, we have developed rest mass condition which leads us to the concept of hidden wave. Classical Klein-Gordon equation fails to explain a chargeless system as well as a single-particle system. Using the fractional Klein-Gordon equation, we can overcome the problem. The fractional Klein-Gordon equation also leads to the smoothness parameter which is the measurement of the bumpiness of space. Here, by using this smoothness parameter, we have defined and interpreted the various cases.

Continuous care and patients' basic needs during weaning from mechanical ventilation: A qualitative study.

PubMed

Khalafi, Ali; Elahi, Nasrin; Ahmadi, Fazlollah

2016-12-01

Mechanical ventilation is associated with a number of risks and complications. Thus, rapid and safe weaning from mechanical ventilation is of great importance. Weaning is a complex and challenging process, requiring continuous care and knowledge of the patient. The aim of the present study was to describe the continuous care process during weaning as well as to analyse the facilitators and obstacles to the weaning process from start to finish from the perspective of intensive care unit (ICU) staff, particularly nurses. Twenty-two ICU staff members, including nurses and physicians, and three patients hospitalised in the ICU were enrolled in this qualitative study. Semi-structured interviews were used for data collection and the transcripts were analysed using qualitative content analysis. 'Continuous care' was found to be the patients' basic need during weaning from mechanical ventilation. Uninterrupted, stable, comprehensive and dynamic care and monitoring with immediate response to all physiological and psychological changes were features of continuous care. The three main themes identified by this study were time spent with the patient, comprehensive supervision and maintenance of the quality of care during shifts. Continuous and constant care should be provided during the weaning process. Such care will help to provide health care staff with a deeper understanding of the patient and his or her continuous changes, leading to a timely and favourable response during weaning. To achieve this goal, skill, communication and organisational changes are essential. Copyright © 2016 Elsevier Ltd. All rights reserved.

Systems Biology Methods for Alzheimer's Disease Research Toward Molecular Signatures, Subtypes, and Stages and Precision Medicine: Application in Cohort Studies and Trials.

PubMed

Castrillo, Juan I; Lista, Simone; Hampel, Harald; Ritchie, Craig W

2018-01-01

Alzheimer's disease (AD) is a complex multifactorial disease, involving a combination of genomic, interactome, and environmental factors, with essential participation of (a) intrinsic genomic susceptibility and (b) a constant dynamic interplay between impaired pathways and central homeostatic networks of nerve cells. The proper investigation of the complexity of AD requires new holistic systems-level approaches, at both the experimental and computational level. Systems biology methods offer the potential to unveil new fundamental insights, basic mechanisms, and networks and their interplay. These may lead to the characterization of mechanism-based molecular signatures, and AD hallmarks at the earliest molecular and cellular levels (and beyond), for characterization of AD subtypes and stages, toward targeted interventions according to the evolving precision medicine paradigm. In this work, an update on advanced systems biology methods and strategies for holistic studies of multifactorial diseases-particularly AD-is presented. This includes next-generation genomics, neuroimaging and multi-omics methods, experimental and computational approaches, relevant disease models, and latest genome editing and single-cell technologies. Their progressive incorporation into basic research, cohort studies, and trials is beginning to provide novel insights into AD essential mechanisms, molecular signatures, and markers toward mechanism-based classification and staging, and tailored interventions. Selected methods which can be applied in cohort studies and trials, with the European Prevention of Alzheimer's Dementia (EPAD) project as a reference example, are presented and discussed.

Training Basic Visual Attention Leads to Changes in Responsiveness to Social-Communicative Cues in 9-Month-Olds.

PubMed

Forssman, Linda; Wass, Sam V

2018-05-01

This study investigated transfer effects of gaze-interactive attention training to more complex social and cognitive skills in infancy. Seventy 9-month-olds were assigned to a training group (n = 35) or an active control group (n = 35). Before, after, and at 6-week follow-up both groups completed an assessment battery assessing transfer to nontrained aspects of attention control, including table top tasks assessing social attention in seminaturalistic contexts. Transfer effects were found on nontrained screen-based tasks but importantly also on a structured observation task assessing the infants' likelihood to respond to an adult's social-communication cues. The results causally link basic attention skills and more complex social-communicative skills and provide a principle for studying causal mechanisms of early development. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

Allelic variants of hereditary prions: The bimodularity principle.

PubMed

Tikhodeyev, Oleg N; Tarasov, Oleg V; Bondarev, Stanislav A

2017-01-02

Modern biology requires modern genetic concepts equally valid for all discovered mechanisms of inheritance, either "canonical" (mediated by DNA sequences) or epigenetic. Applying basic genetic terms such as "gene" and "allele" to protein hereditary factors is one of the necessary steps toward these concepts. The basic idea that different variants of the same prion protein can be considered as alleles has been previously proposed by Chernoff and Tuite. In this paper, the notion of prion allele is further developed. We propose the idea that any prion allele is a bimodular hereditary system that depends on a certain DNA sequence (DNA determinant) and a certain epigenetic mark (epigenetic determinant). Alteration of any of these 2 determinants may lead to establishment of a new prion allele. The bimodularity principle is valid not only for hereditary prions; it seems to be universal for any epigenetic hereditary factor.

The SUMO Pathway Promotes Basic Helix-Loop-Helix Proneural Factor Activity via a Direct Effect on the Zn Finger Protein Senseless

PubMed Central

Chen, Angela; Huang, Yan Chang; Wang, Pin Yao; Kemp, Sadie E.

2012-01-01

During development, proneural transcription factors of the basic helix-loop-helix (bHLH) family are required to commit cells to a neural fate. In Drosophila neurogenesis, a key mechanism promoting sense organ precursor (SOP) fate is the synergy between proneural factors and their coactivator Senseless in transcriptional activation of target genes. Here we present evidence that posttranslational modification by SUMO enhances this synergy via an effect on Senseless protein. We show that Senseless is a direct target for SUMO modification and that mutagenesis of a predicted SUMOylation motif in Senseless reduces Senseless/proneural synergy both in vivo and in cell culture. We propose that SUMOylation of Senseless via lysine 509 promotes its synergy with proneural proteins during transcriptional activation and hence regulates an important step in neurogenesis leading to the formation and maturation of the SOPs. PMID:22586269

Allelic variants of hereditary prions: The bimodularity principle

PubMed Central

Tikhodeyev, Oleg N.; Tarasov, Oleg V.; Bondarev, Stanislav A.

2017-01-01

ABSTRACT Modern biology requires modern genetic concepts equally valid for all discovered mechanisms of inheritance, either “canonical” (mediated by DNA sequences) or epigenetic. Applying basic genetic terms such as “gene” and “allele” to protein hereditary factors is one of the necessary steps toward these concepts. The basic idea that different variants of the same prion protein can be considered as alleles has been previously proposed by Chernoff and Tuite. In this paper, the notion of prion allele is further developed. We propose the idea that any prion allele is a bimodular hereditary system that depends on a certain DNA sequence (DNA determinant) and a certain epigenetic mark (epigenetic determinant). Alteration of any of these 2 determinants may lead to establishment of a new prion allele. The bimodularity principle is valid not only for hereditary prions; it seems to be universal for any epigenetic hereditary factor. PMID:28281926

Basic Engineer Equipment Mechanic.

ERIC Educational Resources Information Center

Marine Corps Inst., Washington, DC.

This student guide, one of a series of correspondence training courses designed to improve the job performance of members of the Marine Corps, deals with the skills needed by basic engineer equipment mechanics. Addressed in the four individual units of the course are the following topics: mechanics and their tools (mechanics, hand tools, and power…

14 CFR 147.23 - Instructor requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... mechanic certificates and ratings that the Administrator determines necessary to provide adequate... mechanics, to teach mathematics, physics, basic electricity, basic hydraulics, drawing, and similar subjects...

14 CFR 147.23 - Instructor requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... mechanic certificates and ratings that the Administrator determines necessary to provide adequate... mechanics, to teach mathematics, physics, basic electricity, basic hydraulics, drawing, and similar subjects...

14 CFR 147.23 - Instructor requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... mechanic certificates and ratings that the Administrator determines necessary to provide adequate... mechanics, to teach mathematics, physics, basic electricity, basic hydraulics, drawing, and similar subjects...

14 CFR 147.23 - Instructor requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... mechanic certificates and ratings that the Administrator determines necessary to provide adequate... mechanics, to teach mathematics, physics, basic electricity, basic hydraulics, drawing, and similar subjects...

14 CFR 147.23 - Instructor requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... mechanic certificates and ratings that the Administrator determines necessary to provide adequate... mechanics, to teach mathematics, physics, basic electricity, basic hydraulics, drawing, and similar subjects...

Auto Mechanics. Performance Objectives. Basic Course.

ERIC Educational Resources Information Center

Carter, Thomas G., Sr.

Several intermediate performance objectives and corresponding criterion measures are listed for each of 14 terminal objectives for a basic automotive mechanics course. The materials were developed for a two-semester course (2 hours daily) designed to provide training in the basic fundamentals in diagnosis and repair including cooling system and…

Role of Network Science in the Study of Anesthetic State Transitions.

PubMed

Lee, UnCheol; Mashour, George A

2018-04-23

The heterogeneity of molecular mechanisms, target neural circuits, and neurophysiologic effects of general anesthetics makes it difficult to develop a reliable and drug-invariant index of general anesthesia. No single brain region or mechanism has been identified as the neural correlate of consciousness, suggesting that consciousness might emerge through complex interactions of spatially and temporally distributed brain functions. The goal of this review article is to introduce the basic concepts of networks and explain why the application of network science to general anesthesia could be a pathway to discover a fundamental mechanism of anesthetic-induced unconsciousness. This article reviews data suggesting that reduced network efficiency, constrained network repertoires, and changes in cortical dynamics create inhospitable conditions for information processing and transfer, which lead to unconsciousness. This review proposes that network science is not just a useful tool but a necessary theoretical framework and method to uncover common principles of anesthetic-induced unconsciousness.

Is Utilitarianism Risky? How the Same Antecedents and Mechanism Produce Both Utilitarian and Risky Choices.

PubMed

Lucas, Brian J; Galinsky, Adam D

2015-07-01

Philosophers and psychologists have long been interested in identifying factors that influence moral judgment. In the current analysis, we compare the literatures on moral psychology and decision making under uncertainty to propose that utilitarian choices are driven by the same forces that lead to risky choices. Spanning from neurocognitive to hormonal to interpersonal levels of analysis, we identify six antecedents that increase both utilitarian and risky choices (ventromedial prefrontal cortex brain lesions, psychopathology, testosterone, incidental positive affect, power, and social connection) and one antecedent that reduces these choices (serotonin activity). We identify the regulation of negative affect as a common mechanism through which the effects of each antecedent on utilitarian and risky choices are explained. By demonstrating that the same forces and the same underlying mechanism that produce risky choices also promote utilitarian choices, we offer a deeper understanding of how basic psychological systems underlie moral judgment. © The Author(s) 2015.

Animal models of pancreatitis: Can it be translated to human pain study?

PubMed Central

Zhao, Jing-Bo; Liao, Dong-Hua; Nissen, Thomas Dahl

2013-01-01

Chronic pancreatitis affects many individuals around the world, and the study of the underlying mechanisms leading to better treatment possibilities are important tasks. Therefore, animal models are needed to illustrate the basic study of pancreatitis. Recently, animal models of acute and chronic pancreatitis have been thoroughly reviewed, but few reviews address the important aspect on the translation of animal studies to human studies. It is well known that pancreatitis is associated with epigastric pain, but the understanding regarding to mechanisms and appropriate treatment of this pain is still unclear. Using animal models to study pancreatitis associated visceral pain is difficult, however, these types of models are a unique way to reveal the mechanisms behind pancreatitis associated visceral pain. In this review, the animal models of acute, chronic and un-common pancreatitis are briefly outlined and animal models related to pancreatitis associated visceral pain are also addressed. PMID:24259952

Electron and Ion Reactions in Molecular Solids: from water ice to DNA

NASA Astrophysics Data System (ADS)

Huels, Michael A.

2002-05-01

Wherever ionizing radiation interacts with matter, it initiates reaction cascades involving non-thermal ions, radicals, and ballistic secondary electrons, which in turn may lead to substantial physical and chemical modifications of a medium. The detailed study of the fundamental reaction mechanisms which occur on a molecular level aids our general understanding of radiation induced processes in a variety of contexts, ranging from radiobiology to astrochemistry. Here I present measurements of electron (1 - 80 eV) and some ion (1 - 8 eV) mediated reactions in molecular films that resemble biological model systems. These consist of cryogenic films (pure or mixed) of rare gases, oxygen, water, methane, or aromatic hydrocarbons of increasing complexity, including bases, sugars, single and double stranded DNA. Although the basic nature of the electron or ion reaction mechanisms are found to be similar to those in the gas phase, they are often modulated by the physico-chemical characteristics of the medium. Depending on the latter, some reaction channels may be strongly enhanced, some may be quenched, and new reaction pathways, unavailable in the gas phase, may open. Thus, a given reaction cascade may lead to different end-points even in the same target. Although the goal of these studies is to unravel some of the nascent secondary-electron and reactive-ion induced events that contribute to radiation damage in living tissue, the basic observed reactions relate to other areas of application which will be briefly discussed. This research is supported by the Canadian Institutes of Health Research (CIHR), the National Cancer Institutes of Canada, the Natural Science and Engineering Research Council, and NATO.

Barriers to the Preclinical Development of Therapeutics that Target Aging Mechanisms

PubMed Central

Burd, Christin E.; Gill, Matthew S.; Niedernhofer, Laura J.; Robbins, Paul D.; Austad, Steven N.; Barzilai, Nir

2016-01-01

Through the progress of basic science research, fundamental mechanisms that contribute to age-related decline are being described with increasing depth and detail. Although these efforts have identified new drug targets and compounds that extend life span in model organisms, clinical trials of therapeutics that target aging processes remain scarce. Progress in aging research is hindered by barriers associated with the translation of basic science discoveries into the clinic. This report summarizes discussions held at a 2014 Geroscience Network retreat focused on identifying hurdles that currently impede the preclinical development of drugs targeting fundamental aging processes. From these discussions, it was evident that aging researchers have varied perceptions of the ideal preclinical pipeline. To forge a clear and cohesive path forward, several areas of controversy must first be resolved and new tools developed. Here, we focus on five key issues in preclinical drug development (drug discovery, lead compound development, translational preclinical biomarkers, funding, and integration between researchers and clinicians), expanding upon discussions held at the Geroscience Retreat and suggesting areas for further research. By bringing these findings to the attention of the aging research community, we hope to lay the foundation for a concerted preclinical drug development pipeline. PMID:27535964

Identification of an adenylyl cyclase inhibitor for treating neuropathic and inflammatory pain.

PubMed

Wang, Hansen; Xu, Hui; Wu, Long-Jun; Kim, Susan S; Chen, Tao; Koga, Kohei; Descalzi, Giannina; Gong, Bo; Vadakkan, Kunjumon I; Zhang, Xuehan; Kaang, Bong-Kiun; Zhuo, Min

2011-01-12

Neuropathic pain, often caused by nerve injury, is commonly observed among patients with different diseases. Because its basic mechanisms are poorly understood, effective medications are limited. Previous investigations of basic pain mechanisms and drug discovery efforts have focused mainly on early sensory neurons such as dorsal root ganglion and spinal dorsal horn neurons, and few synaptic-level studies or new drugs are designed to target the injury-related cortical plasticity that accompanies neuropathic pain. Our previous work has demonstrated that calcium-stimulated adenylyl cyclase 1 (AC1) is critical for nerve injury-induced synaptic changes in the anterior cingulate cortex. Through rational drug design and chemical screening, we have identified a lead candidate AC1 inhibitor, NB001, which is relatively selective for AC1 over other adenylate cyclase isoforms. Using a variety of behavioral tests and toxicity studies, we have found that NB001, when administered intraperitoneally or orally, has an analgesic effect in animal models of neuropathic pain, without any apparent side effects. Our study thus shows that AC1 could be a productive therapeutic target for neuropathic pain and describes a new agent for the possible treatment of neuropathic pain.

The Crucial Role of Early Mitochondrial Injury in L-Lysine-Induced Acute Pancreatitis

PubMed Central

Biczó, György; Hegyi, Péter; Dósa, Sándor; Shalbuyeva, Natalia; Berczi, Sándor; Sinervirta, Riitta; Hracskó, Zsuzsanna; Siska, Andrea; Kukor, Zoltán; Jármay, Katalin; Venglovecz, Viktória; Varga, Ilona S.; Iványi, Béla; Alhonen, Leena; Wittmann, Tibor; Gukovskaya, Anna; Takács, Tamás

2011-01-01

Abstract Aims Large doses of intraperitoneally injected basic amino acids, L-arginine, or L-ornithine, induce acute pancreatitis in rodents, although the mechanisms mediating pancreatic toxicity remain unknown. Another basic amino acid, L-lysine, was also shown to cause pancreatic acinar cell injury. The aim of the study was to get insight into the mechanisms through which L-lysine damages the rat exocrine pancreas, in particular to characterize the kinetics of L-lysine-induced mitochondrial injury, as well as the pathologic responses (including alteration of antioxidant systems) characteristic of acute pancreatitis. Results We showed that intraperitoneal administration of 2 g/kg L-lysine induced severe acute necrotizing pancreatitis. L-lysine administration caused early pancreatic mitochondrial damage that preceded the activation of trypsinogen and the proinflammatory transcription factor nuclear factor-κB (NF-κB), which are commonly thought to play an important role in the development of acute pancreatitis. Our data demonstrate that L-lysine impairs adenosine triphosphate synthase activity of isolated pancreatic, but not liver, mitochondria. Innovation and Conclusion Taken together, early mitochondrial injury caused by large doses of L-lysine may lead to the development of acute pancreatitis independently of pancreatic trypsinogen and NF-κB activation. PMID:21644850

Topographic-baroclinic instability and formation of Kuroshio current loop

NASA Astrophysics Data System (ADS)

Guo, Jingsong; Zhang, Zhixin; Xia, Changshui; Guo, Binghuo; Yuan, Yeli

2018-03-01

Using time-series figures of sea-level anomaly and geostrophic currents from merged absolute dynamic topography, we analyzed the formation and evolution of the Kuroshio current loop (KCL). The main results are as follows. Perturbation origins of the KCLs are in three areas (eastern, western, and southern) surrounding the Hengchun Submarine Ridge. There are two basic types of KCL formation, i.e., "Kuroshio bend pushing" and "Kuroshio Branch rewinding", plus their combination. The KCLs propagate westward at 1.6-4.5 cm/s. There are two forms of KCL evolution into a shed eddy. The first is such that the northern KCL section initially divides to become an eddy joining the Kuroshio Branch current, which then separates from that current to become a shed eddy. The second form is such that the northern and southern sections of the KCL are separated almost simultaneously in westward elongated process. To understand the KCL formation mechanism, we derive linear equations in phase space from the governing equations in σ-coordinates, ultimately obtaining two groups of analytical solutions for interactions between waves, topography, and the basic current field. The solutions lead to the following results. The KCL propagates westward with the group velocity of the Kuroshio center region. The Kuroshio generally sweeps over the Hengchun Submarine Ridge, especially in winter, such that there is topographic-baroclinic instability. The analytical solutions effectively reveal the dynamic mechanism of the two basic types of KCL formation.

Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

PubMed Central

Greenwood-Van Meerveld, Beverley; Johnson, Anthony C.

2017-01-01

Visceral pain is generally poorly localized and characterized by hypersensitivity to a stimulus such as organ distension. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. Evidence suggests that long term stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders such as irritable bowel syndrome (IBS). Early life stress (ELS) is a risk-factor for the development of IBS, however the mechanisms responsible for the persistent effects of ELS on visceral perception in adulthood remain incompletely understood. In rodent models, stress in adult animals induced by restraint and water avoidance has been employed to investigate the mechanisms of stress-induce pain. ELS models such as maternal separation, limited nesting, or odor-shock conditioning, which attempt to model early childhood experiences such as neglect, poverty, or an abusive caregiver, can produce chronic, sexually dimorphic increases in visceral sensitivity in adulthood. Chronic visceral pain is a classic example of gene × environment interaction which results from maladaptive changes in neuronal circuitry leading to neuroplasticity and aberrant neuronal activity-induced signaling. One potential mechanism underlying the persistent effects of stress on visceral sensitivity could be epigenetic modulation of gene expression. While there are relatively few studies examining epigenetically mediated mechanisms involved in visceral nociception, stress-induced visceral pain has been linked to alterations in DNA methylation and histone acetylation patterns within the brain, leading to increased expression of pro-nociceptive neurotransmitters. This review will discuss the potential neuronal pathways and mechanisms responsible for stress-induced exacerbation of chronic visceral pain. Additionally, we will review the importance of specific experimental models of adult stress and ELS in enhancing our understanding of the basic molecular mechanisms of pain processing. PMID:29213232

14 CFR 147.36 - Maintenance of instructor requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... holding appropriate mechanic certificates and ratings that the Administrator determines necessary to... certificated mechanics to teach mathematics, physics, drawing, basic electricity, basic hydraulics, and similar...

14 CFR 147.36 - Maintenance of instructor requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... holding appropriate mechanic certificates and ratings that the Administrator determines necessary to... certificated mechanics to teach mathematics, physics, drawing, basic electricity, basic hydraulics, and similar...

14 CFR 147.36 - Maintenance of instructor requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... holding appropriate mechanic certificates and ratings that the Administrator determines necessary to... certificated mechanics to teach mathematics, physics, drawing, basic electricity, basic hydraulics, and similar...

14 CFR 147.36 - Maintenance of instructor requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... holding appropriate mechanic certificates and ratings that the Administrator determines necessary to... certificated mechanics to teach mathematics, physics, drawing, basic electricity, basic hydraulics, and similar...

14 CFR 147.36 - Maintenance of instructor requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... holding appropriate mechanic certificates and ratings that the Administrator determines necessary to... certificated mechanics to teach mathematics, physics, drawing, basic electricity, basic hydraulics, and similar...

Basic Scientific and Engineering Research at U.S. Universities. AAU Data & Policy Brief. No. 1

ERIC Educational Resources Information Center

Association of American Universities, 2015

2015-01-01

"Discovery," wrote William Press in a 2013 article in "Science," "leads to technology and invention, which lead to new products, jobs, and industries." Basic, curiosity-driven research continually expands the boundaries of knowledge across fields, providing insights that enrich lives. Such research helps drive the…

Physical mechanisms of self-organization and formation of current patterns in gas discharges of the Townsend and glow types

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raizer, Yu. P.; Mokrov, M. S.

The paper discusses current filamentation and formation of current structures (in particular, hexagonal current patterns) in discharges of the Townsend and glow types. The aim of the paper, which is in part a review, is to reveal basic reasons for formation of current patterns in different cases, namely, in dielectric barrier discharge, discharge with semiconductor cathode, and micro-discharge between metallic electrodes. Pursuing this goal, we give a very brief review of observations and discuss only those theoretical, computational, and experimental papers that shed light on the physical mechanisms involved. The mechanisms are under weak currents—the thermal expansion of the gasmore » as a result of Joule heating; under enhanced currents—the electric field and ionization rate redistribution induced by space charge. Both mechanisms lead to instability of the homogeneous discharges. In addition, we present new results of numerical simulations of observed short-living current filaments which are chaotic in space and time.« less

Biphasic responses in multi-site phosphorylation systems.

PubMed

Suwanmajo, Thapanar; Krishnan, J

2013-12-06

Multi-site phosphorylation systems are repeatedly encountered in cellular biology and multi-site modification is a basic building block of post-translational modification. In this paper, we demonstrate how distributive multi-site modification mechanisms by a single kinase/phosphatase pair can lead to biphasic/partial biphasic dose-response characteristics for the maximally phosphorylated substrate at steady state. We use simulations and analysis to uncover a hidden competing effect which is responsible for this and analyse how it may be accentuated. We build on this to analyse different variants of multi-site phosphorylation mechanisms showing that some mechanisms are intrinsically not capable of displaying this behaviour. This provides both a consolidated understanding of how and under what conditions biphasic responses are obtained in multi-site phosphorylation and a basis for discriminating between different mechanisms based on this. We also demonstrate how this behaviour may be combined with other behaviour such as threshold and bistable responses, demonstrating the capacity of multi-site phosphorylation systems to act as complex molecular signal processors.

In vitro three-dimensional cancer metastasis modeling: Past, present, and future

NASA Astrophysics Data System (ADS)

Wei-jing, Han; Wei, Yuan; Jiang-rui, Zhu; Qihui, Fan; Junle, Qu; Li-yu, Liu

2016-01-01

Metastasis is the leading cause of most cancer deaths, as opposed to dysregulated cell growth of the primary tumor. Molecular mechanisms of metastasis have been studied for decades and the findings have evolved our understanding of the progression of malignancy. However, most of the molecular mechanisms fail to address the causes of cancer and its evolutionary origin, demonstrating an inability to find a solution for complete cure of cancer. After being a neglected area of tumor biology for quite some time, recently several studies have focused on the impact of the tumor microenvironment on cancer growth. The importance of the tumor microenvironment is gradually gaining attention, particularly from the perspective of biophysics. In vitro three-dimensional (3-D) metastatic models are an indispensable platform for investigating the tumor microenvironment, as they mimic the in vivo tumor tissue. In 3-D metastatic in vitro models, static factors such as the mechanical properties, biochemical factors, as well as dynamic factors such as cell-cell, cell-ECM interactions, and fluid shear stress can be studied quantitatively. With increasing focus on basic cancer research and drug development, the in vitro 3-D models offer unique advantages in fundamental and clinical biomedical studies. Project supported by the National Basic Research Program of China (Grant No. 2013CB837200), the National Natural Science Foundation of China (Grant No. 11474345), and the Beijing Natural Science Foundation, China (Grant No. 7154221).

Basic research in PCOS: are we reaching new frontiers?

PubMed

Ben-Shlomo, Izhar; Younis, Johnny S

2014-06-01

Polycystic ovarian syndrome (PCOS) is the leading cause for anovulatory infertility. It is diagnosed by two of the following three clinical criteria: oligomenorrhoea, hyperandrogenism and polycystic appearance of the ovaries. Weight loss and physical activity can lead to ovulation and conception. Lowering of serum insulin normalizes androgen concentrations whereas ovulation induction often causes ovarian hyperstimulation. Theca cells from PCOS ovaries may be more responsive to insulin than cells from non-PCOS ovaries. Herein we review the research efforts at the genomic and cell function levels, as well as animal models, which have been made to elucidate the underlying mechanism that leads to PCOS. It appears that, despite the impressive amount of data that have been generated in these studies, the mechanism of this syndrome is still only partially understood. Polycystic ovarian syndrome (PCOS) is the leading cause for infertility, which is caused by anovulation. It is diagnosed by two of the following three clinical criteria: irregular and prolonged menstrual cycles, overt symptoms of excess androgens, which is revealed by acne and excess hair, and ultrasonographic appearance of the ovaries with multiple small follicles spread mainly near the ovarian surface, which gave it its name. Intentional weight loss and physical activity can lead to resumption of ovulation and not infrequently to conception as well. It was shown that lowering of serum insulin accounts for normalization of serum androgen levels, whereas ovulation induction with FSH often causes ovarian hyperstimulation. It is suggested that theca cells from PCOS ovaries may be more responsive to insulin than cells from non-PCOS ovaries. In this article we review the efforts to define the genes responsible for the syndrome and the studies at the cell function level, as well as animal models, which have been done to elucidate the underlying mechanism that leads to PCOS. Overall, it appears that despite the impressive amount of data that have been generated in these studies, the mechanism of this syndrome is still only partially understood. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Primary Spinal OPC Culture System from Adult Zebrafish to Study Oligodendrocyte Differentiation In Vitro.

PubMed

Kroehne, Volker; Tsata, Vasiliki; Marrone, Lara; Froeb, Claudia; Reinhardt, Susanne; Gompf, Anne; Dahl, Andreas; Sterneckert, Jared; Reimer, Michell M

2017-01-01

Endogenous oligodendrocyte progenitor cells (OPCs) are a promising target to improve functional recovery after spinal cord injury (SCI) by remyelinating denuded, and therefore vulnerable, axons. Demyelination is the result of a primary insult and secondary injury, leading to conduction blocks and long-term degeneration of the axons, which subsequently can lead to the loss of their neurons. In response to SCI, dormant OPCs can be activated and subsequently start to proliferate and differentiate into mature myelinating oligodendrocytes (OLs). Therefore, researchers strive to control OPC responses, and utilize small molecule screening approaches in order to identify mechanisms of OPC activation, proliferation, migration and differentiation. In zebrafish, OPCs remyelinate axons of the optic tract after lysophosphatidylcholine (LPC)-induced demyelination back to full thickness myelin sheaths. In contrast to zebrafish, mammalian OPCs are highly vulnerable to excitotoxic stress, a cause of secondary injury, and remyelination remains insufficient. Generally, injury induced remyelination leads to shorter internodes and thinner myelin sheaths in mammals. In this study, we show that myelin sheaths are lost early after a complete spinal transection injury, but are re-established within 14 days after lesion. We introduce a novel, easy-to-use, inexpensive and highly reproducible OPC culture system based on dormant spinal OPCs from adult zebrafish that enables in vitro analysis. Zebrafish OPCs are robust, can easily be purified with high viability and taken into cell culture. This method enables to examine why zebrafish OPCs remyelinate better than their mammalian counterparts, identify cell intrinsic responses, which could lead to pro-proliferating or pro-differentiating strategies, and to test small molecule approaches. In this methodology paper, we show efficient isolation of OPCs from adult zebrafish spinal cord and describe culture conditions that enable analysis up to 10 days in vitro . Finally, we demonstrate that zebrafish OPCs differentiate into Myelin Basic Protein (MBP)-expressing OLs when co-cultured with human motor neurons differentiated from induced pluripotent stem cells (iPSCs). This shows that the basic mechanisms of oligodendrocyte differentiation are conserved across species and that understanding the regulation of zebrafish OPCs can contribute to the development of new treatments to human diseases.

Statistical thermodynamics unveils the dissolution mechanism of cellobiose.

PubMed

Nicol, Thomas W J; Isobe, Noriyuki; Clark, James H; Shimizu, Seishi

2017-08-30

In the study of the cellulose dissolution mechanism opinion is still divided. Here, the solution interaction components of the most prominent hypotheses for the driving force of cellulose dissolution were evaluated quantitatively. Combining a rigorous statistical thermodynamic theory and cellobiose solubility data in the presence of chloride salts, whose cations progress in the Hofmeister series (KCl, NaCl, LiCl and ZnCl 2 ), we have shown that cellobiose solubilization is driven by the preferential accumulation of salts around the solutes which is stronger than cellobiose hydration. Yet contrary to the classical chaotropy hypothesis, increasing salt concentration leads to cellobiose dehydration in the presence of the strongest solubilizer ZnCl 2 . However, thanks to cellobiose dehydration, cellobiose-salt interaction still remains preferential despite weakening salt accumulation. Based on such insights, the previous hypotheses based on hydrophobicity and polymer charging have also been evaluated quantitatively. Thus, our present study successfully paved a way towards identifying the basic driving forces for cellulose solubilization in a quantitative manner for the first time. When combined with unit additivity methods this quantitative information could lead to a full understanding of cellulose solubility.

Photo-oxidation degradation mechanisms in P3HT for organic solar cells: Insights from first-principles simulations

NASA Astrophysics Data System (ADS)

Leung, Kevin; Sai, Na; Zador, Judit; Henkelman, Graeme

2014-03-01

Photo-oxidation is one of the leading chemical degradation mechanisms in polymer solar cells. In this work, using hybrid density functional theory and periodic boundary condition, we investigate reaction pathways that may lead to the sulfur oxidation in poly(3-hexylthiophene)(P3HT) as a step toward breaking the macromolecule backbone. We calculate energy barriers for reactions of P3HT backbone with oxidizing radicals suggested by infrared spectroscopy (IR) and XPS studies. Our results strongly suggest that an attack of hydroxyl radical on sulfur as proposed in the literature is unlikely to be thermodynamically favored. On the other hand, a reaction between the alkylperoxyl radical and the polymer backbone may provide low barrier reaction pathways to photo-oxidation of conjugated polymers with side chains. Our work paves way for future studies using ab-initio calculations in a condensed phase setting to model complex chemical reactions relevant to photochemical stability of novel polymers. Supported by the Energy Frontier Research Center funded by the U.S. DOE Office of Basic Energy Sciences under Award #DE-SC0001091.

Cryo-EM Structures Reveal Mechanism and Inhibition of DNA Targeting by a CRISPR-Cas Surveillance Complex.

PubMed

Guo, Tai Wei; Bartesaghi, Alberto; Yang, Hui; Falconieri, Veronica; Rao, Prashant; Merk, Alan; Eng, Edward T; Raczkowski, Ashleigh M; Fox, Tara; Earl, Lesley A; Patel, Dinshaw J; Subramaniam, Sriram

2017-10-05

Prokaryotic cells possess CRISPR-mediated adaptive immune systems that protect them from foreign genetic elements, such as invading viruses. A central element of this immune system is an RNA-guided surveillance complex capable of targeting non-self DNA or RNA for degradation in a sequence- and site-specific manner analogous to RNA interference. Although the complexes display considerable diversity in their composition and architecture, many basic mechanisms underlying target recognition and cleavage are highly conserved. Using cryoelectron microscopy (cryo-EM), we show that the binding of target double-stranded DNA (dsDNA) to a type I-F CRISPR system yersinia (Csy) surveillance complex leads to large quaternary and tertiary structural changes in the complex that are likely necessary in the pathway leading to target dsDNA degradation by a trans-acting helicase-nuclease. Comparison of the structure of the surveillance complex before and after dsDNA binding, or in complex with three virally encoded anti-CRISPR suppressors that inhibit dsDNA binding, reveals mechanistic details underlying target recognition and inhibition. Published by Elsevier Inc.

Postdoctoral Fellow | Center for Cancer Research

Cancer.gov

The Neural Development Section (NDS) headed by Dr. Lino Tessarollo has an open postdoctoral fellow position. The candidate should have a background in neurobiology and basic expertise in molecular biology, cell biology, immunoistochemistry and biochemistry.  Experience in confocal analysis is desired. The NDS study the biology of neurotrophin and Trk receptors function by using both in vitro and in vivo approaches. Our group makes extensive use of engineered mouse models and cell culture models. The current research emphasis is on understanding the molecular mechanisms by which activated trk receptor function. Specifically, we are dissecting the molecular mechanism responsible for modulating Trk receptors activity, including their interaction with specific scaffold proteins and proteins leading to de-activation of Trk signaling. Moreover, we are attempting to identify new signaling pathways activated by truncated Trk receptors.

Evidence that Singlet Oxygen-induced Human T Helper Cell Apoptosis Is the Basic Mechanism of Ultraviolet-A Radiation Phototherapy

PubMed Central

Morita, Akimichi; Werfel, Thomas; Stege, Helger; Ahrens, Constanze; Karmann, Karin; Grewe, Markus; Grether-Beck, Susanne; Ruzicka, Thomas; Kapp, Alexander; Klotz, Lars-Oliver; Sies, Helmut; Krutmann, Jean

1997-01-01

Ultraviolet A (UVA) irradiation is effectively used to treat patients with atopic dermatitis and other T cell mediated, inflammatory skin diseases. In the present study, successful phototherapy of atopic dermatitis was found to result from UVA radiation-induced apoptosis in skin-infiltrating T helper cells, leading to T cell depletion from eczematous skin. In vitro, UVA radiation-induced human T helper cell apoptosis was mediated through the FAS/FAS-ligand system, which was activated in irradiated T cells as a consequence of singlet oxygen generation. These studies demonstrate that singlet oxygen is a potent trigger for the induction of human T cell apoptosis. They also identify singlet oxygen generation as a fundamental mechanism of action operative in phototherapy. PMID:9362536

1986 Annual Conference on Nuclear and Space Radiation Effects, 23rd, Providence, RI, July 21-23, 1986, Proceedings

NASA Technical Reports Server (NTRS)

Ellis, Thomas D. (Editor)

1986-01-01

The present conference on the effects of nuclear and space radiation on electronic hardware gives attention to topics in the basic mechanisms of radiation effects, dosimetry and energy-dependent effects, electronic device radiation hardness assurance, SOI/SOS radiation effects, spacecraft charging and space radiation, IC radiation effects and hardening, single-event upset (SEU) phenomena and hardening, and EMP/SGEMP/IEMP phenomena. Specific treatments encompass the generation of interface states by ionizing radiation in very thin MOS oxides, the microdosimetry of meson energy deposited on 1-micron sites in Si, total dose radiation and engineering studies, plasma interactions with biased concentrator solar cells, the transient imprint memory effect in MOS memories, mechanisms leading to SEU, and the vaporization and breakdown of thin columns of water.

Computation as the mechanistic bridge between precision medicine and systems therapeutics.

PubMed

Hansen, J; Iyengar, R

2013-01-01

Over the past 50 years, like molecular cell biology, medicine and pharmacology have been driven by a reductionist approach. The focus on individual genes and cellular components as disease loci and drug targets has been a necessary step in understanding the basic mechanisms underlying tissue/organ physiology and drug action. Recent progress in genomics and proteomics, as well as advances in other technologies that enable large-scale data gathering and computational approaches, is providing new knowledge of both normal and disease states. Systems-biology approaches enable integration of knowledge from different types of data for precision medicine and systems therapeutics. In this review, we describe recent studies that contribute to these emerging fields and discuss how together these fields can lead to a mechanism-based therapy for individual patients.

Computation as the Mechanistic Bridge Between Precision Medicine and Systems Therapeutics

PubMed Central

Hansen, J; Iyengar, R

2014-01-01

Over the past 50 years, like molecular cell biology, medicine and pharmacology have been driven by a reductionist approach. The focus on individual genes and cellular components as disease loci and drug targets has been a necessary step in understanding the basic mechanisms underlying tissue/organ physiology and drug action. Recent progress in genomics and proteomics, as well as advances in other technologies that enable large-scale data gathering and computational approaches, is providing new knowledge of both normal and disease states. Systems-biology approaches enable integration of knowledge from different types of data for precision medicine and systems therapeutics. In this review, we describe recent studies that contribute to these emerging fields and discuss how together these fields can lead to a mechanism-based therapy for individual patients. PMID:23212109

Metabolomic Analysis of Blood Plasma after Oral Administration of N-acetyl-d-Glucosamine in Dogs

PubMed Central

Osaki, Tomohiro; Kurozumi, Seiji; Sato, Kimihiko; Terashi, Taro; Azuma, Kazuo; Murahata, Yusuke; Tsuka, Takeshi; Ito, Norihiko; Imagawa, Tomohiro; Minami, Saburo; Okamoto, Yoshiharu

2015-01-01

N-acetyl-d-glucosamine (GlcNAc) is a monosaccharide that polymerizes linearly through (1,4)-β-linkages. GlcNAc is the monomeric unit of the polymer chitin. GlcNAc is a basic component of hyaluronic acid and keratin sulfate found on the cell surface. The aim of this study was to examine amino acid metabolism after oral GlcNAc administration in dogs. Results showed that plasma levels of ectoine were significantly higher after oral administration of GlcNAc than prior to administration (p < 0.001). To our knowledge, there have been no reports of increased ectoine concentrations in the plasma. The mechanism by which GlcNAc administration leads to increased ectoine plasma concentration remains unclear; future studies are required to clarify this mechanism. PMID:26262626

Is quantum theory a form of statistical mechanics?

NASA Astrophysics Data System (ADS)

Adler, S. L.

2007-05-01

We give a review of the basic themes of my recent book: Adler S L 2004 Quantum Theory as an Emergent Phenomenon (Cambridge: Cambridge University Press). We first give motivations for considering the possibility that quantum mechanics is not exact, but is instead an accurate asymptotic approximation to a deeper level theory. For this deeper level, we propose a non-commutative generalization of classical mechanics, that we call "trace dynamics", and we give a brief survey of how it works, considering for simplicity only the bosonic case. We then discuss the statistical mechanics of trace dynamics and give our argument that with suitable approximations, the Ward identities for trace dynamics imply that ensemble averages in the canonical ensemble correspond to Wightman functions in quantum field theory. Thus, quantum theory emerges as the statistical thermodynamics of trace dynamics. Finally, we argue that Brownian motion corrections to this thermodynamics lead to stochastic corrections to the Schrödinger equation, of the type that have been much studied in the "continuous spontaneous localization" model of objective state vector reduction. In appendices to the talk, we give details of the existence of a conserved operator in trace dynamics that encodes the structure of the canonical algebra, of the derivation of the Ward identities, and of the proof that the stochastically-modified Schrödinger equation leads to state vector reduction with Born rule probabilities.

Approximation methods for stochastic petri nets

NASA Technical Reports Server (NTRS)

Jungnitz, Hauke Joerg

1992-01-01

Stochastic Marked Graphs are a concurrent decision free formalism provided with a powerful synchronization mechanism generalizing conventional Fork Join Queueing Networks. In some particular cases the analysis of the throughput can be done analytically. Otherwise the analysis suffers from the classical state explosion problem. Embedded in the divide and conquer paradigm, approximation techniques are introduced for the analysis of stochastic marked graphs and Macroplace/Macrotransition-nets (MPMT-nets), a new subclass introduced herein. MPMT-nets are a subclass of Petri nets that allow limited choice, concurrency and sharing of resources. The modeling power of MPMT is much larger than that of marked graphs, e.g., MPMT-nets can model manufacturing flow lines with unreliable machines and dataflow graphs where choice and synchronization occur. The basic idea leads to the notion of a cut to split the original net system into two subnets. The cuts lead to two aggregated net systems where one of the subnets is reduced to a single transition. A further reduction leads to a basic skeleton. The generalization of the idea leads to multiple cuts, where single cuts can be applied recursively leading to a hierarchical decomposition. Based on the decomposition, a response time approximation technique for the performance analysis is introduced. Also, delay equivalence, which has previously been introduced in the context of marked graphs by Woodside et al., Marie's method and flow equivalent aggregation are applied to the aggregated net systems. The experimental results show that response time approximation converges quickly and shows reasonable accuracy in most cases. The convergence of Marie's method and flow equivalent aggregation are applied to the aggregated net systems. The experimental results show that response time approximation converges quickly and shows reasonable accuracy in most cases. The convergence of Marie's is slower, but the accuracy is generally better. Delay equivalence often fails to converge, while flow equivalent aggregation can lead to potentially bad results if a strong dependence of the mean completion time on the interarrival process exists.

Analytical model for investigation of interior noise characteristics in aircraft with multiple propellers including synchrophasing

NASA Technical Reports Server (NTRS)

Fuller, C. R.

1986-01-01

A simplified analytical model of transmission of noise into the interior of propeller-driven aircraft has been developed. The analysis includes directivity and relative phase effects of the propeller noise sources, and leads to a closed form solution for the coupled motion between the interior and exterior fields via the shell (fuselage) vibrational response. Various situations commonly encountered in considering sound transmission into aircraft fuselages are investigated analytically and the results obtained are compared to measurements in real aircraft. In general the model has proved successful in identifying basic mechanisms behind noise transmission phenomena.

Regenerative endodontics and tissue engineering: what the future holds?

PubMed

Goodis, Harold E; Kinaia, Bassam Michael; Kinaia, Atheel M; Chogle, Sami M A

2012-07-01

The work performed by researchers in regenerative endodontics and tissue engineering over the last decades has been superb; however, many questions remain to be answered. The basic biologic mechanisms must be elucidated that will allow the development of dental pulp and dentin in situ. Stress must be placed on the many questions that will lead to the design of effective, safe treatment options and therapies. This article discusses those questions, the answers to which may become the future of regenerative endodontics. The future remains bright, but proper support and patience are required. Copyright © 2012 Elsevier Inc. All rights reserved.

Spinors in Hilbert Space

NASA Astrophysics Data System (ADS)

Plymen, Roger; Robinson, Paul

1995-01-01

Infinite-dimensional Clifford algebras and their Fock representations originated in the quantum mechanical study of electrons. In this book, the authors give a definitive account of the various Clifford algebras over a real Hilbert space and of their Fock representations. A careful consideration of the latter's transformation properties under Bogoliubov automorphisms leads to the restricted orthogonal group. From there, a study of inner Bogoliubov automorphisms enables the authors to construct infinite-dimensional spin groups. Apart from assuming a basic background in functional analysis and operator algebras, the presentation is self-contained with complete proofs, many of which offer a fresh perspective on the subject.

Standardized Curriculum for Diesel Engine Mechanics.

ERIC Educational Resources Information Center

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…

Linear models for assessing mechanisms of sperm competition: the trouble with transformations.

PubMed

Eggert, Anne-Katrin; Reinhardt, Klaus; Sakaluk, Scott K

2003-01-01

Although sperm competition is a pervasive selective force shaping the reproductive tactics of males, the mechanisms underlying different patterns of sperm precedence remain obscure. Parker et al. (1990) developed a series of linear models designed to identify two of the more basic mechanisms: sperm lotteries and sperm displacement; the models can be tested experimentally by manipulating the relative numbers of sperm transferred by rival males and determining the paternity of offspring. Here we show that tests of the model derived for sperm lotteries can result in misleading inferences about the underlying mechanism of sperm precedence because the required inverse transformations may lead to a violation of fundamental assumptions of linear regression. We show that this problem can be remedied by reformulating the model using the actual numbers of offspring sired by each male, and log-transforming both sides of the resultant equation. Reassessment of data from a previous study (Sakaluk and Eggert 1996) using the corrected version of the model revealed that we should not have excluded a simple sperm lottery as a possible mechanism of sperm competition in decorated crickets, Gryllodes sigillatus.

Atomic-scale mechanisms of helium bubble hardening in iron

DOE PAGES

Osetskiy, Yury N.; Stoller, Roger E.

2015-06-03

Generation of helium due to (n,α) transmutation reactions changes the response of structural materials to neutron irradiation. The whole process of radiation damage evolution is affected by He accumulation and leads to significant changes in the material s properties. A population of nanometric He-filled bubbles affects mechanical properties and the impact can be quite significant because of their high density. Understanding how these basic mechanisms affect mechanical properties is necessary for predicting radiation effects. In this paper we present an extensive study of the interactions between a moving edge dislocation and bubbles using atomic-scale modeling. We focus on the effectmore » of He bubble size and He concentration inside bubbles. Thus, we found that ability of bubbles to act as an obstacle to dislocation motion is close to that of voids when the He-to-vacancy ratio is in the range from 0 to 1. A few simulations made at higher He contents demonstrated that the interaction mechanism is changed for over-pressurized bubbles and they become weaker obstacles. The results are discussed in light of post-irradiation materials testing.« less

Silicosis and coal workers' pneumoconiosis.

PubMed Central

Castranova, V; Vallyathan, V

2000-01-01

Exposure to coal mine dust and/or crystalline silica results in pneumoconiosis with initiation and progression of pulmonary fibrosis. This review presents characteristics of simple and complicated coal workers' pneumoconiosis (CWP) as well as pathologic indices of acute and chronic silicosis by summarizing results of in vitro, animal, and human investigations. These results support four basic mechanisms in the etiology of CWP and silicosis: a) direct cytotoxicity of coal dust or silica, resulting in lung cell damage, release of lipases and proteases, and eventual lung scarring; b) activation of oxidant production by pulmonary phagocytes, which overwhelms the antioxidant defenses and leads to lipid peroxidation, protein nitrosation, cell injury, and lung scarring; c) activation of mediator release from alveolar macrophages and epithelial cells, which leads to recruitment of polymorphonuclear leukocytes and macrophages, resulting in the production of proinflammatory cytokines and reactive species and in further lung injury and scarring; d) secretion of growth factors from alveolar macrophages and epithelial cells, stimulating fibroblast proliferation and eventual scarring. Results of in vitro and animal studies provide a basis for proposing these mechanisms for the initiation and progression of pneumoconiosis. Data obtained from exposed workers lend support to these mechanisms. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:10931786

Desorption of hydrocarbon chains by association with ionic and nonionic surfactants under flow as a mechanism for enhanced oil recovery.

PubMed

Terrón-Mejía, Ketzasmin A; López-Rendón, Roberto; Goicochea, Armando Gama

2017-08-29

The need to extract oil from wells where it is embedded on the surfaces of rocks has led to the development of new and improved enhanced oil recovery techniques. One of those is the injection of surfactants with water vapor, which promotes desorption of oil that can then be extracted using pumps, as the surfactants encapsulate the oil in foams. However, the mechanisms that lead to the optimal desorption of oil and the best type of surfactants to carry out desorption are not well known yet, which warrants the need to carry out basic research on this topic. In this work, we report non equilibrium dissipative particle dynamics simulations of model surfactants and oil molecules adsorbed on surfaces, with the purpose of studying the efficiency of the surfactants to desorb hydrocarbon chains, that are found adsorbed over flat surfaces. The model surfactants studied correspond to nonionic and cationic surfactants, and the hydrocarbon desorption is studied as a function of surfactant concentration under increasing Poiseuille flow. We obtain various hydrocarbon desorption isotherms for every model of surfactant proposed, under flow. Nonionic surfactants are found to be the most effective to desorb oil and the mechanisms that lead to this phenomenon are presented and discussed.

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

PubMed

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.

Achieving reversibility of ultra-high mechanical stress by hydrogen loading of thin films

NASA Astrophysics Data System (ADS)

Hamm, M.; Burlaka, V.; Wagner, S.; Pundt, A.

2015-06-01

Nano-materials are commonly stabilized by supports to maintain their desired shape and size. When these nano-materials take up interstitial atoms, this attachment to the support induces mechanical stresses. These stresses can be high when the support is rigid. High stress in the nano-material is typically released by delamination from the support or by the generation of defects, e.g., dislocations. As high mechanical stress can be beneficial for tuning the nano-materials properties, it is of general interest to deduce how real high mechanical stress can be gained. Here, we show that below a threshold nano-material size, dislocation formation can be completely suppressed and, when delamination is inhibited, even the ultrahigh stress values of the linear elastic limit can be reached. Specifically, for hydrogen solved in epitaxial niobium films on sapphire substrate supports a threshold film thickness of 6 nm was found and mechanical stress of up to (-10 ± 1) GPa was reached. This finding is of basic interest for hydrogen energy applications, as the hydride stability in metals itself is affected by mechanical stress. Thus, tuning of the mechanical stress-state in nano-materials may lead to improved storage properties of nano-sized materials.

Cancer Treatment–Related Cardiotoxicity: Current State of Knowledge and Future Research Priorities

PubMed Central

Adhikari, Bishow; Brell, Joanna; Davis, Myrtle; Desvigne-Nickens, Patrice; Freedman, Andrew; Minasian, Lori; Force, Thomas; Remick, Scot C.

