Sample records for underlying mechanisms include

  1. Transformations of organic compounds under the action of mechanical stress

    NASA Astrophysics Data System (ADS)

    Dubinskaya, Aleksandra M.

    1999-08-01

    Transformations of organic compounds (monomeric and polymeric) under the action of mechanical stress are considered. Two types of processes occur under these conditions. The first type involves disordering and amorphisation of crystal structure and conformational transformations as a result of rupture of intermolecular bonds. The second type includes mechanochemical reactions activated by deformation of valence bonds and angles under mechanical stress, namely, the rupture of bonds, oxidation and hydrolysis. Data on the organic mechanochemical synthesis of new compounds or molecular complexes are systematised and generalised. It is demonstrated that mechanical treatment ensures mass transfer and the contact of reacting species in these reactions. Proteins are especially sensitive to mechanical stress and undergo denaturation; enzymes are inactivated. The bibliography includes 115 references.

  2. Locking mechanism for orthopedic braces

    NASA Technical Reports Server (NTRS)

    Chao, J. I.; Epps, C. H., Jr.

    1981-01-01

    An orthopedic brace locking mechanism is described which under standing or walking conditions cannot be unlocked, however under sitting conditions the mechanism can be simply unlocked so as to permit bending of the patient's knee. Other features of the device include: (1) the mechanism is rendered operable, and inoperable, dependent upon the relative inclination of the brace with respect to the ground; (2) the mechanism is automatically locked under standing or walking conditions and is manually unlocked under sitting conditions; and (3) the mechanism is light in weight and is relatively small in size.

  3. Mechanisms Underlying Sexual Violence Exposure and Psychosocial Sequelae: A Theoretical and Empirical Review

    PubMed Central

    Walsh, Kate; Galea, Sandro; Koenen, Karestan C.

    2015-01-01

    Sexual violence is associated with a range of negative mental health and behavioral sequelae, including posttraumatic stress disorder (PTSD), depression, substance abuse/dependence, risky sexual behavior, and interpersonal relationship problems. However, mechanisms underlying these associations are not well understood. Identifying mechanisms that explain linkages between sexual violence and poor outcomes is of paramount importance in determining when and how to intervene to prevent or reduce the magnitude of these outcomes. This review focuses on theories that have been proposed to explain risk of negative outcomes among sexual violence victims, including the development of traumagenic dynamics and emotion dysregulation. We also review promising biological mechanisms that may explain the risk of negative outcomes among sexual violence victims, including studies concerned with epigenetic and neurobiological mechanisms. PMID:25762853

  4. Hemiplegic shoulder pain: a common clinical consequence of stroke.

    PubMed

    Coskun Benlidayi, Ilke; Basaran, Sibel

    2014-04-01

    Hemiplegic shoulder pain is common in stroke survivors, developing in up to 54% of patients. The underlying mechanisms include soft tissue lesions, impaired motor function and central nervous system-related phenomena. Hemiplegic shoulder pain has many underlying causes and is challenging to manage, requiring a team approach, including physicians, therapists and caregivers. The management strategy must target the underlying causes. Preventative measures, such as positioning and handling, can reduce the risk of developing hemiplegic shoulder pain. We have reviewed the literature on hemiplegic shoulder pain, and used this to categorise the underlying mechanisms, and to explore the best management strategies.

  5. The underlying toxicological mechanism of chemical mixtures: A case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum

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

    Tian, Dayong; Department of Chemical and Environmental Engineering, Anyang Institute of Technology, Anyang 455000; Lin, Zhifen, E-mail: lzhifen@tongji.edu.cn

    Intracellular chemical reaction of chemical mixtures is one of the main reasons that cause synergistic or antagonistic effects. However, it still remains unclear what the influencing factors on the intracellular chemical reaction are, and how they influence on the toxicological mechanism of chemical mixtures. To reveal this underlying toxicological mechanism of chemical mixtures, a case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum was employed, and both their joint effects and mixture toxicity were observed. Then series of two-step linear regressions were performed to describe the relationships between joint effects, the expected additive toxicities and descriptorsmore » of individual chemicals (including concentrations, binding affinity to receptors, octanol/water partition coefficients). Based on the quantitative relationships, the underlying joint toxicological mechanisms were revealed. The result shows that, for mixtures with their joint effects resulting from intracellular chemical reaction, their underlying toxicological mechanism depends on not only their interaction with target proteins, but also their transmembrane actions and their concentrations. In addition, two generic points of toxicological mechanism were proposed including the influencing factors on intracellular chemical reaction and the difference of the toxicological mechanism between single reactive chemicals and their mixtures. This study provided an insight into the understanding of the underlying toxicological mechanism for chemical mixtures with intracellular chemical reaction. - Highlights: • Joint effects of nitriles and aldehydes at non-equitoxic ratios were determined. • A novel descriptor, ligand–receptor interaction energy (E{sub binding}), was employed. • Quantitative relationships for mixtures were developed based on a novel descriptor. • The underlying toxic mechanism was revealed based on quantitative relationships. • Two generic points of toxicological mechanism were elucidated.« less