2014-01-01

Cardiotoxicity resulting from direct myocyte damage has been a known complication of cancer treatment for decades. More recently, the emergence of hypertension as a clinically significant side effect of several new agents has been recognized as adversely affecting cancer treatment outcomes. With cancer patients living longer, in part because of treatment advances, these adverse events have become increasingly important to address. However, little is known about the cardiovascular pathogenic mechanisms associated with cancer treatment and even less about how to optimally prevent and manage short- and long-term cardiovascular complications, leading to improved patient safety and clinical outcomes. To identify research priorities, allocate resources, and establish infrastructure required to address cardiotoxicity associated with cancer treatment, the National Cancer Institute (NCI) and National Heart, Lung and Blood Institute (NHLBI) sponsored a two-day workshop, “Cancer treatment–related cardiotoxicity: Understanding the current state of knowledge and future research priorities,” in March 2013 in Bethesda, MD. Participants included leading oncology and cardiology researchers and health professionals, patient advocates and industry representatives, with expertise ranging from basic to clinical science. Attendees were charged with identifying research opportunities to advance the understanding of cancer treatment–related cardiotoxicity across basic and clinical science. This commentary highlights the key discussion points and overarching recommendations from that workshop. PMID:25210198

Reflecting on the Liberal Reflex: Rhetoric and the Politics of Acknowledgement in Basic Writing

ERIC Educational Resources Information Center

Pavesich, Matthew

2011-01-01

In the 1990s, leading rhetoric and composition scholars criticized basic writing programs for their "liberalism." Basic writing had its defenders, however, and the ensuing debate exposed deep rifts in the field. This article argues that neither side in this formative debate nor the more recent alternative models of teaching basic writing…

Auto-Mechanics Course. Bilingual Vocational Instructional Materials.

ERIC Educational Resources Information Center

Lopez-Cox, Guadalupe

This auto-mechanics course, one of a series of bilingual English-Spanish vocational education courses, is designed to introduce the basic skills that an automotive mechanics student should know. It is geared to teach the student basic manipulative skills, safety judgments, proper work habits, desirable attitudes, and proper behavior for initial…

How do we make models that are useful in understanding partial epilepsies?

PubMed

Prince, David A

2014-01-01

The goals of constructing epilepsy models are (1) to develop approaches to prophylaxis of epileptogenesis following cortical injury; (2) to devise selective treatments for established epilepsies based on underlying pathophysiological mechanisms; and (3) use of a disease (epilepsy) model to explore brain molecular, cellular and circuit properties. Modeling a particular epilepsy syndrome requires detailed knowledge of key clinical phenomenology and results of human experiments that can be addressed in critically designed laboratory protocols. Contributions to understanding mechanisms and treatment of neurological disorders has often come from research not focused on a specific disease-relevant issue. Much of the foundation for current research in epilepsy falls into this category. Too strict a definition of the relevance of an experimental model to progress in preventing or curing epilepsy may, in the long run, slow progress. Inadequate exploration of the experimental target and basic laboratory results in a given model can lead to a failed effort and false negative or positive results. Models should be chosen based on the specific issues to be addressed rather than on convenience of use. Multiple variables including maturational age, species and strain, lesion type, severity and location, latency from injury to experiment and genetic background will affect results. A number of key issues in clinical and basic research in partial epilepsies remain to be addressed including the mechanisms active during the latent period following injury, susceptibility factors that predispose to epileptogenesis, injury - induced adaptive versus maladaptive changes, mechanisms of pharmaco-resistance and strategies to deal with multiple pathophysiological processes occurring in parallel.

Novel aspects of glucocorticoid actions.

PubMed

Uchoa, E T; Aguilera, G; Herman, J P; Fiedler, J L; Deak, T; de Sousa, M B C

2014-09-01

Normal hypothalamic-pituitary-adrenal (HPA) axis activity leading to the rhythmic and episodic release of adrenal glucocorticoids (GCs) is essential for body homeostasis and survival during stress. Acting through specific intracellular receptors in the brain and periphery, GCs regulate behaviour, as well as metabolic, cardiovascular, immune and neuroendocrine activities. By contrast to chronic elevated levels, circadian and acute stress-induced increases in GCs are necessary for hippocampal neuronal survival and memory acquisition and consolidation, as a result of the inhibition of apoptosis, the facilitation of glutamatergic neurotransmission and the formation of excitatory synapses, and the induction of immediate early genes and dendritic spine formation. In addition to metabolic actions leading to increased energy availability, GCs have profound effects on feeding behaviour, mainly via the modulation of orexigenic and anorixegenic neuropeptides. Evidence is also emerging that, in addition to the recognised immune suppressive actions of GCs by counteracting adrenergic pro-inflammatory actions, circadian elevations have priming effects in the immune system, potentiating acute defensive responses. In addition, negative-feedback by GCs involves multiple mechanisms leading to limited HPA axis activation and prevention of the deleterious effects of excessive GC production. Adequate GC secretion to meet body demands is tightly regulated by a complex neural circuitry controlling hypothalamic corticotrophin-releasing hormone (CRH) and vasopressin secretion, which are the main regulators of pituitary adrenocorticotrophic hormone (ACTH). Rapid feedback mechanisms, likely involving nongenomic actions of GCs, mediate the immediate inhibition of hypothalamic CRH and ACTH secretion, whereas intermediate and delayed mechanisms mediated by genomic actions involve the modulation of limbic circuitry and peripheral metabolic messengers. Consistent with their key adaptive roles, HPA axis components are evolutionarily conserved, being present in the earliest vertebrates. An understanding of these basic mechanisms may lead to novel approaches for the development of diagnostic and therapeutic tools for disorders related to stress and alterations of GC secretion. © 2014 British Society for Neuroendocrinology.

The NMR solution structure of a mutant of the Max b/HLH/LZ free of DNA: insights into the specific and reversible DNA binding mechanism of dimeric transcription factors.

PubMed

Sauvé, Simon; Tremblay, Luc; Lavigne, Pierre

2004-09-17

Basic region-helix1-loop-helix2-leucine zipper (b/H(1)LH(2)/LZ) transcription factors bind specific DNA sequence in their target gene promoters as dimers. Max, a b/H(1)LH(2)/LZ transcription factor, is the obligate heterodimeric partner of the related b/H(1)LH(2)/LZ proteins of the Myc and Mad families. These heterodimers specifically bind E-box DNA sequence (CACGTG) to activate (e.g. c-Myc/Max) and repress (e.g. Mad1/Max) transcription. Max can also homodimerize and bind E-box sequences in c-Myc target gene promoters. While the X-ray structure of the Max b/H(1)LH(2)/LZ/DNA complex and that of others have been reported, the precise sequence of events leading to the reversible and specific binding of these important transcription factors is still largely unknown. In order to provide insights into the DNA binding mechanism, we have solved the NMR solution structure of a covalently homodimerized version of a Max b/H(1)LH(2)/LZ protein with two stabilizing mutations in the LZ, and characterized its backbone dynamics from (15)N spin-relaxation measurements in the absence of DNA. Apart from minor differences in the pitch of the LZ, possibly resulting from the mutations in the construct, we observe that the packing of the helices in the H(1)LH(2) domain is almost identical to that of the two crystal structures, indicating that no important conformational change in these helices occurs upon DNA binding. Conversely to the crystal structures of the DNA complexes, the first 14 residues of the basic region are found to be mostly unfolded while the loop is observed to be flexible. This indicates that these domains undergo conformational changes upon DNA binding. On the other hand, we find the last four residues of the basic region form a persistent helical turn contiguous to H(1). In addition, we provide evidence of the existence of internal motions in the backbone of H(1) that are of larger amplitude and longer time-scale (nanoseconds) than the ones in the H(2) and LZ domain. Most interestingly, we note that conformers in the ensemble of calculated structures have highly conserved basic residues (located in the persistent helical turn of the basic region and in the loop) known to be important for specific binding in a conformation that matches that of the DNA-bound state. These partially prefolded conformers can directly fit into the major groove of DNA and as such are proposed to lie on the pathway leading to the reversible and specific DNA binding. In these conformers, the conserved basic side-chains form a cluster that elevates the local electrostatic potential and could provide the necessary driving force for the generation of the internal motions localized in the H(1) and therefore link structural determinants with the DNA binding function. Overall, our results suggests that the Max homodimeric b/H(1)LH(2)/LZ can rapidly and preferentially bind DNA sequence through transient and partially prefolded states and subsequently, adopt the fully helical bound state in a DNA-assisted mechanism or induced-fit.

Advanced electric propulsion system concept for electric vehicles

NASA Technical Reports Server (NTRS)

Raynard, A. E.; Forbes, F. E.

1979-01-01

Seventeen propulsion system concepts for electric vehicles were compared to determine the differences in components and battery pack to achieve the basic performance level. Design tradeoffs were made for selected configurations to find the optimum component characteristics required to meet all performance goals. The anticipated performance when using nickel-zinc batteries rather than the standard lead-acid batteries was also evaluated. The two systems selected for the final conceptual design studies included a system with a flywheel energy storage unit and a basic system that did not have a flywheel. The flywheel system meets the range requirement with either lead-acid or nickel-zinc batteries and also the acceleration of zero to 89 km/hr in 15 s. The basic system can also meet the required performance with a fully charged battery, but, when the battery approaches 20 to 30 percent depth of discharge, maximum acceleration capability gradually degrades. The flywheel system has an estimated life-cycle cost of $0.041/km using lead-acid batteries. The basic system has a life-cycle cost of $0.06/km. The basic system, using batteries meeting ISOA goals, would have a life-cycle cost of $0.043/km.

75 FR 61219 - Entergy Operations, Inc.; River Bend Station, Unit 1; Environmental Assessment and Finding of No...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-04

... Emergencies,'' for repair and corrective actions states that two individuals, one Mechanical Maintenance... actions will be taken to ensure basic electrical/l&C tasks can be performed by Mechanical Maintenance personnel. Mechanical Maintenance personnel will receive training in basic electrical and I&C tasks to...

Kuhn's Paradigm and Example-Based Teaching of Newtonian Mechanics.

ERIC Educational Resources Information Center

Whitaker, M. A. B.

1980-01-01

Makes a recommendation for more direct teaching of the basic principles of mechanics. Contends that students currently learn mechanics in terms of standard examples. This causes difficulty when the student is confronted with a problem that can be solved from basic principles, but which does not fit a standard category. (GS)

Diesel Mechanics. Performance Objectives. Basic Course.

ERIC Educational Resources Information Center

Tidwell, Joseph

Several intermediate performance objectives and corresponding criterion measures are listed for each of 12 terminal objectives for a basic diesel mechanics course. The course is designed as a two-semester (2 hour daily) course for 10th graders interested in being diesel service and repair mechanics; it would serve as the first year of a 3-year…

The relationship between basic need satisfaction and emotional eating.

PubMed

Timmerman, G M; Acton, G J

2001-01-01

Eating in response to emotions may lead to the consumption of excessive calories which typically leads to weight gain. This study examined the relationship between basic need satisfaction as identified by Maslow's hierarchy and emotional eating. According to Modeling and Role-Modeling theory, when lack of basic need satisfaction functions as a stressor, individuals may be more likely to engage in emotional eating as a substitute for fulfilling their needs in order to maintain homeostasis. The Basic Need Satisfaction Inventory (BNSI) had a strong, negative correlation (r = -.49; p < .001) to the Emotional Eating Scale (EES) indicating that the lower the level of basic need satisfaction, the more likely one engaged in emotional eating. In predicting EES score, 27.7% of the variance was explained by the self-esteem subscale of BNSI. This study supports looking at underlying issues contributing to weight gain in order to develop effective interventions for weight management.

Random bursts determine dynamics of active filaments.

PubMed

Weber, Christoph A; Suzuki, Ryo; Schaller, Volker; Aranson, Igor S; Bausch, Andreas R; Frey, Erwin

2015-08-25

Constituents of living or synthetic active matter have access to a local energy supply that serves to keep the system out of thermal equilibrium. The statistical properties of such fluctuating active systems differ from those of their equilibrium counterparts. Using the actin filament gliding assay as a model, we studied how nonthermal distributions emerge in active matter. We found that the basic mechanism involves the interplay between local and random injection of energy, acting as an analog of a thermal heat bath, and nonequilibrium energy dissipation processes associated with sudden jump-like changes in the system's dynamic variables. We show here how such a mechanism leads to a nonthermal distribution of filament curvatures with a non-Gaussian shape. The experimental curvature statistics and filament relaxation dynamics are reproduced quantitatively by stochastic computer simulations and a simple kinetic model.

Surface Modifications and Their Effects on Titanium Dental Implants

PubMed Central

Jemat, A.; Ghazali, M. J.; Razali, M.; Otsuka, Y.

2015-01-01

This review covers several basic methodologies of surface treatment and their effects on titanium (Ti) implants. The importance of each treatment and its effects will be discussed in detail in order to compare their effectiveness in promoting osseointegration. Published literature for the last 18 years was selected with the use of keywords like titanium dental implant, surface roughness, coating, and osseointegration. Significant surface roughness played an important role in providing effective surface for bone implant contact, cell proliferation, and removal torque, despite having good mechanical properties. Overall, published studies indicated that an acid etched surface-modified and a coating application on commercial pure titanium implant was most preferable in producing the good surface roughness. Thus, a combination of a good surface roughness and mechanical properties of titanium could lead to successful dental implants. PMID:26436097

Glycosyltransferases and non-alcoholic fatty liver disease

PubMed Central

Zhan, Yu-Tao; Su, Hai-Ying; An, Wei

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease and its incidence is increasing worldwide. However, the underlying mechanisms leading to the development of NAFLD are still not fully understood. Glycosyltransferases (GTs) are a diverse class of enzymes involved in catalyzing the transfer of one or multiple sugar residues to a wide range of acceptor molecules. GTs mediate a wide range of functions from structure and storage to signaling, and play a key role in many fundamental biological processes. Therefore, it is anticipated that GTs have a role in the pathogenesis of NAFLD. In this article, we present an overview of the basic information on NAFLD, particularly GTs and glycosylation modification of certain molecules and their association with NAFLD pathogenesis. In addition, the effects and mechanisms of some GTs in the development of NAFLD are summarized. PMID:26937136

Random bursts determine dynamics of active filaments

PubMed Central

Weber, Christoph A.; Suzuki, Ryo; Schaller, Volker; Aranson, Igor S.; Bausch, Andreas R.; Frey, Erwin

2015-01-01

Constituents of living or synthetic active matter have access to a local energy supply that serves to keep the system out of thermal equilibrium. The statistical properties of such fluctuating active systems differ from those of their equilibrium counterparts. Using the actin filament gliding assay as a model, we studied how nonthermal distributions emerge in active matter. We found that the basic mechanism involves the interplay between local and random injection of energy, acting as an analog of a thermal heat bath, and nonequilibrium energy dissipation processes associated with sudden jump-like changes in the system’s dynamic variables. We show here how such a mechanism leads to a nonthermal distribution of filament curvatures with a non-Gaussian shape. The experimental curvature statistics and filament relaxation dynamics are reproduced quantitatively by stochastic computer simulations and a simple kinetic model. PMID:26261319

A Program to Train Apprentices to Lead Inservice Workshops for Secondary Teachers of Basic Skills. Developer/Demonstration Project. Final Report.

ERIC Educational Resources Information Center

Stallings, Jane A.

The Development and Demonstration project has trained interns to lead Effective Use of Time inservice workshops for secondary school teachers of basic reading and mathematical skills. These interns then returned to their home bases and trained teachers who could in turn train other teachers to use the Stallings Effective Use of Time methods. The…

Social visual engagement in infants and toddlers with autism: Early developmental transitions and a model of pathogenesis

PubMed Central

Klin, Ami; Shultz, Sarah; Jones, Warren

2014-01-01

Efforts to determine and understand the causes of autism are currently hampered by a large disconnect between recent molecular genetics findings that are associated with the condition and the core behavioral symptoms that define the condition. In this perspective piece, we propose a systems biology framework to bridge that gap between genes and symptoms. The framework focuses on basic mechanisms of socialization that are highly-conserved in evolution and are early-emerging in development. By conceiving of these basic mechanisms of socialization as quantitative endophenotypes, we hope to connect genes and behavior in autism through integrative studies of neurodevelopmental, behavioral, and epigenetic changes. These changes both lead to and are led by the accomplishment of specific social adaptive tasks in a typical infant's life. However, based on recent research that indicates that infants later diagnosed with autism fail to accomplish at least some of these tasks, we suggest that a narrow developmental period, spanning critical transitions from reflexive, subcortically-controlled visual behavior to interactional, cortically-controlled and social visual behavior be prioritized for future study. Mapping epigenetic, neural, and behavioral changes that both drive and are driven by these early transitions may shed a bright light on the pathogenesis of autism. PMID:25445180

Unusual Fluorescent Responses of Morpholine-functionalized Fluorescent Probes to pH via Manipulation of BODIPY’s HOMO and LUMO Energy Orbitals for Intracellular pH Detection

PubMed Central

Zhang, Jingtuo; Yang, Mu; Mazi, Wafa; Adhikari, Kapil; Fang, Mingxi; Xie, Fei; Valenzano, Loredana; Tiwari, Ashutosh; Luo, Fen-Tair; Liu, Haiying

2016-01-01

Three uncommon morpholine-based fluorescent probes (A, B and C) for pH were prepared by introducing morpholine residues to BODIPY dyes at 4,4’- and 2,6-positions, respectively. In contrast to morpholine-based fluorescent probes for pH reported in literature, these fluorescent probes display high fluorescence in a basic condition while they exhibit very weak fluorescence in an acidic condition. The theoretical calculation confirmed that morpholine is unable to function as either an electron donor or an electron acceptor to quench the BODIPY fluorescence in the neutral and basic condition via photo-induced electron transfer (PET) mechanism because the LUMO energy of morpholine is higher than those of the BODIPY dyes while its HOMO energy is lower than those of the BODIPY dyes. However, the protonation of tertiary amines of the morpholine residues in an acidic environment leads to fluorescence quenching of the BODIPY dyes via d-PET mechanism. The fluorescence quenching is because the protonation effectively decreases the LUMO energy which locates between the HOMO and LUMO energies of the BODIPY dyes. Fluorescent probe C with deep-red emission has been successfully used to detect pH changes in mammalian cells. PMID:27547822

Social visual engagement in infants and toddlers with autism: early developmental transitions and a model of pathogenesis.

PubMed

Klin, Ami; Shultz, Sarah; Jones, Warren

2015-03-01

Efforts to determine and understand the causes of autism are currently hampered by a large disconnect between recent molecular genetics findings that are associated with the condition and the core behavioral symptoms that define the condition. In this perspective piece, we propose a systems biology framework to bridge that gap between genes and symptoms. The framework focuses on basic mechanisms of socialization that are highly-conserved in evolution and are early-emerging in development. By conceiving of these basic mechanisms of socialization as quantitative endophenotypes, we hope to connect genes and behavior in autism through integrative studies of neurodevelopmental, behavioral, and epigenetic changes. These changes both lead to and are led by the accomplishment of specific social adaptive tasks in a typical infant's life. However, based on recent research that indicates that infants later diagnosed with autism fail to accomplish at least some of these tasks, we suggest that a narrow developmental period, spanning critical transitions from reflexive, subcortically-controlled visual behavior to interactional, cortically-controlled and social visual behavior be prioritized for future study. Mapping epigenetic, neural, and behavioral changes that both drive and are driven by these early transitions may shed a bright light on the pathogenesis of autism. Copyright © 2014 Elsevier Ltd. All rights reserved.

Barriers to the Preclinical Development of Therapeutics that Target Aging Mechanisms.

PubMed

Burd, Christin E; Gill, Matthew S; Niedernhofer, Laura J; Robbins, Paul D; Austad, Steven N; Barzilai, Nir; Kirkland, James L

2016-11-01

Through the progress of basic science research, fundamental mechanisms that contribute to age-related decline are being described with increasing depth and detail. Although these efforts have identified new drug targets and compounds that extend life span in model organisms, clinical trials of therapeutics that target aging processes remain scarce. Progress in aging research is hindered by barriers associated with the translation of basic science discoveries into the clinic. This report summarizes discussions held at a 2014 Geroscience Network retreat focused on identifying hurdles that currently impede the preclinical development of drugs targeting fundamental aging processes. From these discussions, it was evident that aging researchers have varied perceptions of the ideal preclinical pipeline. To forge a clear and cohesive path forward, several areas of controversy must first be resolved and new tools developed. Here, we focus on five key issues in preclinical drug development (drug discovery, lead compound development, translational preclinical biomarkers, funding, and integration between researchers and clinicians), expanding upon discussions held at the Geroscience Retreat and suggesting areas for further research. By bringing these findings to the attention of the aging research community, we hope to lay the foundation for a concerted preclinical drug development pipeline. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America.

Illustrating the Basic Functioning of Mass Analyzers in Mass Spectrometers with Ball-Rolling Mechanisms

ERIC Educational Resources Information Center

Horikoshi, Ryo; Takeiri, Fumitaka; Mikita, Riho; Kobayashi, Yoji; Kageyama, Hiroshi

2017-01-01

A unique demonstration with ball-rolling mechanisms has been developed to illustrate the basic principles of mass analyzers as components of mass spectrometers. Three ball-rolling mechanisms mimicking the currently used mass analyzers (i.e., a quadrupole mass filter, a magnetic sector, and a time-of- flight) have been constructed. Each mechanism…

Advances in clinical and molecular understanding of the FMR1 premutation and fragile X-associated tremor/ataxia syndrome

PubMed Central

Hagerman, Randi; Hagerman, Paul

2014-01-01

Summary Fragile X syndrome, the leading heritable form of cognitive impairment, is caused by epigenetic silencing of the fragile X (FMR1) gene consequent to large expansions (>200 repeats) of a non-coding CGG-repeat element. Smaller, “premutation” expansions (55–200 repeats) can give rise to a family of neurodevelopmental (ADHD, autism spectrum disorder, seizure disorder) and neurodegenerative (FXTAS) clinical phenotypes through an entirely distinct molecular mechanism involving increased FMR1 mRNA production and toxicity. Basic cellular, animal, and human studies have helped to elucidate the underlying RNA toxicity mechanism, while clinical research is providing a more nuanced picture of the spectrum of clinical involvement. Whereas advances on both mechanistic and clinical fronts are driving new approaches to targeted treatment, two important issues/needs are emerging: to define the extent to which the mechanisms contributing to FXTAS also contribute to other neurodegenerative and medical disorders, and to redefine FXTAS in light of its differing presentations and associated features. PMID:23867198

Cellular and molecular mechanisms of repair in acute and chronic wound healing.

PubMed

Martin, P; Nunan, R

2015-08-01

A considerable understanding of the fundamental cellular and molecular mechanisms underpinning healthy acute wound healing has been gleaned from studying various animal models, and we are now unravelling the mechanisms that lead to chronic wounds and pathological healing including fibrosis. A small cut will normally heal in days through tight orchestration of cell migration and appropriate levels of inflammation, innervation and angiogenesis. Major surgeries may take several weeks to heal and leave behind a noticeable scar. At the extreme end, chronic wounds - defined as a barrier defect that has not healed in 3 months - have become a major therapeutic challenge throughout the Western world and will only increase as our populations advance in age, and with the increasing incidence of diabetes, obesity and vascular disorders. Here we describe the clinical problems and how, through better dialogue between basic researchers and clinicians, we may extend our current knowledge to enable the development of novel potential therapeutic treatments. © 2015 British Association of Dermatologists.

Adaptive Stress Testing of Airborne Collision Avoidance Systems

NASA Technical Reports Server (NTRS)

Lee, Ritchie; Kochenderfer, Mykel J.; Mengshoel, Ole J.; Brat, Guillaume P.; Owen, Michael P.

2015-01-01

This paper presents a scalable method to efficiently search for the most likely state trajectory leading to an event given only a simulator of a system. Our approach uses a reinforcement learning formulation and solves it using Monte Carlo Tree Search (MCTS). The approach places very few requirements on the underlying system, requiring only that the simulator provide some basic controls, the ability to evaluate certain conditions, and a mechanism to control the stochasticity in the system. Access to the system state is not required, allowing the method to support systems with hidden state. The method is applied to stress test a prototype aircraft collision avoidance system to identify trajectories that are likely to lead to near mid-air collisions. We present results for both single and multi-threat encounters and discuss their relevance. Compared with direct Monte Carlo search, this MCTS method performs significantly better both in finding events and in maximizing their likelihood.

Climate Adaptation Training for Natural Resource Professionals

NASA Astrophysics Data System (ADS)

Sorensen, H. L.; Meyer, N.

2016-02-01

The University of Minnesota Sea Grant Program and University of Minensota Extension are coordinating the development of a cohort-based training for natural resource professionals that prepares them with essential aptitude, resources and tools to lead climate adaptation activities in their organizations and municipalities. This course is geared toward the growing cadre of natural resources, water, municipal infrastructure, and human resources professionals who are called upon to lead climate adaptation initiatives but lack core training in climate change science, vulnerability assessment, and adaptation planning. Modeled on pre-existing UMN certificate programs, the online course encompasses approximately 40 contact hours of training. Content builds from basic climate mechanics to change science, vulnerability assessment, downscaled climate modeling, ecosystem response to climate change and strategies communicating climate change to diverse audiences. Minnesota as well as national case studies and expertise will anchor core climate adaptation concepts in a relevant context.

Identifying external influences on global precipitation

PubMed Central

Marvel, Kate; Bonfils, Céline

2013-01-01

Changes in global (ocean and land) precipitation are among the most important and least well-understood consequences of climate change. Increasing greenhouse gas concentrations are thought to affect the zonal-mean distribution of precipitation through two basic mechanisms. First, increasing temperatures will lead to an intensification of the hydrological cycle (“thermodynamic” changes). Second, changes in atmospheric circulation patterns will lead to poleward displacement of the storm tracks and subtropical dry zones and to a widening of the tropical belt (“dynamic” changes). We demonstrate that both these changes are occurring simultaneously in global precipitation, that this behavior cannot be explained by internal variability alone, and that external influences are responsible for the observed precipitation changes. Whereas existing model experiments are not of sufficient length to differentiate between natural and anthropogenic forcing terms at the 95% confidence level, we present evidence that the observed trends result from human activities. PMID:24218561

Identifying external influences on global precipitation.

PubMed

Marvel, Kate; Bonfils, Céline

2013-11-26

Changes in global (ocean and land) precipitation are among the most important and least well-understood consequences of climate change. Increasing greenhouse gas concentrations are thought to affect the zonal-mean distribution of precipitation through two basic mechanisms. First, increasing temperatures will lead to an intensification of the hydrological cycle ("thermodynamic" changes). Second, changes in atmospheric circulation patterns will lead to poleward displacement of the storm tracks and subtropical dry zones and to a widening of the tropical belt ("dynamic" changes). We demonstrate that both these changes are occurring simultaneously in global precipitation, that this behavior cannot be explained by internal variability alone, and that external influences are responsible for the observed precipitation changes. Whereas existing model experiments are not of sufficient length to differentiate between natural and anthropogenic forcing terms at the 95% confidence level, we present evidence that the observed trends result from human activities.

The Evolution of the Stem Cell Theory for Heart Failure.

PubMed

Silvestre, Jean-Sébastien; Menasché, Philippe

2015-12-01

Various stem cell-based approaches for cardiac repair have achieved encouraging results in animal experiments, often leading to their rapid proceeding to clinical testing. However, freewheeling evolutionary developments of the stem cell theory might lead to dystopian scenarios where heterogeneous sources of therapeutic cells could promote mixed clinical outcomes in un-stratified patient populations. This review focuses on the lessons that should be learnt from the first generation of stem cell-based strategies and emphasizes the absolute requirement to better understand the basic mechanisms of stem cell biology and cardiogenesis. We will also discuss about the unexpected "big bang" in the stem cell theory, "blasting" the therapeutic cells to their unchallenged ability to release paracrine factors such as extracellular membrane vesicles. Paradoxically, the natural evolution of the stem cell theory for cardiac regeneration may end with the development of cell-free strategies with multiple cellular targets including cardiomyocytes but also other infiltrating or resident cardiac cells.

Charge-transfer crystallites as molecular electrical dopants

PubMed Central

Méndez, Henry; Heimel, Georg; Winkler, Stefanie; Frisch, Johannes; Opitz, Andreas; Sauer, Katrein; Wegner, Berthold; Oehzelt, Martin; Röthel, Christian; Duhm, Steffen; Többens, Daniel; Koch, Norbert; Salzmann, Ingo

2015-01-01

Ground-state integer charge transfer is commonly regarded as the basic mechanism of molecular electrical doping in both, conjugated polymers and oligomers. Here, we demonstrate that fundamentally different processes can occur in the two types of organic semiconductors instead. Using complementary experimental techniques supported by theory, we contrast a polythiophene, where molecular p-doping leads to integer charge transfer reportedly localized to one quaterthiophene backbone segment, to the quaterthiophene oligomer itself. Despite a comparable relative increase in conductivity, we observe only partial charge transfer for the latter. In contrast to the parent polymer, pronounced intermolecular frontier-orbital hybridization of oligomer and dopant in 1:1 mixed-stack co-crystallites leads to the emergence of empty electronic states within the energy gap of the surrounding quaterthiophene matrix. It is their Fermi–Dirac occupation that yields mobile charge carriers and, therefore, the co-crystallites—rather than individual acceptor molecules—should be regarded as the dopants in such systems. PMID:26440403

MYC Deregulation in Primary Human Cancers

PubMed Central

Kalkat, Manpreet; De Melo, Jason; Hickman, Katherine Ashley; Lourenco, Corey; Redel, Cornelia; Resetca, Diana; Tamachi, Aaliya; Tu, William B.; Penn, Linda Z.

2017-01-01

MYC regulates a complex biological program by transcriptionally activating and repressing its numerous target genes. As such, MYC is a master regulator of many processes, including cell cycle entry, ribosome biogenesis, and metabolism. In cancer, the activity of the MYC transcriptional network is frequently deregulated, contributing to the initiation and maintenance of disease. Deregulation often leads to constitutive overexpression of MYC, which can be achieved through gross genetic abnormalities, including copy number alterations, chromosomal translocations, increased enhancer activity, or through aberrant signal transduction leading to increased MYC transcription or increased MYC mRNA and protein stability. Herein, we summarize the frequency and modes of MYC deregulation and describe both well-established and more recent findings in a variety of cancer types. Notably, these studies have highlighted that with an increased appreciation for the basic mechanisms deregulating MYC in cancer, new therapeutic vulnerabilities can be discovered and potentially exploited for the inhibition of this potent oncogene in cancer. PMID:28587062

Optimization principles and the figure of merit for triboelectric generators.

PubMed

Peng, Jun; Kang, Stephen Dongmin; Snyder, G Jeffrey

2017-12-01

Energy harvesting with triboelectric nanogenerators is a burgeoning field, with a growing portfolio of creative application schemes attracting much interest. Although power generation capabilities and its optimization are one of the most important subjects, a satisfactory elemental model that illustrates the basic principles and sets the optimization guideline remains elusive. We use a simple model to clarify how the energy generation mechanism is electrostatic induction but with a time-varying character that makes the optimal matching for power generation more restrictive. By combining multiple parameters into dimensionless variables, we pinpoint the optimum condition with only two independent parameters, leading to predictions of the maximum limit of power density, which allows us to derive the triboelectric material and device figure of merit. We reveal the importance of optimizing device capacitance, not only load resistance, and minimizing the impact of parasitic capacitance. Optimized capacitances can lead to an overall increase in power density of more than 10 times.

The pulsating orb: solving the wave equation outside a ball

PubMed Central

2016-01-01

Transient acoustic waves are generated by the oscillations of an object or are scattered by the object. This leads to initial-boundary value problems (IBVPs) for the wave equation. Basic properties of this equation are reviewed, with emphasis on characteristics, wavefronts and compatibility conditions. IBVPs are formulated and their properties reviewed, with emphasis on weak solutions and the constraints imposed by the underlying continuum mechanics. The use of the Laplace transform to treat the IBVPs is also reviewed, with emphasis on situations where the solution is discontinuous across wavefronts. All these notions are made explicit by solving simple IBVPs for a sphere in some detail. PMID:27279773

Role of oxidative stress and nitric oxide in atherothrombosis

PubMed Central

Lubos, Edith; Handy, Diane E.; Loscalzo, Joseph

2008-01-01

During the last decade basic and clinical research has highlighted the central role of reactive oxygen species (ROS) in cardiovascular disease. Enhanced production or attenuated degradation of ROS leads to oxidative stress, a process that affects endothelial and vascular function, and contributes to vascular disease. Nitric oxide (NO), a product of the normal endothelium, is a principal determinant of normal endothelial and vascular function. In states of inflammation, NO production by the vasculature increases considerably and, in conjunction with other ROS, contributes to oxidative stress. This review examines the role of oxidative stress and NO in mechanisms of endothelial and vascular dysfunction with an emphasis on atherothrombosis. PMID:18508590

Influence of the carrier-envelope phase of few-cycle pulses on ponderomotive surface-plasmon electron acceleration.

PubMed

Irvine, S E; Dombi, P; Farkas, Gy; Elezzabi, A Y

2006-10-06

Control over basic processes through the electric field of a light wave can lead to new knowledge of fundamental light-matter interaction phenomena. We demonstrate, for the first time, that surface-plasmon (SP) electron acceleration can be coherently controlled through the carrier-envelope phase (CEP) of an excitation optical pulse. Analysis indicates that the physical origin of the CEP sensitivity arises from the electron's ponderomotive interaction with the oscillating electromagnetic field of the SP wave. The ponderomotive electron acceleration mechanism provides sensitive (nJ energies), high-contrast, single-shot CEP measurement capability of few-cycle laser pulses.

Structural and synaptic plasticity in stress-related disorders

PubMed Central

Christoffel, Daniel J.; Golden, Sam A.; Russo, Scott J.

2011-01-01

Stress can have a lasting impact on the structure and function of brain circuitry that results in long-lasting changes in the behavior of an organism. Synaptic plasticity is the mechanism by which information is stored and maintained within individual synapses, neurons, and neuronal circuits to guide the behavior of an organism. Although these mechanisms allow the organism to adapt to its constantly evolving environment, not all of these adaptations are beneficial. Under prolonged bouts of physical or psychological stress, these mechanisms become dysregulated, and the connectivity between brain regions becomes unbalanced, resulting in pathological behaviors. In this review, we highlight the effects of stress on the structure and function of neurons within the mesocorticolimbic brain systems known to regulate mood and motivation. We then discuss the implications of these spine adaptations on neuronal activity and pathological behaviors implicated in mood disorders. Finally, we end by discussing recent brain imaging studies in human depression within the context of these basic findings to provide insight into the underlying mechanisms leading to neural dysfunction in depression. PMID:21967517

CD26-mediated regulation of periostin expression contributes to migration and invasion of malignant pleural mesothelioma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Komiya, Eriko; Ohnuma, Kei, E-mail: kohnuma@juntendo.ac.jp; Yamazaki, Hiroto

Highlights: • CD26-expressing MPM cells upregulate production of periostin. • The intracytoplasmic region of CD26 mediates the upregulation of periostin. • CD26 expression leads to nuclear translocation of Twist1 via phosphorylation of Src. • Secreted periostin enhances migration and invasion of MPM cells. - Abstract: Malignant pleural mesothelioma (MPM) is an aggressive malignancy arising from mesothelial lining of pleura. It is generally associated with a history of asbestos exposure and has a very poor prognosis, partly due to the lack of a precise understanding of the molecular mechanisms associated with its malignant behavior. In the present study, we expanded onmore » our previous studies on the enhanced motility and increased CD26 expression in MPM cells, with a particular focus on integrin adhesion molecules. We found that expression of CD26 upregulates periostin secretion by MPM cells, leading to enhanced MPM cell migratory and invasive activity. Moreover, we showed that upregulation of periostin expression results from the nuclear translocation of the basic helix-loop-helix transcription factor Twist1, a process that is mediated by CD26-associated activation of Src phosphorylation. While providing new and profound insights into the molecular mechanisms involved in MPM biology, these findings may also lead to the development of novel therapeutic strategies for MPM.« less

Breakdown of coral colonial form under reduced pH conditions is initiated in polyps and mediated through apoptosis

PubMed Central

Kvitt, Hagit; Kramarsky-Winter, Esti; Maor-Landaw, Keren; Zandbank, Keren; Kushmaro, Ariel; Rosenfeld, Hanna; Fine, Maoz; Tchernov, Dan

2015-01-01

Certain stony corals can alternate between a calcifying colonial form and noncalcifying solitary polyps, supporting the hypothesis that corals have survived through geologic timescale periods of unfavorable calcification conditions. However, the mechanisms enabling this biological plasticity are yet to be identified. Here we show that incubation of two coral species (Pocillopora damicornis and Oculina patagonica) under reduced pH conditions (pH 7.2) simulating past ocean acidification induce tissue-specific apoptosis that leads to the dissociation of polyps from coenosarcs. This in turn leads to the breakdown of the coenosarc and, as a consequence, to loss of coloniality. Our data show that apoptosis is initiated in the polyps and that once dissociation between polyp and coenosarc terminates, apoptosis subsides. After reexposure of the resulting solitary polyps to normal pH (pH 8.2), both coral species regenerated coenosarc tissues and resumed calcification. These results indicate that regulation of coloniality is under the control of the polyp, the basic modular unit of the colony. A mechanistic explanation for several key evolutionarily important phenomena that occurred throughout coral evolution is proposed, including mechanisms that permitted species to survive the third tier of mass extinctions. PMID:25646434

Dimensioning Principles in Potash and Salt: Stability and Integrity

NASA Astrophysics Data System (ADS)

Minkley, W.; Mühlbauer, J.; Lüdeling, C.

2016-11-01

The paper describes the principal geomechanical approaches to mine dimensioning in salt and potash mining, focusing on stability of the mining system and integrity of the hydraulic barrier. Several common dimensioning are subjected to a comparative analysis. We identify geomechanical discontinuum models as essential physical ingredients for examining the collapse of working fields in potash mining. The basic mechanisms rely on the softening behaviour of salt rocks and the interfaces. A visco-elasto-plastic material model with strain softening, dilatancy and creep describes the time-dependent softening behaviour of the salt pillars, while a shear model with velocity-dependent adhesive friction with shear displacement-dependent softening is used for bedding planes and discontinuities. Pillar stability critically depends on the shear conditions of the bedding planes to the overlying and underlying beds, which provide the necessary confining pressure for the pillar core, but can fail dynamically, leading to large-scale field collapses. We further discuss the integrity conditions for the hydraulic barrier, most notably the minimal stress criterion, the violation of which leads to pressure-driven percolation as the mechanism of fluid transport and hence barrier failure. We present a number of examples where violation of the minimal stress criterion has led to mine floodings.

Graphical review: The redox dark side of e-cigarettes; exposure to oxidants and public health concerns.

PubMed

Cai, Hua; Wang, Chen

2017-10-01

Since the initial marketing in 2005, the use of e-cigarettes has increased exponentially. Nonetheless, accumulating evidence has demonstrated the ineffectiveness of e-cigarettes in leading to smoking cessation, and decreasing the adverse health impacts of cigarette smoking. The number of adolescents adapted to e-cigarettes has been increasing substantially each year, and this adaptation has promoted openness to tobacco smoking. The present review discusses controversies regarding the smoking cessation effects of e-cigarettes, recent governmental policies and regulations of e-cigarette use, toxic components and vaporization products of e-cigarettes, and the novel molecular mechanisms underlying the adverse health impacts of e-cigarettes leading to oxidative stress in target tissues, and consequent development of cardiopulmonary diseases (i.e. COPD), neurodegenerative disorders (i.e. Alzheimer's' disease), and cancer. Health warning signs on the packaging and professional consultation to avoid adaptation in risk groups might be helpful solutions to control negative impacts of e-cigarettes. It is also recommended to further expand basic and clinical investigations to reveal more detailed oxidative stress mechanisms of e-cigarette induced damages, which would ultimately result in more effective protective strategies. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Apoptosis: its origin, history, maintenance and the medical implications for cancer and aging

NASA Astrophysics Data System (ADS)

Kaczanowski, Szymon

2016-06-01

Programmed cell death is a basic cellular mechanism. Apoptotic-like programmed cell death (called apoptosis in animals) occurs in both unicellular and multicellular eukaryotes, and some apoptotic mechanisms are observed in bacteria. Endosymbiosis between mitochondria and eukaryotic cells took place early in the eukaryotic evolution, and some of the apoptotic-like mechanisms of mitochondria that were retained after this event now serve as parts of the eukaryotic apoptotic machinery. Apoptotic mechanisms have several functions in unicellular organisms: they include kin-selected altruistic suicide that controls population size, sharing common goods, and responding to viral infection. Apoptotic factors also have non-apoptotic functions. Apoptosis is involved in the cellular aging of eukaryotes, including humans. In addition, apoptosis is a key part of the innate tumor-suppression mechanism. Several anticancer drugs induce apoptosis, because apoptotic mechanisms are inactivated during oncogenesis. Because of the ancient history of apoptosis, I hypothesize that there is a deep relationship between mitochondrial metabolism, its role in aerobic versus anaerobic respiration, and the connection between apoptosis and cancer. Whereas normal cells rely primarily on oxidative mitochondrial respiration, most cancer cells use anaerobic metabolism. According to the Warburg hypothesis, the remodeling of the metabolism is one of the processes that leads to cancer. Recent studies indicate that anaerobic, non-mitochondrial respiration is particularly active in embryonic cells, stem cells, and aggressive stem-like cancer cells. Mitochondrial respiration is particularly active during the pathological aging of human cells in neurodegenerative diseases. According to the reversed Warburg hypothesis formulated by Demetrius, pathological aging is induced by mitochondrial respiration. Here, I advance the hypothesis that the stimulation of mitochondrial metabolism leads to pathological aging.

English: Basic Mechanics Modules 4 and 5.

ERIC Educational Resources Information Center

Pipeline, 1983

1983-01-01

"English: Basic Mechanics" is a series of computer-based lessons for the Apple II that allow students to practice applying the fundamentals of English grammar and punctuation. The two newest modules covering use of subordinate clauses and use of subordinate phrases are described. (JN)

Basic mechanisms governing solar-cell efficiency

NASA Technical Reports Server (NTRS)

Lindholm, F. A.; Neugroschel, A.; Sah, C. T.

1976-01-01

The efficiency of a solar cell depends on the material parameters appearing in the set of differential equations that describe the transport, recombination, and generation of electrons and holes. This paper describes the many basic mechanisms occurring in semiconductors that can control these material parameters.

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

NASA Astrophysics Data System (ADS)

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.

Achieving reversibility of ultra-high mechanical stress by hydrogen loading of thin films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamm, M.; Burlaka, V.; Wagner, S.

2015-06-15

Nano-materials are commonly stabilized by supports to maintain their desired shape and size. When these nano-materials take up interstitial atoms, this attachment to the support induces mechanical stresses. These stresses can be high when the support is rigid. High stress in the nano-material is typically released by delamination from the support or by the generation of defects, e.g., dislocations. As high mechanical stress can be beneficial for tuning the nano-materials properties, it is of general interest to deduce how real high mechanical stress can be gained. Here, we show that below a threshold nano-material size, dislocation formation can be completelymore » suppressed and, when delamination is inhibited, even the ultrahigh stress values of the linear elastic limit can be reached. Specifically, for hydrogen solved in epitaxial niobium films on sapphire substrate supports a threshold film thickness of 6 nm was found and mechanical stress of up to (−10 ± 1) GPa was reached. This finding is of basic interest for hydrogen energy applications, as the hydride stability in metals itself is affected by mechanical stress. Thus, tuning of the mechanical stress-state in nano-materials may lead to improved storage properties of nano-sized materials.« less

Arsenic Flux Dependence of Island Nucleation in InAs(001) Epitaxial Growth

NASA Astrophysics Data System (ADS)

Gyure, Mark; Grosse, Frank; Barvosa-Carter, Bill; Ross, Richard; Ratsch, Christian; Owen, James; Zinck, Jenna

2001-03-01

In spite of years of research on the epitaxial growth of III-V semiconductor materials, very little is known about basic growth mechanisms. In particular, the effects of As flux on the growth of GaAs and InAs is hardly understood at all even though, for InAs, the effects are clearly noticeable in the regime of interest for device growth. We have investigated the initial stages of InAs(001) epitaxial growth by combining high resolution kinetic Monte Carlo simulations based on ab initio density functional theory and scanning tunneling microscopy. With increasing As pressure, we find that the island number density decreases, consistent with similar recent data for GaAs, but inconsistent with at least one theoretical argument [1] and much of conventional wisdom regarding group III adatom diffusion in the presence of As. We identify the relevant growth mechanisms that depend on the As pressure and find that a higher As deposition rate leads to a decrease in the In adatom density during growth due to a higher incorporation rate for In at island and step edges. This reduces island nucleation and leads to a lower island density. This same mechanism also explains previously observed As flux trends for the step flow transition temperature. [1] J. Tersoff, M.D. Johnson and B.G. Orr, Phys. Rev. Lett. 78, 282 (1997)

Basic Automotive Mechanics. Florida Vocational Program Guide.

ERIC Educational Resources Information Center

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

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

Development of Wing Inlets

NASA Technical Reports Server (NTRS)

Racisz, Stanley F.

1946-01-01

Lift, drag, internal flow, and pressure distribution measurements were made on a low-drag airfoil incorporating various air inlet designs. Two leading-edge air inlets are developed which feature higher lift coefficients and critical Mach than the basic airfoil. Higher lift coefficients and critical speeds are obtained for leading half of these inlet sections but because of high suction pressures near exist, slightly lower critical speeds are obtained for the entire inlet section than the basic airfoil.

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

DOEpatents

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.

The United Nations Basic Space Science Initiative

NASA Astrophysics Data System (ADS)

Haubold, H. J.

2006-08-01

Pursuant to recommendations of the United Nations Conference on the Exploration and Peaceful Uses of Outer Space (UNISPACE III) and deliberations of the United Nations Committee on the Peaceful Uses of Outer Space (UNCOPUOS), annual UN/ European Space Agency workshops on basic space science have been held around the world since 1991. These workshops contribute to the development of astrophysics and space science, particularly in developing nations. Following a process of prioritization, the workshops identified the following elements as particularly important for international cooperation in the field: (i) operation of astronomical telescope facilities implementing TRIPOD, (ii) virtual observatories, (iii) astrophysical data systems, (iv) concurrent design capabilities for the development of international space missions, and (v) theoretical astrophysics such as applications of nonextensive statistical mechanics. Beginning in 2005, the workshops focus on preparations for the International Heliophysical Year 2007 (IHY2007). The workshops continue to facilitate the establishment of astronomical telescope facilities as pursued by Japan and the development of low-cost, ground-based, world-wide instrument arrays as lead by the IHY secretariat. Wamsteker, W., Albrecht, R. and Haubold, H.J.: Developing Basic Space Science World-Wide: A Decade of UN/ESA Workshops. Kluwer Academic Publishers, Dordrecht 2004. http://ihy2007.org http://www.unoosa.org/oosa/en/SAP/bss/ihy2007/index.html http://www.cbpf.br/GrupPesq/StatisticalPhys/biblio.htm

What are the priorities in basic asthma research? A United Kingdom perspective.

PubMed

Hallsworth, Matthew P; Major, Philippa J; Barnes, Jack; Lee, Tak H

2003-02-01

The National Asthma Campaign (in the United Kingdom) has recently completed a strategic review of priorities for basic asthma research over the next 5 to 10 years. Leading asthma experts and representatives of the main funding agencies were involved in a nationwide consultation. Discussions were carried out in 7 thematic areas: Genetics of asthma, early-life events, environmental influences, immunology and immunotherapy, inflammation and anti-inflammation, airway remodeling, and the interface between academia and industry. Discussions were not restricted by considerations of financial affordability but were driven by vision and science. The consultation highlighted a number of generic issues pertaining to the organization of basic asthma research. Phenotypes of asthma require more robust characterization, particularly for genetic studies. Emphasis on longitudinal studies should be encouraged, and more information can still be gained from existing well-characterized asthma cohorts, though this requires some coordination. Human research is particularly strong and should continue, and the use of human tissue is vital to our understanding of the disease at the cellular and molecular levels. Animal models of asthma remain an important tool with which to dissect disease mechanisms, but they must be improved and refined. The consultation covered a wide range of issues and highlighted the need for collaboration at all levels between research groups and with industry and also between funding agencies. The recommendations made have relevance to everyone involved in basic asthma research. This article describes the recommendations and reviews the specific research issues relating to each of the 7 thematic areas.

The neurophysiology of sexual arousal.

PubMed

Schober, Justine M; Pfaff, Donald

2007-09-01

Our understanding of the process and initiation of sexual arousal is being enhanced by both animal and human studies, inclusive of basic science principles and research on clinical outcomes. Sexual arousal is dependent on neural (sensory and cognitive) factors, hormonal factors, genetic factors and, in the human case, the complex influences of culture and context. Sexual arousal activates the cognitive and physiologic processes that can eventually lead to sexual behavior. Sexual arousal comprises a particular subset of central nervous system arousal functions which depend on primitive, fundamental arousal mechanisms that cause generalized brain activity, but are manifest in a sociosexual context. The neurophysiology of sexual arousal is seen as a bidirectional system universal to all vertebrates. The following review includes known neural and genomic mechanisms of a hormone-dependent circuit for simple sex behavior. New information about hormone effects on causal steps related to sex hormones' nuclear receptor isoforms expressed by hypothalamic neurons continues to enrich our understanding of this neurophysiology.

A Time-Space Symmetry Based Cylindrical Model for Quantum Mechanical Interpretations

NASA Astrophysics Data System (ADS)

Vo Van, Thuan

2017-12-01

Following a bi-cylindrical model of geometrical dynamics, our study shows that a 6D-gravitational equation leads to geodesic description in an extended symmetrical time-space, which fits Hubble-like expansion on a microscopic scale. As a duality, the geodesic solution is mathematically equivalent to the basic Klein-Gordon-Fock equations of free massive elementary particles, in particular, the squared Dirac equations of leptons. The quantum indeterminism is proved to have originated from space-time curvatures. Interpretation of some important issues of quantum mechanical reality is carried out in comparison with the 5D space-time-matter theory. A solution of lepton mass hierarchy is proposed by extending to higher dimensional curvatures of time-like hyper-spherical surfaces than one of the cylindrical dynamical geometry. In a result, the reasonable charged lepton mass ratios have been calculated, which would be tested experimentally.

Hawking temperature: an elementary approach based on Newtonian mechanics and quantum theory

NASA Astrophysics Data System (ADS)

Pinochet, Jorge

2016-01-01

In 1974, the British physicist Stephen Hawking discovered that black holes have a characteristic temperature and are therefore capable of emitting radiation. Given the scientific importance of this discovery, there is a profuse literature on the subject. Nevertheless, the available literature ends up being either too simple, which does not convey the true physical significance of the issue, or too technical, which excludes an ample segment of the audience interested in science, such as physics teachers and their students. The present article seeks to remedy this shortcoming. It develops a simple and plausible argument that provides insight into the fundamental aspects of Hawking’s discovery, which leads to an approximate equation for the so-called Hawking temperature. The exposition is mainly intended for physics teachers and their students, and it only requires elementary algebra, as well as basic notions of Newtonian mechanics and quantum theory.

The Value of Comparative Approaches to our Understanding of Puberty as Illustrated by Investigations in Birds and Reptiles

PubMed Central

Ball, Gregory F.; Wade, Juli

2013-01-01

Studies of birds and reptiles have provided many basic insights into the neuroendocrine control of reproductive processes. This research has elucidated mechanisms regulating both early development, including sexual differentiation, and adult neuroendocrine function and behavior. However, phenomena associated with the transition into sexual maturation (puberty) have not been a focus of investigators working on species in these taxonomic classes. Research is complicated in birds and reptiles by a variety of factors, including what can be extended times to maturation, the need to reach particular body size regardless of age, and environmental conditions that can support or inhibit endocrine responses. However, careful selection of model systems, particularly those with available genetic tools, will lead to important comparative studies that can elucidate both generalizability and diversity of mechanisms regulating the onset of reproductive maturity. PMID:23998665

Density functional computational studies on the glucose and glycine Maillard reaction: Formation of the Amadori rearrangement products

NASA Astrophysics Data System (ADS)

Jalbout, Abraham F.; Roy, Amlan K.; Shipar, Abul Haider; Ahmed, M. Samsuddin

Theoretical energy changes of various intermediates leading to the formation of the Amadori rearrangement products (ARPs) under different mechanistic assumptions have been calculated, by using open chain glucose (O-Glu)/closed chain glucose (A-Glu and B-Glu) and glycine (Gly) as a model for the Maillard reaction. Density functional theory (DFT) computations have been applied on the proposed mechanisms under different pH conditions. Thus, the possibility of the formation of different compounds and electronic energy changes for different steps in the proposed mechanisms has been evaluated. B-Glu has been found to be more efficient than A-Glu, and A-Glu has been found more efficient than O-Glu in the reaction. The reaction under basic condition is the most favorable for the formation of ARPs. Other reaction pathways have been computed and discussed in this work.0

Fracture Toughness Evaluation of Space Shuttle External Tank Thermal Protection System Polyurethane Foam Insulation Materials

NASA Technical Reports Server (NTRS)

McGill, Preston; Wells, Doug; Morgan, Kristin

2006-01-01

Experimental evaluation of the basic fracture properties of Thermal Protection System (TPS) polyurethane foam insulation materials was conducted to validate the methodology used in estimating critical defect sizes in TPS applications on the Space Shuttle External Fuel Tank. The polyurethane foam found on the External Tank (ET) is manufactured by mixing liquid constituents and allowing them to react and expand upwards - a process which creates component cells that are generally elongated in the foam rise direction and gives rise to mechanical anisotropy. Similarly, the application of successive foam layers to the ET produces cohesive foam interfaces (knitlines) which may lead to local variations in mechanical properties. This study reports the fracture toughness of BX-265, NCFI 24-124, and PDL-1034 closed-cell polyurethane foam as a function of ambient and cryogenic temperatures and knitline/cellular orientation at ambient pressure.

Chemical origins of frictional aging.

PubMed

Liu, Yun; Szlufarska, Izabela

2012-11-02

Although the basic laws of friction are simple enough to be taught in elementary physics classes and although friction has been widely studied for centuries, in the current state of knowledge it is still not possible to predict a friction force from fundamental principles. One of the highly debated topics in this field is the origin of static friction. For most macroscopic contacts between two solids, static friction will increase logarithmically with time, a phenomenon that is referred to as aging of the interface. One known reason for the logarithmic growth of static friction is the deformation creep in plastic contacts. However, this mechanism cannot explain frictional aging observed in the absence of roughness and plasticity. Here, we discover molecular mechanisms that can lead to a logarithmic increase of friction based purely on interfacial chemistry. Predictions of our model are consistent with published experimental data on the friction of silica.

Learning Computers, Speaking English: Cooperative Activities for Learning English and Basic Word Processing.

ERIC Educational Resources Information Center

Quann, Steve; Satin, Diana

This textbook leads high-beginning and intermediate English-as-a-Second-Language (ESL) students through cooperative computer-based activities that combine language learning with training in basic computer skills and word processing. Each unit concentrates on a basic concept of word processing while also focusing on a grammar topic. Skills are…

Diazo compounds for the bioreversible esterification of proteins† †Electronic supplementary information (ESI) available: Experimental procedures, analytical data, and spectral data for novel compounds. See DOI: 10.1039/c4sc01768d Click here for additional data file.

PubMed Central

McGrath, Nicholas A.; Andersen, Kristen A.; Davis, Amy K. F.; Lomax, Jo E.

2015-01-01

A diazo compound is shown to convert carboxylic acids to esters efficiently in an aqueous environment. The basicity of the diazo compound is critical: low basicity does not lead to a reaction but high basicity leads to hydrolysis. This reactivity extends to carboxylic acid groups in a protein. The ensuing esters are hydrolyzed by human cellular esterases to regenerate protein carboxyl groups. This new mode of chemical modification could enable the key advantages of prodrugs to be translated from small-molecules to proteins. PMID:25544883

Diesel Mechanics: Fundamentals.

ERIC Educational Resources Information Center

Foutes, William; And Others

This publication is the first in a series of three texts for a diesel mechanics curriculum. Its purpose is to teach the basic concepts related to employment in a diesel trade. Six sections contain 29 units. Each instructional unit includes some or all of these basic components: unit and specific (performance) objectives, suggested activities for…

Basic Gasoline Engine Mechanics. Florida Vocational Program Guide.

ERIC Educational Resources Information Center

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

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

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

ERIC Educational Resources Information Center

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.)

Air Pollution.

ERIC Educational Resources Information Center

Scorer, Richard S.

The purpose of this book is to describe the basic mechanisms whereby pollution is transported and diffused in the atmosphere. It is designed to give practitioners an understanding of basic mechanics and physics so they may have a correct basis on which to formulate their decisions related to practical air pollution control problems. Since many…

Economics, ecologics, and mechanics: The dynamics of responding under conditions of varying motivation

PubMed Central

Killeen, Peter R.

1995-01-01

The mechanics of behavior developed by Killeen (1994) is extended to deal with deprivation and satiation and with recovery of arousal at the beginning of sessions. The extended theory is validated against satiation curves and within-session changes in response rates. Anomalies, such as (a) the positive correlation between magnitude of an incentive and response rates in some contexts and a negative correlation in other contexts and (b) the greater prominence of incentive effects when magnitude is varied within the session rather than between sessions, are explained in terms of the basic interplay of drive and incentive motivation. The models are applied to data from closed economies in which changes of satiation levels play a key role in determining the changes in behavior. Relaxation of various assumptions leads to closed-form models for response rates and demand functions in these contexts, ones that show reasonable accord with the data and reinforce arguments for unit price as a controlling variable. The central role of deprivation level in this treatment distinguishes it from economic models. It is argued that traditional experiments should be redesigned to reveal basic principles, that ecologic experiments should be redesigned to test the applicability of those principles in more natural contexts, and that behavioral economics should consist of the applications of these principles to economic contexts, not the adoption of economic models as alternatives to behavioral analysis. PMID:16812776

Crystal Structure of the Minimalist Max-E47 Protein Chimera

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahmadpour, Faraz; Ghirlando, Rodolfo; De Jong, Antonia T.

Max-E47 is a protein chimera generated from the fusion of the DNA-binding basic region of Max and the dimerization region of E47, both members of the basic region/helix-loop-helix (bHLH) superfamily of transcription factors. Like native Max, Max-E47 binds with high affinity and specificity to the E-box site, 5'-CACGTG, both in vivo and in vitro. We have determined the crystal structure of Max-E47 at 1.7 Å resolution, and found that it associates to form a well-structured dimer even in the absence of its cognate DNA. Analytical ultracentrifugation confirms that Max-E47 is dimeric even at low micromolar concentrations, indicating that the Max-E47more » dimer is stable in the absence of DNA. Circular dichroism analysis demonstrates that both non-specific DNA and the E-box site induce similar levels of helical secondary structure in Max-E47. These results suggest that Max-E47 may bind to the E-box following the two-step mechanism proposed for other bHLH proteins. In this mechanism, a rapid step where protein binds to DNA without sequence specificity is followed by a slow step where specific protein:DNA interactions are fine-tuned, leading to sequence-specific recognition. Collectively, these results show that the designed Max-E47 protein chimera behaves both structurally and functionally like its native counterparts.« less

Badminton--Teaching Concepts.

ERIC Educational Resources Information Center

Gibbs, Marilyn J.

1988-01-01

Teaching four basic badminton concepts along with the usual basic skill shots allows players to develop game strategy awareness as well as mechanical skills. These four basic concepts are: (1) ready position, (2) flight trajectory, (3) early shuttle contact, and (4) camouflage. (IAH)

On the Effect of Feedback Control on Benard Convection in a Boussinesq Fluid

NASA Technical Reports Server (NTRS)

Shortis, Trudi A.; Hall, Philip

1996-01-01

The effect of nonlinear feedback control strategies on the platform of convection in a Boussinesq fluid heated from below is investigated. In the absence of the control, given that non-Boussinesq effects may be neglected, it is well known that convection begins in the form of a supercritical bifurcation to rolls. Non-Boussinesq behaviour destroys the symmetry of the basic state, and through a subcritical bifurcation leads to the formation of hexagonal cells. Here we discuss the influence of regulation of the lower surface temperature by means of a control mechanism, made up of a combination of a proportional linear and nonlinear controller, on the stability of the hexagonal cell pattern.

A mathematical model for the deformation of the eyeball by an elastic band.

PubMed

Keeling, Stephen L; Propst, Georg; Stadler, Georg; Wackernagel, Werner

2009-06-01

In a certain kind of eye surgery, the human eyeball is deformed sustainably by the application of an elastic band. This article presents a mathematical model for the mechanics of the combined eye/band structure along with an algorithm to compute the model solutions. These predict the immediate and the lasting indentation of the eyeball. The model is derived from basic physical principles by minimizing a potential energy subject to a volume constraint. Assuming spherical symmetry, this leads to a two-point boundary-value problem for a non-linear second-order ordinary differential equation that describes the minimizing static equilibrium. By comparison with laboratory data, a preliminary validation of the model is given.

GENETICS AND NEUROPATHOLOGY OF HUNTINGTON’S DISEASE

PubMed Central

Reiner, Anton; Dragatsis, Ioannis; Dietrich, Paula

2015-01-01

Huntington’s disease (HD) is an autosomal dominant progressive neurodegenerative disorder that prominently affects the basal ganglia, leading to affective, cognitive, behavioral and motor decline. The basis of HD is a CAG repeat expansion to >35 CAG in a gene that codes for a ubiquitous protein known as huntingtin, resulting in an expanded N-terminal polyglutamine tract. The size of the expansion is correlated with disease severity, with increasing CAG accelerating the age of onset. A variety of possibilities have been proposed as to the mechanism by which the mutation causes preferential injury to the basal ganglia. The present chapter provides a basic overview of the genetics and pathology of HD. PMID:21907094

From quantum foundations to applications and back.

PubMed

Gisin, Nicolas; Fröwis, Florian

2018-07-13

Quantum non-locality has been an extremely fruitful subject of research, leading the scientific revolution towards quantum information science, in particular, to device-independent quantum information processing. We argue that the time is ripe to work on another basic problem in the foundations of quantum physics, the quantum measurement problem, which should produce good physics in theoretical, mathematical, experimental and applied physics. We briefly review how quantum non-locality contributed to physics (including some outstanding open problems) and suggest ways in which questions around macroscopic quantumness could equally contribute to all aspects of physics.This article is part of a discussion meeting issue 'Foundations of quantum mechanics and their impact on contemporary society'. © 2018 The Author(s).

Nanocomposite polymeric materials for high density optical storage

NASA Astrophysics Data System (ADS)

Criante, L.; Castagna, R.; Vita, F.; Lucchetta, D. E.; Simoni, F.

2009-02-01

We report the results of an extended investigation performed on composite polymeric materials with the aim of obtaining compounds suitable for holographic recording. In order to investigate the material properties a characterization of holographic reflection gratings at different writing wavelength (514.5, 457 and 405 nm) has been performed. The volume grating presents high diffraction efficiency (>60%), high sensitivity (>103 cm J-1) and refractive index modulation Δn≈0.01 even for writing wavelength in the blue range. We show that following a strategy of two basic components leading to phase separation during the photopolymerization process, most of the requirements for holographic data storage are achieved. The one that needs further improvement concerns long term mechanical stability.

The influence of occupational chronic lead exposure on the levels of selected pro-inflammatory cytokines and angiogenic factors.

PubMed

Machoń-Grecka, A; Dobrakowski, M; Boroń, M; Lisowska, G; Kasperczyk, A; Kasperczyk, S

2017-05-01

The aim of the study was to determine the effect of occupational exposure to lead on the blood levels of pro-inflammatory cytokines and selected factors that influence angiogenesis. The study population was divided into two groups. The first group consisted of 56 male workers chronically exposed to lead. The second group (control) was comprised of 24 male administrative workers. The serum levels of interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) were significantly higher in the group of workers chronically exposed to lead compared to control values by 38%, 68%, and 57%, respectively. Similarly, the values of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and fibroblast growth factor-basic (FGF-basic) were higher by 19% and 63%, respectively. In the group of workers chronically exposed to lead, there were positive correlations between the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and angiogenic factors (VEGF, FGF-basic, sVEGFR-1, and soluble angiopoietin receptor). In the control group, there were no correlations between the levels of the abovementioned parameters. Results of the present study indicate that chronic occupational lead exposure promotes inflammatory processes via induction of pro-inflammatory cytokines, modulates angiogenesis, and elicits interdependencies between the immune response and angiogenic factors.

mTOR inhibitor-induced interstitial lung disease in cancer patients: Comprehensive review and a practical management algorithm.

PubMed

Willemsen, Annelieke E C A B; Grutters, Jan C; Gerritsen, Winald R; van Erp, Nielka P; van Herpen, Carla M L; Tol, Jolien

2016-05-15

Mammalian target of rapamycin inhibitors (mTORi) have clinically significant activity against various malignancies, such as renal cell carcinoma and breast cancer, but their use can be complicated by several toxicities. Interstitial lung disease (ILD) is an adverse event of particular importance. Mostly, mTORi-induced ILD remains asymptomatic or mildly symptomatic, but it can also lead to severe morbidity and even mortality. Therefore, careful diagnosis and management of ILD is warranted. The reported incidence of mTORi-induced ILD varies widely because of a lack of uniform diagnostic criteria and active surveillance. Because of the nonspecific clinical features, a broad differential diagnosis that includes (opportunistic) infections should be considered in case of suspicion of mTORi-induced ILD. The exact mechanism or interplay of mechanisms leading to the development of ILD remains to be defined. Suggested mechanisms are either a direct toxic effect or immune-mediated mechanisms, considering mTOR inhibitors have several effects on the immune system. The clinical course of ILD varies widely and is difficult to predict. Consequently, the discrimination between when mTOR inhibitors can be continued safely and when discontinuation is indicated is challenging. In this review, we give a comprehensive review of the incidence, clinical presentation and pathophysiology of mTORi-induced ILD in cancer patients. We present newly developed diagnostic criteria for ILD, which include clinical symptoms as well as basic pulmonary function tests and radiological abnormalities. In conjunction with these diagnostic criteria, we provide a detailed and easily applicable clinical management algorithm. © 2015 UICC.

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

ERIC Educational Resources Information Center

Dade County Public Schools, Miami, FL.

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

Gasoline Engine Mechanics. Performance Objectives. Basic Course.

ERIC Educational Resources Information Center

Jones, Marion

Several intermediate performance objectives and corresponding criterion measures are listed for each of five terminal objectives presented in this curriculum guide for a basic gasoline engine mechanics course at the secondary level. (For the intermediate course guide see CE 010 946.) The materials were developed for a two semester (2 hours daily)…

Quantum Social Science

NASA Astrophysics Data System (ADS)

Haven, Emmanuel; Khrennikov, Andrei

2013-01-01

Preface; Part I. Physics Concepts in Social Science? A Discussion: 1. Classical, statistical and quantum mechanics: all in one; 2. Econophysics: statistical physics and social science; 3. Quantum social science: a non-mathematical motivation; Part II. Mathematics and Physics Preliminaries: 4. Vector calculus and other mathematical preliminaries; 5. Basic elements of quantum mechanics; 6. Basic elements of Bohmian mechanics; Part III. Quantum Probabilistic Effects in Psychology: Basic Questions and Answers: 7. A brief overview; 8. Interference effects in psychology - an introduction; 9. A quantum-like model of decision making; Part IV. Other Quantum Probabilistic Effects in Economics, Finance and Brain Sciences: 10. Financial/economic theory in crisis; 11. Bohmian mechanics in finance and economics; 12. The Bohm-Vigier Model and path simulation; 13. Other applications to economic/financial theory; 14. The neurophysiological sources of quantum-like processing in the brain; Conclusion; Glossary; Index.

The chromatin-binding protein Smyd1 restricts adult mammalian heart growth

PubMed Central

Kimball, Todd; Rasmussen, Tara L.; Rosa-Garrido, Manuel; Chen, Haodong; Tran, Tam; Miller, Mickey R.; Gray, Ricardo; Jiang, Shanxi; Ren, Shuxun; Wang, Yibin; Tucker, Haley O.; Vondriska, Thomas M.

2016-01-01

All terminally differentiated organs face two challenges, maintaining their cellular identity and restricting organ size. The molecular mechanisms responsible for these decisions are of critical importance to organismal development, and perturbations in their normal balance can lead to disease. A hallmark of heart failure, a condition affecting millions of people worldwide, is hypertrophic growth of cardiomyocytes. The various forms of heart failure in human and animal models share conserved transcriptome remodeling events that lead to expression of genes normally silenced in the healthy adult heart. However, the chromatin remodeling events that maintain cell and organ size are incompletely understood; insights into these mechanisms could provide new targets for heart failure therapy. Using a quantitative proteomics approach to identify muscle-specific chromatin regulators in a mouse model of hypertrophy and heart failure, we identified upregulation of the histone methyltransferase Smyd1 during disease. Inducible loss-of-function studies in vivo demonstrate that Smyd1 is responsible for restricting growth in the adult heart, with its absence leading to cellular hypertrophy, organ remodeling, and fulminate heart failure. Molecular studies reveal Smyd1 to be a muscle-specific regulator of gene expression and indicate that Smyd1 modulates expression of gene isoforms whose expression is associated with cardiac pathology. Importantly, activation of Smyd1 can prevent pathological cell growth. These findings have basic implications for our understanding of cardiac pathologies and open new avenues to the treatment of cardiac hypertrophy and failure by modulating Smyd1. PMID:27663768

The chromatin-binding protein Smyd1 restricts adult mammalian heart growth.

PubMed

Franklin, Sarah; Kimball, Todd; Rasmussen, Tara L; Rosa-Garrido, Manuel; Chen, Haodong; Tran, Tam; Miller, Mickey R; Gray, Ricardo; Jiang, Shanxi; Ren, Shuxun; Wang, Yibin; Tucker, Haley O; Vondriska, Thomas M

2016-11-01

All terminally differentiated organs face two challenges, maintaining their cellular identity and restricting organ size. The molecular mechanisms responsible for these decisions are of critical importance to organismal development, and perturbations in their normal balance can lead to disease. A hallmark of heart failure, a condition affecting millions of people worldwide, is hypertrophic growth of cardiomyocytes. The various forms of heart failure in human and animal models share conserved transcriptome remodeling events that lead to expression of genes normally silenced in the healthy adult heart. However, the chromatin remodeling events that maintain cell and organ size are incompletely understood; insights into these mechanisms could provide new targets for heart failure therapy. Using a quantitative proteomics approach to identify muscle-specific chromatin regulators in a mouse model of hypertrophy and heart failure, we identified upregulation of the histone methyltransferase Smyd1 during disease. Inducible loss-of-function studies in vivo demonstrate that Smyd1 is responsible for restricting growth in the adult heart, with its absence leading to cellular hypertrophy, organ remodeling, and fulminate heart failure. Molecular studies reveal Smyd1 to be a muscle-specific regulator of gene expression and indicate that Smyd1 modulates expression of gene isoforms whose expression is associated with cardiac pathology. Importantly, activation of Smyd1 can prevent pathological cell growth. These findings have basic implications for our understanding of cardiac pathologies and open new avenues to the treatment of cardiac hypertrophy and failure by modulating Smyd1. Copyright © 2016 the American Physiological Society.

Lead (Environmental Health Student Portal)

MedlinePlus

... limit your exposure. Enviro-Health Links - Lead and Human Health (National Library of Medicine) - Resources on basic information, ... Medicine National Institutes of Health U.S. Department of Health and Human Services

Mismatch repair defects and Lynch syndrome: The role of the basic scientist in the battle against cancer.

PubMed

Heinen, Christopher D

2016-02-01

We have currently entered a genomic era of cancer research which may soon lead to a genomic era of cancer treatment. Patient DNA sequencing information may lead to a personalized approach to managing an individual's cancer as well as future cancer risk. The success of this approach, however, begins not necessarily in the clinician's office, but rather at the laboratory bench of the basic scientist. The basic scientist plays a critical role since the DNA sequencing information is of limited use unless one knows the function of the gene that is altered and the manner by which a sequence alteration affects that function. The role of basic science research in aiding the clinical management of a disease is perhaps best exemplified by considering the case of Lynch syndrome, a hereditary disease that predisposes patients to colorectal and other cancers. This review will examine how the diagnosis, treatment and even prevention of Lynch syndrome-associated cancers has benefitted from extensive basic science research on the DNA mismatch repair genes whose alteration underlies this condition. Copyright © 2015 Elsevier B.V. All rights reserved.

Aerodynamic Inner Workings of Circumferential Grooves in a Transonic Axial Compressor

NASA Technical Reports Server (NTRS)

Hah, Chunill; Mueller, Martin; Schiffer, Heinz-Peter

2007-01-01

The current paper reports on investigations of the fundamental flow mechanisms of circumferential grooves applied to a transonic axial compressor. Experimental results show that the compressor stall margin is significantly improved with the current set of circumferential grooves. The primary focus of the current investigation is to advance understanding of basic flow mechanics behind the observed improvement of stall margin. Experimental data and numerical simulations of a circumferential groove were analyzed in detail to unlock the inner workings of the circumferential grooves in the current transonic compressor rotor. A short length scale stall inception occurs when a large flow blockage is built on the pressure side of the blade near the leading edge and incoming flow spills over to the adjacent blade passage due to this blockage. The current study reveals that a large portion of this blockage is created by the tip clearance flow originating from 20% to 50% chord of the blade from the leading edge. Tip clearance flows originating from the leading edge up to 20% chord form a tip clearance core vortex and this tip clearance core vortex travels radially inward. The tip clearance flows originating from 20% to 50% chord travels over this tip clearance core vortex and reaches to the pressure side. This part of tip clearance flow is of low momentum as it is coming from the casing boundary layer and the blade suction surface boundary layer. The circumferential grooves disturb this part of the tip clearance flow close to the casing. Consequently the buildup of the induced vortex and the blockage near the pressure side of the passage is reduced. This is the main mechanism of the circumferential grooves that delays the formation of blockage near the pressure side of the passage and delays the onset of short length scale stall inception. The primary effect of the circumferential grooves is preventing local blockage near the pressure side of the blade leading edge that directly determines flow spillage around the leading edge. The circumferential grooves do not necessarily reduce the over all blockage built up at the rotor tip section.

High precision measurements on fission-fragment de-excitation

NASA Astrophysics Data System (ADS)

Oberstedt, Stephan; Gatera, Angélique; Geerts, Wouter; Göök, Alf; Hambsch, Franz-Josef; Vidali, Marzio; Oberstedt, Andreas

2017-11-01

In recent years nuclear fission has gained renewed interest both from the nuclear energy community and in basic science. The first, represented by the OECD Nuclear Energy Agency, expressed the need for more accurate fission cross-section and fragment yield data for safety assessments of Generation IV reactor systems. In basic science modelling made much progress in describing the de-excitation mechanism of neutron-rich isotopes, e.g. produced in nuclear fission. Benchmarking the different models require a precise experimental data on prompt fission neutron and γ-ray emission, e.g. multiplicity, average energy per particle and total dissipated energy per fission, preferably as function of fission-fragment mass and total kinetic energy. A collaboration of scientists from JRC Geel (formerly known as JRC IRMM) and other institutes took the lead in establishing a dedicated measurement programme on prompt fission neutron and γ-ray characteristics, which has triggered even more measurement activities around the world. This contribution presents new advanced instrumentation and methodology we use to generate high-precision spectral data and will give a flavour of future data needs and opportunities.

The physics of MRI safety.

PubMed

Panych, Lawrence P; Madore, Bruno

2018-01-01

The main risks associated with magnetic resonance imaging (MRI) have been extensively reported and studied; for example, everyday objects may turn into projectiles, energy deposition can cause burns, varying fields can induce nerve stimulation, and loud noises can lead to auditory loss. The present review article is geared toward providing intuition about the physical mechanisms that give rise to these risks. On the one hand, excellent literature already exists on the practical aspect of risk management, with clinical workflow and recommendations. On the other hand, excellent technical articles also exist that explain these risks from basic principles of electromagnetism. We felt that an underserved niche might be found between the two, ie, somewhere between basic science and practical advice, to help develop intuition about electromagnetism that might prove of practical value when working around MR scanners. Following a wide-ranging introduction, risks originating from the main magnetic field, the excitation RF electromagnetic field, and switching of the imaging gradients will be presented in turn. 5 Technical Efficacy: 1 J. Magn. Reson. Imaging 2018;47:28-43. © 2017 International Society for Magnetic Resonance in Medicine.

Modification of the Surface Topography and Composition of Ultrafine and Coarse Grained Titanium by Chemical Etching.

PubMed

Nazarov, Denis V; Zemtsova, Elena G; Solokhin, Alexandr Yu; Valiev, Ruslan Z; Smirnov, Vladimir M

2017-01-13

In this study, we present the detailed investigation of the influence of the etching medium (acidic or basic Piranha solutions) and the etching time on the morphology and surface relief of ultrafine grained (UFG) and coarse grained (CG) titanium. The surface relief and morphology have been studied by means of scanning electron microscopy (SEM), atomic force microscopy (AFM), and the spectral ellipsometry. The composition of the samples has been determined by X-ray fluorescence analysis (XRF) and X-ray Photoelectron Spectroscopy (XPS). Significant difference in the etching behavior of UFG and CG titanium has been found. UFG titanium exhibits higher etching activity independently of the etching medium. Formed structures possess higher homogeneity. The variation of the etching medium and time leads to micro-, nano-, or hierarchical micro/nanostructures on the surface. Significant difference has been found between surface composition for UFG titanium etched in basic and acidic Piranha solution. Based on the experimental data, the possible reasons and mechanisms are considered for the formation of nano- and microstructures. The prospects of etched UFG titanium as the material for implants are discussed.

Advanced electric propulsion system concept for electric vehicles. Addendum 1: Voltage considerations

NASA Technical Reports Server (NTRS)

Raynard, A. E.; Forbes, F. E.

1980-01-01

The two electric vehicle propulsion systems that best met cost and performance goals were examined to assess the effect of battery pack voltage on system performance and cost. A voltage range of 54 to 540 V was considered for a typical battery pack capacity of 24 k W-hr. The highest battery specific energy (W-hr/kg) and the lowest cost ($/kW-hr) were obtained at the minimum voltage level. The flywheel system traction motor is a dc, mechanically commutated with shunt field control, and due to the flywheel the traction motor and the battery are not subject to extreme peaks of power demand. The basic system uses a permanent-magnet motor with electronic commutation supplied by an ac power control unit. In both systems battery cost were the major factor in system voltage selection, and a battery pack with the minimum voltage of 54 V produced the lowest life-cycle cost. The minimum life-cycle cost for the basic system with lead-acid batteries was $0.057/km and for the flywheel system was $0.037/km.

Patterned control of human locomotion

PubMed Central

Lacquaniti, Francesco; Ivanenko, Yuri P; Zago, Myrka

2012-01-01

There is much experimental evidence for the existence of biomechanical constraints which simplify the problem of control of multi-segment movements. In addition, it has been hypothesized that movements are controlled using a small set of basic temporal components or activation patterns, shared by several different muscles and reflecting global kinematic and kinetic goals. Here we review recent studies on human locomotion showing that muscle activity is accounted for by a combination of few basic patterns, each one timed at a different phase of the gait cycle. Similar patterns are involved in walking and running at different speeds, walking forwards or backwards, and walking under different loading conditions. The corresponding weights of distribution to different muscles may change as a function of the condition, allowing highly flexible control. Biomechanical correlates of each activation pattern have been described, leading to the hypothesis that the co-ordination of limb and body segments arises from the coupling of neural oscillators between each other and with limb mechanical oscillators. Muscle activations need only intervene during limited time epochs to force intrinsic oscillations of the system when energy is lost. PMID:22411012

Patterned control of human locomotion.

PubMed

Lacquaniti, Francesco; Ivanenko, Yuri P; Zago, Myrka

2012-05-15

There is much experimental evidence for the existence of biomechanical constraints which simplify the problem of control of multi-segment movements. In addition, it has been hypothesized that movements are controlled using a small set of basic temporal components or activation patterns, shared by several different muscles and reflecting global kinematic and kinetic goals. Here we review recent studies on human locomotion showing that muscle activity is accounted for by a combination of few basic patterns, each one timed at a different phase of the gait cycle. Similar patterns are involved in walking and running at different speeds, walking forwards or backwards, and walking under different loading conditions. The corresponding weights of distribution to different muscles may change as a function of the condition, allowing highly flexible control. Biomechanical correlates of each activation pattern have been described, leading to the hypothesis that the co-ordination of limb and body segments arises from the coupling of neural oscillators between each other and with limb mechanical oscillators. Muscle activations need only intervene during limited time epochs to force intrinsic oscillations of the system when energy is lost.

Translational atherosclerosis research: From experimental models to coronary artery disease in humans.

PubMed

Gleissner, Christian A

2016-05-01

Atherosclerosis is the leading cause of death worldwide. Research on the pathophysiological mechanisms of atherogenesis has made tremendous progress over the past two decades. However, despite great advances there is still a lack of therapies that reduce adverse cardiovascular events to an acceptable degree. This review addresses successes, but also questions, challenges, and chances regarding the translation of basic science results into clinical practice, i.e. the capability to apply the results of basic and/or clinical research in order to design therapies suitable to improve patient outcome. Specifically, it discusses problems in translating findings from the most broadly used murine models of atherosclerosis into clinically feasible therapies and strategies potentially improving the results of clinical trials. Most likely, the key to success will be a multimodal approach employing novel imaging methods as well as large scale screening tools-summarized as "omics" approach. Using individually tailored therapies, plaque stabilization and regression could prevent adverse cardiovascular events thereby improving outcome of a large number of patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Modification of the Surface Topography and Composition of Ultrafine and Coarse Grained Titanium by Chemical Etching

PubMed Central

Nazarov, Denis V.; Zemtsova, Elena G.; Solokhin, Alexandr Yu.; Valiev, Ruslan Z.; Smirnov, Vladimir M.

2017-01-01

In this study, we present the detailed investigation of the influence of the etching medium (acidic or basic Piranha solutions) and the etching time on the morphology and surface relief of ultrafine grained (UFG) and coarse grained (CG) titanium. The surface relief and morphology have been studied by means of scanning electron microscopy (SEM), atomic force microscopy (AFM), and the spectral ellipsometry. The composition of the samples has been determined by X-ray fluorescence analysis (XRF) and X-ray Photoelectron Spectroscopy (XPS). Significant difference in the etching behavior of UFG and CG titanium has been found. UFG titanium exhibits higher etching activity independently of the etching medium. Formed structures possess higher homogeneity. The variation of the etching medium and time leads to micro-, nano-, or hierarchical micro/nanostructures on the surface. Significant difference has been found between surface composition for UFG titanium etched in basic and acidic Piranha solution. Based on the experimental data, the possible reasons and mechanisms are considered for the formation of nano- and microstructures. The prospects of etched UFG titanium as the material for implants are discussed. PMID:28336849

Role of Airway Recruitment and Derecruitment in Lung Injury

PubMed Central

Ghadiali, S. N.; Huang, Y.

2011-01-01

The mechanical forces generated during the ventilation of patients with acute lung injury causes significant lung damage and inflammation. Low-volume ventilation protocols are commonly used to prevent stretch-related injury that occurs at high lung volumes. However, the cyclic closure and reopening of pulmonary airways at low lung volumes, i.e., derecruitment and recruitment, also causes significant lung damage and inflammation. In this review, we provide an overview of how biomedical engineering techniques are being used to elucidate the complex physiological and biomechanical mechanisms responsible for cellular injury during recruitment/derecruitment. We focus on the development of multiscale, multiphysics computational models of cell deformation and injury during airway reopening. These models, and the corresponding in vitro experiments, have been used to both elucidate the basic mechanisms responsible for recruitment/derecruitment injury and to develop alternative therapies that make the epithelium more resistant to injury. For example, models and experiments indicate that fluidization of the cytoskeleton is cytoprotective and that changes in cytoskeletal structure and cell mechanics can be used to mitigate the mechanotransduction of oscillatory pressure into inflammatory signaling. The continued application of biomedical engineering techniques to the problem of recruitment/derecruitment injury may therefore lead to novel and more effective therapies. PMID:22011235

A sensorless method for measuring the point mobility of mechanical structures

NASA Astrophysics Data System (ADS)

Boulandet, R.; Michau, M.; Herzog, P.; Micheau, P.; Berry, A.

2016-09-01

This paper presents a convenient and cost-effective experimental tool for measuring the mobility characteristics of a mechanical structure. The objective is to demonstrate that the point mobility measurement can be performed using only an electrodynamic inertial exciter. Unlike previous work based on voice coil actuators, no load cell or accelerometer is needed. Instead, it is theoretically shown that the mobility characteristics of the structure can be estimated from variations in the electrical input impedance of the actuator fixed onto it, provided that the electromechanical parameters of the actuator are known. The proof of concept is made experimentally using a cheap commercially available actuator on a simply supported plate, leading to a good dynamic range from 100 Hz to 1 kHz. The methodology to assess the basic parameters of the actuator is also given. Measured data are compared to a standard shaker testing and the strengths and weaknesses of the sensorless mobility measuring device are discussed. It is believed that this sensorless mobility measuring device can be a convenient experimental tool to determine the dynamic characteristics of a wide range of mechanical structures.

The Anticonvulsant Effects of Ketogenic Diet on Epileptic Seizures and Potential Mechanisms.

PubMed

Zhang, Yifan; Xu, Jingwei; Zhang, Kun; Yang, Wei; Li, Bingjin

2018-01-01

Epilepsy is a syndrome of brain dysfunction induced by the aberrant excitability of certain neurons. Despite advances in surgical technique and anti-epileptic drug in recent years, recurrent epileptic seizures remain intractable and lead to a serious morbidity in the world. The ketogenic diet refers to a high-fat, low-carbohydrate and adequate-protein diet. Currently, its beneficial effects on epileptic seizure reduction have been well established. However, the detailed mechanisms underlying the anti-epileptic effects of ketogenic diet are still poorly understood. In this article, the possible roles of ketogenic diet on epilepsy were discussed. Data was obtained from the websites including Web of Science, Medline, Pubmed, Scopus, based on these keywords: "Ketogenic diet" and "epilepsy". As shown in both clinical and basic studies, the therapeutic effects of ketogenic diet might involve neuronal metabolism, neurotransmitter function, neuronal membrane potential and neuron protection against ROS. In this review, we systematically reviewed the effects and possible mechanisms of ketogenic diet on epilepsy, which may optimize the therapeutic strategies against epilepsy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Corneal structure and transparency

PubMed Central

Meek, Keith M.; Knupp, Carlo

2015-01-01

The corneal stroma plays several pivotal roles within the eye. Optically, it is the main refracting lens and thus has to combine almost perfect transmission of visible light with precise shape, in order to focus incoming light. Furthermore, mechanically it has to be extremely tough to protect the inner contents of the eye. These functions are governed by its structure at all hierarchical levels. The basic principles of corneal structure and transparency have been known for some time, but in recent years X-ray scattering and other methods have revealed that the details of this structure are far more complex than previously thought and that the intricacy of the arrangement of the collagenous lamellae provides the shape and the mechanical properties of the tissue. At the molecular level, modern technologies and theoretical modelling have started to explain exactly how the collagen fibrils are arranged within the stromal lamellae and how proteoglycans maintain this ultrastructure. In this review we describe the current state of knowledge about the three-dimensional stromal architecture at the microscopic level, and about the control mechanisms at the nanoscopic level that lead to optical transparency. PMID:26145225

A duplication of the mouth associated with a dysontogenic cyst: a case report and discussion of theories of origin.

PubMed

Mews, Lorissa; Isaac, Andre; Leonard, Norma; Lacson, Atilano G; AlQudehy, Zeinab Ali; El-Hakim, Hamdy

2014-05-01

IMPORTANCE Diprosopus is a medical condition that refers to full or partial craniofacial duplication. A particular subset of this condition, duplication of the mouth, is an exceedingly rare condition, with 7 reported cases in the medical literature. The embryogenesis and mechanism of disease are not well understood. The objective of this report was to describe a case of partial facial duplication with a discussion of the previous literature, leading to a proposed theory of embryogenesis for this rare anomaly. OBSERVATIONS We present a rare case of duplication of the mouth associated with an intraoral dysontogenic cyst, which presented with upper airway obstruction. The diagnostic and management strategies are discussed, as well as the histopathological features and theories of embryogenesis. CONCLUSIONS AND RELEVANCE On the basis of our findings, we propose the mechanism of origin for duplication of the mouth to be duplication of the first branchial arch. This case offers a deeper understanding of the mechanism of this disease than previously reported. Additional basic science and clinical research is needed to corroborate this theory.

The avian respiratory system: a unique model for studies of respiratory toxicosis and for monitoring air quality.

PubMed Central

Brown, R E; Brain, J D; Wang, N

1997-01-01

There are many distinct differences (morphologic, physiologic, and mechanical) between the bird's lung-air-sac respiratory system and the mammalian bronchoalveolar lung. In this paper, we review the physiology of the avian respiratory system with attention to those mechanisms that may lead to significantly different results, relative to those in mammals, following exposure to toxic gases and airborne particulates. We suggest that these differences can be productively exploited to further our understanding of the basic mechanisms of inhalant toxicology (gases and particulates). The large mass-specific gas uptake by the avian respiratory system, at rest and especially during exercise, could be exploited as a sensitive monitor of air quality. Birds have much to offer in our understanding of respiratory toxicology, but that expectation can only be realized by investigating, in a wide variety of avian taxa, the pathophysiologic interactions of a broad range of inhaled toxicants on the bird's unique respiratory system. Images p188-a Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. A Figure 5. B Figure 5. C Figure 6. Figure 7. Figure 8. PMID:9105794

Empathy as a driver of prosocial behaviour: highly conserved neurobehavioural mechanisms across species

PubMed Central

Decety, Jean; Bartal, Inbal Ben-Ami; Uzefovsky, Florina; Knafo-Noam, Ariel

2016-01-01

Empathy reflects the natural ability to perceive and be sensitive to the emotional states of others, coupled with a motivation to care for their well-being. It has evolved in the context of parental care for offspring, as well as within kinship bonds, to help facilitate group living. In this paper, we integrate the perspectives of evolution, animal behaviour, developmental psychology, and social and clinical neuroscience to elucidate our understanding of the proximate mechanisms underlying empathy. We focus, in particular, on processing of signals of distress and need, and their relation to prosocial behaviour. The ability to empathize, both in animals and humans, mediates prosocial behaviour when sensitivity to others' distress is paired with a drive towards their welfare. Disruption or atypical development of the neural circuits that process distress cues and integrate them with decision value leads to callous disregard for others, as is the case in psychopathy. The realization that basic forms of empathy exist in non-human animals is crucial for gaining new insights into the underlying neurobiological and genetic mechanisms of empathy, enabling translation towards therapeutic and pharmacological interventions. PMID:26644596

Effect of Intrinsic Twist on Length of Crystalline and Disordered Regions in Cellulose Microfibrils

NASA Astrophysics Data System (ADS)

Nili, Abdolmadjid; Shklyaev, Oleg; Zhao, Zhen; Zhong, Linghao; Crespi, Vincent

2013-03-01

Cellulose is the most abundant biological material in the world. It provides mechanical reinforcement for plant cell wall, and could potentially serve as renewable energy source for biofuel. Native cellulose forms a non-centrosymmetric chiral crystal due to lack of roto-inversion symmetry of constituent glucose chains. Chirality of cellulose crystal could result in an overall twist. Competition between unwinding torsional/extensional and twisting energy terms leads to twist induced frustration along fibril's axis. The accumulated frustration could be the origin of periodic disordered regions observed in cellulose microfibrils. These regions could play significant role in properties of cellulose bundles and ribbons as well as biological implications on plant cell walls. We propose a mechanical model based on Frenkel-Kontorova mechanism to investigate effects of radius dependent twist on crystalline size in cellulose microfibrils. Parameters of the model are adjusted according to all-atom molecular simulations. This work is supported by the US Department of Energy, Office of Basic Energy Sciences as part of The Center for LignoCellulose Structure and Formation, an Energy Frontier Research Center

Controversies and Evolving New Mechanisms in Subarachnoid Hemorrhage

PubMed Central

Chen, Sheng; Feng, Hua; Sherchan, Prativa; Klebe, Damon; Zhao, Gang; Sun, Xiaochuan; Zhang, Jianmin; Tang, Jiping; Zhang, John H.

2013-01-01

Despite decades of study, subarachnoid hemorrhage (SAH) continues to be a serious and significant health problem in the United States and worldwide. The mechanisms contributing to brain injury after SAH remain unclear. Traditionally, most in vivo research has heavily emphasized the basic mechanisms of SAH over the pathophysiological or morphological changes of delayed cerebral vasospasm after SAH. Unfortunately, the results of clinical trials based on this premise have mostly been disappointing, implicating some other pathophysiological factors, independent of vasospasm, as contributors to poor clinical outcomes. Delayed cerebral vasospasm is no longer the only culprit. In this review, we summarize recent data from both experimental and clinical studies of SAH and discuss the vast array of physiological dysfunctions following SAH that ultimately lead to cell death. Based on the progress in neurobiological understanding of SAH, the terms “early brain injury” and “delayed brain injury” are used according to the temporal progression of SAH-induced brain injury. Additionally, a new concept of the vasculo-neuronal-glia triad model for SAH study is highlighted and presents the challenges and opportunities of this model for future SAH applications. PMID:24076160

Modeling of transient heat pipe operation

NASA Technical Reports Server (NTRS)

Colwell, Gene T.

1987-01-01

The use of heat pipes is being considered as a means of reducing the peak temperature and large thermal gradients at the leading edges of reentry vehicles and hypersonic aircraft and in nuclear reactors. In the basic cooling concept, the heat pipe covers the leading edge, a portion of the lower wing surface, and a portion of the upper wing surface. Aerodynamic heat is mainly absorbed at the leading edge and transported through the heat pipe to the upper and lower wing surface, where it is rejected by thermal radiation and convection. Basic governing equations are written to determine the startup, transient, and steady state performance of a haet pipe which has initially frozen alkali-metal as the working fluid.

Peritoneal dialysis: from bench to bedside

PubMed Central

Krediet, Raymond T.

2013-01-01

Peritoneal dialysis was first employed in patients with acute renal failure in the 1940s and since the 1960s for those with end-stage renal disease. Its popularity increased enormously after the introduction of continuous ambulatory peritoneal dialysis in the end of 1970s. This stimulated both clinical and basic research. In an ideal situation, this should lead to cross-fertilization between the two. The present review describes two examples of interactions: one where it worked out very well and another where basic science missed the link with clinical findings. Those on fluid transport are examples of how old physiological findings on absorption of saline and glucose solutions were adopted in peritoneal dialysis by the use of glucose as an osmotic agent. The mechanism behind this in patients was first solved mathematically by the assumption of ultrasmall intracellular pores allowing water transport only. At the same time, basic science discovered the water channel aquaporin-1 (AQP-1), and a few years later, studies in transgenic mice confirmed that AQP-1 was the ultrasmall pore. In clinical medicine, this led to its assessment in patients and the notion of its impairment. Drugs for treatment have been developed. Research on biocompatibility is not a success story. Basic science has focussed on dialysis solutions with a low pH and lactate, and effects of glucose degradation products, although the first is irrelevant in patients and effects of continuous exposure to high glucose concentrations were largely neglected. Industry believed the bench more than the bedside, resulting in ‘biocompatible’ dialysis solutions. These solutions have some beneficial effects, but are evidently not the final answer. PMID:26120456

5 CFR 772.101 - Basic authority.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Basic authority. 772.101 Section 772.101 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) INTERIM RELIEF General § 772.101 Basic authority. This part establishes a mechanism for agencies to provide...

5 CFR 772.101 - Basic authority.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Basic authority. 772.101 Section 772.101 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) INTERIM RELIEF General § 772.101 Basic authority. This part establishes a mechanism for agencies to provide...

Structural, morphological, dielectric and impedance spectroscopy of lead-free Bi(Zn2/3Ta1/3)O3 electronic material

NASA Astrophysics Data System (ADS)

Halder, S.; Bhuyan, S.; Das, S. N.; Sahoo, S.; Choudhary, R. N. P.; Das, P.; Parida, K.

2017-12-01

A lead-free dielectric material [Bi(Zn2/3Ta1/3)O3] has been prepared using a solid state reaction technique at high-temperature. The resistive, conducting and capacitive characteristics of the prepared electronic material have been studied in different experimental conditions. The determination of basic crystal parameters and reflection indices confirm the development of polycrystalline compound with orthorhombic crystal structure. The study of frequency-temperature dependence of ac conductivity illustrates the nature and conduction mechanism of the material. On the basis of observed impedance data and detailed dielectric analysis, the existence of non-Debye type relaxation has been affirmed. The electronic charge carriers of compound have short range order that has been validated from the complex modulus and impedance spectrum. The detailed studies of resistive, capacitive, microstructural characteristics of the prepared material provide some useful data for considering the material as an electronic component for fabrication of devices.

The Evolution of the Stem Cell Theory for Heart Failure

PubMed Central

Silvestre, Jean-Sébastien; Menasché, Philippe

2015-01-01

Various stem cell-based approaches for cardiac repair have achieved encouraging results in animal experiments, often leading to their rapid proceeding to clinical testing. However, freewheeling evolutionary developments of the stem cell theory might lead to dystopian scenarios where heterogeneous sources of therapeutic cells could promote mixed clinical outcomes in un-stratified patient populations. This review focuses on the lessons that should be learnt from the first generation of stem cell-based strategies and emphasizes the absolute requirement to better understand the basic mechanisms of stem cell biology and cardiogenesis. We will also discuss about the unexpected “big bang” in the stem cell theory, “blasting” the therapeutic cells to their unchallenged ability to release paracrine factors such as extracellular membrane vesicles. Paradoxically, the natural evolution of the stem cell theory for cardiac regeneration may end with the development of cell-free strategies with multiple cellular targets including cardiomyocytes but also other infiltrating or resident cardiac cells. PMID:26844266

Homocysteine and disease: Causal associations or epiphenomenons?

PubMed

Hannibal, Luciana; Blom, Henk J

2017-02-01

Nutritional and genetic deficiencies of folate and vitamin B 12 lead to elevation of cellular homocysteine (Hcy), which translates in increased plasma Hcy. The sources and role of elevated plasma Hcy in pathology continues to be a subject of intense scientific debate. Whether a cause, mediator or marker, little is known about the molecular mechanisms and interactions of Hcy with cellular processes that lead to disease. The use of folic acid reduces the incidence of neural tube defects, but the effect of Hcy-lowering interventions with folic acid in cardiovascular disease and cognitive impairment remains controversial. The fact that levels of Hcy in plasma do not always reflect cellular status of this amino acid may account for the substantial gaps that exist between epidemiological, intervention and basic research studies. Understanding whether plasma Hcy is a mechanistic player or an epiphenomenon in pathogenesis requires further investigation, and this research is essential to improve the assessment and potential treatment of hyperhomocysteinemias. Copyright © 2016 Elsevier Ltd. All rights reserved.

Toward advanced gamma rays radiation resistance and shielding efficiency with phthalonitrile resins and composites

NASA Astrophysics Data System (ADS)

Derradji, Mehdi; Zegaoui, Abdeldjalil; Xu, Yi-Le; Wang, An-ran; Dayo, Abdul Qadeer; Wang, Jun; Liu, Wen-bin; Liu, Yu-Guang; Khiari, Karim

2018-04-01

The phthalonitrile resins have claimed the leading place in the field of high performance polymers thanks to their combination of outstanding properties. The present work explores for the first time the gamma rays radiation resistance and shielding efficiency of the phthalonitrile resins and its related tungsten-reinforced nanocomposites. The primary goal of this research is to define the basic behavior of the phthalonitrile resins under highly ionizing gamma rays. The obtained results confirmed that the neat phthalonitrile resins can resist absorbed doses as high as 200 kGy. Meanwhile, the remarkable shielding efficiency of the phthalonitrile polymers was confirmed to be easily improved by preparing lead-free nanocomposites. In fact, the gamma rays screening ratio reached the exceptional value of 42% for the nanocomposites of 50 wt% of nano-tungsten loading. Thus, this study confirms that the remarkable performances of the phthalonitrile resins are not limited to the thermal and mechanical properties and can be extended to the gamma rays radiation and shielding resistances.

Ultrasonic fatigue of a high strength steel

NASA Astrophysics Data System (ADS)

Koster, M.; Wagner, G.; Eifler, D.

2010-07-01

At the Institute of Materials Science and Engineering at the University of Kaiserslautern an ultrasonic testing system for the fatigue assessment of metallic materials in the very high cycle fatigue (VHCF) regime was developed. The ultrasonic testing system allows to control the test and to measure detailed fatigue data. The achieved results can be used to describe the cyclic deformation behaviour of wheel steels at ultrasonic frequencies. In load increase tests (LIT), the critical stress amplitude can be determined, which leads to a defined change of process parameters like generator power, dissipated energy and specimen temperature. With SEM investigations it was proved that the change of the process parameters correlates with irreversible changes in the microstructure. It can be shown that the stress amplitude, leading to first irreversible changes in the microstructure, strongly depends on the depth position within the original wheel rim. New and basic results on the fatigue mechanisms of high strength steels in the VHCF-regime can be achieved.

Validation of Computational Models in Biomechanics

PubMed Central

Henninger, Heath B.; Reese, Shawn P.; Anderson, Andrew E.; Weiss, Jeffrey A.