  6. Novel instrument for characterizing comprehensive physical properties under multi-mechanical loads and multi-physical field coupling conditions

    NASA Astrophysics Data System (ADS)

    Liu, Changyi; Zhao, Hongwei; Ma, Zhichao; Qiao, Yuansen; Hong, Kun; Ren, Zhuang; Zhang, Jianhai; Pei, Yongmao; Ren, Luquan

    2018-02-01

    Functional materials represented by ferromagnetics and ferroelectrics are widely used in advanced sensor and precision actuation due to their special characterization under coupling interactions of complex loads and external physical fields. However, the conventional devices for material characterization can only provide a limited type of loads and physical fields and cannot simulate the actual service conditions of materials. A multi-field coupling instrument for characterization has been designed and implemented to overcome this barrier and measure the comprehensive physical properties under complex service conditions. The testing forms include tension, compression, bending, torsion, and fatigue in mechanical loads, as well as different external physical fields, including electric, magnetic, and thermal fields. In order to offer a variety of information to reveal mechanical damage or deformation forms, a series of measurement methods at the microscale are integrated with the instrument including an indentation unit and in situ microimaging module. Finally, several coupling experiments which cover all the loading and measurement functions of the instrument have been implemented. The results illustrate the functions and characteristics of the instrument and then reveal the variety in mechanical and electromagnetic properties of the piezoelectric transducer ceramic, TbDyFe alloy, and carbon fiber reinforced polymer under coupling conditions.

  7. Quiet Clean Short-haul Experimental Engine (QCSEE) Under-The-Wing (UTW) engine composite nacelle test report. Volume 1: Summary, aerodynamic and mechanical performance

    NASA Technical Reports Server (NTRS)

    1979-01-01

    The performance test results of the final under-the-wing engine configuration are presented. One hundred and six hours of engine operation were completed, including mechanical and performance checkout, baseline acoustic testing with a bellmouth inlet, reverse thrust testing, acoustic technology tests, and limited controls testing. The engine includes a variable pitch fan having advanced composite fan blades and using a ball-spline pitch actuation system.

  8. 29 CFR 1.1 - Purpose and scope.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., including fringe benefits, to laborers and mechanics engaged in construction activity under contracts... prevailing for the corresponding classes of laborers and mechanics employed on projects similar to the...

  9. 29 CFR 1.1 - Purpose and scope.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., including fringe benefits, to laborers and mechanics engaged in construction activity under contracts... prevailing for the corresponding classes of laborers and mechanics employed on projects similar to the...

  10. 29 CFR 1.1 - Purpose and scope.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., including fringe benefits, to laborers and mechanics engaged in construction activity under contracts... prevailing for the corresponding classes of laborers and mechanics employed on projects similar to the...

  11. The Mediated MIMIC Model for Understanding the Underlying Mechanism of DIF

    ERIC Educational Resources Information Center

    Cheng, Ying; Shao, Can; Lathrop, Quinn N.

    2016-01-01

    Due to its flexibility, the multiple-indicator, multiple-causes (MIMIC) model has become an increasingly popular method for the detection of differential item functioning (DIF). In this article, we propose the mediated MIMIC model method to uncover the underlying mechanism of DIF. This method extends the usual MIMIC model by including one variable…

  12. [The mechanisms of formation of liver injuries associated with the blunt abdominal trauma].