2010-01-01

The topics of verification and validation (V&V) have increasingly been discussed in the field of computational biomechanics, and many recent articles have applied these concepts in an attempt to build credibility for models of complex biological systems. V&V are evolving techniques that, if used improperly, can lead to false conclusions about a system under study. In basic science these erroneous conclusions may lead to failure of a subsequent hypothesis, but they can have more profound effects if the model is designed to predict patient outcomes. While several authors have reviewed V&V as they pertain to traditional solid and fluid mechanics, it is the intent of this manuscript to present them in the context of computational biomechanics. Specifically, the task of model validation will be discussed with a focus on current techniques. It is hoped that this review will encourage investigators to engage and adopt the V&V process in an effort to increase peer acceptance of computational biomechanics models. PMID:20839648

Electron and Ion Reactions in Molecular Solids: from astrochemistry to radiobiology

NASA Astrophysics Data System (ADS)

Huels, Michael A.

2001-05-01

Wherever ionizing radiation interacts with matter, it initiates reaction cascades involving ions, radicals, and ballistic secondary electrons; these reactions occur on fs time-scales, and may lead to substantial physical and chemical modifications of a medium. Here I present measurements of 0-80 eV electron and ion reactions in condensed films ranging from simple to complex, and astrophysical to biological in nature. Targets contain either: small molecules, hydrocarbons of increasing complexity (incl. bases, sugars, single/double stranded DNA), molecules on rare gas matrices, or mixed cryogenic films resembling astrophysical or planetary surface ices containing O2, H2O, methane, and aromatic hydrocarbons. The basic electron or ion reaction mechanisms and pathways are found to be fundamentally universal, but are modulated by the physical and chemical nature of the medium; depending on the latter, a reaction cascade may lead to different end-points, e.g. a decrease in molecular complexity via molecular fragmentations, or increases in complexity via secondary ion collision induced synthesis of larger molecules in hydrocarbon rich surface ices.

“I Need my Own Place to get Better”: Patient Perspectives on the Role of Housing in Potentially Preventable Hospitalizations

PubMed Central

Quensell, Michelle L.; Taira, Deborah A.; Seto, Todd B.; Braun, Kathryn L.; Sentell, Tetine L.

2017-01-01

Objective To analyze patient perspectives on the role of housing in their potentially preventable hospitalization. Methods Individuals admitted with cardiovascular-or diabetes-related diagnoses (n = 90) in a major medical center in Hawai‘i completed an in-person interview eliciting patient perspectives on key factors leading to hospitalization. Using the framework approach, two independent coders identified themes. This study focused on housing-related findings. Results Overall, 23% of participants reported housing as a precipitating factor to their hospitalization, including 12 with no regular place to stay. Four housing-related themes emerged: challenges meeting basic needs, complex chronic care management difficulties, stigma and relationship with provider, and stress and other mental health issues. Discussion Almost 25% of patients identified housing as a key factor to their hospital stay. Patient-reported themes highlight specific mechanisms by which housing challenges may lead to hospitalization. Addressing housing issues could help reduce the number and associated cost burden of preventable hospitalizations. PMID:28529224

Leading the Way to Solutions to the Opioid Epidemic: AOA Critical Issues.

PubMed

Seymour, Rachel B; Ring, David; Higgins, Thomas; Hsu, Joseph R

2017-11-01

In the past 2 decades, overdoses and deaths from prescription opioids have reached epidemic proportions in the United States. The widespread use of opioids complicates management of the orthopaedic surgery patient in the acute and chronic settings. Orthopaedic surgeons are some of the top prescribers of opioids in the complex setting of chronic use, abuse, and diversion. The literature regarding the basic science of pharmacologic options for pain management (e.g., opioids and nonsteroidal anti-inflammatory drugs), the impact of strategies on bone and soft-tissue healing, and pain relief are summarized as they relate to the management of orthopaedic injuries and conditions. Additionally, a section on designing solutions to address the current opioid crisis is presented. The mechanism of action of different classes of analgesic medications is discussed, as well as the basic scientific evidence regarding the impact of narcotic and nonnarcotic analgesic medications on bone-healing and on other organ systems. Differences between pain and nociception, various treatment strategies, and clinical comparisons of the effectiveness of various analgesics compared with opioids are summarized. Finally, options for addressing the opioid crisis, including the description of a large system-wide intervention to impact prescriber behavior at the point of care using health-information solutions, are presented. Orthopaedic leaders, armed with information and strategies, can help lead the way to solutions to the opioid epidemic in their respective communities, institutions, and subspecialty societies. Through leadership and education, orthopaedic surgeons can help shape the solution for this critical public health issue.

DEMONSTRATION BULLETIN: BESCORP SOIL WASHING SYSTEM ALASKAN BATTERY ENTERPRISES SITE - BRICE ENVIRONMENTAL SERVICES CORPORATION

EPA Science Inventory

The BESCORP Soil Washing System is an aqueous volume reduction system that utilizes trommel agitation, high-pressure washing, sizing, and density separation to remove lead, lead compounds, and battery casing chips from soil contaminated by broken lead batteries. The basic concept...

A high arctic experience of uniting research and monitoring

NASA Astrophysics Data System (ADS)

Schmidt, Niels Martin; Christensen, Torben R.; Roslin, Tomas

2017-07-01

Monitoring is science keeping our thumb on the pulse of the environment to detect any changes of concern for societies. Basic science is the question-driven search for fundamental processes and mechanisms. Given the firm root of monitoring in human interests and needs, basic sciences have often been regarded as scientifically "purer"—particularly within university-based research communities. We argue that the dichotomy between "research" and "monitoring" is an artificial one, and that this artificial split clouds the definition of scientific goals and leads to suboptimal use of resources. We claim that the synergy between the two scientific approaches is well distilled by science conducted under extreme logistic constraints, when scientists are forced to take full advantage of both the data and the infrastructure available. In evidence of this view, we present our experiences from two decades of uniting research and monitoring at the remote research facility Zackenberg in High Arctic Greenland. For this site, we show how the combination of insights from monitoring with the mechanistic understanding obtained from basic research has yielded the most complete understanding of the system—to the benefit of all, and as an example to follow. We therefore urge scientists from across the continuum from monitoring to research to come together, to disregard old division lines, and to work together to expose a comprehensive picture of ecosystem change and its consequences.

The United Nations Basic Space Science Initiative

NASA Astrophysics Data System (ADS)

Haubold, H. J.

Pursuant to recommendations of the United Nations Conference on the Exploration and Peaceful Uses of Outer Space UNISPACE III and deliberations of the United Nations Committee on the Peaceful Uses of Outer Space UNCOPUOS annual UN European Space Agency workshops on basic space science have been held around the world since 1991 These workshops contribute to the development of astrophysics and space science particularly in developing nations Following a process of prioritization the workshops identified the following elements as particularly important for international cooperation in the field i operation of astronomical telescope facilities implementing TRIPOD ii virtual observatories iii astrophysical data systems iv concurrent design capabilities for the development of international space missions and v theoretical astrophysics such as applications of nonextensive statistical mechanics Beginning in 2005 the workshops focus on preparations for the International Heliophysical Year 2007 IHY2007 The workshops continue to facilitate the establishment of astronomical telescope facilities as pursued by Japan and the development of low-cost ground-based world-wide instrument arrays as lead by the IHY secretariat Further information Wamsteker W Albrecht R and Haubold H J Developing Basic Space Science World-Wide A Decade of UN ESA Workshops Kluwer Academic Publishers Dordrecht 2004 http ihy2007 org http www oosa unvienna org SAP bss ihy2007 index html http www cbpf br GrupPesq StatisticalPhys biblio htm

Compliant leg behaviour explains basic dynamics of walking and running

PubMed Central

Geyer, Hartmut; Seyfarth, Andre; Blickhan, Reinhard

2006-01-01

The basic mechanics of human locomotion are associated with vaulting over stiff legs in walking and rebounding on compliant legs in running. However, while rebounding legs well explain the stance dynamics of running, stiff legs cannot reproduce that of walking. With a simple bipedal spring–mass model, we show that not stiff but compliant legs are essential to obtain the basic walking mechanics; incorporating the double support as an essential part of the walking motion, the model reproduces the characteristic stance dynamics that result in the observed small vertical oscillation of the body and the observed out-of-phase changes in forward kinetic and gravitational potential energies. Exploring the parameter space of this model, we further show that it not only combines the basic dynamics of walking and running in one mechanical system, but also reveals these gaits to be just two out of the many solutions to legged locomotion offered by compliant leg behaviour and accessed by energy or speed. PMID:17015312

The relationship between selected VDR, HFE and ALAD gene polymorphisms and several basic toxicological parameters among persons occupationally exposed to lead.

PubMed

Szymańska-Chabowska, Anna; Łaczmański, Łukasz; Jędrychowska, Iwona; Chabowski, Mariusz; Gać, Paweł; Janus, Agnieszka; Gosławska, Katarzyna; Smyk, Beata; Solska, Urszula; Mazur, Grzegorz; Poręba, Rafał

2015-08-06

The aim of this study was to find a relationship between polymorphisms of ALAD rs1805313, rs222808, rs1139488, VDR FokI and HFE C282Y and H63D and basic toxicological parameters (lead and ZnPP blood concentration) in people occupationally exposed to lead. We collected data of 101 workers (age 25-63 years) directly exposed to lead. The toxicological lab tests included blood lead, cadmium and ZnPP concentration measurement and arsenic urine concentration measurement. Workers were genotyped for ALAD (rs1805313, rs222808, rs1139488), HFE (C282Y, H63D) and VDR (FokI). Individuals with the lead exposure and coexisting F allel in the locus Fok-I of VDR gene are suspected of higher zinc protoporphyrins concentrations. Workers exposed to the lead with the Y allel in the locus C282Y of the HFE gene are predisposed to lower ZnPP levels and individuals with coexisting H allel in the locus H63D HFE gene are predisposed to lower Pb-B levels. The T allel in the locus rs1805313 of the ALAD gene determines lower Pb-B and ZnPP levels in lead-exposed individuals. The heterozigosity of the locus rs2228083 of the ALAD gene has a strong predilection to higher Pb-B levels. The carriage of the C allel in the locus rs1139488 of the ALAD gene might determine higher Pb-B levels and the heterozigosity of the locus rs1139488 of the ALAD gene might result in higher ZnPP levels. The study revealed relationship between VDR, HFE and ALAD genes polymorphism and basic toxicological parameters in occupationally exposed workers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

On the Acquisition of Some Basic Word Spelling Mechanisms in a Deep (French) and a Shallow (Spanish) System

ERIC Educational Resources Information Center

Carrillo, Maria Soledad; Alegria, Jesus; Marin, Javier

2013-01-01

An experiment was carried out to compare the time course of the acquisition of two basic spelling mechanisms in Spanish, a shallow system, and French, a deep system. The first was lexical. It relies on the orthographic lexicon, a hypothetical structure containing the orthographic representations of words accessible for word spelling. To evaluate…

Understanding and Observing Subglacial Friction Using Seismology

NASA Astrophysics Data System (ADS)

Tsai, V. C.

2017-12-01

Glaciology began with a focus on understanding basic mechanical processes and producing physical models that could explain the principal observations. Recently, however, more attention has been paid to the wealth of recent observations, with many modeling efforts relying on data assimilation and empirical scalings, rather than being based on first-principles physics. Notably, ice sheet models commonly assume that subglacial friction is characterized by a "slipperiness" coefficient that is determined by inverting surface velocity observations. Predictions are usually then made by assuming these slipperiness coefficients are spatially and temporally fixed. However, this is only valid if slipperiness is an unchanging material property of the bed and, despite decades of work on subglacial friction, it has remained unclear how to best account for such subglacial physics in ice sheet models. Here, we describe how basic seismological concepts and observations can be used to improve our understanding and determination of subglacial friction. First, we discuss how standard models of granular friction can and should be used in basal friction laws for marine ice sheets, where very low effective pressures exist. We show that under realistic West Antarctic Ice Sheet conditions, standard Coulomb friction should apply in a relatively narrow zone near the grounding line and that this should transition abruptly as one moves inland to a different, perhaps Weertman-style, dependence of subglacial stress on velocity. We show that this subglacial friction law predicts significantly different ice sheet behavior even as compared with other friction laws that include effective pressure. Secondly, we explain how seismological observations of water flow noise and basal icequakes constrain subglacial physics in important ways. Seismically observed water flow noise can provide constraints on water pressures and channel sizes and geometry, leading to important data on subglacial friction. Basal icequake mechanisms also provide unique constraints on subglacial stress state as well as variations in water pressures. Together, the use of standard seismological concepts and new observations thus promises to provide new constraints on subglacial mechanics and focus attention back on the basic physical processes involved.

Amended Ballistic Sand Studies to Provide Low Maintenance Lead Containment at Active Small Arms Firing Range Systems

DTIC Science & Technology

2007-09-01

Pb2+. Under alkaline conditions, elemental lead will oxidize under most circumstances to form a lead hydroxide complex Pb(OH)53-. Lead that exists...lead hydroxide [Pb(OH)2], lead carbonate [PbCO3, cerrusite], or basic lead carbonate [Pb3(OH)2 (CO3)2, hydrocerrusite]. The overall lead solubility...in a natural system is fundamentally determined by the concentrations of the anions in solution (e.g., the hydroxide and carbonate ions) and by the

29 CFR 5.24 - The basic hourly rate of pay.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 1 2012-07-01 2012-07-01 false The basic hourly rate of pay. 5.24 Section 5.24 Labor... Provisions of the Davis-Bacon Act § 5.24 The basic hourly rate of pay. “The basic hourly rate of pay” is that part of a laborer's or mechanic's wages which the Secretary of Labor would have found and included in...

29 CFR 5.24 - The basic hourly rate of pay.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true The basic hourly rate of pay. 5.24 Section 5.24 Labor Office... Provisions of the Davis-Bacon Act § 5.24 The basic hourly rate of pay. “The basic hourly rate of pay” is that part of a laborer's or mechanic's wages which the Secretary of Labor would have found and included in...

29 CFR 5.24 - The basic hourly rate of pay.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 1 2011-07-01 2011-07-01 false The basic hourly rate of pay. 5.24 Section 5.24 Labor... Provisions of the Davis-Bacon Act § 5.24 The basic hourly rate of pay. “The basic hourly rate of pay” is that part of a laborer's or mechanic's wages which the Secretary of Labor would have found and included in...

29 CFR 5.24 - The basic hourly rate of pay.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 1 2014-07-01 2013-07-01 true The basic hourly rate of pay. 5.24 Section 5.24 Labor Office... Provisions of the Davis-Bacon Act § 5.24 The basic hourly rate of pay. “The basic hourly rate of pay” is that part of a laborer's or mechanic's wages which the Secretary of Labor would have found and included in...

29 CFR 5.24 - The basic hourly rate of pay.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 1 2013-07-01 2013-07-01 false The basic hourly rate of pay. 5.24 Section 5.24 Labor... Provisions of the Davis-Bacon Act § 5.24 The basic hourly rate of pay. “The basic hourly rate of pay” is that part of a laborer's or mechanic's wages which the Secretary of Labor would have found and included in...

Development of a Mechanism and Standards for the Assessment of Adult Basic Education Students as They Relate to Post-Secondary Vocational Education Programs. Final Report.

ERIC Educational Resources Information Center

Grosskoph, Arlys; And Others

The purpose of this project was to develop a process that would reduce the attrition rate of adult basic education students entering occupational programs. To accomplish this goal, adult basic education students in occupational programs, adult basic education students who had dropped out of occupational programs, and their instructors were…

A whole-process progressive training mode to foster optoelectronic students' innovative practical ability

NASA Astrophysics Data System (ADS)

Zhong, Hairong; Xu, Wei; Hu, Haojun; Duan, Chengfang

2017-08-01

This article analyzes the features of fostering optoelectronic students' innovative practical ability based on the knowledge structure of optoelectronic disciplines, which not only reveals the common law of cultivating students' innovative practical ability, but also considers the characteristics of the major: (1) The basic theory is difficult, and the close combination of science and technology is obvious; (2)With the integration of optics, mechanics, electronics and computer, the system technology is comprehensive; (3) It has both leading-edge theory and practical applications, so the benefit of cultivating optoelectronic students is high ; (4) The equipment is precise and the practice is costly. Considering the concept and structural characteristics of innovative and practical ability, and adhering to the idea of running practice through the whole process, we put forward the construction of three-dimensional innovation and practice platform which consists of "Synthetically Teaching Laboratory + Innovation Practice Base + Scientific Research Laboratory + Major Practice Base + Joint Teaching and Training Base", and meanwhile build a whole-process progressive training mode to foster optoelectronic students' innovative practical ability, following the process of "basic experimental skills training - professional experimental skills training - system design - innovative practice - scientific research project training - expanded training - graduation project": (1) To create an in - class practical ability cultivation environment that has distinctive characteristics of the major, with the teaching laboratory as the basic platform; (2) To create an extra-curricular innovation practice activities cultivation environment that is closely linked to the practical application, with the innovation practice base as a platform for improvement; (3) To create an innovation practice training cultivation environment that leads the development of cutting-edge, with the scientific research laboratory as a platform to explore; (4) To create an out-campus expanded training environment of optoelectronic major practice and optoelectronic system teaching and training, with the major practice base as an expansion of the platform; (5) To break students' "pre-job training barriers" between school and work, with graduation design as the comprehensive training and testing link.

Opting out against defection leads to stable coexistence with cooperation.

PubMed

Zhang, Bo-Yu; Fan, Song-Jia; Li, Cong; Zheng, Xiu-Deng; Bao, Jian-Zhang; Cressman, Ross; Tao, Yi

2016-10-24

Cooperation coexisting with defection is a common phenomenon in nature and human society. Previous studies for promoting cooperation based on kin selection, direct and indirect reciprocity, graph selection and group selection have provided conditions that cooperators outcompete defectors. However, a simple mechanism of the long-term stable coexistence of cooperation and defection is still lacking. To reveal the effect of direct reciprocity on the coexistence of cooperation and defection, we conducted a simple experiment based on the Prisoner's Dilemma (PD) game, where the basic idea behind our experiment is that all players in a PD game should prefer a cooperator as an opponent. Our experimental and theoretical results show clearly that the strategies allowing opting out against defection are able to maintain this stable coexistence.

Impulse-induced localized control of chaos in starlike networks.

PubMed

Chacón, Ricardo; Palmero, Faustino; Cuevas-Maraver, Jesús

2016-06-01

Locally decreasing the impulse transmitted by periodic pulses is shown to be a reliable method of taming chaos in starlike networks of dissipative nonlinear oscillators, leading to both synchronous periodic states and equilibria (oscillation death). Specifically, the paradigmatic model of damped kicked rotators is studied in which it is assumed that when the rotators are driven synchronously, i.e., all driving pulses transmit the same impulse, the networks display chaotic dynamics. It is found that the taming effect of decreasing the impulse transmitted by the pulses acting on particular nodes strongly depends on their number and degree of connectivity. A theoretical analysis is given explaining the basic physical mechanism as well as the main features of the chaos-control scenario.

Avalanches and plastic flow in crystal plasticity: an overview

NASA Astrophysics Data System (ADS)

Papanikolaou, Stefanos; Cui, Yinan; Ghoniem, Nasr

2018-01-01

Crystal plasticity is mediated through dislocations, which form knotted configurations in a complex energy landscape. Once they disentangle and move, they may also be impeded by permanent obstacles with finite energy barriers or frustrating long-range interactions. The outcome of such complexity is the emergence of dislocation avalanches as the basic mechanism of plastic flow in solids at the nanoscale. While the deformation behavior of bulk materials appears smooth, a predictive model should clearly be based upon the character of these dislocation avalanches and their associated strain bursts. We provide here a comprehensive overview of experimental observations, theoretical models and computational approaches that have been developed to unravel the multiple aspects of dislocation avalanche physics and the phenomena leading to strain bursts in crystal plasticity.

Do Active Learning Approaches in Recitation Sections Improve Student Performance? A Case Study from an Introductory Mechanics Course

NASA Astrophysics Data System (ADS)

Tobin, R. G.

2018-01-01

Abundant research leaves little question that pedagogical approaches involving active student engagement with the material, and opportunities for student-to-student discussions, lead to much better learning outcomes than traditional instructor-led, expository instructional formats, in physics and in many other fields. In introductory college physics classes, some departments have departed radically from conventional lecture-recitation-laboratory course structures, but many, including my own, retain the basic format of large-group classroom sessions (lectures) supplemented by smaller-group meetings focused on problem solving (recitations) and separate laboratory meetings. Active student engagement in the lectures is encouraged through approaches such as Peer Instruction and Interactive Lecture Demonstrations, and these approaches have been demonstrably successful.

Summer Arctic sea ice character from satellite microwave data

NASA Technical Reports Server (NTRS)

Carsey, F. D.

1985-01-01

It is pointed out that Arctic sea ice and its environment undergo a number of changes during the summer period. Some of these changes affect the ice cover properties and, in turn, their response to thermal and mechanical forcing throughout the year. The main objective of this investigation is related to the development of a method for estimating the areal coverage of exposed ice, melt ponds, and leads, which are the basic surface variables determining the local surface albedo. The study is based on data obtained in a field investigation conducted from Mould Bay (NWT), Nimbus 5 satellite data, and Seasat data. The investigation demonstrates that microwave data from satellites, especially microwave brightness temperature, provide good data for estimating important characteristics of summer sea ice cover.

The Prevention of Noise Induced Hearing Loss in Children

PubMed Central

Harrison, Robert V.

2012-01-01

Increasingly, our acoustic environment is filled with amplified sound sources (e.g., MP3 players, video game stations, and sports/entertainment venues). There is serious concern and also some controversy about the risks of acoustic trauma in children. This overview provides some basic information on the physiological mechanisms that lead to noise induced hearing loss, a survey of various studies that, on balance, indicates that there is cause for concern, and finally a discussion on measures that can help to prevent noise induced hearing loss in children. This paper is designed for public health and other healthcare professions (ENT, audiologists, family doctors, and pediatricians) who should understand the risks of noise induced hearing loss and its prevention. PMID:23304173

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

PubMed Central

Koyama, Ryuta; Ikegaya, Yuji

2018-01-01

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. PMID:29896153

Seed dormancy and germination—emerging mechanisms and new hypotheses

PubMed Central

Nonogaki, Hiroyuki

2014-01-01

Seed dormancy has played a significant role in adaptation and evolution of seed plants. While its biological significance is clear, molecular mechanisms underlying seed dormancy induction, maintenance and alleviation still remain elusive. Intensive efforts have been made to investigate gibberellin and abscisic acid metabolism in seeds, which greatly contributed to the current understanding of seed dormancy mechanisms. Other mechanisms, which might be independent of hormones, or specific to the seed dormancy pathway, are also emerging from genetic analysis of “seed dormancy mutants.” These studies suggest that chromatin remodeling through histone ubiquitination, methylation and acetylation, which could lead to transcription elongation or gene silencing, may play a significant role in seed dormancy regulation. Small interfering RNA and/or long non-coding RNA might be a trigger of epigenetic changes at the seed dormancy or germination loci, such as DELAY OF GERMINATION1. While new mechanisms are emerging from genetic studies of seed dormancy, novel hypotheses are also generated from seed germination studies with high throughput gene expression analysis. Recent studies on tissue-specific gene expression in tomato and Arabidopsis seeds, which suggested possible “mechanosensing” in the regulatory mechanisms, advanced our understanding of embryo-endosperm interaction and have potential to re-draw the traditional hypotheses or integrate them into a comprehensive scheme. The progress in basic seed science will enable knowledge translation, another frontier of research to be expanded for food and fuel production. PMID:24904627

The phenoptosis problem: what is causing the death of an organism? Lessons from acute kidney injury.

PubMed

Zorov, D B; Plotnikov, E Y; Jankauskas, S S; Isaev, N K; Silachev, D N; Zorova, L D; Pevzner, I B; Pulkova, N V; Zorov, S D; Morosanova, M A

2012-07-01

Programmed execution of various cells and intracellular structures is hypothesized to be not the only example of elimination of biological systems - the general mechanism can also involve programmed execution of organs and organisms. Modern rating of programmed cell death mechanisms includes 13 mechanistic types. As for some types, the mechanism of actuation and manifestation of cell execution has been basically elucidated, while the causes and intermediate steps of the process of fatal failure of organs and organisms remain unknown. The analysis of deaths resulting from a sudden heart arrest or multiple organ failure and other acute and chronic pathologies leads to the conclusion of a special role of mitochondria and oxidative stress activating the immune system. Possible mechanisms of mitochondria-mediated induction of the signaling cascades involved in organ failure and death of the organism are discussed. These mechanisms include generation of reactive oxygen species and damage-associated molecular patterns in mitochondria. Some examples of renal failure-induced deaths are presented with mechanisms and settings determined by some hypothetical super system rather than by the kidneys themselves. This system plays the key role in the process of physiological senescence and termination of an organism. The facts presented suggest that it is the immune system involved in mitochondrial signaling that can act as the system responsible for the organism's death.

Palatal Seam Disintegration: To Die or Not to Die? That Is No Longer the Question

PubMed Central

Nawshad, Ali

2008-01-01

Formation of the medial epithelial seam (MES) by palatal shelf fusion is a crucial step of palate development. Complete disintegration of the MES is the final essential phase of palatal confluency with surrounding mesenchymal cells. In general, the mechanisms of palatal seam disintegration are not overwhelmingly complex, but given the large number of interacting constituents; their complicated circuitry involving feedforward, feedback, and crosstalk; and the fact that the kinetics of interaction matter, this otherwise simple mechanism can be quite difficult to interpret. As a result of this complexity, apparently simple but highly important questions remain unanswered. One such question pertains to the fate of the palatal seam. Such questions may be answered by detailed and extensive quantitative experimentation of basic biological studies (cellular, structural) and the newest molecular biological determinants (genetic/dye cell lineage, gene activity, kinase/enzyme activity), as well as animal model (knockouts, transgenic) approaches. System biology and cellular kinetics play a crucial role in cellular MES function; omissions of such critical contributors may lead to inaccurate understanding of the fate of MES. Excellent progress has been made relevant to elucidation of the mechanism(s) of palatal seam disintegration. Current understanding of palatal seam disintegration suggests epithelial–mesenchymal transition and/or programmed cell death as two most common mechanisms of MES disintegration. In this review, I discuss those two mechanisms and the differences between them. PMID:18629865

Mechanisms of material removal and mass transport in focused ion beam nanopore formation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Das, Kallol, E-mail: das7@illinois.edu; Johnson, Harley T., E-mail: htj@illinois.edu; Freund, Jonathan B., E-mail: jbfreund@illinois.edu

2015-02-28

Despite the widespread use of focused ion beam (FIB) processing as a material removal method for applications ranging from electron microscope sample preparation to nanopore processing for DNA sequencing, the basic material removal mechanisms of FIB processing are not well understood. We present the first complete atomistic simulation of high-flux FIB using large-scale parallel molecular dynamics (MD) simulations of nanopore fabrication in freestanding thin films. We focus on the root mechanisms of material removal and rearrangement and describe the role of explosive boiling in forming nanopores. FIB nanopore fabrication is typically understood to occur via sputter erosion. This can bemore » shown to be the case in low flux systems, where individual ion impacts are sufficiently separated in time that they may be considered as independent events. But our detailed MD simulations show that in high flux FIB processing, above a threshold level at which thermal effects become significant, the primary mechanism of material removal changes to a significantly accelerated, thermally dominated process. Under these conditions, the target is heated by the ion beam faster than heat is conducted away by the material, leading quickly to melting, and then continued heating to nearly the material critical temperature. This leads to explosive boiling of the target material with spontaneous bubble formation and coalescence. Mass is rapidly rearranged at the atomistic scale, and material removal occurs orders of magnitude faster than would occur by simple sputtering. While the phenomenology is demonstrated computationally in silicon, it can be expected to occur at lower beam fluxes in other cases where thermal conduction is suppressed due to material properties, geometry, or ambient thermal conditions.« less

The Role of Deep Creep in the Timing of Large Earthquakes

NASA Astrophysics Data System (ADS)

Sammis, C. G.; Smith, S. W.

2012-12-01

The observed temporal clustering of the world's largest earthquakes has been largely discounted for two reasons: a) it is consistent with Poisson clustering, and b) no physical mechanism leading to such clustering has been proposed. This lack of a mechanism arises primarily because the static stress transfer mechanism, commonly used to explain aftershocks and the clustering of large events on localized fault networks, does not work at global distances. However, there is recent observational evidence that the surface waves from large earthquakes trigger non-volcanic tremor at the base of distant fault zones at global distances. Based on these observations, we develop a simple non-linear coupled oscillator model that shows how the triggering of such tremor can lead to the synchronization of large earthquakes on a global scale. A basic assumption of the model is that induced tremor is a proxy for deep creep that advances the seismic cycle of the fault. We support this hypothesis by demonstrating that the 2010 Maule Chile and the 2011 Fukushima Japan earthquakes, which have been shown to induce tremor on the Parkfield segment of the San Andreas Fault, also produce changes in off-fault seismicity that are spatially and temporally consistent with episodes of deep creep on the fault. The observed spatial pattern can be simulated using an Okada dislocation model for deep creep (below 20 km) on the fault plane in which the slip rate decreases from North to South consistent with surface creep measurements and deepens south of the "Parkfield asperity" as indicated by recent tremor locations. The model predicts the off-fault events should have reverse mechanism consistent with observed topography.

Osteoarthritis year in review 2014: mechanics--basic and clinical studies in osteoarthritis.

PubMed

Moyer, R F; Ratneswaran, A; Beier, F; Birmingham, T B

2014-12-01

The purpose of this review was to highlight recent research in mechanics and osteoarthritis (OA) by summarizing results from selected studies spanning basic and clinical research methods. Databases were searched from January 2013 through to March 2014. Working in pairs, reviewers selected 67 studies categorized into four themes--mechanobiology, ambulatory mechanics, biomechanical interventions and mechanical risk factors. Novel developments in mechanobiology included the identification of cell signaling pathways that mediated cellular responses to loading of articular cartilage. Studies in ambulatory mechanics included an increased focus on instrumented knee implants and progress in computational models, both emphasizing the importance of muscular contributions to load. Several proposed biomechanical interventions (e.g., shoe insoles and knee braces) produced variable changes in external knee joint moments during walking, while meta-analysis of randomized clinical trials did not support the use of lateral wedge insoles for decreasing pain. Results from high quality randomized trials suggested diet with or without exercise decreased indicators of knee joint load during walking, whereas similar effects from exercise alone were not detected with the measures used. Data from longitudinal cohorts suggested mechanical alignment was a risk factor for incidence and progression of OA, with the mechanism involving damage to the meniscus. In combination, the basic and clinical studies highlight the importance of considering multiple contributors to joint loading that can evoke both protective and damaging responses. Although challenges clearly exist, future studies should strive to integrate basic and clinical research methods to gain a greater understanding of the interactions among mechanical factors in OA and to develop improved preventive and therapeutic strategies. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Basic Mechanics of DNA Methylation and the Unique Landscape of the DNA Methylome in Metal-Induced Carcinogenesis

PubMed Central

Brocato, Jason; Costa, Max

2013-01-01

DNA methylation plays an intricate role in the regulation of gene expression and events that compromise the integrity of the methylome may potentially contribute to disease development. DNA methylation is a reversible and regulatory modification that elicits a cascade of events leading to chromatin condensation and gene silencing. In general, normal cells are characterized by gene-specific hypomethylation and global hypermethylation, while cancer cells portray a reverse profile to this norm. The unique methylome displayed in cancer cells is induced after exposure to carcinogenic metals such as nickel, arsenic, cadmium, and chromium (VI). These metals alter the DNA methylation profile by provoking both hyper- and hypomethylation events. The metal-stimulated deviations to the methylome are possible mechanisms for metal-induced carcinogenesis and may provide potential biomarkers for cancer detection. Development of therapies based on the cancer methylome requires further research including human studies that supply results with larger impact and higher human relevance. PMID:23844698

How synthetic membrane systems contribute to the understanding of lipid-driven endocytosis.

PubMed

Schubert, Thomas; Römer, Winfried

2015-11-01

Synthetic membrane systems, such as giant unilamellar vesicles and solid supported lipid bilayers, have widened our understanding of biological processes occurring at or through membranes. Artificial systems are particularly suited to study the inherent properties of membranes with regard to their components and characteristics. This review critically reflects the emerging molecular mechanism of lipid-driven endocytosis and the impact of model membrane systems in elucidating the complex interplay of biomolecules within this process. Lipid receptor clustering induced by binding of several toxins, viruses and bacteria to the plasma membrane leads to local membrane bending and formation of tubular membrane invaginations. Here, lipid shape, and protein structure and valency are the essential parameters in membrane deformation. Combining observations of complex cellular processes and their reconstitution on minimal systems seems to be a promising future approach to resolve basic underlying mechanisms. This article is part of a Special Issue entitled: Mechanobiology. Copyright © 2015 Elsevier B.V. All rights reserved.

Basic mechanics of DNA methylation and the unique landscape of the DNA methylome in metal-induced carcinogenesis.

PubMed

Brocato, Jason; Costa, Max

2013-07-01

DNA methylation plays an intricate role in the regulation of gene expression and events that compromise the integrity of the methylome may potentially contribute to disease development. DNA methylation is a reversible and regulatory modification that elicits a cascade of events leading to chromatin condensation and gene silencing. In general, normal cells are characterized by gene-specific hypomethylation and global hypermethylation, while cancer cells portray a reverse profile to this norm. The unique methylome displayed in cancer cells is induced after exposure to carcinogenic metals such as nickel, arsenic, cadmium, and chromium (VI). These metals alter the DNA methylation profile by provoking both hyper- and hypo-methylation events. The metal-stimulated deviations to the methylome are possible mechanisms for metal-induced carcinogenesis and may provide potential biomarkers for cancer detection. Development of therapies based on the cancer methylome requires further research including human studies that supply results with larger impact and higher human relevance.

Aging and Adipose Tissue: Potential Interventions for Diabetes and Regenerative Medicine

PubMed Central

Palmer, Allyson K.; Kirkland, James L.

2016-01-01

Adipose tissue dysfunction occurs with aging and has systemic effects, including peripheral insulin resistance, ectopic lipid deposition, and inflammation. Fundamental aging mechanisms, including cellular senescence and progenitor cell dysfunction, occur in adipose tissue with aging and may serve as potential therapeutic targets in age-related disease. In this review, we examine the role of adipose tissue in healthy individuals and explore how aging leads to adipose tissue dysfunction, redistribution, and changes in gene regulation. Adipose tissue plays a central role in longevity, and interventions restricted to adipose tissue may impact lifespan. Conversely, obesity may represent a state of accelerated aging. We discuss the potential therapeutic potential of targeting basic aging mechanisms, including cellular senescence, in adipose tissue, using type II diabetes and regenerative medicine as examples. We make the case that aging should not be neglected in the study of adipose-derived stem cells for regenerative medicine strategies, as elderly patients make up a large portion of individuals in need of such therapies. PMID:26924669

Cognitive neuroscience of cognitive retraining for addiction medicine: From mediating mechanisms to questions of efficacy.

PubMed

Gladwin, Thomas E; Wiers, Corinde E; Wiers, Reinout W

2016-01-01

Cognitive retraining or cognitive bias modification (CBM) involves having subjects repeatedly perform a computerized task designed to reduce the impact of automatic processes that lead to harmful behavior. We first discuss the theory underlying CBM and provide a brief overview of important research progress in its application to addiction. We then focus on cognitive- and neural-mediating mechanisms. We consider recent criticism of both CBM and its theoretical foundations. Evaluations of CBM could benefit from considering theory-driven factors that may determine variations in efficacy, such as motivation. Concerning theory, while there is certainly room for fundamental advances in current models, we argue that the basic view of impulsive behavior and its control remains a useful and productive heuristic. Finally, we briefly discuss some interesting new directions for CBM research: enhancement of training via transcranial direct current stimulation, online training, and gamification, i.e., the use of gameplay elements to increase motivation. © 2016 Elsevier B.V. All rights reserved.

Oscillatory mechanisms of process binding in memory.

PubMed

Klimesch, Wolfgang; Freunberger, Roman; Sauseng, Paul

2010-06-01

A central topic in cognitive neuroscience is the question, which processes underlie large scale communication within and between different neural networks. The basic assumption is that oscillatory phase synchronization plays an important role for process binding--the transient linking of different cognitive processes--which may be considered a special type of large scale communication. We investigate this question for memory processes on the basis of different types of oscillatory synchronization mechanisms. The reviewed findings suggest that theta and alpha phase coupling (and phase reorganization) reflect control processes in two large memory systems, a working memory and a complex knowledge system that comprises semantic long-term memory. It is suggested that alpha phase synchronization may be interpreted in terms of processes that coordinate top-down control (a process guided by expectancy to focus on relevant search areas) and access to memory traces (a process leading to the activation of a memory trace). An analogous interpretation is suggested for theta oscillations and the controlled access to episodic memories. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Protein-protein interaction networks (PPI) and complex diseases

PubMed Central

Safari-Alighiarloo, Nahid; Taghizadeh, Mohammad; Rezaei-Tavirani, Mostafa; Goliaei, Bahram

2014-01-01

The physical interaction of proteins which lead to compiling them into large densely connected networks is a noticeable subject to investigation. Protein interaction networks are useful because of making basic scientific abstraction and improving biological and biomedical applications. Based on principle roles of proteins in biological function, their interactions determine molecular and cellular mechanisms, which control healthy and diseased states in organisms. Therefore, such networks facilitate the understanding of pathogenic (and physiologic) mechanisms that trigger the onset and progression of diseases. Consequently, this knowledge can be translated into effective diagnostic and therapeutic strategies. Furthermore, the results of several studies have proved that the structure and dynamics of protein networks are disturbed in complex diseases such as cancer and autoimmune disorders. Based on such relationship, a novel paradigm is suggested in order to confirm that the protein interaction networks can be the target of therapy for treatment of complex multi-genic diseases rather than individual molecules with disrespect the network. PMID:25436094

Process, mechanism, and explanation related to externalizing behavior in developmental psychopathology.

PubMed

Hinshaw, Stephen P

2002-10-01

Advances in conceptualization and statistical modeling, on the one hand, and enhanced appreciation of transactional pathways, gene-environment correlations and interactions, and moderator and mediator variables, on the other, have heightened awareness of the need to consider factors and processes that explain the development and maintenance of psychopathology. With a focus on attentional problems, impulsivity, and disruptive behavior patterns, I address the kinds of conceptual approaches most likely to lead to advances regarding explanatory models in the field. Findings from my own research program on processes and mechanisms reveal both promise and limitations. Progress will emanate from use of genetically informative designs, blends of variable and person-centered research, explicit testing of developmental processes, systematic approaches to moderation and mediation, exploitation of "natural experiments," and the conduct of prevention and intervention trials designed to accentuate explanation as well as outcome. In all, breakthroughs will occur only with advances in translational research-linking basic and applied science-and with the further development of transactional, systemic approaches to explanation.

Molecular mechanism of Mg2+-dependent gating in CorA

NASA Astrophysics Data System (ADS)

Dalmas, Olivier; Sompornpisut, Pornthep; Bezanilla, Francisco; Perozo, Eduardo

2014-04-01

CorA is the major transport system responsible for Mg2+ uptake in bacteria and can functionally substitute for its homologue Mrs2p in the yeast inner mitochondrial membrane. Although several CorA crystal structures are available, the molecular mechanism of Mg2+ uptake remains to be established. Here we use electron paramagnetic resonance spectroscopy, electrophysiology and molecular dynamic simulations to show that CorA is regulated by cytoplasmic Mg2+ acting as a ligand and elucidate the basic conformational rearrangements responsible for Mg2+-dependent gating. Mg2+ unbinding at the divalent cation sensor triggers a conformational change that leads to the inward motion of the stalk helix, which propagates to the pore-forming transmembrane helix TM1. Helical tilting and rotation in TM1 generates an iris-like motion that increases the diameter of the permeation pathway, triggering ion conduction. This work establishes the molecular basis of a Mg2+-driven negative feedback loop in CorA as the key physiological event controlling Mg2+ uptake and homeostasis in prokaryotes.

The modern theory of biological evolution: an expanded synthesis.

PubMed

Kutschera, Ulrich; Niklas, Karl J

2004-06-01

In 1858, two naturalists, Charles Darwin and Alfred Russel Wallace, independently proposed natural selection as the basic mechanism responsible for the origin of new phenotypic variants and, ultimately, new species. A large body of evidence for this hypothesis was published in Darwin's Origin of Species one year later, the appearance of which provoked other leading scientists like August Weismann to adopt and amplify Darwin's perspective. Weismann's neo-Darwinian theory of evolution was further elaborated, most notably in a series of books by Theodosius Dobzhansky, Ernst Mayr, Julian Huxley and others. In this article we first summarize the history of life on Earth and provide recent evidence demonstrating that Darwin's dilemma (the apparent missing Precambrian record of life) has been resolved. Next, the historical development and structure of the "modern synthesis" is described within the context of the following topics: paleobiology and rates of evolution, mass extinctions and species selection, macroevolution and punctuated equilibrium, sexual reproduction and recombination, sexual selection and altruism, endosymbiosis and eukaryotic cell evolution, evolutionary developmental biology, phenotypic plasticity, epigenetic inheritance and molecular evolution, experimental bacterial evolution, and computer simulations (in silico evolution of digital organisms). In addition, we discuss the expansion of the modern synthesis, embracing all branches of scientific disciplines. It is concluded that the basic tenets of the synthetic theory have survived, but in modified form. These sub-theories require continued elaboration, particularly in light of molecular biology, to answer open-ended questions concerning the mechanisms of evolution in all five kingdoms of life.

Transport of aspartic acid, arginine, and tyrosine by the opportunistic protist Pneumocystis carinii.

PubMed

Basselin, M; Lipscomb, K J; Qiu, Y H; Kaneshiro, E S

2001-04-02

In order to improve culture media and to discover potential drug targets, uptake of an acidic, a basic, and an aromatic amino acid were investigated. Current culture systems, axenic or co-cultivation with mammalian cells, do not provide either the quantity or quality of cells needed for biochemical studies of this organism. Insight into nutrient acquisition can be expected to lead to improved culture media and improved culture growth. Aspartic acid uptake was directly related to substrate concentration, Q(10) was 1.10 at pH 7.4. Hence the organism acquired this acidic amino acid by simple diffusion. Uptake of the basic amino acid arginine and the aromatic amino acid tyrosine exhibited saturation kinetics consistent with carrier-mediated mechanisms. Kinetic parameters indicated two carriers (K(m)=22.8+/-2.5 microM and K(m)=3.6+/-0.3 mM) for arginine and a single carrier for tyrosine (K(m)=284+/-23 microM). The effects of other L-amino acids showed that the tyrosine carrier was distinct from the arginine carriers. Tyrosine and arginine transport were independent of sodium and potassium ions, and did not appear to require energy from ATP or a proton motive force. Thus facilitated diffusion was identified as the mechanism of uptake. After 30 min of incubation, these amino acids were incorporated into total lipids and the sedimentable material following lipid extraction; more than 90% was in the cellular soluble fraction.

The modern theory of biological evolution: an expanded synthesis

NASA Astrophysics Data System (ADS)

Kutschera, Ulrich; Niklas, Karl J.

In 1858, two naturalists, Charles Darwin and Alfred Russel Wallace, independently proposed natural selection as the basic mechanism responsible for the origin of new phenotypic variants and, ultimately, new species. A large body of evidence for this hypothesis was published in Darwin's Origin of Species one year later, the appearance of which provoked other leading scientists like August Weismann to adopt and amplify Darwin's perspective. Weismann's neo-Darwinian theory of evolution was further elaborated, most notably in a series of books by Theodosius Dobzhansky, Ernst Mayr, Julian Huxley and others. In this article we first summarize the history of life on Earth and provide recent evidence demonstrating that Darwin's dilemma (the apparent missing Precambrian record of life) has been resolved. Next, the historical development and structure of the ``modern synthesis'' is described within the context of the following topics: paleobiology and rates of evolution, mass extinctions and species selection, macroevolution and punctuated equilibrium, sexual reproduction and recombination, sexual selection and altruism, endosymbiosis and eukaryotic cell evolution, evolutionary developmental biology, phenotypic plasticity, epigenetic inheritance and molecular evolution, experimental bacterial evolution, and computer simulations (in silico evolution of digital organisms). In addition, we discuss the expansion of the modern synthesis, embracing all branches of scientific disciplines. It is concluded that the basic tenets of the synthetic theory have survived, but in modified form. These sub-theories require continued elaboration, particularly in light of molecular biology, to answer open-ended questions concerning the mechanisms of evolution in all five kingdoms of life.

Exploring cognitive integration of basic science and its effect on diagnostic reasoning in novices.

PubMed

Lisk, Kristina; Agur, Anne M R; Woods, Nicole N

2016-06-01

Integration of basic and clinical science knowledge is increasingly being recognized as important for practice in the health professions. The concept of 'cognitive integration' places emphasis on the value of basic science in providing critical connections to clinical signs and symptoms while accounting for the fact that clinicians may not spontaneously articulate their use of basic science knowledge in clinical reasoning. In this study we used a diagnostic justification test to explore the impact of integrated basic science instruction on novices' diagnostic reasoning process. Participants were allocated to an integrated basic science or clinical science training group. The integrated basic science group was taught the clinical features along with the underlying causal mechanisms of four musculoskeletal pathologies while the clinical science group was taught only the clinical features. Participants completed a diagnostic accuracy test immediately after initial learning, and one week later a diagnostic accuracy and justification test. The results showed that novices who learned the integrated causal mechanisms had superior diagnostic accuracy and better understanding of the relative importance of key clinical features. These findings further our understanding of cognitive integration by providing evidence of the specific changes in clinical reasoning when basic and clinical sciences are integrated during learning.

Recruitment and Retention of New Emergency Medical Technician (EMT)-Basics and Paramedics.

PubMed

Chapman, Susan A; Crowe, Remle P; Bentley, Melissa A

2016-12-01

The purpose of this paper is to describe factors important for the recruitment and retention of Emergency Medical Technician (EMT)-Basics and EMT-Paramedics new to the Emergency Medical Services (EMS) field (defined as two years or less of EMS employment) through an analysis of 10 years of Longitudinal EMT Attributes and Demographic Study (LEADS) data. Data were obtained from 10 years of LEADS surveys (1999-2008). Individuals new to the profession were identified through responses to a survey item. Their responses were analyzed using weights reflecting each individual's probability of selection. Means, proportions, and 95% confidence intervals (CIs) were determined and used to identify statistically significant differences. There were few changes in the demographic characteristics of new EMT-Basics and Paramedics across survey years. New EMT-Basics tended to be older and less likely to have a college degree than new EMT-Paramedics. More new EMT-Basics than EMT-Paramedics worked in rural areas and small towns and reported that they were working as a volunteer. There were differences between new EMT-Basics and EMT-Paramedics in several of the reasons for entering the profession and in facets of job satisfaction. The findings provide guidance for recruiters, educators, employers, and governmental EMS policy organizations and will provide better insight into how to attract and retain new entrants to the field. Chapman SA , Crowe RP , Bentley MA . Recruitment and retention of new Emergency Medical Technician (EMT)-Basics and Paramedics. Prehosp Disaster Med. 2016;31(Suppl. 1):s70-s86.

Lead in Drinking Water in Schools and Childcare Facilities

MedlinePlus

... Lead in Drinking Water in Schools and Childcare Facilities Basic Information 3Ts Full Toolkit Partners Related Links ... Best Management Practices For Schools and Child Care Facilities Drinking water best management practices for schools and ...

Girls' Touch Football, Physical Education: 5551.03.

ERIC Educational Resources Information Center

King, Kathy

This course outline is a guide for teaching basic understanding of fundamental skills and rules of girls' touch football in grades 7-12. The course format includes lectures, demonstrations, practice of basic skills, visual aids, lead-up games, presentation and practice of officiating techniques, tournaments, and written and skills tests. Course…

Cell biology: at the center of modern biomedicine.

PubMed

Budde, Priya Prakash; Williams, Elizabeth H; Misteli, Tom

2012-10-01

How does basic cell biology contribute to biomedicine? A new series of Features in JCB provides a cross section of compelling examples of how basic cell biology findings can lead to therapeutics. These articles highlight the fruitful, essential, and increasingly prominent bridge that exists between cell biology and the clinic.

Beyond the blank slate: routes to learning new coordination patterns depend on the intrinsic dynamics of the learner—experimental evidence and theoretical model

PubMed Central

Kostrubiec, Viviane; Zanone, Pier-Giorgio; Fuchs, Armin; Kelso, J. A. Scott

2012-01-01

Using an approach that combines experimental studies of bimanual movements to visual stimuli and theoretical modeling, the present paper develops a dynamical account of sensorimotor learning, that is, how new skills are acquired and old ones modified. A significant aspect of our approach is the focus on the individual learner as the basic unit of analysis, in particular the quantification of predispositions and capabilities that the individual learner brings to the learning environment. Such predispositions constitute the learner's behavioral repertoire, captured here theoretically as a dynamical landscape (“intrinsic dynamics”). The learning process is demonstrated to not only lead to a relatively permanent improvement of performance in the required task—the usual outcome—but also to alter the individual's entire repertoire. Changes in the dynamical landscape due to learning are shown to result from two basic mechanisms or “routes”: bifurcation and shift. Which mechanism is selected depends the initial individual repertoire before new learning begins. Both bifurcation and shift mechanisms are accommodated by a dynamical model, a relatively straightforward development of the well-established HKB model of movement coordination. Model simulations show that although environmental or task demands may be met equally well using either mechanism, the bifurcation route results in greater stabilization of the to-be-learned behavior. Thus, stability not (or not only) error is demonstrated to be the basis of selection, both of a new pattern of behavior and the path (smooth shift versus abrupt qualitative change) that learning takes. In line with these results, recent neurophysiological evidence indicates that stability is a relevant feature around which brain activity is organized while an individual performs a coordination task. Finally, we explore the consequences of the dynamical approach to learning for theories of biological change. PMID:22876227

Learning Genetics with Paper Pets

ERIC Educational Resources Information Center

Finnerty, Valerie Raunig

2006-01-01

By the end of the eighth grade, students are expected to have a basic understanding of the mechanism of basic genetic inheritance. However, these concepts can be difficult to teach. In this article, the author introduces a new learning tool that will help facilitate student learning and enthusiasm to the basic concepts of genetic inheritance. This…

Framework for Interpretation of Trypsin–antitrypsin Imbalance and Genetic Heterogeneity in Pancreatitis

PubMed Central

Lin, Kun; Gao, Feng; Chen, Qingquan; Liu, Qicai; Chen, Shu

2015-01-01

Early intracellular premature trypsinogen activation was interpreted as the key initiator of pancreatitis. When the balance in the homeostasis of trypsin and antitrypsin system is disequilibrated, elevated aggressive enzymes directly attack the pancreatic tissue, which leads to pancreatic destruction and inflammation. However, trypsin alone is not enough to cause complications in pancreatitis, which may play a crucial role in modulating signaling events in the initial phase of the disease. NFκB activation is the major inflammatory pathway involved in the occurrence and development of pancreatitis and it can be induced by intrapancreatic activation of trypsinogen. Synthesis of trypsinogen occurs in endoplasmic reticulum (ER), and ER stress is an important early acinar cell event. Components of ER stress response are known to be able to trigger cell death as well as NFκB signaling cascade. The strongest evidence supporting the trypsin-centered theory is that gene mutations, which lead to the generation of more trypsin, or reduce the activity of trypsin inhibitors or trypsin degradation, are associated with pancreatitis. Thus, trypsin–antitrypsin imbalance may be the first step leading to pancreatic autodigestion and inducing other pathways. Continued experimental studies are necessary to determine the specific relationships between trypsin–antitrypsin imbalance and genetic heterogeneity in pancreatitis. In this article, we review the latest advances that contributed to the understanding of the basic mechanisms behind the occurrence and development of pancreatitis with a focus on the interpretation of trypsin–antitrypsin imbalance and their relationships with other inflammation pathways. We additionally highlight genetic predispositions to pancreatitis and possible mechanisms associated with them. PMID:26228362

Thermal behavior of metal carboxylates—II. Lead formate

NASA Astrophysics Data System (ADS)

Baraldi, Pietro

Experimental data obtained by i.r. emission spectrometry indicate that the thermal behavior of lead formate is complex. By heating in air, after a phase transition at 115°C, decomposition takes place which may lead directly to metal and oxide or to carbonate, to a basic carbonate and finally to oxide. Under vacuum the same transformations occur at higher temperatures and lead to metal.

High performance positive electrode for a lead-acid battery

NASA Technical Reports Server (NTRS)

Kao, Wen-Hong (Inventor); Bullock, Norma K. (Inventor); Petersen, Ralph A. (Inventor)

1994-01-01

An electrode suitable for use as a lead-acid battery plate is formed of a paste composition which enhances the performance of the plate. The paste composition includes a basic lead sulfate, a persulfate and water. The paste may also include lead oxide and fibers. An electrode according to the invention is characterized by good strength in combination with high power density, porosity and surface area.

An assessment of calcite crystal growth mechanisms based on crystal size distributions

USGS Publications Warehouse

Kile, D.E.; Eberl, D.D.; Hoch, A.R.; Reddy, M.M.

2000-01-01

Calcite crystal growth experiments were undertaken to test a recently proposed model that relates crystal growth mechanisms to the shapes of crystal size distributions (CSDs). According to this approach, CSDs for minerals have three basic shapes: (1) asymptotic, which is related to a crystal growth mechanism having constant-rate nucleation accompanied by surface-controlled growth; (2) lognormal, which results from decaying-rate nucleation accompanied by surface-controlled growth; and (3) a theoretical, universal, steady-state curve attributed to Ostwald ripening. In addition, there is a fourth crystal growth mechanism that does not have a specific CSD shape, but which preserves the relative shapes of previously formed CSDs. This mechanism is attributed to supply-controlled growth. All three shapes were produced experimentally in the calcite growth experiments by modifying nucleation conditions and solution concentrations. The asymptotic CSD formed when additional reactants were added stepwise to the surface of solutions that were supersaturated with respect to calcite (initial Ω = 20, where Ω = 1 represents saturation), thereby leading to the continuous nucleation and growth of calcite crystals. Lognormal CSDs resulted when reactants were added continuously below the solution surface, via a submerged tube, to similarly supersaturated solutions (initial Ω = 22 to 41), thereby leading to a single nucleation event followed by surface-controlled growth. The Ostwald CSD resulted when concentrated reactants were rapidly mixed, leading initially to high levels of supersaturation (Ω >100), and to the formation and subsequent dissolution of very small nuclei, thereby yielding CSDs having small crystal size variances. The three CSD shapes likely were produced early in the crystallization process, in the nanometer crystal size range, and preserved during subsequent growth. Preservation of the relative shapes of the CSDs indicates that a supply-controlled growth mechanism was established and maintained during the constant-composition experiments. CSDs having shapes intermediate between lognormal and Ostwald also were generated by varying the initial levels of supersaturation (initial Ω = 28.2 to 69.2) in rapidly mixed solutions. Lognormal CSDs were observed for natural calcite crystals that are found in septarian concretions occurring in southeastern Colorado. Based on the model described above, these CSDs indicate initial growth by surface control, followed by supply-controlled growth. Thus, CSDs may be used to deduce crystal growth mechanisms from which geologic conditions early in the growth history of a mineral can be inferred. Conversely, CSD shape can be predicted during industrial crystallization by applying the appropriate conditions for a particular growth mechanism.

A reciprocal effects model of the temporal ordering of basic psychological needs and motivation.

PubMed

Martinent, Guillaume; Guillet-Descas, Emma; Moiret, Sophie

2015-04-01

Using self-determination theory as the framework, we examined the temporal ordering between satisfaction and thwarting of basic psychological needs and motivation. We accomplished this goal by using a two-wave 7-month partial least squares path modeling approach (PLS-PM) among a sample of 94 adolescent athletes (Mage = 15.96) in an intensive training setting. The PLS-PM results showed significant paths leading: (a) from T1 satisfaction of basic psychological need for competence to T2 identified regulation, (b) from T1 external regulation to T2 thwarting and satisfaction of basic psychological need for competence, and (c) from T1 amotivation to T2 satisfaction of basic psychological need for relatedness. Overall, our results suggest that the relationship between basic psychological need and motivation varied depending on the type of basic need and motivation assessed. Basic psychological need for competence predicted identified regulation over time whereas amotivation and external regulation predicted basic psychological need for relatedness or competence over time.

Mechanical failure modes of chronically implanted planar silicon-based neural probes for laminar recording

PubMed Central

Kozai, Takashi D. Y.; Catt, Kasey; Li, Xia; Gugel, Zhannetta V.; Olafsson, Valur T.; Vazquez, Alberto L.; Cui, X. Tracy

2014-01-01

Penetrating intracortical electrode arrays that record brain activity longitudinally are powerful tools for basic neuroscience research and emerging clinical applications. However, regardless of the technology used, signals recorded by these electrodes degrade over time. The failure mechanisms of these electrodes are understood to be a complex combination of the biological reactive tissue response and material failure of the device over time. While mechanical mismatch between the brain tissue and implanted neural electrodes have been studied as a source of chronic inflammation and performance degradation, the electrode failure caused by mechanical mismatch between different material properties and different structural components within a device have remained poorly characterized. Using Finite Element Model (FEM) we simulate the mechanical strain on a planar silicon electrode. The results presented here demonstrate that mechanical mismatch between iridium and silicon leads to concentrated strain along the border of the two materials. This strain is further focused on small protrusions such as the electrical traces in planar silicon electrodes. These findings are confirmed with chronic in vivo data (133–189 days) in mice by correlating a combination of single-unit electrophysiology, evoked multi-unit recordings, electrochemical impedance spectroscopy, and scanning electron microscopy from traces and electrode sites with our modeling data. Several modes of mechanical failure of chronically implanted planar silicon electrodes are found that result in degradation and/or loss of recording. These findings highlight the importance of strains and material properties of various subcomponents within an electrode array. PMID:25453935

[Separation of purines, pyrimidines, pterins and flavonoids on magnolol-bonded silica gel stationary phase by high performance liquid chromatography].

PubMed

Chen, Hong; Li, Laishen; Zhang, Yang; Zhou, Rendan

2012-10-01

A new magnolol-bonded silica gel stationary phase (MSP) was used to separate the basic drugs including four purines, eight pyrimidines, four pterins and five flavonoids as polar representative samples by high performance liquid chromatography (HPLC). To clarify the separation mechanism, a commercial ODS column was also tested under the same chromatographic conditions. The high selectivities and fast baseline separations of the above drugs were achieved by using simple mobile phases on MSP. Although there is no end-caped treatment, the peak shapes of basic drugs containing nitrogen such as purines, pyrimidines and pterins were rather symmetrical on MSP, which indicated the the magnolol as ligand with multi-sites could shield the side effect of residual silanol groups on the surface of silica gel. Although somewhat different in the separation resolution, it was found that the elution orders of some drugs were generally similar on both MSP and ODS. The hydrophobic interaction should play a significant role in the separations of the above basic drugs, which was attributed to their reversed-phase property in the nature. However, MSP could provide the additional sites for many polar solutes, which was a rational explanation for the high selectivity of MSP. For example, in the separation of purines, pyrimidines and pterins on MSP, hydrogen-bonding and dipole-dipole interactions played leading roles besides hydrophobic interaction. Some solute molecules (such as mercaptopurine, vitexicarpin) and MSP can form the strong pi-pi stacking in the separation process. All enhanced the retention and improved the separation selectivity of MSP, which facilitated the separation of the basic drugs.

Luteolin: A Flavonoid that Has Multiple Cardio-Protective Effects and Its Molecular Mechanisms

PubMed Central

Luo, Yuanyuan; Shang, Pingping; Li, Dongye

2017-01-01

Cardiovascular disease (CVD) has become the leading cause of morbidity and mortality worldwide. A well-monitored diet with a sufficient intake of fruits and vegetables has been confirmed as a primary prevention of CVD. Plant constituents such as flavonoids have been shown to confer healthy benefits. Luteolin (Lut), a kind of flavonoid, possesses anti-oxidative, anti-tumor, and anti-inflammatory properties. Recent scientific literature has reported the cardiac protective effects of Lut in vitro and in vivo. Therefore, the aim of this review is to provide an update and detailed overview with cardio-protective molecular mechanisms of Lut with a focus on multiple intrinsic and extrinsic effectors. We further explore how these mechanisms participate in ischemia/reperfusion (I/R) injury, heart failure (HF) and atherosclerosis (AS). A proper understanding of the cardiovascular protective effects and the relative mechanisms of Lut may provide the possibility of new drug design and development for CVD. With the previous studies mainly focused on basic research, we need to advance the prospects of its further clinical utilization against CVD, large prospective clinical trials of Lut are needed to observe its therapeutic effects on patients with I/R injury, HF and AS, especially on the effective therapeutic dosage, and safety of long-term administration. PMID:29056912

Ideas for the rapid development of the structural models in mechanical engineering

NASA Astrophysics Data System (ADS)

Oanta, E.; Raicu, A.; Panait, C.

2017-08-01

Conceiving computer based instruments is a long run concern of the authors. Some of the original solutions are: optimal processing of the large matrices, interfaces between the programming languages, approximation theory using spline functions, numerical programming increased accuracy based on the extended arbitrary precision libraries. For the rapid development of the models we identified the following directions: atomization, ‘librarization’, parameterization, automatization and integration. Each of these directions has some particular aspects if we approach mechanical design problems or software development. Atomization means a thorough top-down decomposition analysis which offers an insight regarding the basic features of the phenomenon. Creation of libraries of reusable mechanical parts and libraries of programs (data types, functions) save time, cost and effort when a new model must be conceived. Parameterization leads to flexible definition of the mechanical parts, the values of the parameters being changed either using a dimensioning program or in accord to other parts belonging to the same assembly. The resulting templates may be also included in libraries. Original software applications are useful for the model’s input data generation, to input the data into CAD/FEA commercial applications and for the data integration of the various types of studies included in the same project.

Mechanism of action of glucocorticoids in nasal polyposis.

PubMed

Fernandes, Atílio Maximino; Valera, Fabiana Cardoso Pereira; Anselmo-Lima, Wilma T

2008-01-01

Glucocorticoids (GC) are the drugs of choice for the clinical treatment of nasal polyposis, according to the medical literature. Its mechanism of action in the regression of clinical symptoms and polyps, however, is not fully understood. The topical and/or systemic use of glucocorticoids lead to variable expression of cytokines, chemokines and lymphokines, as well as changes in cells. It is known that GC suppresses the expression of pro-inflammatory cytokines, chemokines and adhesion molecules such as ICAM-1 and E-selectin; GC also stimulate the transcription of anti-inflammatory cytokines such as TGF-b. GC suppress pro-fibrotic cytokines related to polyp growth, such as IL-11, the basic fibroblast growth factor (b-FGF), and the vascular endotelial growth factor (VEGF). The action of GC depends fundamentally on their interaction with receptors (GR); certain subjects have a degree of resistance to its effect, which appears to be related with the presence of a b isoform of GR. GC also act variably on the genes involved in immunoglobulin production, presentation, and antigen processing. We present a review of the literature on the mechanisms of GC action in nasal polyosis. Understanding the mechanism of action of GC in nasal polyposis will aid in the development of new, more efficient, drugs.

Lead extraction by selective operation of a nanosecond-pulsed 355nm laser

NASA Astrophysics Data System (ADS)

Herzog, Amir; Bogdan, Stefan; Glikson, Michael; Ishaaya, Amiel A.; Love, Charles

2016-03-01

Lead extraction (LE) is necessary for patients who are suffering from a related infection, or in opening venous occlusions that prevent the insertion of additional lead. In severe cases of fibrous encapsulation of the lead within a vein, laser-based cardiac LE has become one of the foremost methods of removal. In cases where the laser radiation (typically at 308 nm wavelength) interacts with the vein wall rather than with the fibrotic lesion, severe injury and subsequent bleeding may occur. Selective tissue ablation was previously demonstrated by a laser operating in the UV regime; however, it requires the use of sensitizers (e.g.: tetracycline). In this study, we present a preliminary examination of efficacy and safety aspects in the use of a nanosecond-pulsed solid-state laser radiation, at 355 nm wavelength, guided in a catheter consisting of optical fibers, in LE. Specifically, we demonstrate a correlation between the tissue elasticity and the catheter advancement rate, in ex-vivo experiments. Our results indicate a selectivity property for specific parameters of the laser radiation and catheter design. The selectivity is attributed to differences in the mechanical properties of the fibrotic tissue and a normal vein wall, leading to a different photomechanical response of the tissue's extracellular matrix. Furthermore, we performed successful in-vivo animal trials, providing a basic proof of concept for using the suggested scheme in LE. Selective operation using a 355 nm laser may reduce the risk of blood vessel perforation as well as the incidence of major adverse events.

29 CFR 5.32 - Overtime payments.

Code of Federal Regulations, 2014 CFR

2014-07-01

....25 an hour to a mechanic as his basic cash wage plus 50 cents an hour as a contribution to a welfare... prevailing wage statutes. It is clear from the legislative history that in no event can the regular or basic... less than the amount determined by the Secretary of Labor as the basic hourly rate (i.e. cash rate...

29 CFR 5.32 - Overtime payments.

Code of Federal Regulations, 2013 CFR

2013-07-01

....25 an hour to a mechanic as his basic cash wage plus 50 cents an hour as a contribution to a welfare... prevailing wage statutes. It is clear from the legislative history that in no event can the regular or basic... less than the amount determined by the Secretary of Labor as the basic hourly rate (i.e. cash rate...

29 CFR 5.32 - Overtime payments.

Code of Federal Regulations, 2012 CFR

2012-07-01

....25 an hour to a mechanic as his basic cash wage plus 50 cents an hour as a contribution to a welfare... prevailing wage statutes. It is clear from the legislative history that in no event can the regular or basic... less than the amount determined by the Secretary of Labor as the basic hourly rate (i.e. cash rate...

Object Categorization: Reversals and Explanations of the Basic-Level Advantage

ERIC Educational Resources Information Center

Rogers, Timothy T.; Patterson, Karalyn

2007-01-01

People are generally faster and more accurate to name or categorize objects at the basic level (e.g., dog) relative to more general (animal) or specific (collie) levels, an effect replicated in Experiment 1 for categorization of object pictures. To some, this pattern suggests a dual-process mechanism, in which objects first activate basic-level…

Didactics and History of Mathematics: Knowledge and Self-Knowledge

ERIC Educational Resources Information Center

Fried, Michael N.

2007-01-01

The basic assumption of this paper is that mathematics and history of mathematics are both forms of knowledge and, therefore, represent different ways of knowing. This was also the basic assumption of Fried (2001) who maintained that these ways of knowing imply different conceptual and methodological commitments, which, in turn, lead to a conflict…

10 CFR 430.24 - Units to be tested.

Code of Federal Regulations, 2011 CFR

2011-01-01

... efficiency ratio or other measure of energy consumption of a basic model for which consumers would favor..., and (ii) Any represented value of the annual fuel utilization efficiency or other measure of energy... tested basic models by only the design of oven doors the use of which leads to improved efficiency and...

Motivational Factors for Participating in Basic Instruction Programs

ERIC Educational Resources Information Center

Hardin, Robin; Andrew, Damon P. S.; Koo, Gi-Yong; Bemiller, Jim

2009-01-01

Enrollment trends in Basic Instruction Programs (BIPs) have shown a gradual decrease during the past four decades. This trend is significant because of the numerous studies that have declared Americans as unfit, inactive and leading unhealthy lifestyles. College and university BIPs are a means in which adults can be introduced to healthy…

Optics education in an optometric setting

NASA Astrophysics Data System (ADS)

Lakshminarayanan, Vasudevan; Raghuram, Aparna

2003-10-01

We discuss optics education within the context of an Optometric professional program leading to a degree of Doctor of Optometry (O.D.). Basic course work in Geometric, Physical, Ophthalmic and Visual Optics will be described and we will discuss how basic optical phenomena can be made relevant to the Optometric student with different academic backgrounds.

Lead carbonate scintillator materials

DOEpatents

Derenzo, Stephen E.; Moses, William W.

1991-01-01

Improved radiation detectors containing lead carbonate or basic lead carbonate as the scintillator element are disclosed. Both of these scintillators have been found to provide a balance of good stopping power, high light yield and short decay constant that is superior to other known scintillator materials. The radiation detectors disclosed are favorably suited for use in general purpose detection and in medical uses.

Demystifying rotors and their place in clinical translation of atrial fibrillation mechanisms.

PubMed

Nattel, Stanley; Xiong, Feng; Aguilar, Martin

2017-09-01

Treatment of atrial fibrillation (AF), the most common arrhythmia in clinical practice, remains challenging. Improved understanding of underlying mechanisms is needed to improve therapy. Functional re-entry is central to AF maintenance. The first detailed, quantitative theory of functional re-entry, the 'leading circle' model, was developed 40 years ago. Subsequently, an alternative paradigm based on 'spiral waves' has evolved. Spiral-wave generators, or 'rotors', have been identified using advanced mapping methods in experimental and clinical AF. A central tool in the analysis of spiral-wave rotors is the phase transformation, allowing for easier visualization of rotors and tracking of 'phase singularity' points at the rotor tip. In contrast to leading circle theory, which is expressed in terms familiar to (and easily understood by) cardiologists, the ideas needed to understand rotors are much more theoretical and harder for clinicians to apply. In this Review, we summarize the basic notions of phase mapping and spiral-wave rotors, and the ways in which rotor sources might be involved in AF maintenance. We discuss competing observations about the role of spatially confined rotors, short-lived rotors clustered at the edge of fibrotic zones, endocardial-epicardial interactive breeder properties and transmural re-entry, as well as studies underway to resolve them. We conclude with consideration of the clinical relevance of the issues discussed and their potential implications for the management of patients with AF.

A consumer-resource approach to the density-dependent population dynamics of mutualism.

PubMed

Holland, J Nathaniel; DeAngelis, Donald L

2010-05-01

Like predation and competition, mutualism is now recognized as a consumer-resource (C-R) interaction, including, in particular, bi-directional (e.g., coral, plant-mycorrhizae) and uni-directional (e.g., ant-plant defense, plant-pollinator) C-R mutualisms. Here, we develop general theory for the density-dependent population dynamics of mutualism based on the C-R mechanism of interspecific interaction. To test the influence of C-R interactions on the dynamics and stability of bi- and uni-directional C-R mutualisms, we developed simple models that link consumer functional response of one mutualistic species with the resources supplied by another. Phase-plane analyses show that the ecological dynamics of C-R mutualisms are stable in general. Most transient behavior leads to an equilibrium of mutualistic coexistence, at which both species densities are greater than in the absence of interactions. However, due to the basic nature of C-R interactions, certain density-dependent conditions can lead to C-R dynamics characteristic of predator-prey interactions, in which one species overexploits and causes the other to go extinct. Consistent with empirical phenomena, these results suggest that the C-R interaction can provide a broad mechanism for understanding density-dependent population dynamics of mutualism. By unifying predation, competition, and mutualism under the common ecological framework of consumer-resource theory, we may also gain a better understanding of the universal features of interspecific interactions in general.

A consumer-resource approach to the density-dependent population dynamics of mutualism

USGS Publications Warehouse

Holland, J. Nathaniel; DeAngelis, Donald L.

2010-01-01

Like predation and competition, mutualism is now recognized as a consumer resource (C-R) interaction, including, in particular, bi-directional (e.g., coral, plant- mycorrhizae) and uni-directional (e.g., ant-plant defense, plant-pollinator) C-R mutualisms. Here, we develop general theory for the density-dependent population dynamics of mutualism based on the C-R mechanism of interspecific interaction. To test the influence of C-R interactions on the dynamics and stability of bi- and uni-directional C-R mutualisms, we developed simple models that link consumer functional response of one mutualistic species with the resources supplied by another. Phase-plane analyses show that the ecological dynamics of C-R mutualisms are stable in general. Most transient behavior leads to an equilibrium of mutualistic coexistence, at which both species densities are greater than in the absence of interactions. However, due to the basic nature of C-R interactions, certain density-dependent conditions can lead to C-R dynamics characteristic of predator-prey interactions, in which one species overexploits and causes the other to go extinct. Consistent with empirical phenomena, these results suggest that the C-R interaction can provide a broad mechanism for understanding density-dependent population dynamics of mutualism. By unifying predation, competition, and mutualism under the common ecological framework of consumer-resource theory, we may also gain a better understanding of the universal features of interspecific interactions in general.

Amplification of the basic reproduction number in cattle farm networks

PubMed Central

2018-01-01

The popularly known 20–80 rule or Pareto rule states that 20% of efforts leads to 80% of results. This rule has been applied to the study of infection transmission in contact networks, and specifically, contact networks between cattle farms. Woolhouse and collaborators showed that targeting interventions for disease control and prevention to the 20% of the farms that contribute the most to the basic reproduction number (Ro), could reduce it by 80%. The rule results from the number of incoming and outgoing contacts per farm being highly heterogeneous. Besides, Woolhouse and collaborators showed that this high contact heterogeneity, together with a high positive correlation between the number of incoming and outgoing animal movements per farm leads to an amplification in the Ro. Two previous studies carried out with Scottish cattle transport data found either no correlation or only a weak correlation (rho up to 0.33) when using weighted data. Using data from the contacts between Swiss cattle farms in 2015, we found that the 20–80 rule applies with respect to Ro, although the proportion of highly active farms is smaller (11%). Besides, a positive strong correlation (rho = 0.64, weighted data) between the incoming and outgoing contacts of farms exists. This means that the amplification of Ro (due to the contact heterogeneities and the existing correlation) in cattle contact networks can be much higher than known until now. Our results highlight the importance of an effective active surveillance, more so than in other countries were these amplification mechanisms are absent. PMID:29672512

The EUCLID/V1 Integrated Code for Safety Assessment of Liquid Metal Cooled Fast Reactors. Part 1: Basic Models

NASA Astrophysics Data System (ADS)

Mosunova, N. A.

2018-05-01

The article describes the basic models included in the EUCLID/V1 integrated code intended for safety analysis of liquid metal (sodium, lead, and lead-bismuth) cooled fast reactors using fuel rods with a gas gap and pellet dioxide, mixed oxide or nitride uranium-plutonium fuel under normal operation, under anticipated operational occurrences and accident conditions by carrying out interconnected thermal-hydraulic, neutronics, and thermal-mechanical calculations. Information about the Russian and foreign analogs of the EUCLID/V1 integrated code is given. Modeled objects, equation systems in differential form solved in each module of the EUCLID/V1 integrated code (the thermal-hydraulic, neutronics, fuel rod analysis module, and the burnup and decay heat calculation modules), the main calculated quantities, and also the limitations on application of the code are presented. The article also gives data on the scope of functions performed by the integrated code's thermal-hydraulic module, using which it is possible to describe both one- and twophase processes occurring in the coolant. It is shown that, owing to the availability of the fuel rod analysis module in the integrated code, it becomes possible to estimate the performance of fuel rods in different regimes of the reactor operation. It is also shown that the models implemented in the code for calculating neutron-physical processes make it possible to take into account the neutron field distribution over the fuel assembly cross section as well as other features important for the safety assessment of fast reactors.

Stabilization of sulfuric acid dimers by ammonia, methylamine, dimethylamine, and trimethylamine

NASA Astrophysics Data System (ADS)

Jen, Coty N.; McMurry, Peter H.; Hanson, David R.

2014-06-01

This study experimentally explores how ammonia (NH3), methylamine (MA), dimethylamine (DMA), and trimethylamine (TMA) affect the chemical formation mechanisms of electrically neutral clusters that contain two sulfuric acid molecules (dimers). Dimers may also contain undetectable compounds, such as water or bases, that evaporate upon ionization and sampling. Measurements were conducted using a glass flow reactor which contained a steady flow of humidified nitrogen with sulfuric acid concentrations of 107 to 109 cm-3. A known molar flow rate of a basic gas was injected into the flow reactor. The University of Minnesota Cluster Chemical Ionization Mass Spectrometer was used to measure the resulting sulfuric acid vapor and cluster concentrations. It was found that, for a given concentration of sulfuric acid vapor, the dimer concentration increases with increasing concentration of the basic gas, eventually reaching a plateau. The base concentrations at which the dimer concentrations saturate suggest NH3 < MA < TMA ≲ DMA in forming stabilized sulfuric acid dimers. Two heuristic models for cluster formation by acid-base reactions are developed to interpret the data. The models provide ranges of evaporation rate constants that are consistent with observations and leads to an analytic expression for nucleation rates that is consistent with atmospheric observations.

Causes and consequences of coagulation activation in sepsis: an evolutionary medicine perspective.

PubMed

Fiusa, Maiara Marx Luz; Carvalho-Filho, Marco Antonio; Annichino-Bizzacchi, Joyce M; De Paula, Erich V

2015-05-06

Coagulation and innate immunity have been linked together for at least 450 million years of evolution. Sepsis, one of the world's leading causes of death, is probably the condition in which this evolutionary link is more evident. However, the biological and the clinical relevance of this association have only recently gained the attention of the scientific community. During sepsis, the host response to a pathogen is invariably associated with coagulation activation. For several years, coagulation activation has been solely regarded as a mechanism of tissue damage, a concept that led to several clinical trials of anticoagulant agents for sepsis. More recently, this paradigm has been challenged by the failure of these clinical trials, and by a growing bulk of evidence supporting the concept that coagulation activation is beneficial for pathogen clearance. In this article we discuss recent basic and clinical data that point to a more balanced view of the detrimental and beneficial consequences of coagulation activation in sepsis. Reappraisal of the association between coagulation and immune activation from an evolutionary medicine perspective offers a unique opportunity to gain new insights about the pathogenesis of sepsis, paving the way to more successful approaches in both basic and clinical research in this field.

Effect of trehalose coating on basic fibroblast growth factor release from tailor-made bone implants.

PubMed

Choi, Sungjin; Lee, Jongil; Igawa, Kazuyo; Suzuki, Shigeki; Mochizuki, Manabu; Nishimura, Ryohei; Chung, Ung-il; Sasaki, Nobuo

2011-12-01

Artificial bone implants are often incorporated with osteoinductive factors to facilitate early bone regeneration. Calcium phosphate, the main component in artificial bone implants, strongly binds these factors, and in a few cases, the incorporated proteins are not released from the implant under conditions of physiological pH, thereby leading to reduction in their osteoinductivity. In this study, we coated tailor-made bone implants with trehalose to facilitate the release of basic fibroblast growth factor (bFGF). In an in vitro study, mouse osteoblastic cells were separately cultured for 48 hr in a medium with a untreated implant (T-), trehalose-coated implant (T+), bFGF-incorporated implant (FT-), and bFGF-incorporated implant with trehalose coating (FT+). In the FT+ group, cell viability was significantly higher than that in the other groups (P<0.05). Scanning electron microscopy (SEM) and X-ray diffraction (XRD) revealed that trehalose effectively covered the surface of the artificial bone implant without affecting the crystallinity or the mechanical strength of the artificial bone implant. These results suggest that coating artificial bone implants with trehalose could limit the binding of bFGF to calcium phosphate.

Structuring in Cement Systems with Introduction of Graphene Nano-Additives

NASA Astrophysics Data System (ADS)

Yanturina, R. A.; Trofimov, B. Ya; Ahmedjanov, R. M.

2017-11-01

At present, one of the most promising areas in the field of concrete research is the study of the effect of nano-additives for the production of highly effective concretes. Many authors have already obtained primary results which testify to the very effective role of nanoadditives based on carbon in modifying concrete. In this paper, the influence of a nano-additive of graphene on the phase composition and microstructure of the cement stone was studied. It has been found that, when a nano-additive of graphene is introduced, low-basic calcium hydrosilicates are mainly formed. This leads to an increase in the compressive strength of concrete. The results of the study of the microstructure of cement stone with nano-additive graphene showed that the high compressive strength of concrete modified with nano-additive graphene is explained by the cement stone dense structure. Thus, it was found that the nanoadditive of graphene contributes to the formation of a dense structure of cement stone, composed mainly of low-basic calcium hydrosilicates, and due to this, the physical and mechanical characteristics of concrete and its resistance to frost and other forms of aggression.

Biosynthesis and molecular actions of specialized 1,4-naphthoquinone natural products produced by horticultural plants

PubMed Central

Widhalm, Joshua R; Rhodes, David

2016-01-01

The 1,4-naphthoquinones (1,4-NQs) are a diverse group of natural products found in every kingdom of life. Plants, including many horticultural species, collectively synthesize hundreds of specialized 1,4-NQs with ecological roles in plant–plant (allelopathy), plant–insect and plant–microbe interactions. Numerous horticultural plants producing 1,4-NQs have also served as sources of traditional medicines for hundreds of years. As a result, horticultural species have been at the forefront of many basic studies conducted to understand the metabolism and function of specialized plant 1,4-NQs. Several 1,4-NQ natural products derived from horticultural plants have also emerged as promising scaffolds for developing new drugs. In this review, the current understanding of the core metabolic pathways leading to plant 1,4-NQs is provided with additional emphasis on downstream natural products originating from horticultural species. An overview on the biochemical mechanisms of action, both from an ecological and pharmacological perspective, of 1,4-NQs derived from horticultural plants is also provided. In addition, future directions for improving basic knowledge about plant 1,4-NQ metabolism are discussed. PMID:27688890

Important role of translational science in rare disease innovation, discovery, and drug development.

PubMed

Pariser, Anne R; Gahl, William A

2014-08-01

Rare diseases play a leading role in innovation and the advancement of medical and pharmaceutical science. Most rare diseases are genetic disorders or atypical manifestations of infectious, immunologic, or oncologic diseases; they all provide opportunities to study extremes of human pathology and provide insight into both normal and aberrant physiology. Recently, drug development has become increasingly focused on classifying diseases largely on genetic grounds; this has allowed the identification of molecularly defined targets and the development of targeted therapies. Clinical trials are now focusing on progressively smaller subgroups within both common and rare disease populations, often based on genetic tests or biomarkers. Drug developers, researchers, and regulatory agencies face a variety of challenges throughout the life cycle of drug research and development for rare diseases. These include the small numbers of patients available for study, lack of knowledge of the disease's natural history, incomplete understanding of the basic mechanisms causing the disorder, and variability in disease severity, expression, and course. Traditional approaches to rare disease clinical research have not kept pace with advances in basic science, and increased attention to translational science is needed to address these challenges, especially diagnostic testing, registries, and novel trial designs.

The bead on a rotating hoop revisited: an unexpected resonance

NASA Astrophysics Data System (ADS)

Raviola, Lisandro A.; Véliz, Maximiliano E.; Salomone, Horacio D.; Olivieri, Néstor A.; Rodríguez, Eduardo E.

2017-01-01

The bead on a rotating hoop is a typical problem in mechanics, frequently posed to junior science and engineering students in basic physics courses. Although this system has a rich dynamics, it is usually not analysed beyond the point particle approximation in undergraduate textbooks, nor empirically investigated. Advanced textbooks show the existence of bifurcations owing to the system's nonlinear nature, and some papers demonstrate, from a theoretical standpoint, its points of contact with phase transition phenomena. However, scarce experimental research has been conducted to better understand its behaviour. We show in this paper that a minor modification to the problem leads to appealing consequences that can be studied both theoretically and empirically with the basic conceptual tools and experimental skills available to junior students. In particular, we go beyond the point particle approximation by treating the bead as a rigid spherical body, and explore the effect of a slightly non-vertical hoop's rotation axis that gives rise to a resonant behaviour not considered in previous works. This study can be accomplished by means of digital video and open source software. The experience can motivate an engaging laboratory project by integrating standard curriculum topics, data analysis and experimental exploration.

Dissipation of contractile forces: the missing piece in cell mechanics.

PubMed

Kurzawa, Laetitia; Vianay, Benoit; Senger, Fabrice; Vignaud, Timothée; Blanchoin, Laurent; Théry, Manuel

2017-07-07

Mechanical forces are key regulators of cell and tissue physiology. The basic molecular mechanism of fiber contraction by the sliding of actin filament upon myosin leading to conformational change has been known for decades. The regulation of force generation at the level of the cell, however, is still far from elucidated. Indeed, the magnitude of cell traction forces on the underlying extracellular matrix in culture is almost impossible to predict or experimentally control. The considerable variability in measurements of cell-traction forces indicates that they may not be the optimal readout to properly characterize cell contractile state and that a significant part of the contractile energy is not transferred to cell anchorage but instead is involved in actin network dynamics. Here we discuss the experimental, numerical, and biological parameters that may be responsible for the variability in traction force production. We argue that limiting these sources of variability and investigating the dissipation of mechanical work that occurs with structural rearrangements and the disengagement of force transmission is key for further understanding of cell mechanics. © 2017 Kurzawa et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Computer-based mechanical design of overhead lines

NASA Astrophysics Data System (ADS)

Rusinaru, D.; Bratu, C.; Dinu, R. C.; Manescu, L. G.

2016-02-01

Beside the performance, the safety level according to the actual standards is a compulsory condition for distribution grids’ operation. Some of the measures leading to improvement of the overhead lines reliability ask for installations’ modernization. The constraints imposed to the new lines components refer to the technical aspects as thermal stress or voltage drop, and look for economic efficiency, too. The mechanical sizing of the overhead lines is after all an optimization problem. More precisely, the task in designing of the overhead line profile is to size poles, cross-arms and stays and locate poles along a line route so that the total costs of the line's structure to be minimized and the technical and safety constraints to be fulfilled.The authors present in this paper an application for the Computer-Based Mechanical Design of the Overhead Lines and the features of the corresponding Visual Basic program, adjusted to the distribution lines. The constraints of the optimization problem are adjusted to the existing weather and loading conditions of Romania. The outputs of the software application for mechanical design of overhead lines are: the list of components chosen for the line: poles, cross-arms, stays; the list of conductor tension and forces for each pole, cross-arm and stay for different weather conditions; the line profile drawings.The main features of the mechanical overhead lines design software are interactivity, local optimization function and high-level user-interface

Treatments and compositions targeting α-synuclein: a patent review (2010-2016).

PubMed

Jęśko, Henryk; Lenkiewicz, Anna M; Adamczyk, Agata

2017-04-01

Abnormal deposition of α-synuclein (ASN) is a hallmark and possible central mechanism of Parkinson's disease and other synucleinopathies. Their therapy is currently hampered by the lack of early, screening-compatible diagnostic methods and efficient treatments. Areas covered: Patent applications related to synucleinopathies obtained from Patentscope and Espacenet databases are described against the background of current knowledge regarding the regulatory mechanisms of ASN behavior including alternative splicing, post-translational modifications, molecular interactions, aggregation, degradation, and changes in localization. Expert opinion: As the central pathological feature and possibly one of root causes in a number of neurodegenerative diseases, deregulation of ASN is a potentially optimal diagnostic and therapeutic target. Changes in total ASN may have diagnostic value, especially if non-invasive /peripheral tissue tests can be developed. Targeting the whole ASN pool for therapeutic purposes may be problematic, however. ASN mutations, truncation, and post-translational modifications have great potential value; therapeutic approaches selective towards aggregated or aggregation-prone ASN forms may lead to more successful and safe treatments. Numerous ASN interactions with signaling pathways, protein degradation and stress mechanisms widen its potential therapeutic significance dramatically. However, significant improvement in the basic knowledge on ASN is necessary to fully exploit these opportunities.

Current advances in esophageal cancer proteomics.

PubMed

Uemura, Norihisa; Kondo, Tadashi

2015-06-01

We review the current status of proteomics for esophageal cancer (EC) from a clinician's viewpoint. The ultimate goal of cancer proteomics is the improvement of clinical outcome. The proteome as a functional translation of the genome is a straightforward representation of genomic mechanisms that trigger carcinogenesis. Cancer proteomics has identified the mechanisms of carcinogenesis and tumor progression, detected biomarker candidates for early diagnosis, and provided novel therapeutic targets for personalized treatments. Our review focuses on three major topics in EC proteomics: diagnostics, treatment, and molecular mechanisms. We discuss the major histological differences between EC types, i.e., esophageal squamous cell carcinoma and adenocarcinoma, and evaluate the clinical significance of published proteomics studies, including promising diagnostic biomarkers and novel therapeutic targets, which should be further validated prior to launching clinical trials. Multi-disciplinary collaborations between basic scientists, clinicians, and pathologists should be established for inter-institutional validation. In conclusion, EC proteomics has provided significant results, which after thorough validation, should lead to the development of novel clinical tools and improvement of the clinical outcome for esophageal cancer patients. This article is part of a Special Issue entitled: Medical Proteomics. Copyright © 2014 Elsevier B.V. All rights reserved.

Empathy as a driver of prosocial behaviour: highly conserved neurobehavioural mechanisms across species.

PubMed

Decety, Jean; Bartal, Inbal Ben-Ami; Uzefovsky, Florina; Knafo-Noam, Ariel

2016-01-19

Empathy reflects the natural ability to perceive and be sensitive to the emotional states of others, coupled with a motivation to care for their well-being. It has evolved in the context of parental care for offspring, as well as within kinship bonds, to help facilitate group living. In this paper, we integrate the perspectives of evolution, animal behaviour, developmental psychology, and social and clinical neuroscience to elucidate our understanding of the proximate mechanisms underlying empathy. We focus, in particular, on processing of signals of distress and need, and their relation to prosocial behaviour. The ability to empathize, both in animals and humans, mediates prosocial behaviour when sensitivity to others' distress is paired with a drive towards their welfare. Disruption or atypical development of the neural circuits that process distress cues and integrate them with decision value leads to callous disregard for others, as is the case in psychopathy. The realization that basic forms of empathy exist in non-human animals is crucial for gaining new insights into the underlying neurobiological and genetic mechanisms of empathy, enabling translation towards therapeutic and pharmacological interventions. © 2015 The Author(s).

Electrochemical behavior of lead dioxide deposited on reticulated vitreous carbon (RVC)

NASA Astrophysics Data System (ADS)

Czerwiński, Andrzej; Żelazowska, Malgorzata

The electrochemical performance of lead dioxide deposited on reticulated vitreous carbon (RVC) has been investigated in basic and acidic solutions (0.1 M NaOH, 0.1 M Na 2BB 4OO 7 and 0.5 M H 2SSO 4)). For comparison, pure lead and lead dioxide deposited on platinized RVC (Pt/ RVC) were also included in the study. Our results indicate that the behavior of RVC covered with lead dioxide (without platinum) resembles that of lead dioxide generated electrochemically on metallic lead.

Response of Primary Explosives to Gaseous Discharges in an Improved Approaching-Electrode Electrostatic Sensitivity Apparatus

DTIC Science & Technology

1976-10-01

and Identify by block number) This report describes an improved, approaching-needle electrostatic sensitivity apparatus as well as the...category. Thus, basic lead styphnate, RD1333 lead azide, dextrinated lead azide and tetracene all ignited. But, as expected, tetryl, PETN, superfine PETN... dextrinated lead azide obtained using the same apparatus and procedure and conducted at the same time. Sample Preparation, Electrode Replacement, and

Mosquito vectors and the spread of cancer: an overlooked connection?

PubMed

Benelli, Giovanni; Lo Iacono, Annalisa; Canale, Angelo; Mehlhorn, Heinz

2016-06-01

Mosquitoes (Diptera: Culicidae) represent a key threat for millions of humans and animals worldwide, vectoring important pathogens and parasites, including malaria, dengue, filariasis, and Zika virus. Besides mosquito-borne diseases, cancers figure among the leading causes of mortality worldwide. It is expected that annual cancer cases will rise from 14 million in 2012 to 22 million within the next two decades. Notably, there are few contrasting evidences of the relationship between cancer and mosquito-borne diseases, with special reference to malaria. However, analogies at the cellular level for the two diseases were reported. Recently, a significant association of malaria incidence with all cancer mortality in 50 USA states was highlighted and may be explained by the ability of Plasmodium to induce suppression of the immune system. However, it was hypothesized that Anopheles vectors may transmit obscure viruses linked with cancer development. The possible activation of cancer pathways by mosquito feeding events is not rare. For instance, the hamster reticulum cell sarcoma can be transmitted through the bites of Aedes aegypti by a transfer of tumor cells. Furthermore, mosquito bites may influence human metabolic pathways following different mechanisms, leading to other viral infections and/or oncogenesis. Hypersensitivity to mosquito bites is routed by a unique pathogenic mechanism linking Epstein-Barr virus infection, allergy, and oncogenesis. During dengue virus infection, high viral titers, macrophage infiltration, and tumor necrosis factor alpha production in the local tissues are the three key important events that lead to hemorrhage. Overall, basic epidemiological knowledge on the relationships occurring between mosquito vector activity and the spread of cancer is urgently needed, as well as detailed information about the ability of Culicidae to transfer viruses or tumor cells among hosts over time. Current evidences on nanodrugs with multipotency against mosquito-borne diseases and cancers are reviewed, with peculiar attention to their mechanisms of action.

Ratio

NASA Astrophysics Data System (ADS)

Webster, Nathan A. S.; Pownceby, Mark I.; Madsen, Ian C.; Studer, Andrew J.; Manuel, James R.; Kimpton, Justin A.

2014-12-01

Effects of basicity, B (CaO:SiO2 ratio) on the thermal range, concentration, and formation mechanisms of silico-ferrite of calcium and aluminum (SFCA) and SFCA-I iron ore sinter bonding phases have been investigated using an in situ synchrotron X-ray diffraction-based methodology with subsequent Rietveld refinement-based quantitative phase analysis. SFCA and SFCA-I phases are the key bonding materials in iron ore sinter, and improved understanding of the effects of processing parameters such as basicity on their formation and decomposition may assist in improving efficiency of industrial iron ore sintering operations. Increasing basicity significantly increased the thermal range of SFCA-I, from 1363 K to 1533 K (1090 °C to 1260 °C) for a mixture with B = 2.48, to ~1339 K to 1535 K (1066 °C to 1262 °C) for a mixture with B = 3.96, and to ~1323 K to 1593 K (1050 °C to 1320 °C) at B = 4.94. Increasing basicity also increased the amount of SFCA-I formed, from 18 wt pct for the mixture with B = 2.48 to 25 wt pct for the B = 4.94 mixture. Higher basicity of the starting sinter mixture will, therefore, increase the amount of SFCA-I, considered to be more desirable of the two phases. Basicity did not appear to significantly influence the formation mechanism of SFCA-I. It did, however, affect the formation mechanism of SFCA, with the decomposition of SFCA-I coinciding with the formation of a significant amount of additional SFCA in the B = 2.48 and 3.96 mixtures but only a minor amount in the highest basicity mixture. In situ neutron diffraction enabled characterization of the behavior of magnetite after melting of SFCA produced a magnetite plus melt phase assemblage.

[Mechanism of action of intravesical BCG. Biological bases and clinical applicability.

PubMed

Carballido, Joaquín A; Rodríguez Monsalve, María

2018-05-01

The therapeutic approaches developed around immune system modulation find the therapeutic contribution of intravesical Bacillus Calmette Guerin (BCG) for transitional cell bladder cancer an unquestionable example as a proof of concept of antitumor immunotherapy since more than 30 years ago. Intravesical immunotherapy for urothelial carcinomas is considered with periodic intravesical instillations schedules, and the one with longer historic development and wider diffusion is BCG in the form of suspension. BCG is a unique strain obtained from Mycobacterium bovis at the end of the first third of the XX century and represents the historically most successful immunotherapeutic modality of all tumors with a high level body of evidence. Currently, we even see an unpredictable development potential of this therapeutic modality based on immunomodulation related with activation or suppression of T lymphocytes by blocking the immune system checkpoints. This option is at this time a decisive step in the treatment of chemotherapy refractory metastatic urothelial carcinoma. Over the last years, there have been advances in the intimate mechanism of action of intravesical BCG, but there are many open questions that will only be answered from complex basic and translational research platforms. The objective of this review article is to try to translate the basic mechanisms currently implicated in the different phases of antitumor response of BCG in its routine use in clinical practice. Also, to analyze the future lines already active under clinical research with and without implications of the mechanisms of action of BCG. We describe the role of interactions basally established between urothelial tumor cells and cellular and molecular elements of the immune system of the patients with ulterior antitumor effector capacity. After intravesical BCG therapy and its interaction, we describe the various phases of its mechanism of action, namely fixation, internalization and triggering of the lytic cytotoxic antitumor response, and its integration in the current intravesical treatment regimens The implication of all these mechanisms in the varied capacity of clinical response observed in patients, reviewing the current status of knowledge of BCG mechanisms of action, leads unavoidably to the search of better clinical efficacy through eventual immune response markers and to set the approach to the knowledge of the individual reactivity of the immune system of each patient as a determinant factor to be able to adopt adjusted therapeutic patterns.

Making Basic Science Studies in Glaucoma More Clinically Relevant: The Need for a Consensus.

PubMed

Toris, Carol B; Gelfman, Claire; Whitlock, Andy; Sponsel, William E; Rowe-Rendleman, Cheryl L

2017-09-01

Glaucoma is a chronic, progressive, and debilitating optic neuropathy that causes retinal damage and visual defects. The pathophysiologic mechanisms of glaucoma remain ill-defined, and there is an indisputable need for contributions from basic science researchers in defining pathways for translational research. However, glaucoma researchers today face significant challenges due to the lack of a map of integrated pathways from bench to bedside and the lack of consensus statements to guide in choosing the right research questions, techniques, and model systems. Here, we present the case for the development of such maps and consensus statements, which are critical for faster development of the most efficacious glaucoma therapy. We underscore that interrogating the preclinical path of both successful and unsuccessful clinical programs is essential to defining future research. One aspect of this is evaluation of available preclinical research tools. To begin this process, we highlight the utility of currently available animal models for glaucoma and emphasize that there is a particular need for models of glaucoma with normal intraocular pressure. In addition, we outline a series of discoveries from cell-based, animal, and translational research that begin to reveal a map of glaucoma from cell biology to physiology to disease pathology. Completion of these maps requires input and consensus from the global glaucoma research community. This article sets the stage by outlining various approaches to such a consensus. Together, these efforts will help accelerate basic science research, leading to discoveries with significant clinical impact for people with glaucoma.

Fundamentals of neurogastroenterology: basic science.

PubMed

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.

Probing the mechanisms of drug release from amorphous solid dispersions in medium-soluble and medium-insoluble carriers.

PubMed

Sun, Dajun D; Lee, Ping I

2015-08-10

The objective of the current study is to mechanistically differentiate the dissolution and supersaturation behaviors of amorphous drugs from amorphous solid dispersions (ASDs) based on medium-soluble versus medium-insoluble carriers under nonsink dissolution conditions through a direct head-to-head comparison. ASDs of indomethacin (IND) were prepared in several polymers which exhibit different solubility behaviors in acidic (pH1.2) and basic (pH7.4) dissolution media. The selected polymers range from water-soluble (e.g., PVP and Soluplus) and water-insoluble (e.g., ethylcellulose and Eudragit RL PO) to those only soluble in an acidic or basic dissolution medium (e.g., Eudragit E100, Eudragit L100, and HPMCAS). At 20wt.% drug loading, DSC and powder XRD analysis confirmed that the majority of incorporated IND was present in an amorphous state. Our nonsink dissolution results confirm that whether the carrier matrix is medium soluble determines the release mechanism of amorphous drugs from ASD systems which has a direct impact on the rate of supersaturation generation, thus in turn affecting the evolution of supersaturation in amorphous systems. For example, under nonsink dissolution conditions, the release of amorphous IND from medium-soluble carriers is governed by a dissolution-controlled mechanism leading to an initial surge of supersaturation followed by a sharp decline in drug concentration due to rapid nucleation and crystallization. In contrast, the dissolution of IND ASD from medium-insoluble carriers is more gradual as drug release is regulated by a diffusion-controlled mechanism by which drug supersaturation is built up gradually and sustained over an extended period of time without any apparent decline. Since several tested carrier polymers can be switched from soluble to insoluble by simply changing the pH of the dissolution medium, the results obtained here provide unequivocal evidence of the proposed transition of kinetic solubility profiles from the same ASD system induced by changes in the drug release mechanism in dissolution medium of a different pH. Copyright © 2015 Elsevier B.V. All rights reserved.

Preloaded joint analysis methodology for space flight systems

NASA Technical Reports Server (NTRS)

Chambers, Jeffrey A.

1995-01-01

This report contains a compilation of some of the most basic equations governing simple preloaded joint systems and discusses the more common modes of failure associated with such hardware. It is intended to provide the mechanical designer with the tools necessary for designing a basic bolted joint. Although the information presented is intended to aid in the engineering of space flight structures, the fundamentals are equally applicable to other forms of mechanical design.

Some important considerations in the development of stress corrosion cracking test methods.

NASA Technical Reports Server (NTRS)

Wei, R. P.; Novak, S. R.; Williams, D. P.

1972-01-01

Discussion of some of the precaution needs the development of fracture-mechanics based test methods for studying stress corrosion cracking involves. Following a review of pertinent analytical fracture mechanics considerations and of basic test methods, the implications for test corrosion cracking studies of the time-to-failure determining kinetics of crack growth and life are examined. It is shown that the basic assumption of the linear-elastic fracture mechanics analyses must be clearly recognized and satisfied in experimentation and that the effects of incubation and nonsteady-state crack growth must also be properly taken into account in determining the crack growth kinetics, if valid data are to be obtained from fracture-mechanics based test methods.

Mechanical modeling for magnetorheological elastomer isolators based on constitutive equations and electromagnetic analysis

NASA Astrophysics Data System (ADS)

Wang, Qi; Dong, Xufeng; Li, Luyu; Ou, Jinping

2018-06-01

As constitutive models are too complicated and existing mechanical models lack universality, these models are beyond satisfaction for magnetorheological elastomer (MRE) devices. In this article, a novel universal method is proposed to build concise mechanical models. Constitutive model and electromagnetic analysis were applied in this method to ensure universality, while a series of derivations and simplifications were carried out to obtain a concise formulation. To illustrate the proposed modeling method, a conical MRE isolator was introduced. Its basic mechanical equations were built based on equilibrium, deformation compatibility, constitutive equations and electromagnetic analysis. An iteration model and a highly efficient differential equation editor based model were then derived to solve the basic mechanical equations. The final simplified mechanical equations were obtained by re-fitting the simulations with a novel optimal algorithm. In the end, verification test of the isolator has proved the accuracy of the derived mechanical model and the modeling method.