    PubMed

    Pigolkin, Iu I; Dubrovina, I A; Dubrovin, I A

    2012-01-01

    The mechanisms of liver damage associated with the blunt abdominal trauma are considered based on the analysis of the literature publications. The general characteristic of these mechanisms and the processes underlying the development of liver injuries is presented. It is argued that the mechanisms underlying the formation of damages to the liver differ depending on the form of the traumatic impact, the injurious factor, and the processes leading to the destruction of the hepatic tissue. The main forms of traumatic impact in the case of a blunt abdominal trauma include the strike (blow), pressure, and concussion of the organ while the major traumatic factors are deformation, displacement, and "shock-resistant effects". The mechanisms underlying tissue destruction are compression and stretching. These two mechanisms are responsible for the formation of different variants of liver destruction. The results of the study suggest the necessity of the search for other mechanisms of degradation of the hepatic tissue following a blunt abdominal trauma for the improvement of forensic medical diagnostics of its cause and the underlying mechanism.

  13. Feeding Problems and Their Underlying Mechanisms in the Esophageal Atresia–Tracheoesophageal Fistula Patient

    PubMed Central

    Mahoney, Lisa; Rosen, Rachel

    2017-01-01

    Feeding difficulties such as dysphagia, coughing, choking, or vomiting during meals, slow eating, oral aversion, food refusal, and stressful mealtimes are common in children with repaired esophageal atresia (EA) and the reasons for this are often multifactorial. The aim of this review is to describe the possible underlying mechanisms contributing to feeding difficulties in patients with EA and approaches to management. Underlying mechanisms for these feeding difficulties include esophageal dysphagia, oropharyngeal dysphagia and aspiration, and aversions related to prolonged gastrostomy tube feeding. The initial diagnostic evaluation for feeding difficulties in a patient with EA may involve an esophagram, videofluoroscopic imaging or fiberoptic endoscopic evaluation during swallowing, upper endoscopy with biopsies, pH-impedance testing, and/or esophageal motility studies. The main goal of management is to reduce the factors contributing to feeding difficulties and may include reducing esophageal stasis, maximizing reflux therapies, treating underlying lung disease, dilating strictures, and altering feeding methods, routes, or schedules. PMID:28620597

  14. Epigenetic Mechanisms Impacting Aging: A Focus on Histone Levels and Telomeres

    PubMed Central

    Song, Shufei

    2018-01-01

    Aging and age-related diseases pose some of the most significant and difficult challenges to modern society as well as to the scientific and medical communities. Biological aging is a complex, and, under normal circumstances, seemingly irreversible collection of processes that involves numerous underlying mechanisms. Among these, chromatin-based processes have emerged as major regulators of cellular and organismal aging. These include DNA methylation, histone modifications, nucleosome positioning, and telomere regulation, including how these are influenced by environmental factors such as diet. Here we focus on two interconnected categories of chromatin-based mechanisms impacting aging: those involving changes in the levels of histones or in the functions of telomeres. PMID:29642537

  15. Modeling of rolling element bearing mechanics

    NASA Technical Reports Server (NTRS)

    Greenhill, L. M.

    1991-01-01

    Roller element bearings provide the primary mechanical interface between rotating and nonrotating components in the high performance turbomachinery of the Space Shuttle Main Engine (SSME). Knowledge of bearing behavior under various loading and environmental conditions is essential to predicting and understanding the overall behavior of turbopumps, including rotordynamic stability, critical speeds and bearing life. The objective is to develop mathematical models and computer programs to describe the mechanical behavior of ball and cylinder roller bearings under the loading and environmental conditions encountered in the SSME and future high performance rocket engines. This includes characteristics such as nonlinear load/motion relationships, stiffness and damping, rolling element loads for life prediction, and roller and cage stability.

  16. Pharmacological Interventions for the MATRICS Cognitive Domains in Schizophrenia: What’s the Evidence?

    PubMed Central

    Vingerhoets, Wilhelmina A. M.; Bloemen, Oswald J. N.; Bakker, Geor; van Amelsvoort, Therese A. M. J.

    2013-01-01

    Schizophrenia is a disabling, chronic psychiatric disorder with a prevalence rate of 0.5–1% in the general population. Symptoms include positive (e.g., delusions, hallucinations), negative (e.g., blunted affect, social withdrawal), as well as cognitive symptoms (e.g., memory and attention problems). Although 75–85% of patients with schizophrenia report cognitive impairments, the underlying neuropharmacological mechanisms are not well understood and currently no effective treatment is available for these impairments. This has led to the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative, which established seven cognitive domains that are fundamentally impaired in schizophrenia. These domains include verbal learning and memory, visual learning and memory, working memory, attention and vigilance, processing speed, reasoning and problem solving, and social cognition. Recently, a growing number of studies have been conducted trying to identify the underlying neuropharmacological mechanisms of cognitive impairments in schizophrenia patients. Specific cognitive impairments seem to arise from different underlying neuropharmacological mechanisms. However, most review articles describe cognition in general and an overview of the mechanisms involved in these seven separate cognitive domains is currently lacking. Therefore, we reviewed the underlying neuropharmacological mechanisms focusing on the domains as established by the MATRICS initiative which are considered most crucial in schizophrenia. PMID:24363646