Limits to ground control in autonomous spacecraft

NASA Technical Reports Server (NTRS)

Wan, Alfred D. M.; Braspenning, Peter J.; Vreeswijk, Gerrard A. W.

1995-01-01

In this paper the autonomy concept used by ESA and NASA is critically evaluated. Moreover, a more proper ground control/spacecraft organizational structure is proposed on the basis of a new, more elaborated concept of autonomy. In an extended theoretical discussion its definitional properties and functionalities are established. The rather basic property of adaptivity leads to the categorization of behaviour into the modes of satisfaction and avoidance behaviour. However, the autonomy property with the most profound consequences is goal-robustness. The mechanism that implements goal-robustness tests newly generated goals and externally received goals on consistency with high-level goals. If goals appear not to be good instantiations or more acceptable replacements of existing goals, they are rejected. This means that ground control has to cooperate with the spacecraft instead of (intermittently) commanding it.

Defence reactions of plants to fungal pathogens: principles and perspectives, using powdery mildew on cereals as an example

NASA Astrophysics Data System (ADS)

Heitefuss, Rudolf

2001-06-01

Diseases of crop plants may lead to considerable yield losses. To control fungal diseases, fungicides are used extensively in present-day agricultural production. In order to reduce such external inputs, cultivars with natural resistance to important fungal pathogens are recommended in systems of integrated plant protection. Basic research, including genetics and molecular methods, is required to elucidate the mechanisms by which plants react to an attack by fungal pathogens and successfully defend themselves. This review examines our knowledge with respect to the multicomponent systems of resistance in plants, using powdery mildew on barley as an example. In addition, the question is adressed whether systemic acquired resistance and plants with transgenic resistance may be utilized in future plant protection strategies.

The daily timing of gene expression and physiology in mammals

PubMed Central

Schibler, Ueli

2007-01-01

Mammalian behavior and physiology undergo daily rhythms that are coordinated by an endogenous circadian timing system. This system has a hierarchical structure, in that a master pacemaker, residing in the suprachiasmatic nucleus of the ventral hypothalamus, synchronizes peripheral oscillators in virtually all body cells. While the basic molecular mechanisms generating the daily rhythms are similar in aIl cells, most clock out-puts are cell-specific. This conclusion is based on genomewide transcriptome profiling studies in several tissues that have revealed hundreds of rhythmically expressed genes. Cyclic gene expression in the various organs governs overt rhythms in behavior and physiology, encompassing sleep-wake cycles, metabolism, xenobiotic detoxification, and cellularproliferation. As a consequence, chronic perturbation of this temporal organization may lead to increased morbidity and reduced lifespan. PMID:17969863

Mechanism-based approaches to treating fragile X.

PubMed

Dölen, Gül; Carpenter, Randall L; Ocain, Timothy D; Bear, Mark F

2010-07-01

Fragile X is the leading inherited cause of mental retardation and autism. Recent advances in our mechanistic understanding of the disease have led to the identification of the metabotropic glutamate receptor (mGluR) as a therapeutic target for the disease. These studies have revealed that core defects in multiple animal models can be corrected by down regulation of mGluR5 signaling. Although it remains to be seen if mGluR5 antagonists or related approaches will succeed in humans with fragile X, the progress in fragile X stands as a strong testament to the power of applying knowledge of basic neurobiology to understand pathophysiology in a genetically validated model of human psychiatric disease. These breakthroughs and several of the resulting drug development efforts are reviewed. (c) 2010 Elsevier Inc. All rights reserved.

Temperature distribution in the crust and mantle

NASA Technical Reports Server (NTRS)

Jeanloz, R.; Morris, S.

1986-01-01

In an attempt to understand the temperature distribution in the earth, experimental constraints on the geotherm in the crust and mantle are considered. The basic form of the geotherm is interpreted on the basis of two dominant mechanisms by which heat is transported in the earth: (1) conduction through the rock, and (2) advection by thermal flow. Data reveal that: (1) the temperature distributions through continental lithosphere and through oceanic lithosphere more than 60 million years old are practically indistinguishable, (2) crustal uplift is instrumental in modifying continental geotherms, and (3) the average temperature through the Archean crust and mantle was similar to that at present. It is noted that current limitations in understanding the constitution of the lower mantle can lead to significant uncertainties in the thermal response time of the planetary interior.

The use of wood for wind turbine blade construction

NASA Technical Reports Server (NTRS)

Gougeon, M.; Zuteck, M.

1979-01-01

The interrelationships between moisture and wood, conditions for dry rot spore activity, the protection of wood fibers from moisture, wood resin composites, wood laminating, quality control, and the mechanical properties of wood are discussed. The laminated veneer and the bonded sawn stock fabrication techniques, used in the construction of a turbine blade with a monocoque 'D' section forming the leading edge and a built up trailing edge section, are described. A 20 foot root end sample complete with 24 bonded-in studs was successfully subjected to large onetime loads in both the flatwise and edgewise directions, and to fatigue tests. Results indicate that wood is both a viable and advantageous material for use in wind turbine blades. The basic material is reasonably priced, domestically available, ecologically sound, and easily fabricated with low energy consumption.

The active centre of triose phosphate isomerase

PubMed Central

Burton, Pamela M.; Waley, S. G.

1966-01-01

The molecular weight and amino acid composition of triose phosphate isomerase have been determined. The molecular weight (43000) is lower and the molecular activity (500000) higher than those of most other glycolytic enzymes. Reaction with iodoacetate (studied with radioactive reagent) takes place in two phases: in the first phase, at pH6·3, cysteine and methionine groups react and enzymic activity is unimpaired; in the second phase, histidine reacts and enzymic activity is lost. Photo-oxidation leads to inactivation, with loss of cysteine, of histidine and of tryptophan, but little loss of tyrosine. The mechanism postulated for the action of the enzyme demands the intervention of a group functioning as a base, and the results obtained are consistent with histidine's being the basic group in the active centre. PMID:5969283

A life prediction methodology for encapsulated solar cells

NASA Technical Reports Server (NTRS)

Coulbert, C. D.

1978-01-01

This paper presents an approach to the development of a life prediction methodology for encapsulated solar cells which are intended to operate for twenty years or more in a terrestrial environment. Such a methodology, or solar cell life prediction model, requires the development of quantitative intermediate relationships between local environmental stress parameters and the basic chemical mechanisms of encapsulant aging leading to solar cell failures. The use of accelerated/abbreviated testing to develop these intermediate relationships and in revealing failure modes is discussed. Current field and demonstration tests of solar cell arrays and the present laboratory tests to qualify solar module designs provide very little data applicable to predicting the long-term performance of encapsulated solar cells. An approach to enhancing the value of such field tests to provide data for life prediction is described.

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

PubMed Central

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

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

PubMed Central

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

Multi-scale mechanics from molecules to morphogenesis

PubMed Central

Davidson, Lance; von Dassow, Michelangelo; Zhou, Jian

2009-01-01

Dynamic mechanical processes shape the embryo and organs during development. Little is understood about the basic physics of these processes, what forces are generated, or how tissues resist or guide those forces during morphogenesis. This review offers an outline of some of the basic principles of biomechanics, provides working examples of biomechanical analyses of developing embryos, and reviews the role of structural proteins in establishing and maintaining the mechanical properties of embryonic tissues. Drawing on examples we highlight the importance of investigating mechanics at multiple scales from milliseconds to hours and from individual molecules to whole embryos. Lastly, we pose a series of questions that will need to be addressed if we are to understand the larger integration of molecular and physical mechanical processes during morphogenesis and organogenesis. PMID:19394436

Temperature-dependent mechanical behavior of silicon dioxide, gold and gold-vanadium thin films for VLSI integrated circuits and MicroElectroMechanical systems (MEMs)

NASA Astrophysics Data System (ADS)

Lin, Ming-Tzer

The Semiconductor Industry has grown rapidly in the last twenty years. The national technology roadmap for semiconductors plans for developing the complexity and packing density of semiconductor devices into the next decade, allowing ever smaller and more densely packed structures to be fabricated. Recently, MEMS (Micro-Electro-Mechanical Systems) have become important in modern technology. The goal of MEMs is to integrate many types of miniature devices on a single chip, creating a new micro-world. The oxidation of silicon is one of the most important processes in semiconductor technology. Producing high-quality IC's and MEMS devices requires an understanding of the basic oxidation mechanism. In addition, for the reliability of IC's and MEMS devices, the mechanical properties of the oxide play a critical role. There has been an apparent convergence of opinion on the relevant mechanism leading to the "standard computational model" for stress effects on silicon oxidation. This model has recently become suspect. Most of the reasonably direct experimental data on the flow properties of SiO 2 thin film do not support a stress-dependent viscosity of the sort envisioned by the model. Gold and gold vanadium alloys are used in electrical interconnections and in radio frequency switch contacts for the semiconductor industry, MEMs sensors for the aerospace industry and also in brain probes by the bioelectronics mechanical industry. Despite the strong potential usage of gold and gold vanadium thin films at the small scale, very little is known about their mechanical properties. Our goal was to experimentally investigate stress and its influence on SiO2 thin films and the mechanical properties of gold and gold vanadium thin films at room temperature and at elevated temperature of different vanadium concentration. We found that the application of relatively small amounts of bending to an oxidizing silicon substrate leads to significant decreases in oxide thickness in the ultrathin oxide regime. Both tensile and compressive bending retard oxide growth, although compressive bending results in somewhat thinner oxides than does tensile bending. We also determined the modulus of gold and gold vanadium, and discovered that there is some evidence for a vanadium concentration dependence of the mechanical properties.

Surface modification of a natural zeolite by treatment with cold oxygen plasma: Characterization and application in water treatment

NASA Astrophysics Data System (ADS)

De Velasco-Maldonado, Paola S.; Hernández-Montoya, Virginia; Montes-Morán, Miguel A.; Vázquez, Norma Aurea-Rangel; Pérez-Cruz, Ma. Ana

2018-03-01

In the present work the possible surface modification of natural zeolite using cold oxygen plasma was studied. The sample with and without treatment was characterized using nitrogen adsorption isotherms at -196 °C, FT-IR spectroscopy, SEM/EDX analysis and X-Ray Diffraction. Additionally, the two samples were used for the removal of lead and acid, basic, reactive and food dyes in batch systems. The natural zeolite was found to be a mesoporous material with a low specific surface area (23 m2/g). X-ray patterns confirmed that clinoptilolite was the main crystal structure present in the natural zeolite. The molecular properties of dyes and the zeolitic structure were studied using molecular simulation, with the purpose to understand the adsorption mechanism. The results pointed out that only the roughness of the clinoptilolite was affected by the plasma treatment, whereas the specific surface area, chemical functionality and crystal structure remained constant. Finally, adsorption results confirmed that the plasma treatment had no significant effects on the dyes and lead retention capacities of the natural zeolite.

[Discovery-based teaching and learning strategies in health: problematization and problem-based learning].

PubMed

Cyrino, Eliana Goldfarb; Toralles-Pereira, Maria Lúcia

2004-01-01

Considering the changes in teaching in the health field and the demand for new ways of dealing with knowledge in higher learning, the article discusses two innovative methodological approaches: problem-based learning (PBL) and problematization. Describing the two methods' theoretical roots, the article attempts to identify their main foundations. As distinct proposals, both contribute to a review of the teaching and learning process: problematization, focused on knowledge construction in the context of the formation of a critical awareness; PBL, focused on cognitive aspects in the construction of concepts and appropriation of basic mechanisms in science. Both problematization and PBL lead to breaks with the traditional way of teaching and learning, stimulating participatory management by actors in the experience and reorganization of the relationship between theory and practice. The critique of each proposal's possibilities and limits using the analysis of their theoretical and methodological foundations leads us to conclude that pedagogical experiences based on PBL and/or problematization can represent an innovative trend in the context of health education, fostering breaks and more sweeping changes.

Androgens and polycystic ovary syndrome.

PubMed

Nisenblat, Vicki; Norman, Robert J

2009-06-01

Polycystic ovary syndrome (PCOS) is a common complex endocrine genetic disorder, which involves overproduction of androgens, leading to heterogeneous range of symptoms and associated with increased metabolic and cardiovascular morbidity. This review focuses on androgen biosynthesis, use, metabolism in PCOS and clinical consequences of hyperandrogenism. Controversial definition of the disorder and different phenotypic subgroups present a challenge for clinical and basic research. Further investigation of different phenotypes highlights the fact that PCOS probably represents a group of disorders with different etiologies. Prenatal androgen exposure and adolescent studies suggest early in life androgen excess as initiating factor of PCOS, but insufficient evidence available to confirm this hypothesis. Various intracellular signaling pathways implicated in PCOS steroidogenesis and in androgen action have been studied, however, PCOS pathogenesis remains obscure. Growing evidence links androgens with pathophysiology of PCOS and metabolic derangements. Despite intensive investigation, etiology and underlying mechanisms of PCOS remain unclear, warranting further investigation. Better understanding of molecular and genetic basis might lead to invention of novel therapeutic approaches. Long-term interventional studies that lower androgen levels in women with hyperandrogenism might protect against metabolic and cardiovascular comorbidities are needed.

Physiologic bases for anterior ST segment depression in patients with acute inferior wall myocardial infarction.

PubMed

Mirvis, D M

1988-11-01

Patients with acute inferior myocardial infarction commonly have ST segment depression in the anterior precordial leads. This may reflect either reciprocal changes from the inferior ST elevation or primary ST depression from additional anterior subendocardial ischemia. From a biophysical perspective reciprocal changes should be uniformly anticipated from basic dipole theory. Detection will vary with the size, location, orientation, and electrical intensity of the lesion and with the ECG lead system deployed to register the anterior changes. Alternatively, acute occlusion of the right coronary artery may produce ischemia in the anterior left ventricular wall supplied by a stenotic anterior descending coronary artery. Anterior ischemia may result from the abnormal hemodynamics or the reduced collateral flow produced by acute right coronary artery occlusion. Thus both mechanisms are based on sound physiologic principles. A review of the clinical literature suggests that such patients represent a heterogeneous group. In some instances coexistent anterior ischemia is present, whereas in others the anterior ST depression is the passive reflection of inferior ST elevation augmented in many cases by a large infarct size or more extensive posterobasal or septal involvement.

Sedimentary exhalative (sedex) zinc-lead-silver deposit model

USGS Publications Warehouse

Emsbo, Poul; Seal, Robert R.; Breit, George N.; Diehl, Sharon F.; Shah, Anjana K.

2016-10-28

This report draws on previous syntheses and basic research studies of sedimentary exhalative (sedex) deposits to arrive at the defining criteria, both descriptive and genetic, for sedex-type deposits. Studies of the tectonic, sedimentary, and fluid evolution of modern and ancient sedimentary basins have also been used to select defining criteria. The focus here is on the geologic characteristics of sedex deposit-hosting basins that contain greater than 10 million metric tons of zinc and lead. The enormous size of sedex deposits strongly suggests that basin-scale geologic processes are involved in their formation. It follows that mass balance constraints of basinal processes can provide a conceptual underpinning for the evaluation of potential ore-forming mechanisms and the identification of geologic indicators for ore potential in specific sedimentary basins. Empirical data and a genetic understanding of the physicochemical, geologic, and mass balance conditions required for each of these elements are used to establish a hierarchy of quantifiable geologic criteria that can be used in U.S. Geological Survey national assessments.  In addition, this report also provides a comprehensive evaluation of environmental considerations associated with the mining of sedex deposits.

Is What We Have, What We Want?: A Critical Review of Selected Basic Course Textbooks.

ERIC Educational Resources Information Center

Berens, Eileen; Nance, Teresa A.

A two-stage study was designed to offer a comprehensive analysis of current basic public speaking textbooks. The first stage involved a comprehensive classification, enumeration, and comparison of the substance of six textbooks identified by publishers as leading competitors on the public speaking market. Results from the first stage formed the…

Revisiting Preschoolers' Living Things Concept: A Microgenetic Analysis of Conceptual Change in Basic Biology

ERIC Educational Resources Information Center

Opfer, John E.; Siegler, Robert S.

2004-01-01

Many preschoolers know that plants and animals share basic biological properties, but this knowledge does not usually lead them to conclude that plants, like animals, are living things. To resolve this seeming paradox, we hypothesized that preschoolers largely base their judgments of life status on a biological property, capacity for teleological…

Lead carbonate scintillator materials

DOEpatents

Derenzo, S.E.; Moses, W.W.

1991-05-14

Improved radiation detectors containing lead carbonate or basic lead carbonate as the scintillator element are disclosed. Both of these scintillators have been found to provide a balance of good stopping power, high light yield and short decay constant that is superior to other known scintillator materials. The radiation detectors disclosed are favorably suited for use in general purpose detection and in medical uses. 3 figures.

An Analysis of a Nationwide Study on Curricular Emphasis in Basic Mechanics

ERIC Educational Resources Information Center

Raville, M. E.; Lnenicka, W. J.

1976-01-01

Discusses a survey of curricular allocations to mechanics in departments and schools of engineering. Tables show trends of coverage of mechanics topics and faculty perceptions of teaching and learning trends. (MLH)

Platelets in thrombosis and hemostasis: old topic with new mechanisms.

PubMed

Wang, Yiming; Andrews, Marc; Yang, Yan; Lang, Sean; Jin, Joseph W; Cameron-Vendrig, Alison; Zhu, Guangheng; Reheman, Adili; Ni, Heyu

2012-12-01

Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. After being released into the circulation, platelets play key roles in the surveillance of vascular injury, and can quickly adhere and aggregate at the site of injury, which are critical events for vascular repair and hemostasis. However, the same biological processes of platelet adhesion and aggregation may also cause thrombotic disorders. The formation of a platelet plug at sites of atherosclerotic lesion rupture is the most common mechanism leading to myocardial or cerebral infarction. Platelet-related deep vein thrombosis is also one of the leading causes of mortality worldwide. The contribution of several platelet receptors and their ligands has been highlighted in these processes. In platelet adhesion, particularly at high shear stress, GPIbα-von Willebrand factor (VWF) interaction may initiate this event, which is followed by GPVI signalling and firm platelet adhesion mediated by members of the integrin family, such as β3 (αIIbβ3) and β1 (α2β1, α5β1) integrins. In platelet aggregation, although GPIbα-VWF, P selectin-sulfatides, and other molecules, may be involved, the process is mainly mediated by β3 (αIIbβ3) integrin and its ligands, such as fibrinogen and VWF. It is intriguing that platelet adhesion and aggregation still occur in mice lacking both fibrinogen and VWF, suggesting that other unforeseen molecule(s) may also be important in these processes. Identification and characterization of these molecules will enrich our knowledge in the basic science of hemostasis and thrombosis, and may lead to the development of new therapies against bleeding disorders and thrombotic diseases.

The mirror mechanism in the parietal lobe.

PubMed

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.

Beyond the basics: brain injuries.

PubMed

Duncan, Tim; Krost, William S; Mistovich, Joseph J; Limmer, Daniel

2007-07-01

Increased intracranial pressure can be a catastrophic event that may lead to death or permanent disability. Without prompt recognition and reversal of hypoxia, hypotension, hypercarbia, acidosis and increased intracranial pressure, the cerebral blood flow and resultant cerebral perfusion can be inadequate, leading to an exacerbation of secondary brain injury.

Effects of a mutation on the folding mechanism of a beta-hairpin.

PubMed

Juraszek, Jarek; Bolhuis, Peter G

2009-12-17

The folding mechanism of a protein is determined by its primary sequence. Yet, how the mechanism is changed by a mutation is still poorly understood, even for basic secondary structures such as beta-hairpins. We perform an extensive simulation study of the effects of mutating the GB1 beta-hairpin into Trpzip4 (Y5W, F12W, V14W) on the folding mechanism. While Trpzip4 has a much more stable native state due to very strong hydrophobic interactions of the side chains, its folding rate does not differ significantly from the wild type beta-hairpin. We sample the free-energy landscapes of both hairpins with Replica Exchange Molecular Dynamics (REMD) and identify the four (meta)stable states (U, H, F, and N). Using Transition Path Sampling (TPS), we then harvest ensembles of unbiased pathways between the H and F states and between the F and N states to investigate the unbiased folding mechanisms. In both hairpins, the hydrophobic collapse (U-H) is followed by the middle hydrogen bond formation (H-F), and finally a closing of the strands in a zipper-like fashion (F-N). For the Trpzip4, the path ensembles indicate that the final F-N step is much more difficult than for GB1 and involves partial unfolding, rezipping of hydrogen bonds, and rearrangement of the Trp-14 side chain. For the rate-limiting (H-F) step, the path ensembles show that in GB1 desolvation and strand closure go hand in hand, while in Trpzip4 desolvation is decoupled from strand closure. Nevertheless, likelihood maximization shows that the reaction coordinate for both hairpins remains the interstrand distance. We conclude that the folding mechanism of both hairpins is a combination of hydrophobic collapse and zipping of hydrogen bonds but that the zipper mechanism is more visible in Trpzip4. A major difference between the two hairpins is that in the transition state of the rate-limiting step for Trpzip4 one tryptophan is exposed to the solvent due to steric hindrance, making the folding mechanism more complex and leading to an increased F-N barrier. Thus, our results show in atomistic detail how a mutation leads to a different folding mechanism and results in a more frustrated folding free-energy landscape.

Biomechanical concepts applicable to minimally invasive fracture repair in small animals.

PubMed

Chao, Peini; Lewis, Daniel D; Kowaleski, Michael P; Pozzi, Antonio

2012-09-01

Understanding the basic biomechanical principles of surgical stabilization of fractures is essential for developing an appropriate preoperative plan as well as making prudent intraoperative decisions. This article aims to provide basic biomechanical knowledge essential to the understanding of the complex interaction between the mechanics and biology of fracture healing. The type of healing and the outcome can be influenced by several mechanical factors, which depend on the interaction between bone and implant. The surgeon should understand the mechanical principles of fracture fixation and be able to choose the best type of fixation for each specific fracture. Copyright © 2012 Elsevier Inc. All rights reserved.

Fractional vector calculus and fluid mechanics

NASA Astrophysics Data System (ADS)

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.

The Concept of "English Learning Power" and Its Implication for the Design of English Curricula for Primary and Middle Schools in China

ERIC Educational Resources Information Center

Dai, Zhongxin

2015-01-01

In the research on "New Characteristics of Future Basic Education in China," Dina Pei formulates a "three-powered" model to theorize about the characteristics of future basic education in China. The three powers refer to the "Policy-making Power" of the local educational administration, the "Leading Power"…

The Quality of a "Local Values Based" Fuctional Literacy Program: Its Contribution to the Improvement of the Learner's Basic Competencies

ERIC Educational Resources Information Center

Wahyudin, Uyu

2015-01-01

Literacy facilitators across the archipelago are currently faced with the challenge to integrate local values in functional literacy education programs, because its integration is a new aspect. This makes localized literacy content a hard thing to implement. Yet, if properly conducted, it can lead to improved learner's basic competencies. In an…

Improvement of Orthography Test Performance by Relaxation Exercises: Results of a Controlled Field Experiment in Basic Secondary Education

ERIC Educational Resources Information Center

Krampen, Gunter

2010-01-01

The effects of relaxation exercises on orthography performance in language arts education of fifth to seventh graders were experimentally tested. Participants were 399 basic secondary school students and their language arts teachers from the Hauptschule, a German type of secondary education covering grades five to nine that leads to a basic…

Generalized Models for Rock Joint Surface Shapes

PubMed Central

Du, Shigui; Hu, Yunjin; Hu, Xiaofei

2014-01-01

Generalized models of joint surface shapes are the foundation for mechanism studies on the mechanical effects of rock joint surface shapes. Based on extensive field investigations of rock joint surface shapes, generalized models for three level shapes named macroscopic outline, surface undulating shape, and microcosmic roughness were established through statistical analyses of 20,078 rock joint surface profiles. The relative amplitude of profile curves was used as a borderline for the division of different level shapes. The study results show that the macroscopic outline has three basic features such as planar, arc-shaped, and stepped; the surface undulating shape has three basic features such as planar, undulating, and stepped; and the microcosmic roughness has two basic features such as smooth and rough. PMID:25152901

Accuracy analysis of pointing control system of solar power station

NASA Technical Reports Server (NTRS)

Hung, J. C.; Peebles, P. Z., Jr.

1978-01-01

The first-phase effort concentrated on defining the minimum basic functions that the retrodirective array must perform, identifying circuits that are capable of satisfying the basic functions, and looking at some of the error sources in the system and how they affect accuracy. The initial effort also examined three methods for generating torques for mechanical antenna control, performed a rough analysis of the flexible body characteristics of the solar collector, and defined a control system configuration for mechanical pointing control of the array.

Neutron Diffraction Studies of Fluid Bilayers with Transmembrane Proteins: Structural Consequences of the Achondroplasia Mutation

PubMed Central

Han, Xue; Mihailescu, Mihaela; Hristova, Kalina

2006-01-01

Achondroplasia, the most common form of human dwarfism, is due to a G380R mutation in the transmembrane domain of fibroblast growth factor receptor 3 (FGFR3) in >97% of the studied cases. While the molecular mechanism of pathology induction is under debate, the structural consequences of the mutation have not been studied. Here we use neutron diffraction to determine the disposition of FGFR3 transmembrane domain in fluid lipid bilayers, and investigate whether the G380R mutation affects the topology of the protein in the bilayer. Our results demonstrate that, in a model system, the G380R mutation induces a shift in the segment that is embedded in the membrane. The center of the hydrocarbon core-embedded segment in the mutant is close to the midpoint between R380 and R397, supporting previous measurements of arginine insertion energetics into the endoplasmic reticulum. The presented results further our knowledge about basic amino-acid insertion into bilayers, and may lead to new insights into the mechanism of pathogenesis in achondroplasia. PMID:16950849

On two alternative mechanisms of ethane activation over ZSM-5 zeolite modified by Zn2+ and Ga1+ cations.

PubMed

Kazansky, V B; Subbotina, I R; Rane, N; van Santen, R A; Hensen, E J M

2005-08-21

The activation of ethane over zinc- and gallium-modified HZSM-5 dehydrogenation catalysts was studied by diffuse reflectance infrared spectroscopy. Hydrocarbon activation on HZSM-5 modified by bivalent Zn and univalent Ga cations proceeds via two distinctly different mechanisms. The stronger molecular adsorption of ethane by the acid-base pairs formed by distantly separated cationic Zn2+ and basic oxygen sites results already at room temperature in strong polarizability of adsorbed ethane and subsequent heterolytic dissociative adsorption at moderate temperatures. In contrast, molecular adsorption of ethane on Ga+ cations is weak. At high temperatures dissociative hydrocarbon adsorption takes place, resulting in the formation of ethyl and hydride fragments coordinating to the cationic gallium species. Whereas in the zinc case a Brønsted acid proton is formed upon ethane dissociation, decomposition of the ethyl fragment on gallium results in gallium dihydride species and does not lead to Brønsted acid protons. This difference in alkane activation has direct consequences for hydrocarbon conversions involving dehydrogenation.

Fundamental mechanisms of fatigue and fracture.

PubMed

Christ, Hans-Jürgen

2008-01-01

A brief overview is given in this article on the main design philosophies and the resulting description concepts used for components which undergo monotonic and cyclic loading. Emphasis is put on a mechanistic approach avoiding a plain reproduction of empirical laws. After a short consideration of fracture as a result of monotonic loading using fracture mechanics basics, the phenomena taking place as a consequence of cyclic plasticity are introduced. The development of fatigue damage is treated by introducing the physical processes which (i) are responsible for microstructural changes, (ii) lead to crack initiation and (iii) determine crack propagation. From the current research topics within the area of metal fatigue, two aspects are dealt with in more detail because of their relevance to biomechanics. The first one is the growth behaviour of microstructural short cracks, which controls cyclic life of smooth parts at low stress amplitudes. The second issue addresses the question of the existence of a true fatigue limit and is of particular interest for components which must sustain a very high number of loading cycles (very high cycle fatigue).

Moderate point: Balanced entropy and enthalpy contributions in soft matter

NASA Astrophysics Data System (ADS)

He, Baoji; Wang, Yanting

2017-03-01

Various soft materials share some common features, such as significant entropic effect, large fluctuations, sensitivity to thermodynamic conditions, and mesoscopic characteristic spatial and temporal scales. However, no quantitative definitions have yet been provided for soft matter, and the intrinsic mechanisms leading to their common features are unclear. In this work, from the viewpoint of statistical mechanics, we show that soft matter works in the vicinity of a specific thermodynamic state named moderate point, at which entropy and enthalpy contributions among substates along a certain order parameter are well balanced or have a minimal difference. Around the moderate point, the order parameter fluctuation, the associated response function, and the spatial correlation length maximize, which explains the large fluctuation, the sensitivity to thermodynamic conditions, and mesoscopic spatial and temporal scales of soft matter, respectively. Possible applications to switching chemical bonds or allosteric biomachines determining their best working temperatures are also briefly discussed. Project supported by the National Basic Research Program of China (Grant No. 2013CB932804) and the National Natural Science Foundation of China (Grant Nos. 11274319 and 11421063).

Aging and adipose tissue: potential interventions for diabetes and regenerative medicine.

PubMed

Palmer, Allyson K; Kirkland, James L

2016-12-15

Adipose tissue dysfunction occurs with aging and has systemic effects, including peripheral insulin resistance, ectopic lipid deposition, and inflammation. Fundamental aging mechanisms, including cellular senescence and progenitor cell dysfunction, occur in adipose tissue with aging and may serve as potential therapeutic targets in age-related disease. In this review, we examine the role of adipose tissue in healthy individuals and explore how aging leads to adipose tissue dysfunction, redistribution, and changes in gene regulation. Adipose tissue plays a central role in longevity, and interventions restricted to adipose tissue may impact lifespan. Conversely, obesity may represent a state of accelerated aging. We discuss the potential therapeutic potential of targeting basic aging mechanisms, including cellular senescence, in adipose tissue, using type II diabetes and regenerative medicine as examples. We make the case that aging should not be neglected in the study of adipose-derived stem cells for regenerative medicine strategies, as elderly patients make up a large portion of individuals in need of such therapies. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The Influence of Friction Stir Weld Tool Form and Welding Parameters on Weld Structure and Properties: Nugget Bulge in Self-Reacting Friction Stir Welds

NASA Technical Reports Server (NTRS)

Schneider, Judy; Nunes, Arthur C., Jr.; Brendel, Michael S.

2010-01-01

Although friction stir welding (FSW) was patented in 1991, process development has been based upon trial and error and the literature still exhibits little understanding of the mechanisms determining weld structure and properties. New concepts emerging from a better understanding of these mechanisms enhance the ability of FSW engineers to think about the FSW process in new ways, inevitably leading to advances in the technology. A kinematic approach in which the FSW flow process is decomposed into several simple flow components has been found to explain the basic structural features of FSW welds and to relate them to tool geometry and process parameters. Using this modelling approach, this study reports on a correlation between the features of the weld nugget, process parameters, weld tool geometry, and weld strength. This correlation presents a way to select process parameters for a given tool geometry so as to optimize weld strength. It also provides clues that may ultimately explain why the weld strength varies within the sample population.

Functions of tocopherols in the cells of plants and other photosynthetic organisms.

PubMed

Mokrosnop, V M

2014-01-01

Tocopherol synthesis has only been observed in photosynthetic organisms (plants, algae and some cyanobacteria). Tocopherol is synthesized in the inner membrane of chloroplasts and distributed between chloroplast membranes, thylakoids and plastoglobules. Physiological significance of tocopherols for human and animal is well-studied, but relatively little is known about their function in plant organisms. Among the best characterized functions oftocopherols in cells is their ability to scavenge and quench reactive oxygen species and fat-soluble by-products of oxidative stress. There are the data on the participation of different mechanisms of α-tocopherol action in protecting photosystem II (PS II) from photoinhibition both by deactivation of singlet oxygen produced by PSII and by reduction of proton permeability of thylakoid membranes, leading to acidification of lumen under high light conditions and activation of violaxanthin de-epoxidase. Additional biological activity of tocopherols, independent of its antioxidant functions have been demonstrated. Basic mechanisms for these effects are connected with the modulation of signal transduction pathways by specific tocopherols and, in some instances, by transcriptional activation of gene expression.

Intestinal mucositis: mechanisms and management.

PubMed

Keefe, Dorothy M

2007-07-01

To describe the advances in the rapidly evolving field of intestinal (or alimentary) mucositis during the past year. Major advances have been made in both the clinical and preclinical setting, with the publication of a suite of articles regarding the pathobiology and management of mucositis, as well as several articles on important basic research in the area. The mechanism of mucositis development is now understood to be much more complex than previously thought, with an interplay of host and drug factors leading to overt damage, and variation in manifestation of that damage depending on the specific region of the gut. The MASCC/ISOO management guidelines for mucositis have been updated: a recommendation for the use of palifermin in the hematology transplant setting has been added, and a couple of previous recommendations have been revoked. This marks an important milestone in mucositis, as it is the first time a drug has been available that substantially reduces the occurrence and severity of mucositis. There is still much to be done to abolish the severe toxicity of chemotherapy and radiotherapy; however, progress is accelerating, and new targeted drugs are becoming available.

Head trauma in sport and neurodegenerative disease: an issue whose time has come?

PubMed

Pearce, Neil; Gallo, Valentina; McElvenny, Damien

2015-03-01

A number of small studies and anecdotal reports have been suggested that sports involving repeated head trauma may have long-term risks of neurodegenerative disease. There are now plausible mechanisms for these effects, and a recognition that these problems do not just occur in former boxers, but in a variety of sports involving repeated concussions, and possibly also in sports in which low-level head trauma is common. These neurodegenerative effects potentially include increased risks of impaired cognitive function and dementia, Parkinson's disease, and amyotrophic lateral sclerosis. Many would argue for taking a precautionary approach and immediately banning or restricting sports such as boxing. However, there are important public health issues in terms of how wide the net should be cast in terms of other sports, and what remedial measures could be taken? This in turn requires a major research effort involving both clinical and basic research to understand the underlying mechanisms, leading from head trauma to neurodegenerative disease and epidemiologic studies to assess the long-term consequences. Copyright © 2015 Elsevier Inc. All rights reserved.

Multimodal second harmonic generation and two photon fluorescence imaging of microdomain calcium contraction coupling in single cardiomyocytes

NASA Astrophysics Data System (ADS)

Chan, James; Awasthi, Samir; Izu, Leighton; Mao, Ziliang; Jian, Zhong; Landas, Trevor; Lerner, Aaron; Shimkunas, Rafael; Woldeyesus, Rahwa; Bossuyt, Julie; Wood, Brittani; Chen, Yi-Je; Matthews, Dennis; Lieu, Deborah; Chiamvimonvat, Nipavan; Lam, Kit; Chen-Izu, Ye

2016-11-01

The objective of this study was to develop a method for simultaneously measuring the calcium and contraction dynamics of single, live cardiomyocytes at high spatial resolutions. Such measurements are important to investigate local calcium release and the mechanical response at the sarcomere level (i.e. the basic unit of contraction), which have important implications in cardiac dysfunction and arrhythmias in conditions such as hypertension, atrial fibrillation, and myocardial infarction. Here, we describe a multimodal second harmonic generation (SHG) and two photon fluorescence (2PF) microscopy technique that is used to simultaneously measure subsarcomere calcium and contraction events at high spatial and temporal resolutions. The method takes advantage of the label-free nature of SHG for imaging the sarcomeres and the high spatial colocalization of the SHG signal and the fluorescence signal excited from calcium indicators. This microscope was used to measure calcium sparks and waves and associated contractions in subcellular microdomains, leading to the generation of subcellular strain. We anticipate this new imaging tool will play an important role in studying mechanical stress-induced heart disease.

The effect on slurry water as a fresh water replacement in concrete properties

NASA Astrophysics Data System (ADS)

Kadir, Aeslina Abdul; Shahidan, Shahiron; Hai Yee, Lau; Ikhmal Haqeem Hassan, Mohd; Bakri Abdullah, Mohd Mustafa Al

2016-06-01

Concrete is the most widely used engineering material in the world and one of the largest water consuming industries. Consequently, the concrete manufacturer, ready mixed concrete plant is increased dramatically due to high demand from urban development project. At the same time, slurry water was generated and leading to environmental problems. Thus, this paper is to investigate the effect of using slurry water on concrete properties in term of mechanical properties. The basic wastewater characterization was investigated according to USEPA (Method 150.1 & 300.0) while the mechanical property of concrete with slurry water was compared according to ASTM C1602 and BS EN 1008 standards. In this research, the compressive strength, modulus of elasticity and tensile strength were studied. The percentage of wastewater replaced in concrete mixing was ranging from 0% up to 50%. In addition, the resulted also suggested that the concrete with 20% replacement of slurry water was achieved the highest compressive strength and modulus of elasticity compared to other percentages. Moreover, the results also recommended that concrete with slurry water mix have better compressive strength compared to control mix concrete.

The Impact of Sleep Deprivation on the Brain

PubMed

Trošt Bobić, Tatjana; Šečić, Ana; Zavoreo, Iris; Matijević, Valentina; Filipović, Branimir; Kolak, Željka; Bašić Kes, Vanja; Ciliga, Dubravka; Sajković, Dubravka

2016-09-01

Each sleep phase is characterized by specific chemical, cellular and anatomic events of vital importance for normal neural functioning. Different forms of sleep deprivation may lead to a decline of cognitive functions in individuals. Studies in this field make a distinction between total sleep deprivation, chronic sleep restriction, and the situation of sleep disruption. Investigations covering the acute effects of sleep deprivation on the brain show that the discovered behavioral deficits in most cases regenerate after two nights of complete sleep. However, some studies done on mice emphasize the possible chronic effects of long-term sleep deprivation or chronic restriction on the occurrence of neurodegenerative diseases such as Alzheimer’s disease and dementia. In order to better understand the acute and chronic effects of sleep loss, the mechanisms of neural adaptation in the situations of insufficient sleep need to be further investigated. Future integrative research on the impact of sleep deprivation on neural functioning measured through the macro level of cognitive functions and the micro molecular and cell level could contribute to more accurate conclusions about the basic cellular mechanisms responsible for the detected behavioral deficits occurring due to sleep deprivation.

Gene- and cell-based bio-artificial pacemaker: what basic and translational lessons have we learned?

PubMed Central

Li, RA

2012-01-01

Normal rhythms originate in the sino-atrial node, a specialized cardiac tissue consisting of only a few thousands of pacemaker cells. Malfunction of pacemaker cells due to diseases or aging leads to rhythm generation disorders (for example, bradycardias and sick-sinus syndrome (SSS)), which often necessitate the implantation of electronic pacemakers. Although effective, electronic devices are associated with such shortcomings as limited battery life, permanent implantation of leads, lead dislodging, the lack of autonomic responses and so on. Here, various gene- and cell-based approaches, with a particular emphasis placed on the use of pluripotent stem cells and the hyperpolarization-activated cyclic nucleotide-gated-encoded pacemaker gene family, that have been pursued in the past decade to reconstruct bio-artificial pacemakers as alternatives will be discussed in relation to the basic biological insights and translational regenerative potential. PMID:22673497

Gene- and cell-based bio-artificial pacemaker: what basic and translational lessons have we learned?

PubMed

Li, R A

2012-06-01

Normal rhythms originate in the sino-atrial node, a specialized cardiac tissue consisting of only a few thousands of nodal pacemaker cells. Malfunction of pacemaker cells due to diseases or aging leads to rhythm generation disorders (for example, bradycardias and sick-sinus syndrome (SSS)), which often necessitate the implantation of electronic pacemakers. Although effective, electronic devices are associated with such shortcomings as limited battery life, permanent implantation of leads, lead dislodging, the lack of autonomic responses and so on. Here, various gene- and cell-based approaches, with a particular emphasis placed on the use of pluripotent stem cells and the hyperpolarization-activated cyclic nucleotide-gated-encoded pacemaker gene family, that have been pursued in the past decade to reconstruct bio-artificial pacemakers as alternatives will be discussed in relation to the basic biological insights and translational regenerative potential.

Morphometric, densitometric and mechanical properties of mandibular deciduous teeth in 5-month-old Polish Merino sheep

PubMed Central

2014-01-01

Background Caries, enamel hypoplasia, molar incisor hipomineralization, amylogenesis imperfecta, dentine dysplasia, hypophosphatasia and other dental disorders lead to tooth mineralization disturbances and structural abnormalities, decreasing masticatory organ functions. Dental disorders in sheep can lead to premature slaughter before they have attained final stage of their reproductive life and induce economic loss due to high flock replacement costs. Growth rate, health status and meat quality of sheep depends on tooth properties and quality determining in large extent efficiency of the masticatory apparatus and initial food break up. Considering lack of basic anatomical and physiological data on teeth properties in sheep, the aim of the study was to evaluate morphometric, densitometric and mechanical traits of deciduous mandibular incisor, canine and the second premolar obtained at the slaughter age of 5 months of life. Results The obtained results have shown the highest values of weight, total tooth volume, enamel volume and dentine volume in second premolar. Morphometric and mechanical parameters of incisors reached the highest values in first incisor and decreased gradually in second and third incisor, and in canine. Densitometric measurements have not revealed significant differences of the volumetric tooth mineral density in hard dental tissues between the investigated teeth. Conclusions In conclusion, proposed methodological approach is noninvasive since the deciduous teeth undergo physiological replacement with permanent teeth. Deciduous teeth can be easy collected for analyses from large animal population and may reflect mineral status and metabolism resulting from postnatal growth and development of the whole flock. In individual cases, evaluation of properties of deciduous teeth may serve for breeding selection and further reproduction of sheep possessing favorable traits of teeth and better masticatory system functions. PMID:24548814

Von Neumann's impossibility proof: Mathematics in the service of rhetorics

NASA Astrophysics Data System (ADS)

Dieks, Dennis

2017-11-01

According to what has become a standard history of quantum mechanics, in 1932 von Neumann persuaded the physics community that hidden variables are impossible as a matter of principle, after which leading proponents of the Copenhagen interpretation put the situation to good use by arguing that the completeness of quantum mechanics was undeniable. This state of affairs lasted, so the story continues, until Bell in 1966 exposed von Neumann's proof as obviously wrong. The realization that von Neumann's proof was fallacious then rehabilitated hidden variables and made serious foundational research possible again. It is often added in recent accounts that von Neumann's error had been spotted almost immediately by Grete Hermann, but that her discovery was of no effect due to the dominant Copenhagen Zeitgeist. We shall attempt to tell a story that is more historically accurate and less ideologically charged. Most importantly, von Neumann never claimed to have shown the impossibility of hidden variables tout court, but argued that hidden-variable theories must possess a structure that deviates fundamentally from that of quantum mechanics. Both Hermann and Bell appear to have missed this point; moreover, both raised unjustified technical objections to the proof. Von Neumann's argument was basically that hidden-variables schemes must violate the ;quantum principle; that physical quantities are to be represented by operators in a Hilbert space. As a consequence, hidden-variables schemes, though possible in principle, necessarily exhibit a certain kind of contextuality. As we shall illustrate, early reactions to Bohm's theory are in agreement with this account. Leading physicists pointed out that Bohm's theory has the strange feature that pre-existing particle properties do not generally reveal themselves in measurements, in accordance with von Neumann's result. They did not conclude that the ;impossible was done; and that von Neumann had been shown wrong.

A New Folding Kinetic Mechanism for Human Transthyretin and the Influence of the Amyloidogenic V30M Mutation.

PubMed

Jesus, Catarina S H; Almeida, Zaida L; Vaz, Daniela C; Faria, Tiago Q; Brito, Rui M M

2016-08-31

Protein aggregation into insoluble amyloid fibrils is the hallmark of several neurodegenerative diseases, chief among them Alzheimer's and Parkinson's. Although caused by different proteins, these pathologies share some basic molecular mechanisms with familial amyloidotic polyneuropathy (FAP), a rare hereditary neuropathy caused by amyloid formation and deposition by transthyretin (TTR) in the peripheral and autonomic nervous systems. Among the amyloidogenic TTR mutations known, V30M-TTR is the most common in FAP. TTR amyloidogenesis (ATTR) is triggered by tetramer dissociation, followed by partial unfolding and aggregation of the low conformational stability monomers formed. Thus, tetramer dissociation kinetics, monomer conformational stability and competition between refolding and aggregation pathways do play a critical role in ATTR. Here, we propose a new model to analyze the refolding kinetics of WT-TTR and V30M-TTR, showing that at pH and protein concentrations close to physiological, a two-step mechanism with a unimolecular first step followed by a second-order second step adjusts well to the experimental data. Interestingly, although sharing the same kinetic mechanism, V30M-TTR refolds at a much slower rate than WT-TTR, a feature that may favor the formation of transient species leading to kinetic partition into amyloidogenic pathways and, thus, significantly increasing the probability of amyloid formation in vivo.

A New Folding Kinetic Mechanism for Human Transthyretin and the Influence of the Amyloidogenic V30M Mutation

PubMed Central

Jesus, Catarina S. H.; Almeida, Zaida L.; Vaz, Daniela C.; Faria, Tiago Q.; Brito, Rui M. M.

2016-01-01

Protein aggregation into insoluble amyloid fibrils is the hallmark of several neurodegenerative diseases, chief among them Alzheimer’s and Parkinson’s. Although caused by different proteins, these pathologies share some basic molecular mechanisms with familial amyloidotic polyneuropathy (FAP), a rare hereditary neuropathy caused by amyloid formation and deposition by transthyretin (TTR) in the peripheral and autonomic nervous systems. Among the amyloidogenic TTR mutations known, V30M-TTR is the most common in FAP. TTR amyloidogenesis (ATTR) is triggered by tetramer dissociation, followed by partial unfolding and aggregation of the low conformational stability monomers formed. Thus, tetramer dissociation kinetics, monomer conformational stability and competition between refolding and aggregation pathways do play a critical role in ATTR. Here, we propose a new model to analyze the refolding kinetics of WT-TTR and V30M-TTR, showing that at pH and protein concentrations close to physiological, a two-step mechanism with a unimolecular first step followed by a second-order second step adjusts well to the experimental data. Interestingly, although sharing the same kinetic mechanism, V30M-TTR refolds at a much slower rate than WT-TTR, a feature that may favor the formation of transient species leading to kinetic partition into amyloidogenic pathways and, thus, significantly increasing the probability of amyloid formation in vivo. PMID:27589730

Basic Research on the Composition of Heavy Cosmic Rays: The Trans-Iron Galactic Element Recorder Experiment (TIGER)

NASA Technical Reports Server (NTRS)

Binns, W. Robert

2004-01-01

Among the most fundamental astrophysical problems is understanding the mechanism by which particles are accelerated to the enormous energies observed in the cosmic rays. That problem can be conveniently divided into two questions: (1) What is the source of the energy and the mechanism for converting the energy of that source into the energy of individual cosmic-ray nuclei, and (2) what is the source of the material that is accelerated and the mechanism for injecting that material into the cosmic-ray accelerator? There is a general consensus that the answer to the first of these questions, for nuclei with energy eV, is that the source of their energy is almost certainly from supernova explosions (e.g., Ginzburg & Syrovatskii, 1964). The answer to the second question is still uncertain, although evidence in favor of a superbubble origin of cosmic rays is becoming quite significant (Higdon et al, 2203 and Binns, 2005 (Submitted to ApJ). There are several ways of interpreting available data that lead to quite different models for the source of the material and its injection mechanism. With the The Trans-Iron Galactic Element Recorder Experiment (TIGER) instrument we have obtained data that will help to distinguish among these possible models. In the report, the TIGER flights, the instrument itself, results, and a publication list as a result of the work are presented.

pH-Dependence of Binding Constants and Desorption Rates of Phosphonate- and Hydroxamate-Anchored [Ru(bpy)3]2+ on TiO2 and WO3.

PubMed

Esarey, Samuel L; Bartlett, Bart M

2018-04-17

The binding constants and rate constants for desorption of the modified molecular dye [Ru(bpy) 3 ] 2+ anchored by either phosphonate or hydroxamate on the bipyridine ligand to anatase TiO 2 and WO 3 have been measured. In aqueous media at pH 1-10, repulsive electrostatic interactions between the negatively charged anchor and the negatively charged surface govern phosphonate desorption under neutral and basic conditions for TiO 2 anatase due to the high acidity of phosphonic acid (p K a,4 = 5.1). In contrast, the lower acidity of hydroxamate (p K a,1 = 6.5, p K a,2 = 9.1) leads to little change in adsorption/desorption properties as a function of pH from 1 to 7. The binding constant for hydroxamate is 10 3 in water, independent of pH in this range. These results are true for WO 3 as well, but are not reported at pH > 4 due to its Arrhenius acidity. Kinetics for desorption as a function of pH are reported, with a proposed mechanism for phosphonate desorption at high pH being the electrostatic repulsion of negative charges between the surface and the anionic anchor. Further, the hydroxamic acid anchor itself is likely the site of quasi-reversible redox activity in [Ru(bpy) 2 (2,2'-bpy-4,4'-(C(O)N(OH)) 2 )] 2+ , which does not lead to any measurable deterioration of the complex within 2 h of dark cyclic voltammogram scans in aqueous media. These results posit phosphonate as the preferred anchoring group under acidic conditions and hydroxamate for neutral/basic conditions.

Mediators of Physical Activity on Neurocognitive Function: A Review at Multiple Levels of Analysis.

PubMed

Stillman, Chelsea M; Cohen, Jamie; Lehman, Morgan E; Erickson, Kirk I

2016-01-01

Physical activity (PA) is known to maintain and improve neurocognitive health. However, there is still a poor understanding of the mechanisms by which PA exerts its effects on the brain and cognition in humans. Many of the most widely discussed mechanisms of PA are molecular and cellular and arise from animal models. While information about basic cellular and molecular mechanisms is an important foundation from which to build our understanding of how PA promotes cognitive health in humans, there are other pathways that could play a role in this relationship. For example, PA-induced changes to cellular and molecular pathways likely initiate changes to macroscopic properties of the brain and/or to behavior that in turn influence cognition. The present review uses a more macroscopic lens to identify potential brain and behavioral/socioemotional mediators of the association between PA and cognitive function. We first summarize what is known regarding cellular and molecular mechanisms, and then devote the remainder of the review to discussing evidence for brain systems and behavioral/socioemotional pathways by which PA influences cognition. It is our hope that discussing mechanisms at multiple levels of analysis will stimulate the field to examine both brain and behavioral mediators. Doing so is important, as it could lead to a more complete characterization of the processes by which PA influences neurocognitive function, as well as a greater variety of targets for modifying neurocognitive function in clinical contexts.

Basic criteria for formation of growth twins in high stacking fault energy metals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, K. Y.; Zhang, X.; Department of Mechanical Engineering, Texas A and M University, College Station, Texas 77843

Nanotwinned metals received significant interest lately as twin boundaries may enable simultaneous enhancement of strength, ductility, thermal stability, and radiation tolerance. However, nanotwins have been the privilege of metals with low-to-intermediate stacking fault energy (SFE). Recent scattered studies show that nanotwins could be introduced into high SFE metals, such as Al. In this paper, we examine several sputter-deposited, (111) textured Ag/Al, Cu/Ni, and Cu/Fe multilayers, wherein growth twins were observed in Al, Ni, and face-centered cubic (fcc) Fe. The comparisons lead to two important design criteria that dictate the introduction of growth twins in high SFE metals. The validity ofmore » these criteria was then examined in Ag/Ni multilayers. Furthermore, another twin formation mechanism in high SFE metals was discovered in Ag/Ni system.« less

Epigenetics: relevance and implications for public health.

PubMed

Rozek, Laura S; Dolinoy, Dana C; Sartor, Maureen A; Omenn, Gilbert S

2014-01-01

Improved understanding of the multilayer regulation of the human genome has led to a greater appreciation of environmental, nutritional, and epigenetic risk factors for human disease. Chromatin remodeling, histone tail modifications, and DNA methylation are dynamic epigenetic changes responsive to external stimuli. Careful interpretation can provide insights for actionable public health through collaboration between population and basic scientists and through integration of multiple data sources. We review key findings in environmental epigenetics both in human population studies and in animal models, and discuss the implications of these results for risk assessment and public health protection. To ultimately succeed in identifying epigenetic mechanisms leading to complex phenotypes and disease, researchers must integrate the various animal models, human clinical approaches, and human population approaches while paying attention to life-stage sensitivity, to generate effective prescriptions for human health evaluation and disease prevention.

Pathophysiology of white-nose syndrome in bats: a mechanistic model linking wing damage to mortality

USGS Publications Warehouse

Warnecke, Lisa; Turner, James M.; Bollinger, Trent K.; Misra, Vikram; Cryan, Paul M.; Blehert, David S.; Wibbelt, Gudrun; Willis, Craig K.R.

2013-01-01

White-nose syndrome is devastating North American bat populations but we lack basic information on disease mechanisms. Altered blood physiology owing to epidermal invasion by the fungal pathogen Geomyces destructans (Gd) has been hypothesized as a cause of disrupted torpor patterns of affected hibernating bats, leading to mortality. Here, we present data on blood electrolyte concentration, haematology and acid–base balance of hibernating little brown bats, Myotis lucifugus, following experimental inoculation with Gd. Compared with controls, infected bats showed electrolyte depletion (i.e. lower plasma sodium), changes in haematology (i.e. increased haematocrit and decreased glucose) and disrupted acid–base balance (i.e. lower CO2 partial pressure and bicarbonate). These findings indicate hypotonic dehydration, hypovolaemia and metabolic acidosis. We propose a mechanistic model linking tissue damage to altered homeostasis and morbidity/mortality.

Analysis of DNA interactions using single-molecule force spectroscopy.

PubMed

Ritzefeld, Markus; Walhorn, Volker; Anselmetti, Dario; Sewald, Norbert

2013-06-01

Protein-DNA interactions are involved in many biochemical pathways and determine the fate of the corresponding cell. Qualitative and quantitative investigations on these recognition and binding processes are of key importance for an improved understanding of biochemical processes and also for systems biology. This review article focusses on atomic force microscopy (AFM)-based single-molecule force spectroscopy and its application to the quantification of forces and binding mechanisms that lead to the formation of protein-DNA complexes. AFM and dynamic force spectroscopy are exciting tools that allow for quantitative analysis of biomolecular interactions. Besides an overview on the method and the most important immobilization approaches, the physical basics of the data evaluation is described. Recent applications of AFM-based force spectroscopy to investigate DNA intercalation, complexes involving DNA aptamers and peptide- and protein-DNA interactions are given.

Material interactions with the Low Earth Orbital (LEO) environment: Accurate reaction rate measurements

NASA Technical Reports Server (NTRS)

Visentine, James T.; Leger, Lubert J.

1987-01-01

To resolve uncertainties in estimated LEO atomic oxygen fluence and provide reaction product composition data for comparison to data obtained in ground-based simulation laboratories, a flight experiment has been proposed for the space shuttle which utilizes an ion-neutral mass spectrometer to obtain in-situ ambient density measurements and identify reaction products from modeled polymers exposed to the atomic oxygen environment. An overview of this experiment is presented and the methodology of calibrating the flight mass spectrometer in a neutral beam facility prior to its use on the space shuttle is established. The experiment, designated EOIM-3 (Evaluation of Oxygen Interactions with Materials, third series), will provide a reliable materials interaction data base for future spacecraft design and will furnish insight into the basic chemical mechanisms leading to atomic oxygen interactions with surfaces.

Synthesis of Novel Thiazole Based Carbaldehyde as Potential Sensor for Fluoride Anion and their Spectroscopic Properties.

PubMed

Tayade, Rajratna P; Sekar, Nagaiyan

2017-05-01

A novel thiazole based carbaldehyde bearing benzimidazole fluorophore as the receptor unit for F - anion was prepared by multi steps synthesis. Density functional theory was used to understand the structural and electronic properties the receptor. The anion sensing activities of receptor 4 were studied for various anions in acetonitrile solvent. The receptor showed fluorescence enhancement in the presence of fluoride anion due to intramolecular charge transfer (ICT) mechanism. No significant changes were observed upon addition of less basic anions such as OAc - , Cl - , Br - , I - , HSO 4 - . After the interaction of fluoride anion with the receptor 4 leads to an 88 nm red shift in emission maxima. [TBA]OH and 1 H NMR titration experiments indicated that deprotonation of N-H in the benzimidazole due to interaction with fluoride anions.

The short-lived African turquoise killifish: an emerging experimental model for ageing

PubMed Central

Kim, Yumi; Nam, Hong Gil; Valenzano, Dario Riccardo

2016-01-01

ABSTRACT Human ageing is a fundamental biological process that leads to functional decay, increased risk for various diseases and, ultimately, death. Some of the basic biological mechanisms underlying human ageing are shared with other organisms; thus, animal models have been invaluable in providing key mechanistic and molecular insights into the common bases of biological ageing. In this Review, we briefly summarise the major applications of the most commonly used model organisms adopted in ageing research and highlight their relevance in understanding human ageing. We compare the strengths and limitations of different model organisms and discuss in detail an emerging ageing model, the short-lived African turquoise killifish. We review the recent progress made in using the turquoise killifish to study the biology of ageing and discuss potential future applications of this promising animal model. PMID:26839399

Enhancing the efficacy of cytotoxic agents for cancer therapy using photochemical internalisation

PubMed Central

Moore, Caroline M.; Loizidou, Marilena; MacRobert, Alexander J.; Woodhams, Josephine H.

2016-01-01

Photochemical internalisation (PCI) is a technique for improving cellular delivery of certain bioactive agents which are prone to sequestration within endolysosomes. There is a wide range of agents suitable for PCI‐based delivery including toxins, oligonucleotides, genes and immunoconjugates which demonstrates the versatility of this technique. The basic mechanism of PCI involves triggering release of the agent from endolysosomes within the target cells using a photosensitiser which is selectively retained with the endolysosomal membranes. Excitation of the photosensitiser by visible light leads to disruption of the membranes via photooxidative damage thereby releasing the agent into the cytosol. This treatment enables the drugs to reach their intended subcellular target more efficiently and improves their efficacy. In this review we summarise the applications of this technique with the main emphasis placed on cancer chemotherapy. PMID:25758607

Research progress on combat trauma treatment in cold regions.

PubMed

Wang, Hui-Shan; Han, Jin-Song

2014-01-01

Cold regions are a special combat environment in which low temperatures have a great impact on human metabolism and other vital functions, including the nervous, motion, cardiovascular, circulatory, respiratory, and urinary systems; consequently, low temperatures often aggravate existing trauma, leading to high mortality rates if rapid and appropriate treatment is not provided. Hypothermia is an independent risk factor of fatality following combat trauma; therefore, proactive preventative measures are needed to reduce the rate of mortality. After summarizing the basic research on battlefield environments and progress in the prevention and treatment of trauma, this article concludes that current treatment and prevention measures for combat trauma in cold regions are inadequate. Future molecular biology studies are needed to elucidate the mechanisms and relevant cell factors underlying bodily injury caused by cold environment, a research goal will also allow further exploration of corresponding treatments.

Ergonomics content in the physical education teacher's guide in Rwanda.

PubMed

Nellutla, Manobhiram; Patel, Hetal; Kabanda, Aline; Nuhu, Assuman

2012-01-01

An important aspect that affects the effectiveness of ergonomic programs is that inefficient mechanical functioning start at an early age and that back pain and posture problems are already evident in children. Children, from a very early age, as well as adults spend an ever increasing amount of their time in front of computer and television screens. The cumulative effect of this sedentary lifestyle leads to improper posture, as well as inefficient and harmful movement patterns and loss of basic physical skills. Physical Education course should deal not only with sports and physical activities, but also with broader aspects of life-skills and physical functionality. It should offer a solution to the modern technology-based society. Keeping this in perspective, Ergonomics content was introduced in Physical Education Teacher's Guide in Rwandan schools with an aim in preventing musculoskeletal disorder in children.

Systemic and localized scleroderma.

PubMed

Chung, Lorinda; Lin, Jan; Furst, Daniel E; Fiorentino, David

2006-01-01

Sclerosing conditions of the skin are manifested by a full spectrum of presentations that includes skin-limited forms as well as those which can involve internal organs and result in death. At this point, we are just beginning to understand the mechanisms of tissue fibrosis, and it is likely that the fibrotic processes are a heterogeneous group of disorders in which perturbation of multiple molecular pathways, including vascular and immunologically mediated pathways, can lead to fibrosis. We now have some moderately effective therapies for vascular aspects of systemic sclerosis (eg, bosentan for pulmonary arterial hypertension, calcium-channel blockers for Raynaud's, or angiotensin-converting enzyme inhibitors for renal crisis). We also are beginning to find treatments interrupting the immunologic pathways that manifest as systemic sclerosis (eg, methotrexate for the skin or cyclophosphamide for the lungs). The basic process of fibrosis, however, awaits proven, effective therapy.

Social Ecology, Genomics, and African American Health: A Nonlinear Dynamical Perspective

PubMed Central

Madhere, Serge; Harrell, Jules; Royal, Charmaine D. M.

2009-01-01

This article offers a model that clarifies the degree of interdependence between social ecology and genomic processes. Drawing on principles from nonlinear dynamics, the model delineates major lines of bifurcation involving people's habitat, their family health history, and collective catastrophes experienced by their community. It shows how mechanisms of resource acquisition, depletion, and preservation can lead to disruptions in basic metabolism and in the activity of cytokines, neurotransmitters, and protein kinases, thus giving impetus to epigenetic changes. The hypotheses generated from the model are discussed throughout the article for their relevance to health problems among African Americans. Where appropriate, they are examined in light of data from the National Vital Statistics System. Multiple health outcomes are considered. For any one of them, the model makes clear the unique and converging contributions of multiple antecedent factors. PMID:19672481

Enhancement in photoluminescence performance of carbon-decorated T-ZnO

NASA Astrophysics Data System (ADS)

Jian, Xian; Chen, Guozhang; Wang, Chao; Yin, Liangjun; Li, Gang; Yang, Ping; Chen, Lei; Xu, Bao; Gao, Yang; Feng, Yanyu; Tang, Hui; Luan, Chunhong; Liang, Yinglin; Jiang, Jing; Cao, Yu; Wang, Siyuan; Gao, Xin

2015-03-01

The facile preparation of ZnO possessing high visible luminescence intensity remains challenging due to an unclear luminescence mechanism. Here, two basic approaches are proposed to enhance the luminescent intensity based on the theoretical analysis over surface defects. Based on the deduction, we introduce a methodology for obtaining hybrid tetrapod-like zinc oxide (T-ZnO), decorated by carbon nanomarterials on T-ZnO surfaces through the catalytic chemical vapor deposition approach. The intensity of the T-ZnO green emission can be modulated by topography and the proportion of carbon. Under proper experiment conditions, the carbon decorating leads to dramatically enhanced luminescence intensity of T-ZnO from 400 to 700 nm compared with no carbon decorated, which elevates this approach to a simple and effective method for the betterment of fluorescent materials in practical applications.

Particles, Waves, and the Interpretation of Quantum Mechanics

ERIC Educational Resources Information Center

Christoudouleas, N. D.

1975-01-01

Presents an explanation, without mathematical equations, of the basic principles of quantum mechanics. Includes wave-particle duality, the probability character of the wavefunction, and the uncertainty relations. (MLH)

General morphological and biological features of neoplasms: integration of molecular findings.

PubMed

Diaz-Cano, S J

2008-07-01

This review highlights the importance of morphology-molecular correlations for a proper implementation of new markers. It covers both general aspects of tumorigenesis (which are normally omitted in papers analysing molecular pathways) and the general mechanisms for the acquired capabilities of neoplasms. The mechanisms are also supported by appropriate diagrams for each acquired capability that include overlooked features such as mobilization of cellular resources and changes in chromatin, transcription and epigenetics; fully accepted oncogenes and tumour suppressor genes are highlighted, while the pathways are also presented as activating or inactivating with appropriate colour coding. Finally, the concepts and mechanisms presented enable us to understand the basic requirements for the appropriate implementation of molecular tests in clinical practice. In summary, the basic findings are presented to serve as a bridge to clinical applications. The current definition of neoplasm is descriptive and difficult to apply routinely. Biologically, neoplasms develop through acquisition of capabilities that involve tumour cell aspects and modified microenvironment interactions, resulting in unrestricted growth due to a stepwise accumulation of cooperative genetic alterations that affect key molecular pathways. The correlation of these molecular aspects with morphological changes is essential for better understanding of essential concepts as early neoplasms/precancerous lesions, progression/dedifferentiation, and intratumour heterogeneity. The acquired capabilities include self-maintained replication (cell cycle dysregulation), extended cell survival (cell cycle arrest, apoptosis dysregulation, and replicative lifespan), genetic instability (chromosomal and microsatellite), changes of chromatin, transcription and epigenetics, mobilization of cellular resources, and modified microenvironment interactions (tumour cells, stromal cells, extracellular, endothelium). The acquired capabilities defining neoplasms are the hallmarks of cancer, but they also comprise useful tools to improve diagnosis and prognosis, as well as potential therapeutic targets. The application of these concepts in oncological pathology leads to consideration of the molecular test requirements (Molecular Test Score System) for reliable implementation; these requirements should cover biological effects, molecular pathway, biological validation, and technical validation. Sensible application of molecular markers in tumour pathology always needs solid morphological support.

Basic Mechanisms of the Epilepsies.

ERIC Educational Resources Information Center

Jasper, Herbert H., Ed.; And Others

A collection of highly technical scientific articles by international basic and clinical neuroscientists constitutes a review of their knowledge of the brain and nervous system, particularly the aspects related to loss of brain function control and its explosive discharges which cause epileptic seizures. Anatomy, biophysics, biochemistry, and…

Lessons for Young Scholars Seeking to Publish.

ERIC Educational Resources Information Center

Natriello, Gary

1996-01-01

The lessons offered are in three groups: basic lessons related to social behaviors; lessons related to the basic mechanics of putting together a paper to submit to a journal; and lessons regarding matching the study to the substantive and stylistic preferences of a particular journal. (SM)

Lead Exposure in Military Outdoor Firing Ranges.

PubMed

Greenberg, Nili; Frimer, Ron; Meyer, Robert; Derazne, Estella; Chodick, Gabrial

2016-09-01

Several studies have reported significant airborne lead exposures during training at indoor firing ranges. Scarce attention has been given to airborne lead exposures in outdoor shooting ranges with automatic weapons. To assess the prevalence and magnitude of airborne and blood lead levels (BLL) among firing instructors and shooters in military outdoor ranges. Exposure assessment, for both trainees and instructors, included airborne and BLL during basic and advanced training at outdoor firing ranges. Personal airborne samples were collected in both day and night shooting during both training periods. During basic training, there is 95% likelihood that up to 25% of instructors and 99% likelihood that up to 5% of trainees might be exposed above the action level (AL) (25 μg/m(3)). During advanced training, there is 90% likelihood that 10% of instructors and 99% likelihood that up to 10% of trainees might be exposed above the AL. Military personnel participating in automatic weapon marksmanship training can be exposed to considerable levels of airborne lead during outdoor firing range training. As a result, the Israel Defense Force Medical Corp has classified firing range instructors as workers that require periodic medical examinations. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

Quinolone-based IMPDH inhibitors: introduction of basic residues on ring D and SAR of the corresponding mono, di and benzofused analogues.

PubMed

Dhar, T G Murali; Watterson, Scott H; Chen, Ping; Shen, Zhongqi; Gu, Henry H; Norris, Derek; Carlsen, Marianne; Haslow, Kristin D; Pitts, William J; Guo, Junqing; Chorba, John; Fleener, Catherine A; Rouleau, Katherine A; Townsend, Robert; Hollenbaugh, Diane; Iwanowicz, Edwin J

2003-02-10

The synthesis and the structure-activity relationships (SAR) of analogues derived from the introduction of basic residues on ring D of quinolone-based inhibitors of IMPDH are described. This led to the identification of compound 27 as a potent inhibitor of IMPDH with significantly improved aqueous solubility over the lead compound 1.

General anesthetics and cytotoxicity: possible implications for brain health.

PubMed

Armstrong, Ryden; Xu, Fenglian; Arora, Anish; Rasic, Nivez; Syed, Naweed I

2017-04-01

The search for agents that bring about faster induction and quicker recovery in the operating room have yielded numerous anesthetics whose mechanisms of action and potential toxic side effects remain unknown, especially in the young and aging brain. Taking advantage of our clinical and basic science expertise, here we subject the reader to an interesting perspective vis-à-vis the current applications of general anesthetics, and present evidence for their neurotoxic effects on the developing and elderly brains. Recent studies have called into question the safety of general anesthetics, especially with regards to potentially significant detrimental impacts on the developing brains of young children, and cognitive decline in the elderly - often following multiple episodes of anesthesia. Despite accumulating evidence from animal studies demonstrating that general anesthesia leads to neurodegeneration and cognitive impairment, to date a clear consensus on the impact of anesthetics in humans remains elusive. Because a direct impact of anesthetics on human neuronal networks is often difficult to deduce experimentally, most laboratories have resorted to animal models - albeit with limited success in translating these findings back to the clinic. Moreover, the precise mechanisms that lead to potential cognitive, learning, and memory decline in young and elderly patients also remain to be fully defined. This review will focus primarily on the cytotoxic effects of anesthetics, and offer some practical resolutions that may attenuate their long-term harm. An urgent need for studies on animal models and an increased focus on highly controlled prospective epidemiological studies is also reinforced.

Threshold Laws for Two-Electron Ejection Processes: A Still Controversial Problem in Atomic Physics

NASA Technical Reports Server (NTRS)

Temkin, Aaron

2003-01-01

This talk deals with collision processes of the following kind: (a) an ionizing collision of an electron with a neutral atom, (b) a photon incident of a negative ion resulting in two-electron ejection. In both cases the final state is a positive ion and two outgoing electrons, and in principle both processes should be governed by the same form of threshold law. It is generally conceded that this is one of the most difficult basic problems in nonrelativistic quantum mechanics. The standard treatment (due to Wannier) will be briefly reviewed in terms of the derivation of his well- known threshold law for the yield (Q) of positive ions vs. the excess energy (E): Q(sub w) varies as E(exp 1.127...). The derivation is a brilliant analysis based on Newton's equations, leading to the dominance of events in which the two electrons emerge on opposite sides of the residual ion with similar energies. In contrast, I will argue on the basis of quantum mechanical ideas that in the threshold limit the more likely outcome are events in which the electrons emerge with decidedly different energies, leading to a formally different (Coulomb-dipole) threshold law Q(sub CD) varies as E(1 + C sin(alpha ln(E)+mu)]/[ln(E)](exp 2). Additional aspects of that approach will be discussed . Some: experimental results will be presented, and more incisive predictions involving polarized projectiles and targets will be given.

Influence of platelet aspect ratio on the mechanical behaviour of bio-inspired nanocomposites using molecular dynamics.

PubMed

Mathiazhagan, S; Anup, S

2016-06-01

Superior mechanical properties of biocomposites such as nacre and bone are attributed to their basic building blocks. These basic building blocks have nanoscale features and play a major role in achieving combined stiffening, strengthening and toughening mechanisms. Bioinspired nanocomposites based on these basic building blocks, regularly and stairwise staggered arrangements of hard platelets in soft matrix, have huge potential for developing advanced materials. The study of applicability of mechanical principles of biological materials to engineered materials will guide designing advanced materials. To probe the generic mechanical characteristics of these bioinspired nanocomposites, the model material concept in molecular dynamics (MD) is used. In this paper, the effect of platelets aspect ratio (AR) on the mechanical behaviour of bioinspired nanocomposites is investigated. The obtained Young׳s moduli of both the models and the strengths of the regularly staggered models agree with the available theories. However, the strengths of the stairwise staggered models show significant difference. For the stairwise staggered model, we demonstrate the existence of two critical ARs, a smaller critical AR above which platelet fracture occurs and a higher critical AR above which composite strength remains constant. Our MD study also shows the existence of mechanisms of platelet pull-out and breakage for lower and higher ARs. Pullout mechanism acts as a major source of plasticity. Further, we find that the regularly staggered model can achieve an optimal combination of high Young׳s modulus, flow strength and toughness, and the stairwise staggered model is efficient in obtaining high Young׳s modulus and tensile strength. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tendon basic science: Development, repair, regeneration, and healing.

PubMed

Andarawis-Puri, Nelly; Flatow, Evan L; Soslowsky, Louis J

2015-06-01

Tendinopathy and tendon rupture are common and disabling musculoskeletal conditions. Despite the prevalence of these injuries, a limited number of investigators are conducting fundamental, basic science studies focused on understanding processes governing tendinopathies and tendon healing. Development of effective therapeutics is hindered by the lack of fundamental guiding data on the biology of tendon development, signal transduction, mechanotransduction, and basic mechanisms underlying tendon pathogenesis and healing. To propel much needed progress, the New Frontiers in Tendon Research Conference, co-sponsored by NIAMS/NIH, the Orthopaedic Research Society, and the Icahn School of Medicine at Mount Sinai, was held to promote exchange of ideas between tendon researchers and basic science experts from outside the tendon field. Discussed research areas that are underdeveloped and represent major hurdles to the progress of the field will be presented in this review. To address some of these outstanding questions, conference discussions and breakout sessions focused on six topic areas (Cell Biology and Mechanics, Functional Extracellular Matrix, Development, Mechano-biology, Scarless Healing, and Mechanisms of Injury and Repair), which are reviewed in this special issue and briefly presented in this review. Review articles in this special issue summarize the progress in the field and identify essential new research directions. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Unit mechanisms of fission gas release: Current understanding and future needs

DOE PAGES

Tonks, Michael; Andersson, David; Devanathan, Ram; ...

2018-03-01

Gaseous fission product transport and release has a large impact on fuel performance, degrading fuel and gap properties. While gaseous fission product behavior has been investigated with bulk reactor experiments and simplified analytical models, recent improvements in experimental and modeling approaches at the atomistic and mesoscales are beginning to reveal new understanding of the unit mechanisms that define fission product behavior. Here, existing research on the basic mechanisms of fission gas release during normal reactor operation are summarized and critical areas where work is needed are identified. Here, this basic understanding of the fission gas behavior mechanisms has the potentialmore » to revolutionize our ability to predict fission product behavior and to design fuels with improved performance. In addition, this work can serve as a model on how a coupled experimental and modeling approach can be applied to understand the unit mechanisms behind other critical behaviors in reactor materials.« less

Unit mechanisms of fission gas release: Current understanding and future needs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tonks, Michael; Andersson, David; Devanathan, Ram

Gaseous fission product transport and release has a large impact on fuel performance, degrading fuel and gap properties. While gaseous fission product behavior has been investigated with bulk reactor experiments and simplified analytical models, recent improvements in experimental and modeling approaches at the atomistic and mesoscales are beginning to reveal new understanding of the unit mechanisms that define fission product behavior. Here, existing research on the basic mechanisms of fission gas release during normal reactor operation are summarized and critical areas where work is needed are identified. Here, this basic understanding of the fission gas behavior mechanisms has the potentialmore » to revolutionize our ability to predict fission product behavior and to design fuels with improved performance. In addition, this work can serve as a model on how a coupled experimental and modeling approach can be applied to understand the unit mechanisms behind other critical behaviors in reactor materials.« less

Unit mechanisms of fission gas release: Current understanding and future needs

NASA Astrophysics Data System (ADS)

Tonks, Michael; Andersson, David; Devanathan, Ram; Dubourg, Roland; El-Azab, Anter; Freyss, Michel; Iglesias, Fernando; Kulacsy, Katalin; Pastore, Giovanni; Phillpot, Simon R.; Welland, Michael

2018-06-01

Gaseous fission product transport and release has a large impact on fuel performance, degrading fuel and gap properties. While gaseous fission product behavior has been investigated with bulk reactor experiments and simplified analytical models, recent improvements in experimental and modeling approaches at the atomistic and mesoscales are beginning to reveal new understanding of the unit mechanisms that define fission product behavior. Here, existing research on the basic mechanisms of fission gas release during normal reactor operation are summarized and critical areas where work is needed are identified. This basic understanding of the fission gas behavior mechanisms has the potential to revolutionize our ability to predict fission product behavior and to design fuels with improved performance. In addition, this work can serve as a model on how a coupled experimental and modeling approach can be applied to understand the unit mechanisms behind other critical behaviors in reactor materials.

Evaluation of Scanners for C-Scan Imaging for Nondestructive Inspection of Aircraft

DTIC Science & Technology

1994-09-01

mechanized and nonmechanized designs. * The basic scanner designs were divided for the purposes of this report into eight different Stypes. These are 1...electronic switching through the transducer elements of the array. The basic scanner designs were divided for the purposes of this report into eight...of this project was to evaluate all the basic scanner types that are appropriate for aircraft NDI examinations. A number of vendors sell very similar

Mechanics: Statics; A Syllabus.

ERIC Educational Resources Information Center

Compo, Louis

The instructor's guide presents material for structuring an engineering fundamentals course covering the basic laws of statistics as part of a mechanical technology program. Detailed behavioral objectives are described for the following five areas of course content: principles of mechanics, two-dimensional equilibrium, equilibrium of internal…

Mechanism of oxygen electroreduction on gold surfaces in basic media.

PubMed

Kim, Jongwon; Gewirth, Andrew A

2006-02-16

The mechanism of the electroreduction of oxygen on Au surfaces in basic media is examined using surface-enhanced Raman scattering (SERS) measurements and density functional theory (DFT) calculations. The spectroscopy reveals superoxide species as a reduction intermediate throughout the oxygen electroreduction, while no peroxide is detected. The spectroscopy also shows the presence of superoxide after the addition of hydrogen peroxide. The calculations show no effect of OH addition to the Au(100) surface with regard to O-O length. These results suggest that the four-electron reduction of O(2) on Au(100) in base arises from a disproportionation mechanism which is enhanced on Au(100) relative to the other two low Miller index faces of Au.

Mechanisms of flame stabilisation at low lifted height in a turbulent lifted slot-jet flame

DOE PAGES

Karami, Shahram; Hawkes, Evatt R.; Talei, Mohsen; ...

2015-07-23

A turbulent lifted slot-jet flame is studied using direct numerical simulation (DNS). A one-step chemistry model is employed with a mixture-fraction-dependent activation energy which can reproduce qualitatively the dependence of the laminar burning rate on the equivalence ratio that is typical of hydrocarbon fuels. The basic structure of the flame base is first examined and discussed in the context of earlier experimental studies of lifted flames. Several features previously observed in experiments are noted and clarified. Some other unobserved features are also noted. Comparison with previous DNS modelling of hydrogen flames reveals significant structural differences. The statistics of flow andmore » relative edge-flame propagation velocity components conditioned on the leading edge locations are then examined. The results show that, on average, the streamwise flame propagation and streamwise flow balance, thus demonstrating that edge-flame propagation is the basic stabilisation mechanism. Fluctuations of the edge locations and net edge velocities are, however, significant. It is demonstrated that the edges tend to move in an essentially two-dimensional (2D) elliptical pattern (laterally outwards towards the oxidiser, then upstream, then inwards towards the fuel, then downstream again). It is proposed that this is due to the passage of large eddies, as outlined in Suet al.(Combust. Flame, vol. 144 (3), 2006, pp. 494–512). However, the mechanism is not entirely 2D, and out-of-plane motion is needed to explain how flames escape the high-velocity inner region of the jet. Finally, the time-averaged structure is examined. A budget of terms in the transport equation for the product mass fraction is used to understand the stabilisation from a time-averaged perspective. The result of this analysis is found to be consistent with the instantaneous perspective. The budget reveals a fundamentally 2D structure, involving transport in both the streamwise and transverse directions, as opposed to possible mechanisms involving a dominance of either one direction of transport. Furthermore, it features upstream transport balanced by entrainment into richer conditions, while on the rich side, upstream turbulent transport and entrainment from leaner conditions balance the streamwise convection.« less

High-Temperature High-Current Superconductors: Preparation, Structure, Superconducting Properties, and Flux-Pinning Mechanisms

NASA Astrophysics Data System (ADS)

Hu, Shouxiang

In bulk high-T_{rm c } superconductors, weak links at the grain boundaries and weak flux pinning are the two major causes of low critical current density (J_{ rm c}) at 77 K. In the present study, various processes designed and developed to address these problems are discussed. The novel pressurized-partial -melt-growth process, which leads to a relatively large improvement in the microstructure as well as in the superconducting properties of bulk Y-Ba-Cu-O superconductors, is described. The effects of introducing foreign elements to serve as pinning centers are reported, and the associated anomalous superconducting phenomena are explained on the basis of a detailed study of basic pinning mechanisms related to the presence of small defects. It is demonstrated that in certain cases the pinning force induced by the compression of the vortex line may be comparable to, or even larger than, the usually recognized pinning force due to the condensation energy. Studies of the pinning mechanism corresponding to large boundary defects show that boundary defects associated with certain non-superconducting inclusions and isolated weak links have a very positive role in the enhancement of both the critical current density and the effective activation energy for flux creep. However, even optimized theoretical estimates show that it will be difficult to reach J_ {rm c} values of 5 times 10^5 A/cm^2 at 77 K and H = 1 T by increasing the number of Y_2BaCuO inclusions alone. Although even higher J_{rm c} values may be achieved by introducing other types of defects using alternative approaches such as irradiation, and, probably, chemical doping, the presence of large amount of boundary defects is very important in causing a large increase in the effective activation energy for flux creep. Also studied are the anisotropic electromagnetic features of the grain-aligned YBa_2Cu _3O_{rm x} bulk superconductors. The development of novel processing methods guided by improved understanding of the basic mechanisms involved opens the way for the preparation of high-quality bulk high-T_{rm c} superconducting materials for a wide variety of applications.

Plastic Synaptic Networks of the Amygdala for the Acquisition, Expression, and Extinction of Conditioned Fear

PubMed Central

Pape, Hans-Christian; Pare, Denis

2009-01-01

The last ten years have witnessed a surge of interest for the mechanisms underlying the acquisition and extinction of classically conditioned fear responses. In part, this results from the realization that abnormalities in fear learning mechanisms likely participate to the development and/or maintenance of human anxiety disorders. The simplicity and robustness of this learning paradigm, coupled to the fact that the underlying circuitry is evolutionarily well conserved makes it an ideal model to study the basic biology of memory and identify genetic factors and neuronal systems that regulate the normal and pathological expressions of learned fear. Critical advances have been made in determining how modified neuronal functions upon fear acquisition become stabilized during fear memory consolidation and how these processes are controlled in the course of fear memory extinction. With these advances, came the realization that activity in remote neuronal networks must be coordinated for these events to take place. In this paper, we review these mechanisms of coordinated network activity and the molecular cascades leading to enduring fear memory, and allowing for their extinction. We will focus on Pavlovian fear conditioning as a model and the amygdala as a key component for the acquisition and extinction of fear responses. PMID:20393190

Theoretical analysis of the mechanisms of a gender differentiation in the propensity for orthostatic intolerance after spaceflight

PubMed Central

2010-01-01

Background A tendency to develop reentry orthostasis after a prolonged exposure to microgravity is a common problem among astronauts. The problem is 5 times more prevalent in female astronauts as compared to their male counterparts. The mechanisms responsible for this gender differentiation are poorly understood despite many detailed and complex investigations directed toward an analysis of the physiologic control systems involved. Methods In this study, a series of computer simulation studies using a mathematical model of cardiovascular functioning were performed to examine the proposed hypothesis that this phenomenon could be explained by basic physical forces acting through the simple common anatomic differences between men and women. In the computer simulations, the circulatory components and hydrostatic gradients of the model were allowed to adapt to the physical constraints of microgravity. After a simulated period of one month, the model was returned to the conditions of earth's gravity and the standard postflight tilt test protocol was performed while the model output depicting the typical vital signs was monitored. Conclusions The analysis demonstrated that a 15% lowering of the longitudinal center of gravity in the anatomic structure of the model was all that was necessary to prevent the physiologic compensatory mechanisms from overcoming the propensity for reentry orthostasis leading to syncope. PMID:20298577

Cooling of burns: Mechanisms and models.

PubMed

Wright, E H; Harris, A L; Furniss, D

2015-08-01

The role of cooling in the acute management of burns is widely accepted in clinical practice, and is a cornerstone of basic first aid in burns. This has been underlined in a number of animal models. The mechanism by which it delivers its benefit is poorly understood, but there is a reduction in burns progression over the first 48 h, reduced healing time, and some subjective improvements in scarring when cooling is administered after burning. Intradermal temperature normalises within a matter of seconds to a few minutes, yet the benefits of even delayed cooling persist, implying it is not simply the removal of thermal energy from the damaged tissues. Animal models have used oedema formation, preservation of dermal perfusion, healing time and hair retention as indicators of burns severity, and have shown cooling to improve these indices, but pharmacological or immunological blockade of humoural and cellular mediators of inflammation did not reproduce the benefit of cooling. More recently, some studies of tissue from human and animal burns have shown consistent, reproducible, temporal changes in gene expression in burned tissues. Here, we review the experimental evidence of the role and mechanism of cooling in burns management, and suggest future research directions that may eventually lead to improved treatment outcomes. Copyright © 2015. Published by Elsevier Ltd.

Apico-basal forces exerted by apoptotic cells drive epithelium folding.

PubMed

Monier, Bruno; Gettings, Melanie; Gay, Guillaume; Mangeat, Thomas; Schott, Sonia; Guarner, Ana; Suzanne, Magali

2015-02-12

Epithelium folding is a basic morphogenetic event that is essential in transforming simple two-dimensional epithelial sheets into three-dimensional structures in both vertebrates and invertebrates. Folding has been shown to rely on apical constriction. The resulting cell-shape changes depend either on adherens junction basal shift or on a redistribution of myosin II, which could be driven by mechanical signals. Yet the initial cellular mechanisms that trigger and coordinate cell remodelling remain largely unknown. Here we unravel the active role of apoptotic cells in initiating morphogenesis, thus revealing a novel mechanism of epithelium folding. We show that, in a live developing tissue, apoptotic cells exert a transient pulling force upon the apical surface of the epithelium through a highly dynamic apico-basal myosin II cable. The apoptotic cells then induce a non-autonomous increase in tissue tension together with cortical myosin II apical stabilization in the surrounding tissue, eventually resulting in epithelium folding. Together our results, supported by a theoretical biophysical three-dimensional model, identify an apoptotic myosin-II-dependent signal as the initial signal leading to cell reorganization and tissue folding. This work further reveals that, far from being passively eliminated as generally assumed (for example, during digit individualization), apoptotic cells actively influence their surroundings and trigger tissue remodelling through regulation of tissue tension.

Taste transductions in taste receptor cells: basic tastes and moreover.

PubMed

Iwata, Shusuke; Yoshida, Ryusuke; Ninomiya, Yuzo

2014-01-01

In the oral cavity, taste receptor cells dedicate to detecting chemical compounds in foodstuffs and transmitting their signals to gustatory nerve fibers. Heretofore, five taste qualities (sweet, umami, bitter, salty and sour) are generally accepted as basic tastes. Each of these may have a specific role in the detection of nutritious and poisonous substances; sweet for carbohydrate sources of calories, umami for protein and amino acid contents, bitter for harmful compounds, salty for minerals and sour for ripeness of fruits and spoiled foods. Recent studies have revealed molecular mechanisms for reception and transduction of these five basic tastes. Sweet, umami and bitter tastes are mediated by G-protein coupled receptors (GPCRs) and second-messenger signaling cascades. Salty and sour tastes are mediated by channel-type receptors. In addition to five basic tastes, taste receptor cells may have the ability to detect fat taste, which is elicited by fatty acids, and calcium taste, which is elicited by calcium. Taste compounds eliciting either fat taste or calcium taste may be detected by specific GPCRs expressed in taste receptor cells. This review will focus on transduction mechanisms and cellular characteristics responsible for each of basic tastes, fat taste and calcium taste.

Pectoralis Major Injury During Basic Airborne Training.

PubMed

McIntire, Sean; Boujie, Lee; Leasiolagi, John

2016-01-01

Injuries involving rupture of the pectoralis major are relatively rare. When they do occur, it is mostly frequently in a young, athletic man. The most common cause is weight lifting that results in eccentric muscle contraction (muscle contraction against an overbearing force, leading to muscle lengthening)-specifically, the bench press. Other mechanisms for this injury include forceful abduction and external rotation of the arm. Injury can occur anywhere along the pectoralis major from its medial origin on the sternum and clavicle to its lateral tendinous insertion on the humerus. At the time of injury, patients may report feeling a tearing sensation or hearing a pop, with immediate onset of pain. Physical examination findings can include a deformed appearance of the chest, ecchymosis of the chest and upper arm, pain and weakness with arm adduction and internal rotation, or noticeable asymmetry of the anterior axilla with arm abduction. Magnetic resonance imaging is the imaging study of choice to aid diagnosis. In a young and active population, such as the Special Operations community, appropriate and timely diagnosis is important because surgical intervention often is recommended. This report presents the case of an active-duty Servicemember who sustained a pectoralis major injury while exiting an aircraft during the Basic Airborne Course. 2016.

Spin Choreography: Basic Steps in High Resolution NMR (by Ray Freeman)

NASA Astrophysics Data System (ADS)

Minch, Michael J.

1998-02-01

There are three orientations that NMR courses may take. The traditional molecular structure course focuses on the interpretation of spectra and the use of chemical shifts, coupling constants, and nuclear Overhauser effects (NOE) to sort out subtle details of structure and stereochemistry. Courses can also focus on the fundamental quantum mechanics of observable NMR parameters and processes such a spin-spin splitting and relaxation. More recently there are courses devoted to the manipulation of nuclear spins and the basic steps of one- and two-dimensional NMR experiments. Freeman's book is directed towards the latter audience. Modern NMR methods offer a myriad ways to extract information about molecular structure and motion by observing the behavior of nuclear spins under a variety of conditions. In Freeman's words: "We can lead the spins through an intricate dance, carefully programmed in advance, to enhance, simplify, correlate, decouple, edit or assign NMR spectra." This is a carefully written, well-illustrated account of how this dance is choreographed by pulse programming, double resonance, and gradient effects. Although well written, this book is not an easy read; every word counts. It is recommended for graduate courses that emphasize the fundamentals of magnetic resonance. It is not a text on interpretation of spectra.

On the Occurrence of Hypomyelination in a Transgenic Mouse Model: A Consequence of the Myelin Basic Protein Promoter?

PubMed Central

Gaupp, Stefanie; Arezzo, Joseph; Dutta, Dipankar J.; John, Gareth R.; Raine, Cedric S.

2013-01-01

Central nervous system hypomyelination is a feature common to a number of transgenic (Tg) mouse lines that express a variety of unrelated exogenous (i.e. non-CNS) transgenes. In this report we document hypomyelination structurally by immunocytochemistry and functionally in the Tg line MBP-JE, which overexpresses the chemokine CCL2 (MCP-1) within oligodendrocytes targeted by a myelin basic protein (MBP) promoter. Analysis of hypomyelinated optic nerves of Tg mice revealed progressive decrease in oligodendrocyte numbers with age (p < 0.01). Although molecular mechanisms underlying hypomyelination in this and other Tg models remain largely unknown, we present preliminary findings on oligodendrocyte progenitor cell (OPC) cultures in which, although OPC expressed CCR2, the receptor for CCL2, treatment with CCL2 had no significant effect on OPC proliferation, differentiation or apoptosis. We suggest that hypomyelination in the MBP-JE model might not be due to CCL2 expression but rather the result of transcriptional dysfunction related to random insertion of the MBP promoter that disrupts myelinogenesis and leads to oligodendrocytes demise. Because an MBP promoter is a common denominator in most Tg lines displaying hypomyelination, we hypothesize that use of myelin gene sequences in the regulator region of transgenic constructs might underlie this perturbation of myelination in such models. PMID:22082665

Performance-based interpretation bias in clinically anxious youths: relationships with attention, anxiety, and negative cognition.

PubMed

Rozenman, Michelle; Amir, Nader; Weersing, V Robin

2014-09-01

This preliminary investigation sought to examine basic interpretive biases, as assessed via performance-based means, in the context of anxious symptomatology, attention, and negative cognition in children and adolescents. At a single assessment, 26 youths diagnosed with primary separation anxiety, social phobia, or generalized anxiety disorder completed performance-based assessments of interpretation and attention. Youths and parents also completed diagnostic interviews and youths completed a measure of negative self-statements. Components of interpretation (threat-valence judgments and speed of responding) were examined, and interpretation was explored as a correlate of youth anxiety, attention bias, and negative self-statements. Results found percentage of negative interpretations endorsed as the strongest predictor of anxiety symptoms; this index was also correlated with attention bias. Slower rejection of benign interpretations was also associated with youth-reported negative self-statements.This initial investigation provides support for a relationship between interpretation bias and anxiety and preliminary evidence for a relationship between attention and interpretation biases. Continued research dismantling the stages of basic cognition within the chain of information processing may provide a better understanding of the mechanisms underlying anxiety disorders in youths and lead to continued development and refinement of cognitive interventions. Copyright © 2014. Published by Elsevier Ltd.

Expected Paradigm Shift in Brain Metastases Therapy-Immune Checkpoint Inhibitors.

PubMed

Jindal, Vishal; Gupta, Sorab

2018-01-30

Brain metastasis (BM) is one of the dreadful complications of malignancies. The prognosis after BM is extremely poor and life expectancy is meager. Currently, our treatment modalities are limited to radiotherapy and surgical resection, which also has poor outcomes and leads to various neurological deficits and affects the quality of life of patients. New treatment modality, i.e., immune checkpoint inhibitors, has brought revolution in management of melanoma, renal cancer, and non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors basically enhance the immune response of the body to fight against cancers. Immune response in the brain is highly regulated; therefore, it is challenging to use immune-modulator drugs in BM. The microenvironment of BM is rich in cytotoxic T lymphocytes and which is the target of immune checkpoint inhibitors. Few studies have shown some hope regarding use of immune checkpoint inhibitors in management of BM. It works through inhibiting immune check point gates, i.e., CTLA-4 (cytotoxic T-lymphocyte-associated protein) and PD-1/PD-L1 (programmed cell death protein-1/program death ligand-1). This article explains the basic mechanism of immune check point inhibitors, rationale behind their usage in BM, and some of the clinical studies which have shown the efficacy of immune check point inhibitors in BM.

Radiation from laser-microplasma-waveguide interactions in the ultra-intense regime

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yi, Longqing, E-mail: yi@uni-duesseldorf.de; State Key Laboratory of High Field Laser Physics, Shanghai Institute of Optics and Fine Mechanics, Chinese Academy of Sciences, P.O. Box 800-211, Shanghai 201800; Pukhov, Alexander

When a high-contrast ultra-relativistic (>10{sup 20} W/cm{sup 2}) laser beam enters a micro-sized plasma waveguide, the pulse energy is coupled into waveguide modes, which significantly modifies the interaction between the electrons and electromagnetic wave. Electrons pulled out from the walls of the waveguide form a dense helical bunch inside the channel and are efficiently accelerated by the transverse magnetic modes to hundreds of MeV. The asymmetry in the transverse electric and magnetic fields drives strong oscillations, which lead to the emission of bright, well-collimated, hard X-rays. In this paper, we present our study on the underlying physics in the aforementioned processmore » using 3D particle-in-cell simulations. The mechanism of electron acceleration and the dependence of radiation properties on different laser plasma parameters are addressed. An analytic model and basic scalings for X-ray emission are also presented by considering the lowest optical modes in the waveguide, which is adequate to describe the basic phenomenon. In addition, the effects of high-order modes as well as laser polarization are also qualitatively discussed. The considered X-ray source has promising features, potentially making it a competitive candidate for a future tabletop synchrotron source.« less

Improved wound management by regulated negative pressure-assisted wound therapy and regulated, oxygen- enriched negative pressure-assisted wound therapy through basic science research and clinical assessment.

PubMed

Topaz, Moris

2012-05-01

Regulated negative pressure-assisted wound therapy (RNPT) should be regarded as a state-of-the-art technology in wound treatment and the most important physical, nonpharmaceutical, platform technology developed and applied for wound healing in the last two decades. RNPT systems maintain the treated wound's environment as a semi-closed, semi-isolated system applying external physical stimulations to the wound, leading to biological and biochemical effects, with the potential to substantially influence wound-host interactions, and when properly applied may enhance wound healing. RNPT is a simple, safe, and affordable tool that can be utilized in a wide range of acute and chronic conditions, with reduced need for complicated surgical procedures, and antibiotic treatment. This technology has been shown to be effective and safe, saving limbs and lives on a global scale. Regulated, oxygen-enriched negative pressure-assisted wound therapy (RO-NPT) is an innovative technology, whereby supplemental oxygen is concurrently administered with RNPT for their synergistic effect on treatment and prophylaxis of anaerobic wound infection and promotion of wound healing. Understanding the basic science, modes of operation and the associated risks of these technologies through their fundamental clinical mechanisms is the main objective of this review.

MEMS-based, RF-driven, compact accelerators

NASA Astrophysics Data System (ADS)

Persaud, A.; Seidl, P. A.; Ji, Q.; Breinyn, I.; Waldron, W. L.; Schenkel, T.; Vinayakumar, K. B.; Ni, D.; Lal, A.

2017-10-01

Shrinking existing accelerators in size can reduce their cost by orders of magnitude. Furthermore, by using radio frequency (RF) technology and accelerating ions in several stages, the applied voltages can be kept low paving the way to new ion beam applications. We make use of the concept of a Multiple Electrostatic Quadrupole Array Linear Accelerator (MEQALAC) and have previously shown the implementation of its basic components using printed circuit boards, thereby reducing the size of earlier MEQALACs by an order of magnitude. We now demonstrate the combined integration of these components to form a basic accelerator structure, including an initial beam-matching section. In this presentation, we will discuss the results from the integrated multi-beam ion accelerator and also ion acceleration using RF voltages generated on-board. Furthermore, we will show results from Micro-Electro-Mechanical Systems (MEMS) fabricated focusing wafers, which can shrink the dimension of the system to the sub-mm regime and lead to cheaper fabrication. Based on these proof-of-concept results we outline a scaling path to high beam power for applications in plasma heating in magnetized target fusion and in neutral beam injectors for future Tokamaks. This work was supported by the Office of Science of the US Department of Energy through the ARPA-e ALPHA program under contracts DE-AC02-05CH11231.

Multiple Scale Analysis of the Dynamic State Index (DSI)

NASA Astrophysics Data System (ADS)

Müller, A.; Névir, P.

2016-12-01

The Dynamic State Index (DSI) is a novel parameter that indicates local deviations of the atmospheric flow field from a stationary, inviscid and adiabatic solution of the primitive equations of fluid mechanics. This is in contrast to classical methods, which often diagnose deviations from temporal or spatial mean states. We show some applications of the DSI to atmospheric flow phenomena on different scales. The DSI is derived from the Energy-Vorticity-Theory (EVT) which is based on two global conserved quantities, the total energy and Ertel's potential enstrophy. Locally, these global quantities lead to the Bernoulli function and the PV building together with the potential temperature the DSI.If the Bernoulli function and the PV are balanced, the DSI vanishes and the basic state is obtained. Deviations from the basic state provide an indication of diabatic and non-stationary weather events. Therefore, the DSI offers a tool to diagnose and even prognose different atmospheric events on different scales.On synoptic scale, the DSI can help to diagnose storms and hurricanes, where also the dipole structure of the DSI plays an important role. In the scope of the collaborative research center "Scaling Cascades in Complex Systems" we show high correlations between the DSI and precipitation on convective scale. Moreover, we compare the results with reduced models and different spatial resolutions.

Spiral Growth in Plants: Models and Simulations

ERIC Educational Resources Information Center

Allen, Bradford D.

2004-01-01

The analysis and simulation of spiral growth in plants integrates algebra and trigonometry in a botanical setting. When the ideas presented here are used in a mathematics classroom/computer lab, students can better understand how basic assumptions about plant growth lead to the golden ratio and how the use of circular functions leads to accurate…

How Unexamined Premises Lead to World Oppression: John Locke, The Theory of Private Property and Money. The Iconoclast.

ERIC Educational Resources Information Center

McMurtry, John

1997-01-01

Criticizes some of the basic principles expounded in John Locke's "Second Treatise on Government." Argues that Locke's ideas on private property, capital investment, and social good are inherently contradictory. Asserts that the market theory of property inevitably leads to endemic economic exploitation and oppression. (MJP)

Leading School for Learning: Principal Practices in Taiwan

ERIC Educational Resources Information Center

Pan, Hui-Ling Wendy; Nyeu, Fong-Yee; Cheng, Shu-Huei

2017-01-01

Purpose: The purpose of this paper is to discuss how principals in Taiwan lead student and teacher learning at a time of leadership and learning paradigm shifts and the imminent implementation of the curriculum guideline for 12-year basic education. Design/methodology/approach: This study interviewed 32 elementary and junior high school principals…

Heavy Equipment Mechanic. Instructor Edition.

ERIC Educational Resources Information Center

Hendrix, Laborn J.; And Others

This manual is intended to assist heavy equipment instructors in teaching the latest concepts and functions of heavy equipment. It includes 7 sections and 27 instructional units. Sections (and units) are: orientation (shop safety and first aid, hand tools and miscellaneous tools, measuring, basic rigging and hoisting), engines (basic engine…

Decoupling Object Detection and Categorization

ERIC Educational Resources Information Center

Mack, Michael L.; Palmeri, Thomas J.

2010-01-01

We investigated whether there exists a behavioral dependency between object detection and categorization. Previous work (Grill-Spector & Kanwisher, 2005) suggests that object detection and basic-level categorization may be the very same perceptual mechanism: As objects are parsed from the background they are categorized at the basic level. In…

The Administration of Outdoor Education Programs.

ERIC Educational Resources Information Center

Lewis, Charles A., Jr.

Designed for those interested in the mechanics of establishing outdoor education programs, this text is basically a guide to program development and includes examples of procedures, forms, conceptualizations, etc. Chapters deal with: (1) the contemporary education scene (an overview); (2) the basic concepts of outdoor education (17 concept…

Addressing Unmet Basic Resource Needs as Part of Chronic Cardiometabolic Disease Management.

PubMed

Berkowitz, Seth A; Hulberg, Amy Catherine; Standish, Sara; Reznor, Gally; Atlas, Steven J

2017-02-01

It is unclear if helping patients meet resource needs, such as difficulty affording food, housing, or medications, improves clinical outcomes. To determine the effectiveness of the Health Leads program on improvement in systolic and diastolic blood pressure (SBP and DBP, respectively), low-density lipoprotein cholesterol (LDL-C) level, and hemoglobin A1c (HbA1c) level. A difference-in-difference evaluation of the Health Leads program was conducted from October 1, 2012, through September 30, 2015, at 3 academic primary care practices. Health Leads consists of screening for unmet needs at clinic visits, and offering those who screen positive to meet with an advocate to help obtain resources, or receive brief information provision. Changes in SBP, DBP, LDL-C level, and HbA1c level. We compared those who screened positive for unmet basic needs (Health Leads group) with those who screened negative, using intention-to-treat, and, secondarily, between those who did and did not enroll in Health Leads, using linear mixed modeling, examining the period before and after screening. A total of 5125 people were screened, using a standardized form, for unmet basic resource needs; 3351 screened negative and 1774 screened positive. For those who screened positive, the mean age was 57.6 years and 1811 (56%) were women. For those who screened negative, the mean age was 56.7 years and 909 (57%) were women. Of 5125 people screened, 1774 (35%) reported at least 1 unmet need, and 1021 (58%) of those enrolled in Health Leads. Median follow-up for those who screened positive and negative was 34 and 32 months, respectively. In unadjusted intention-to-treat analyses of 1998 participants with hypertension, the Health Leads group experienced greater reduction in SBP (differential change, -1.2; 95% CI, -2.1 to -0.4) and DBP (differential change, -1.0; 95% CI, -1.5 to -0.5). For 2281 individuals with an indication for LDL-C level lowering, results also favored the Health Leads group (differential change, -3.7; 95% CI -6.7 to -0.6). For 774 individuals with diabetes, the Health Leads group did not show HbA1c level improvement (differential change, -0.04%; 95% CI, -0.17% to 0.10%). Results adjusted for baseline demographic and clinical differences were not qualitatively different. Among those who enrolled in Health Leads program, there were greater BP and LDL-C level improvements than for those who declined (SBP differential change -2.6; 95% CI,-3.5 to -1.7; SBP differential change, -1.4; 95% CI, -1.9 to -0.9; LDL-C level differential change, -6.3; 95% CI, -9.7 to -2.8). Screening for and attempting to address unmet basic resource needs in primary care was associated with modest improvements in blood pressure and lipid, but not blood glucose, levels.

A guide to onboard checkout. Volume 6: Structures/mechanics

NASA Technical Reports Server (NTRS)

1971-01-01

The structures and mechanical subsystem of a space station are considered. The subsystem includes basic structure (pressurization, equipment support, meteoroid protection, radiators, insulation, and docking interfaces), the docking mechanisms, spacecraft access (hatches, airlocks, and view ports), and antenna deployment mechanisms. Checkout is discussed in terms of reliability, failure analysis, and maintenance.

Standardized Curriculum for Automotive Mechanics.

ERIC Educational Resources Information Center

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…

Tolerance Issue in Kazakh Culture

ERIC Educational Resources Information Center

Aubakirova, Saltanat S.; Ismagambetova, Zukhra N.; Karabayeva, Aliya G.; Rysbekova, Shamshiya S.; Mirzabekova, Alma Sh.

2016-01-01

In this article the authors reveal the basic cultural mechanisms that influence the formation of the tolerance strategy in Kazakh and Kazakhstan society, show its basic directions, as well as its importance for the modern Kazakhstan society and the formation of intercultural communication with foreign countries. Tolerance is a necessary element of…

Basic Drafting: Book One.

ERIC Educational Resources Information Center

Davis, Ronald; And Others

The first of a two-book course in drafting, this manual consists of 13 topics in the following units: introduction to drafting, general safety, basic tools and lines, major equipment, applying for a job, media, lettering, reproduction, drawing sheet layout, architect's scale usage, civil engineer's scale usage, mechanical engineer's scale usage,…

Vocational Curriculum Resources for Handicapped Students. A Guide to Print and Non-Print Instructional Materials.

ERIC Educational Resources Information Center

Mangano, R. Michael; And Others

This guide to vocational curriculum resources for handicapped students consists of instructional checklists for resources identified in the following areas: agriculture, auto body repair, automobile mechanics, basic math skills, basic reading skills, business education, career education, carpentry, cosmetology, custodial and maintenance, data…

BASIC STEPS IN DESIGNING SCIENCE LABORATORIES.

ERIC Educational Resources Information Center

WHITNEY, FRANK L.

PLANNERS OF CURRENT UNIVERSITY LABORATORIES OFTEN MAKE THE SAME MISTAKES MADE BY INDUSTRIAL LABORATORIES 20 YEARS AGO. THIS CAN BE REMEDIED BY INCREASED COMMUNICATION BETWEEN SCIENTISTS AND DESIGNERS IN SEMINARS DEFINING THE BASIC NEEDS OF A PARTICULAR LABORATORY SITUATION. ELECTRONIC AND MECHANICAL EQUIPMENT ACCOUNT FOR OVER 50 PER CENT OF TOTAL…

Columbia/Willamette Skill Builders Consortium. Final Performance Report. Appendix 5B Anodizing Inc. (Aluminum Extrusion Manufacturing). Basic Measurement Math. Instructors' Reports and Sample Curriculum Materials.

ERIC Educational Resources Information Center

Taylor, Marjorie; And Others

Anodizing, Inc., Teamsters Local 162, and Mt. Hood Community College (Oregon) developed a workplace literacy program for workers at Anodizing. These workers did not have the basic skill competencies to benefit from company training efforts in statistical process control and quality assurance and were not able to advance to lead and supervisory…

Fuel age and fire spread: Natural conditions versus opportunities for fire suppression

USGS Publications Warehouse

Halsey, Richard W.; Keeley, Jon E.; Wilson, Kit

2009-01-01

Wildfires are driven and restrained by an interplay of variables that can lead to many potential outcomes. As every wildland firefighter learns in basic training, the ability of a fire to spread is determined by three basic variables: fuel type and condition, weather, and topography. Fire suppression obviously plays a significant role in determining fire spread as well, so firefighter activity becomes an additional variable.

BRESEX: On board supervision, basic architecture and preliminary aspects for payload and space shuttle interface

NASA Technical Reports Server (NTRS)

Bergamini, E. W.; Depaula, A. R., Jr.; Martins, R. C. D. O.

1984-01-01

Data relative to the on board supervision subsystem are presented which were considered in a conference between INPE and NASA personnel, with the purpose of initiating a joint effort leading to the implementation of the Brazilian remote sensing experiment - (BRESEX). The BRESEX should consist, basically, of a multispectral camera for Earth observation, to be tested in a future space shuttle flight.

Statistical Extremes of Turbulence and a Cascade Generalisation of Euler's Gyroscope Equation

NASA Astrophysics Data System (ADS)

Tchiguirinskaia, Ioulia; Scherzer, Daniel

2016-04-01

Turbulence refers to a rather well defined hydrodynamical phenomenon uncovered by Reynolds. Nowadays, the word turbulence is used to designate the loss of order in many different geophysical fields and the related fundamental extreme variability of environmental data over a wide range of scales. Classical statistical techniques for estimating the extremes, being largely limited to statistical distributions, do not take into account the mechanisms generating such extreme variability. An alternative approaches to nonlinear variability are based on a fundamental property of the non-linear equations: scale invariance, which means that these equations are formally invariant under given scale transforms. Its specific framework is that of multifractals. In this framework extreme variability builds up scale by scale leading to non-classical statistics. Although multifractals are increasingly understood as a basic framework for handling such variability, there is still a gap between their potential and their actual use. In this presentation we discuss how to dealt with highly theoretical problems of mathematical physics together with a wide range of geophysical applications. We use Euler's gyroscope equation as a basic element in constructing a complex deterministic system that preserves not only the scale symmetry of the Navier-Stokes equations, but some more of their symmetries. Euler's equation has been not only the object of many theoretical investigations of the gyroscope device, but also generalised enough to become the basic equation of fluid mechanics. Therefore, there is no surprise that a cascade generalisation of this equation can be used to characterise the intermittency of turbulence, to better understand the links between the multifractal exponents and the structure of a simplified, but not simplistic, version of the Navier-Stokes equations. In a given way, this approach is similar to that of Lorenz, who studied how the flap of a butterfly wing could generate a cyclone with the help of a 3D ordinary differential system. Being well supported by the extensive numerical results, the cascade generalisation of Euler's gyroscope equation opens new horizons for predictability and predictions of processes having long-range dependences.

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

NASA Astrophysics Data System (ADS)

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.

Manifestations Of Mine-induced Seismicity At Large-scale Mining Operations In Khibiny Massive

NASA Astrophysics Data System (ADS)

Fedotova, I. V.; Kozyrev, A. A.; Yunga, S. L.

The focal mechanisms of seismic events in the Khibiny massive and their interrelation with spent mining operations were investigated. As a result it is detected, that redistri- bution of stresses stipulated by structural features of a rock mass and ore technology, is the basic reason of origin of dynamic rock pressure manifestations. On the basis of the available plan tectonic disturbances of an investigated lease of a massif and anal- ysis of seismic activity, in view of events with the detected focal mechanism, some bands, various on a degree of potential seismic activity are chosen. For each band the calculations of mechanisms of rock bumps with separation of planes of adjustments with engaging of the geologic data are held. As a result of this analysis it is approved, that the basic forerunner of cracking of a separation at a roof fall of the cantilever of hanging wall (on decryption of focal mechanisms) is the reorientation of axes of prin- cipal stresses. And, at conducting coal-face works in a trailing side of ore deposits, at cracking a separation in the cantilever of hanging wall there are seismic events pre- dominantly to a fault type of the focal mechanism. In a massif of soils of the working excavation, located in limits, and under it, most typical focal mechanisms are mainly strike-slip and normal faults. The researches are executed at support of the Russian foundation for basic research, - projects 00-05-64758, 01-05-65340.

Saturation behavior: a general relationship described by a simple second-order differential equation.

PubMed

Kepner, Gordon R

2010-04-13

The numerous natural phenomena that exhibit saturation behavior, e.g., ligand binding and enzyme kinetics, have been approached, to date, via empirical and particular analyses. This paper presents a mechanism-free, and assumption-free, second-order differential equation, designed only to describe a typical relationship between the variables governing these phenomena. It develops a mathematical model for this relation, based solely on the analysis of the typical experimental data plot and its saturation characteristics. Its utility complements the traditional empirical approaches. For the general saturation curve, described in terms of its independent (x) and dependent (y) variables, a second-order differential equation is obtained that applies to any saturation phenomena. It shows that the driving factor for the basic saturation behavior is the probability of the interactive site being free, which is described quantitatively. Solving the equation relates the variables in terms of the two empirical constants common to all these phenomena, the initial slope of the data plot and the limiting value at saturation. A first-order differential equation for the slope emerged that led to the concept of the effective binding rate at the active site and its dependence on the calculable probability the interactive site is free. These results are illustrated using specific cases, including ligand binding and enzyme kinetics. This leads to a revised understanding of how to interpret the empirical constants, in terms of the variables pertinent to the phenomenon under study. The second-order differential equation revealed the basic underlying relations that describe these saturation phenomena, and the basic mathematical properties of the standard experimental data plot. It was shown how to integrate this differential equation, and define the common basic properties of these phenomena. The results regarding the importance of the slope and the new perspectives on the empirical constants governing the behavior of these phenomena led to an alternative perspective on saturation behavior kinetics. Their essential commonality was revealed by this analysis, based on the second-order differential equation.

Local adaptation of plant viruses: lessons from experimental evolution.

PubMed

Elena, Santiago F

2017-04-01

For multihost pathogens, adaptation to multiple hosts has important implications for both applied and basic research. At the applied level, it is one of the main factors determining the probability and severity of emerging disease outbreaks. At the basic level, it is thought to be a key mechanism for the maintenance of genetic diversity both in host and pathogen species. In recent years, a number of evolution experiments have assessed the fate of plant virus populations replicating within and adapting to one single or to multiple hosts species. A first group of these experiments tackled the existence of trade-offs in fitness and virulence for viruses evolving either within a single hosts species or alternating between two different host species. A second set of experiments explored the role of genetic variability in susceptibility and resistance to infection among individuals from the same host species in the extent of virus local adaptation and of virulence. In general, when a single host species or genotype is available, these experiments show that local adaptation takes place, often but not always associated with a fitness trade-off. However, alternating between different host species or infecting resistant host genotypes may select for generalist viruses that experience no fitness cost. Therefore, the expected cost of generalism, arising from antagonistic pleiotropy and other genetic mechanisms generating fitness trade-offs between hosts, could not be generalized and strongly depend on the characteristics of each particular pathosystem. At the genomic level, these studies show pervasive convergent molecular evolution, suggesting that the number of accessible molecular pathways leading to adaptation to novel hosts is limited. © 2016 John Wiley & Sons Ltd.

Sequence-Specific Model for Peptide Retention Time Prediction in Strong Cation Exchange Chromatography.

PubMed

Gussakovsky, Daniel; Neustaeter, Haley; Spicer, Victor; Krokhin, Oleg V

2017-11-07

The development of a peptide retention prediction model for strong cation exchange (SCX) separation on a Polysulfoethyl A column is reported. Off-line 2D LC-MS/MS analysis (SCX-RPLC) of S. cerevisiae whole cell lysate was used to generate a retention dataset of ∼30 000 peptides, sufficient for identifying the major sequence-specific features of peptide retention mechanisms in SCX. In contrast to RPLC/hydrophilic interaction liquid chromatography (HILIC) separation modes, where retention is driven by hydrophobic/hydrophilic contributions of all individual residues, SCX interactions depend mainly on peptide charge (number of basic residues at acidic pH) and size. An additive model (incorporating the contributions of all 20 residues into the peptide retention) combined with a peptide length correction produces a 0.976 R 2 value prediction accuracy, significantly higher than the additive models for either HILIC or RPLC. Position-dependent effects on peptide retention for different residues were driven by the spatial orientation of tryptic peptides upon interaction with the negatively charged surface functional groups. The positively charged N-termini serve as a primary point of interaction. For example, basic residues (Arg, His, Lys) increase peptide retention when located closer to the N-terminus. We also found that hydrophobic interactions, which could lead to a mixed-mode separation mechanism, are largely suppressed at 20-30% of acetonitrile in the eluent. The accuracy of the final Sequence-Specific Retention Calculator (SSRCalc) SCX model (∼0.99 R 2 value) exceeds all previously reported predictors for peptide LC separations. This also provides a solid platform for method development in 2D LC-MS protocols in proteomics and peptide retention prediction filtering of false positive identifications.

Animal models in myopia research.

PubMed

Schaeffel, Frank; Feldkaemper, Marita

2015-11-01

Our current understanding of the development of refractive errors, in particular myopia, would be substantially limited had Wiesel and Raviola not discovered by accident that monkeys develop axial myopia as a result of deprivation of form vision. Similarly, if Josh Wallman and colleagues had not found that simple plastic goggles attached to the chicken eye generate large amounts of myopia, the chicken model would perhaps not have become such an important animal model. Contrary to previous assumptions about the mechanisms of myopia, these animal models suggested that eye growth is visually controlled locally by the retina, that an afferent connection to the brain is not essential and that emmetropisation uses more sophisticated cues than just the magnitude of retinal blur. While animal models have shown that the retina can determine the sign of defocus, the underlying mechanism is still not entirely clear. Animal models have also provided knowledge about the biochemical nature of the signal cascade converting the output of retinal image processing to changes in choroidal thickness and scleral growth; however, a critical question was, and still is, can the results from animal models be applied to myopia in children? While the basic findings from chickens appear applicable to monkeys, some fundamental questions remain. If eye growth is guided by visual feedback, why is myopic development not self-limiting? Why does undercorrection not arrest myopic progression even though positive lenses induce myopic defocus, which leads to the development of hyperopia in emmetropic animals? Why do some spectacle or contact lens designs reduce myopic progression and others not? It appears that some major differences exist between animals reared with imposed defocus and children treated with various optical corrections, although without the basic knowledge obtained from animal models, we would be lost in an abundance of untestable hypotheses concerning human myopia. © 2015 Optometry Australia.

Ferroionic states: coupling between surface electrochemical and bulk ferroelectric functionalities on the nanoscale.

NASA Astrophysics Data System (ADS)

Kalinin, Sergei

Ferroelectricity on the nanoscale has remained a subject of much fascination in condensed matter physics for the last several decades. It is well-recognized that stability of the ferroelectric state necessitates effective polarization screening, and hence screening mechanism and screening charge dynamics become strongly coupled to ferroelectric phase stability and domain behavior. Previously, the role of the screening charge in macroscopic ferroelectrics was observed in phenomena such as potential retention above Curie temperature, back switching of ferroelectric domains, and chaos and intermittency during domain switching. In the last several years, multiple reports claiming ferroelectricity in ultrathin ferroelectrics based on formation of remanent polarization states, local hysteresis loops, and pressure induced switching were made. However, similar phenomena were reported for traditionally non-ferroelectric materials, creating significant level of uncertainty in the field. We pose that in the nanoscale systems, the ferroelectric state is fundamentally inseparable from electrochemical state of the surface, leading to emergence of coupled electrochemical-ferroelectric states. I will present the results of experimental and theoretical work exploring the basic mechanisms of emergence of these coupled states including the basic theory and phase-field formulation for domain evolution. I further discuss the thermodynamics and thickness evolution of this state, and demonstrate the experimental pathway to establish its presence based on spectroscopic version of piezoresponse force microscopy. Finally, the role of chemical screening on domain dynamics is explored using phase-field modelling. This analysis reconciles multiple prior studies, and set forward the predictive pathways for new generations of ferroelectric devices and applications. This research was sponsored by the Division of Materials Sciences and Engineering, BES, DOE, and was conducted at the Center for Nanophase Materials Sciences, sponsored at Oak Ridge National Laboratory by the Scientific User Facilities Division.

A Bayesian analysis of gene flow from crops to their wild relatives: cultivated (Lactuca sativa L.) and prickly lettuce (L. serriola L.) and the recent expansion of L. serriola in Europe.

PubMed

Uwimana, Brigitte; D'Andrea, Luigi; Felber, François; Hooftman, Danny A P; Den Nijs, Hans C M; Smulders, Marinus J M; Visser, Richard G F; Van De Wiel, Clemens C M

2012-06-01

Interspecific gene flow can lead to the formation of hybrid populations that have a competitive advantage over the parental populations, even for hybrids from a cross between crops and wild relatives. Wild prickly lettuce (Lactuca serriola) has recently expanded in Europe and hybridization with the related crop species (cultivated lettuce, L. sativa) has been hypothesized as one of the mechanisms behind this expansion. In a basically selfing species, such as lettuce, assessing hybridization in natural populations may not be straightforward. Therefore, we analysed a uniquely large data set of plants genotyped with SSR (simple sequence repeat) markers with two programs for Bayesian population genetic analysis, STRUCTURE and NewHybrids. The data set comprised 7738 plants, including a complete genebank collection, which provided a wide coverage of cultivated germplasm and a fair coverage of wild accessions, and a set of wild populations recently sampled across Europe. STRUCTURE analysis inferred the occurrence of hybrids at a level of 7% across Europe. NewHybrids indicated these hybrids to be advanced selfed generations of a hybridization event or of one backcross after such an event, which is according to expectations for a basically selfing species. These advanced selfed generations could not be detected effectively with crop-specific alleles. In the northern part of Europe, where the expansion of L. serriola took place, the fewest putative hybrids were found. Therefore, we conclude that other mechanisms than crop/wild gene flow, such as an increase in disturbed habitats and/or climate warming, are more likely explanations for this expansion. © 2012 Blackwell Publishing Ltd.

Adaptation to Lactose in Lactase Non Persistent People: Effects on Intolerance and the Relationship between Dairy Food Consumption and Evalution of Diseases.

PubMed

Szilagyi, Andrew

2015-08-13

Dairy foods contain complex nutrients which interact with the host. Yet, evolution of lactase persistence has divided the human species into those that can or cannot digest lactose in adulthood. Such a ubiquitous trait has differential effects on humanity. The literature is reviewed to explore how the divide affects lactose handling by lactase non persistent persons. There are two basic differences in digesters. Firstly, maldigesters consume less dairy foods, and secondly, excess lactose is digested by colonic microflora. Lactose intolerance in maldigesters may occur with random lactose ingestion. However, lactose intolerance without maldigestion tends to detract from gaining a clear understanding of the mechanisms of symptoms formation and leads to confusion with regards to dairy food consumption. The main consequence of intolerance is withholding dairy foods. However, regular dairy food consumption by lactase non persistent people could lead to colonic adaptation by the microbiome. This process may mimic a prebiotic effect and allows lactase non persistent people to consume more dairy foods enhancing a favorable microbiome. This process then could lead to alterations in outcome of diseases in response to dairy foods in lactose maldigesters. The evidence that lactose is a selective human prebiotic is reviewed and current links between dairy foods and some diseases are discussed within this context. Colonic adaptation has not been adequately studied, especially with modern microbiological techniques.

Adaptation to Lactose in Lactase Non Persistent People: Effects on Intolerance and the Relationship between Dairy Food Consumption and Evalution of Diseases

PubMed Central

Szilagyi, Andrew

2015-01-01

Dairy foods contain complex nutrients which interact with the host. Yet, evolution of lactase persistence has divided the human species into those that can or cannot digest lactose in adulthood. Such a ubiquitous trait has differential effects on humanity. The literature is reviewed to explore how the divide affects lactose handling by lactase non persistent persons. There are two basic differences in digesters. Firstly, maldigesters consume less dairy foods, and secondly, excess lactose is digested by colonic microflora. Lactose intolerance in maldigesters may occur with random lactose ingestion. However, lactose intolerance without maldigestion tends to detract from gaining a clear understanding of the mechanisms of symptoms formation and leads to confusion with regards to dairy food consumption. The main consequence of intolerance is withholding dairy foods. However, regular dairy food consumption by lactase non persistent people could lead to colonic adaptation by the microbiome. This process may mimic a prebiotic effect and allows lactase non persistent people to consume more dairy foods enhancing a favorable microbiome. This process then could lead to alterations in outcome of diseases in response to dairy foods in lactose maldigesters. The evidence that lactose is a selective human prebiotic is reviewed and current links between dairy foods and some diseases are discussed within this context. Colonic adaptation has not been adequately studied, especially with modern microbiological techniques. PMID:26287234

Anatomy and Physiology of the Speech Mechanism.

ERIC Educational Resources Information Center

Sheets, Boyd V.

This monograph on the anatomical and physiological aspects of the speech mechanism stresses the importance of a general understanding of the process of verbal communication. Contents include "Positions of the Body,""Basic Concepts Linked with the Speech Mechanism,""The Nervous System,""The Respiratory System--Sound-Power Source,""The…

The basic mechanism of inotropic action of digitalis glycosides.

PubMed

Smith, T W

1984-01-01

A broad survey of the experimental literature suggests that the only unifying concept of digitalis action is that these drugs, at pharmacologically relevant doses, bind with high affinity and specificity to sites on the NaK-ATPase complex that face the outer surface of nearly all eukaryotic cells. Alternative receptors, if they exist, have not been defined. As might be expected, a broad range of biologic effects results from this basic interaction. The clinical therapeutic effects of digitalis include enhancement of myocardial contractility and changes in the properties of the cardiac conduction system; the latter, in turn, result from both direct and autonomically mediated effects [44]. Autonomic effects involve alterations in both parasympathetic and sympathetic activity, and these are attributable to both central and peripheral neural mechanisms [44]. As we have reviewed, there is compelling evidence that one mechanism leading to sustained positive inotropic effects of digitalis glycosides in heart muscle is partial inhibition of sodium transport. Earlier evidence [16, 17] is now supported by electrophysiologic studies [29, 30, 45, 46], intracellular ion-sensitive microelectrode methods [47, 48], and ion flux measurements using radioisotope tracers [14, 15, 49]. Inhibition of myocardial monovalent cation transport has been documented in intact glycoside-sensitive animal models at doses and plasma and myocardial levels causing a positive inotropic effect without overt toxicity [12]. However, these findings do not preclude other mechanisms that may be operative in addition to, or in some circumstances instead of, myocardial Na-K pump inhibition. In the context of much seemingly conflicting evidence [35, 36, 37, 50, 51], the hypothesis advanced by Akera and Brody is of interest [17]. These authors suggest that interaction of subtoxic digitalis concentrations with myocardial NaK-ATPase reduces maximum sodium transport capacity, resulting in an enhanced transient increase in [Na]i during the early phase of the cardiac cycle. Such an increase in subsarcolemmal [Na+] could cause increased Ca++ influx via Na+-Ca++ exchange, with a consequent positive inotropic effect. If the Na+ increase were cyclic and not cumulative, cell Na+ content could return to normal by the end of a cycle due to enhanced turnover of unblocked Na-K pump sites. This hypothesis suggests a mechanism by which Na-K pump inhibition could cause a positive inotropic effect without any measurable increase in steady-state [Na+]i or decrease in [K+]i.(ABSTRACT TRUNCATED AT 400 WORDS)

The Genetic and Molecular Bases for Hypertrophic Cardiomyopathy: The Role for Calcium Sensitization.

PubMed

Ren, Xianfeng; Hensley, Nadia; Brady, Mary Beth; Gao, Wei Dong

2018-02-01

Hypertrophic cardiomyopathy (HCM) affects millions of people around the world as one of the most common genetic heart disorders and leads to cardiac ischemia, heart failure, dysfunction of other organ systems, and increased risk for sudden unexpected cardiac deaths. HCM can be caused by single-point mutations, insertion or deletion mutations, or truncation of cardiac myofilament proteins. The molecular mechanism that leads to disease progression and presentation is still poorly understood, despite decades of investigations. However, recent research has made dramatic advances in the understanding of HCM disease development. Studies have shown that increased calcium sensitivity is a universal feature in HCM. At the molecular level, increased crossbridge force (or power) generation resulting in hypercontractility is the prominent feature. Thus, calcium sensitization/hypercontractility is emerging as the primary stimulus for HCM disease development and phenotypic expression. Cross-bridge inhibition has been shown to halt HCM presentation, and myofilament desensitization appears to reduce lethal arrhythmias in animal models of HCM. These advances in basic research will continue to deepen the knowledge of HCM pathogenesis and are beginning to revolutionize the management of HCM. Copyright © 2018 Elsevier Inc. All rights reserved.

Most-Critical Transient Disturbances in an Incompressible Flat-Plate Boundary Layer

NASA Astrophysics Data System (ADS)

Monschke, Jason; White, Edward

2015-11-01

Transient growth is a linear disturbance growth mechanism that plays a key role in roughness-induced boundary-layer transition. It occurs when superposed stable, non-orthogonal continuous spectrum modes experience algebraic disturbance growth followed by exponential decay. Algebraic disturbance growth can modify the basic state making it susceptible to secondary instabilities rapidly leading to transition. Optimal disturbance theory was developed to model the most-dangerous disturbances. However, evidence suggests roughness-induced transient growth is sub-optimal yet leads to transition earlier than optimal theory suggests. This research computes initial disturbances most unstable to secondary instabilities to further develop the applicability of transient growth theory to surface roughness. The main approach is using nonlinear adjoint optimization with solutions of the parabolized Navier-Stokes and BiGlobal stability equations. Two objective functions were considered: disturbance kinetic energy growth and sinuous instability growth rate. The first objective function was used as validation of the optimization method. Counter-rotating streamwise vortices located low in the boundary layer maximize the sinuous instability growth rate. The authors would like to acknowledge NASA and the AFOSR for funding this work through AFOSR Grant FA9550-09-1-0341.

A low-friction high-load thrust bearing and the human hip joint.

PubMed

McIlraith, A H

2010-06-01

A hydrostatic thrust bearing operating at a pressure of 130 MPa and with a coefficient of friction rising to 0.004 in 6 days is described. It consists of interleaved oil-coated Mylar and brass sheets, each 0.1 mm thick. At this pressure, the Mylar deforms to reveal a pool of lubricant bounded by contacting layers at its edges where the pressure tapers off to zero. Thus, most of the load is borne by the oil so its effective Coulomb (slip-stick) friction is very low. Expressions for the effective coefficient of friction, the area of the solid-to-solid contact and the torque needed to rotate the bearing are given in terms of its geometry, the viscosity of the lubricant and elapsed time. The mechanism of a bearing with similar geometry and properties, the human hip joint, is compared with this plastic bearing. While their low friction properties arise from the same basic cause, the different natures of their soft deformable materials lead to the hip joint having a much wider range of action. This work is an example of new engineering leading to a fresh insight into an action of Nature, which in turn suggests an improvement in engineering.

Neuroscience of Internet Pornography Addiction: A Review and Update.

PubMed

Love, Todd; Laier, Christian; Brand, Matthias; Hatch, Linda; Hajela, Raju

2015-09-18

Many recognize that several behaviors potentially affecting the reward circuitry in human brains lead to a loss of control and other symptoms of addiction in at least some individuals. Regarding Internet addiction, neuroscientific research supports the assumption that underlying neural processes are similar to substance addiction. The American Psychiatric Association (APA) has recognized one such Internet related behavior, Internet gaming, as a potential addictive disorder warranting further study, in the 2013 revision of their Diagnostic and Statistical Manual. Other Internet related behaviors, e.g., Internet pornography use, were not covered. Within this review, we give a summary of the concepts proposed underlying addiction and give an overview about neuroscientific studies on Internet addiction and Internet gaming disorder. Moreover, we reviewed available neuroscientific literature on Internet pornography addiction and connect the results to the addiction model. The review leads to the conclusion that Internet pornography addiction fits into the addiction framework and shares similar basic mechanisms with substance addiction. Together with studies on Internet addiction and Internet Gaming Disorder we see strong evidence for considering addictive Internet behaviors as behavioral addiction. Future research needs to address whether or not there are specific differences between substance and behavioral addiction.

Identifying pathological biomarkers: histochemistry still ranks high in the omics era

PubMed Central

Pellicciari, C.; Malatesta, M.

2011-01-01

In recent years, omic analyses have been proposed as possible approaches to diagnosis, in particular for tumours, as they should be able to provide quantitative tools to detect and measure abnormalities in gene and protein expression, through the evaluation of transcription and translation products in the abnormal vs normal tissues. Unfortunately, this approach proved to be much less powerful than expected, due to both intrinsic technical limits and the nature itself of the pathological tissues to be investigated, the heterogeneity deriving from polyclonality and tissue phenotype variability between patients being a major limiting factor in the search for unique omic biomarkers. Especially in the last few years, the application of refined techniques for investigating gene expression in situ has greatly increased the diagnostic/prognostic potential of histochemistry, while the progress in light microscopy technology and in the methods for imaging molecules in vivo have provided valuable tools for elucidating the molecular events and the basic mechanisms leading to a pathological condition. Histochemical techniques thus remain irreplaceable in pathologist's armamentarium, and it may be expected that even in the future histochemistry will keep a leading position among the methodological approaches for clinical pathology. PMID:22297448

Neuroscience of Internet Pornography Addiction: A Review and Update

PubMed Central

Love, Todd; Laier, Christian; Brand, Matthias; Hatch, Linda; Hajela, Raju

2015-01-01

Many recognize that several behaviors potentially affecting the reward circuitry in human brains lead to a loss of control and other symptoms of addiction in at least some individuals. Regarding Internet addiction, neuroscientific research supports the assumption that underlying neural processes are similar to substance addiction. The American Psychiatric Association (APA) has recognized one such Internet related behavior, Internet gaming, as a potential addictive disorder warranting further study, in the 2013 revision of their Diagnostic and Statistical Manual. Other Internet related behaviors, e.g., Internet pornography use, were not covered. Within this review, we give a summary of the concepts proposed underlying addiction and give an overview about neuroscientific studies on Internet addiction and Internet gaming disorder. Moreover, we reviewed available neuroscientific literature on Internet pornography addiction and connect the results to the addiction model. The review leads to the conclusion that Internet pornography addiction fits into the addiction framework and shares similar basic mechanisms with substance addiction. Together with studies on Internet addiction and Internet Gaming Disorder we see strong evidence for considering addictive Internet behaviors as behavioral addiction. Future research needs to address whether or not there are specific differences between substance and behavioral addiction. PMID:26393658

Moving forward in uveitis therapy: preclinical to phase II clinical trial drug development.

PubMed

Salazar-Méndez, Raquel; Yilmaz, Taygan; Cordero-Coma, Miguel

2016-01-01

Several advances have been made in the diagnostic approach and therapeutic management of patients with immune-mediated uveitis over the last few decades, which have to lead to an improvement in the visual prognosis of patients. However, the use of available therapies, including steroids and immunosuppressive drugs, is still associated with limited efficacy and potentially serious side effects. Consequently, efforts have been made to develop novel therapeutic alternatives including new molecules and innovative therapeutic approaches. Herein, the authors provide an updated review of those drugs in the initial phases of evaluation for the treatment of immune-mediated uveitides as well as the latest evidence from basic research. Enhanced understanding of the pathogenic mechanisms leading to immune-mediated uveitis has led to the identification of new therapeutic targets and thus to the development of more specific drugs. In addition, considering that the eye is a semi-enclosed chamber and that local therapy has the benefit of sparing the rest of the body from potentially toxic exposure, several attempts of establishing direct ophthalmologic avenues for delivery of the established and emerging drugs have also been made. All these advances have been an unquestionable step forward in the challenging management of uveitis patients.

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

NASA Astrophysics Data System (ADS)

Kohn, Florian; Hauslage, Jens; Hanke, Wolfgang

2017-10-01

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

A comprehensive review of opioid-induced hyperalgesia.

PubMed

Lee, Marion; Silverman, Sanford M; Hansen, Hans; Patel, Vikram B; Manchikanti, Laxmaiah

2011-01-01

Opioid-induced hyperalgesia (OIH) is defined as a state of nociceptive sensitization caused by exposure to opioids. The condition is characterized by a paradoxical response whereby a patient receiving opioids for the treatment of pain could actually become more sensitive to certain painful stimuli. The type of pain experienced might be the same as the underlying pain or might be different from the original underlying pain. OIH appears to be a distinct, definable, and characteristic phenomenon that could explain loss of opioid efficacy in some patients. Findings of the clinical prevalence of OIH are not available. However, several observational, cross-sectional, and prospective controlled trials have examined the expression and potential clinical significance of OIH in humans. Most studies have been conducted using several distinct cohorts and methodologies utilizing former opioid addicts on methadone maintenance therapy, perioperative exposure to opioids in patients undergoing surgery, and healthy human volunteers after acute opioid exposure using human experimental pain testing. The precise molecular mechanism of OIH, while not yet understood, varies substantially in the basic science literature, as well as clinical medicine. It is generally thought to result from neuroplastic changes in the peripheral and central nervous system (CNS) that lead to sensitization of pronociceptive pathways. While there are many proposed mechanisms for OIH, 5 mechanisms involving the central glutaminergic system, spinal dynorphins, descending facilitation, genetic mechanisms, and decreased reuptake and enhanced nociceptive response have been described as the important mechanisms. Of these, the central glutaminergic system is considered the most common possibility. Another is the hypothesis that N-methyl-D-aspartate (NMDA) receptors in OIH include activation, inhibition of the glutamate transporter system, facilitation of calcium regulated intracellular protein kinase C, and cross talk of neural mechanisms of pain and tolerance. Clinicians should suspect OIH when opioid treatment's effect seems to wane in the absence of disease progression, particularly if found in the context of unexplained pain reports or diffuse allodynia unassociated with the original pain, and increased levels of pain with increasing dosages. The treatment involves reducing the opioid dosage, tapering them off, or supplementation with NMDA receptor modulators. This comprehensive review addresses terminology and definition, prevalence, the evidence for mechanism and physiology with analysis of various factors leading to OIH, and effective strategies for preventing, reversing, or managing OIH.

The bile acid-sensitive ion channel (BASIC) is activated by alterations of its membrane environment.

PubMed

Schmidt, Axel; Lenzig, Pia; Oslender-Bujotzek, Adrienne; Kusch, Jana; Lucas, Susana Dias; Gründer, Stefan; Wiemuth, Dominik

2014-01-01

The bile acid-sensitive ion channel (BASIC) is a member of the DEG/ENaC family of ion channels. Channels of this family are characterized by a common structure, their physiological functions and modes of activation, however, are diverse. Rat BASIC is expressed in brain, liver and intestinal tract and activated by bile acids. The physiological function of BASIC and its mechanism of bile acid activation remain a puzzle. Here we addressed the question whether amphiphilic bile acids activate BASIC by directly binding to the channel or indirectly by altering the properties of the surrounding membrane. We show that membrane-active substances other than bile acids also affect the activity of BASIC and that activation by bile acids and other membrane-active substances is non-additive, suggesting that BASIC is sensitive for changes in its membrane environment. Furthermore based on results from chimeras between BASIC and ASIC1a, we show that the extracellular and the transmembrane domains are important for membrane sensitivity.

Electrical Systems. Auto Mechanics Curriculum Guide Module 2. Instructor's Guide.

ERIC Educational Resources Information Center

Hevel, David; Donovan, Roger

This document is one of a series of modules in the Missouri Auto Mechanics Curriculum Guide, which is based on 144 basic auto mechanics competencies identified on the Missouri Auto Mechanics Competency Profile. The instructor's materials in this document are for a 14-unit secondary education course. The following units are included: (1) principles…

Manual Drive Train and Axles. Auto Mechanics Curriculum Guide Module 7. Instructor's Guide.

ERIC Educational Resources Information Center

Colesworthy, Robert; Donovan, Roger

This document is one of a series of modules in the Missouri Auto Mechanics Curriculum Guide, which is based on 144 basic auto mechanics competencies identified on the Missouri Auto Mechanics Competency Profile. The instructor's materials in this document are for a 13-unit secondary education course. The following units are included: (1)…

Futures Thinking, Learning, and Leading: Applying Multiple Intelligences to Success and Innovation

ERIC Educational Resources Information Center

Buchen, Irving H.

2006-01-01

The focus of this book is to explore the extent to which our thinking, learning, and leading is influenced and shaped by the future. In the process, professionals and organizations are classified into three basic types: future-oriented, future-poised, and future-driven. The last typically employs divergent and convergent thinking and planning; and…

76 FR 53057 - Change to the Reporting Date for Certain Data Elements Required Under the Mandatory Reporting of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-25

..., blast furnaces, basic oxygen process furnace shops. Lead Production 331419 Primary lead smelting and.... Chapter 5, generally provides that rules may not take effect earlier than 30 days after they are published... behavior and prepare before the final rule takes effect. Because this final rule defers a reporting...

A model for integrating clinical care and basic science research, and pitfalls of performing complex research projects for addressing a clinical challenge.

PubMed

Steck, R; Epari, D R; Schuetz, M A

2010-07-01

The collaboration of clinicians with basic science researchers is crucial for addressing clinically relevant research questions. In order to initiate such mutually beneficial relationships, we propose a model where early career clinicians spend a designated time embedded in established basic science research groups, in order to pursue a postgraduate qualification. During this time, clinicians become integral members of the research team, fostering long term relationships and opening up opportunities for continuing collaboration. However, for these collaborations to be successful there are pitfalls to be avoided. Limited time and funding can lead to attempts to answer clinical challenges with highly complex research projects characterised by a large number of "clinical" factors being introduced in the hope that the research outcomes will be more clinically relevant. As a result, the complexity of such studies and variability of its outcomes may lead to difficulties in drawing scientifically justified and clinically useful conclusions. Consequently, we stress that it is the basic science researcher and the clinician's obligation to be mindful of the limitations and challenges of such multi-factorial research projects. A systematic step-by-step approach to address clinical research questions with limited, but highly targeted and well defined research projects provides the solid foundation which may lead to the development of a longer term research program for addressing more challenging clinical problems. Ultimately, we believe that it is such models, encouraging the vital collaboration between clinicians and researchers for the work on targeted, well defined research projects, which will result in answers to the important clinical challenges of today. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Modeling the response of normal and ischemic cardiac tissue to electrical stimulation

NASA Astrophysics Data System (ADS)

Kandel, Sunil Mani

Heart disease, the leading cause of death worldwide, is often caused by ventricular fibrillation. A common treatment for this lethal arrhythmia is defibrillation: a strong electrical shock that resets the heart to its normal rhythm. To design better defibrillators, we need a better understanding of both fibrillation and defibrillation. Fundamental mysteries remain regarding the mechanism of how the heart responds to a shock, particularly anodal shocks and the resultant hyperpolarization. Virtual anodes play critical roles in defibrillation, and one cannot build better defibrillators until these mechanisms are understood. We are using mathematical modeling to numerically simulate observed phenomena, and are exploring fundamental mechanisms responsible for the heart's electrical behavior. Such simulations clarify mechanisms and identify key parameters. We investigate how systolic tissue responds to an anodal shock and how refractory tissue reacts to hyperpolarization by studying the dip in the anodal strength-interval curve. This dip is due to electrotonic interaction between regions of depolarization and hyperpolarization following a shock. The dominance of the electrotonic mechanism over calcium interactions implies the importance of the spatial distribution of virtual electrodes. We also investigate the response of localized ischemic tissue to an anodal shock by modeling a regional elevation of extracellular potassium concentration. This heterogeneity leads to action potential instability, 2:1 conduction block (alternans), and reflection-like reentry at the boarder of the normal and ischemic regions. This kind of reflection (reentry) occurs due to the delay between proximal and distal segments to re-excite the proximal segment. Our numerical simulations are based on the bidomain model, the state-of-the-art mathematical description of how cardiac tissue responds to shocks. The dynamic LuoRudy model describes the active properties of the membrane. To model ischemia, the Luo-Rudy model is modified by adding ischemic-related ion currents and concentrations to mimic conditions during the initial phase of ischemia. The stimulus is applied through a unipolar electrode that induces a complicated spatial distribution of transmembrane potential, including adjacent regions of depolarization and hyperpolarization. This research is significant because it uncovers basic properties of excitation that are fundamental for understanding cardiac pacing and defibrillation.

Compensation, benefits, and satisfaction: the Longitudinal Emergency Medical Technician Demographic Study (LEADS) Project.

PubMed

Brown, William E; Dawson, Drew; Levine, Roger

2003-01-01

To determine the compensation, benefit package, and level of satisfaction with the benefits of nationally registered emergency medical technicians (NREMTs) in 2001. The Longitudinal EMT Attribute Demographic Study (LEADS) Project included an 18-question snapshot survey on compensation with the 2001 core survey. This survey was sent to 4,835 randomly selected NREMTs. A total of 1,718 NREMT-Basics and NREMT-Paramedics, from 1,317 different postal zip codes, responded to the survey. Most NREMTs in the survey (86% of the compensated NREMT-Basics and 85% of the compensated NREMT-Paramedics) were employed primarily as patient care providers. For their emergency medical services (EMS) work in the previous 12 months, compensated NREMT-Basics had mean earnings of 18,324 US dollars (standard error, 978 US dollars) and compensated NREMT-Paramedics had mean earnings of 34,654 US dollars (standard error, 646 US dollars). At least 26% of compensated NREMT-Basics and 9% of compensated NREMT-Paramedics had no health insurance. The majority of compensated NREMTs (62% of the Basics and 57% of the Paramedics) reported their retirement plans were not adequate to meet their financial needs. EMTs are not satisfied with the appreciation and recognition they receive from EMS employers. About one-third (35% of the compensated NREMT-Basics and 30% of the compensated NREMT-Paramedics) were not satisfied with all of the benefits they receive from their EMS employer. Nearly all (94% of both compensated NREMT-Basics and NREMT-Paramedics) believed that EMTs should be paid more for the job that they do. The adequacy of EMT compensation and benefit packages is an area of concern. It is not unreasonable to believe that these factors are associated with EMT retention and attrition. Additional longitudinal EMT information on compensation and benefits are anticipated to determine the extent to which compensation and benefits are factors in EMT retention.

Gradual Introduction of Some Aspects of Quantum Mechanics in a High School Curriculum.

ERIC Educational Resources Information Center

Cuppari, A.; Rinaudo, G.; Robutti, O.; Violino, P.

1997-01-01

Suggests that the basic concepts of quantum mechanics can be introduced at the high school level by considering the action of classical mechanics, then introducing Planck's constant as the granularity of that action. Uses the periodic motion of a spring as a practical example. (AIM)

Fundamentals of Diesel Engines.

ERIC Educational Resources Information Center

Marine Corps Inst., Washington, DC.

This student guide, one of a series of correspondence training courses designed to improve the job performance of members of the Marine Corps, deals with the fundamentals of diesel engine mechanics. Addressed in the three individual units of the course are the following topics: basic principles of diesel mechanics; principles, mechanics, and…

Molecular Mechanics: The Method and Its Underlying Philosophy.

ERIC Educational Resources Information Center

Boyd, Donald B.; Lipkowitz, Kenny B.

1982-01-01

Molecular mechanics is a nonquantum mechanical method for solving problems concerning molecular geometries and energy. Methodology based on: the principle of combining potential energy functions of all structural features of a particular molecule into a total force field; derivation of basic equations; and use of available computer programs is…

Students' Conceptual Difficulties in Quantum Mechanics: Potential Well Problems

ERIC Educational Resources Information Center

Ozcan, Ozgur; Didis, Nilufer; Tasar, Mehmet Fatih

2009-01-01

In this study, students' conceptual difficulties about some basic concepts in quantum mechanics like one-dimensional potential well problems and probability density of tunneling particles were identified. For this aim, a multiple choice instrument named Quantum Mechanics Conceptual Test has been developed by one of the researchers of this study…

Using a software-defined computer in teaching the basics of computer architecture and operation

NASA Astrophysics Data System (ADS)

Kosowska, Julia; Mazur, Grzegorz

2017-08-01

The paper describes the concept and implementation of SDC_One software-defined computer designed for experimental and didactic purposes. Equipped with extensive hardware monitoring mechanisms, the device enables the students to monitor the computer's operation on bus transfer cycle or instruction cycle basis, providing the practical illustration of basic aspects of computer's operation. In the paper, we describe the hardware monitoring capabilities of SDC_One and some scenarios of using it in teaching the basics of computer architecture and microprocessor operation.

Analytic Results for e+e- --> tt-bar and gammagamma --> tt-bar Observables near the Threshold up to the Next-to-Next-to-Leading Order of NRQCD

NASA Astrophysics Data System (ADS)

Penin, A. A.; Pivovarov, A. A.

2001-02-01

We present an analytical description of top-antitop pair production near the threshold in $e^+e^-$ annihilation and $\\g\\g$ collisions. A set of basic observables considered includes the total cross sections, forward-backward asymmetry and top quark polarization. The threshold effects relevant for the basic observables are described by three universal functions related to S wave production, P wave production and S-P interference. These functions are computed analytically up to the next-to-next-to-leading order of NRQCD. The total $e^+e^-\\to t\\bar t$ cross section near the threshold is obtained in the next-to-next-to-leading order in the closed form including the contribution due to the axial coupling of top quark and mediated by the Z-boson. The effects of the running of the strong coupling constant and of the finite top quark width are taken into account analytically for the P wave production and S-P wave interference.

Examining the effect of self-explanation on cognitive integration of basic and clinical sciences in novices.

PubMed

Lisk, Kristina; Agur, Anne M R; Woods, Nicole N

2017-12-01

Several studies have shown that cognitive integration of basic and clinical sciences supports diagnostic reasoning in novices; however, there has been limited exploration of the ways in which educators can translate this model of mental activity into sound instructional strategies. The use of self-explanation during learning has the potential to promote and support the development of integrated knowledge by encouraging novices to elaborate on the causal relationship between clinical features and basic science mechanisms. To explore the effect of this strategy, we compared diagnostic efficacy of teaching students (n = 71) the clinical features of four musculoskeletal pathologies using either (1) integrated causal basic science descriptions (BaSci group); (2) integrated causal basic science descriptions combined with self-explanation prompts (SE group); (3) basic science mechanisms segregated from the clinical features (SG group). All participants completed a diagnostic accuracy test immediately after learning and 1-week later. The results showed that the BaSci group performed significantly better compared to the SE (p = 0.019) and SG groups (p = 0.004); however, no difference was observed between the SE and SG groups (p = 0.91). We hypothesize that the structure of the self-explanation task may not have supported the development of a holistic conceptual understanding of each disease. These findings suggest that integration strategies need to be carefully structured and applied in ways that support the holistic story created by integrated basic science instruction in order to foster conceptual coherence and to capitalize on the benefits of cognition integration.

Automotive Mechanics. COM-LINK. Competency Based Vocational Curricula with Basic Skills and Academic Linkages.

ERIC Educational Resources Information Center

Brown, Desmond

This competency-based module uses the Ocean County (New Jersey) Vocational-Technical Schools curriculum-infused model for infusing basic skills instruction into vocational education. The model demonstrates the relationship of vocational skills to communication, mathematics, and science. The document begins with a philosophy statement; preface; a…

China Brain Project: Basic Neuroscience, Brain Diseases, and Brain-Inspired Computing.

PubMed

Poo, Mu-Ming; Du, Jiu-Lin; Ip, Nancy Y; Xiong, Zhi-Qi; Xu, Bo; Tan, Tieniu

2016-11-02

The China Brain Project covers both basic research on neural mechanisms underlying cognition and translational research for the diagnosis and intervention of brain diseases as well as for brain-inspired intelligence technology. We discuss some emerging themes, with emphasis on unique aspects. Copyright © 2016. Published by Elsevier Inc.

The sleep-wake-cycle: basic mechanisms.

PubMed

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.

Vocational Curriculum Resources for Disadvantaged Students. A Guide to Print and Non-Print Instructional Materials. Volume I.

ERIC Educational Resources Information Center

Mangano, R. Michael; And Others

Volume 1 of a three-volume guide to vocational curriculum resources for disadvantaged students consists of instructional checklists for resources identified in the following areas: agriculture, auto body repair, automobile mechanics, basic math skills, basic reading skills, business education, carpentry, cosmetology, custodial and maintenance,…

Enhancing Problem-Solving Capabilities Using Object-Oriented Programming Language

ERIC Educational Resources Information Center

Unuakhalu, Mike F.

2009-01-01

This study integrated object-oriented programming instruction with transfer training activities in everyday tasks, which might provide a mechanism that can be used for efficient problem solving. Specifically, a Visual BASIC embedded with everyday tasks group was compared to another group exposed to Visual BASIC instruction only. Subjects were 40…