  17. 26 CFR 301.6323(h)-1 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... security interest, see § 301.6323(c)-1(e). (b) Mechanic's lienor—(1) In general. The term “mechanic's... construction or improvement (including demolition) of the property. A mechanic's lienor is treated as having a lien on the later of— (i) The date on which the mechanic's lien first becomes valid under local law...

  18. Noncontact minimally invasive technique for the assessment of mechanical properties of single cardiac myocyte via magnetic field loading

    NASA Astrophysics Data System (ADS)

    Yin, Shizhuo; Zhang, Xueqian; Cheung, Joseph; Wu, Juntao; Zhan, Chun; Xue, Jinchao

    2004-07-01

    In this paper, a unique non-contact, minimum invasive technique for the assessment of mechanical properties of single cardiac myocyte is presented. The assessment process includes following major steps: (1) attach a micro magnetic bead to the cell to be measured, (2) measure the contractile performance of the cell under the different magnetic field loading, (3) calculate mechanical loading force, and (4) derive the contractile force from the measured contraction data under different magnetic field loading.

  19. Effects of axial compression and rotation angle on torsional mechanical properties of bovine caudal discs.

    PubMed

    Bezci, Semih E; Klineberg, Eric O; O'Connell, Grace D

    2018-01-01

    The intervertebral disc is a complex joint that acts to support and transfer large multidirectional loads, including combinations of compression, tension, bending, and torsion. Direct comparison of disc torsion mechanics across studies has been difficult, due to differences in loading protocols. In particular, the lack of information on the combined effect of multiple parameters, including axial compressive preload and rotation angle, makes it difficult to discern whether disc torsion mechanics are sensitive to the variables used in the test protocol. Thus, the objective of this study was to evaluate compression-torsion mechanical behavior of healthy discs under a wide range of rotation angles. Bovine caudal discs were tested under a range of compressive preloads (150, 300, 600, and 900N) and rotation angles (± 1, 2, 3, 4, or 5°) applied at a rate of 0.5°/s. Torque-rotation data were used to characterize shape changes in the hysteresis loop and to calculate disc torsion mechanics. Torsional mechanical properties were described using multivariate regression models. The rate of change in torsional mechanical properties with compression depended on the maximum rotation angle applied, indicating a strong interaction between compressive stress and maximum rotation angle. The regression models reported here can be used to predict disc torsion mechanics under axial compression for a given disc geometry, compressive preload, and rotation angle. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. A Place at the Table: LTD as a Mediator of Memory Genesis.

    PubMed

    Connor, Steven A; Wang, Yu Tian

    2016-08-01

    Resolving how our brains encode information requires an understanding of the cellular processes taking place during memory formation. Since the 1970s, considerable effort has focused on determining the properties and mechanisms underlying long-term potentiation (LTP) at glutamatergic synapses and how these processes influence initiation of new memories. However, accumulating evidence suggests that long-term depression (LTD) of synaptic strength, particularly at glutamatergic synapses, is a bona fide learning and memory mechanism in the mammalian brain. The known range of mechanisms capable of inducing LTD has been extended to those including NMDAR-independent forms, neuromodulator-dependent LTD, synaptic depression following stress, and non-synaptically induced forms. The examples of LTD observed at the hippocampal CA1 synapse to date demonstrate features consistent with LTP, including homo- and heterosynaptic expression, extended duration beyond induction (several hours to weeks), and association with encoding of distinct types of memories. Canonical mechanisms through which synapses undergo LTD include activation of phosphatases, initiation of protein synthesis, and dynamic regulation of presynaptic glutamate release and/or postsynaptic glutamate receptor endocytosis. Here, we will discuss the pre- and postsynaptic changes underlying LTD, recent advances in the identification and characterization of novel mechanisms underlying LTD, and how engagement of these processes constitutes a cellular analog for the genesis of specific types of memories. © The Author(s) 2015.

  1. Short- and long-term behavioural, physiological and stoichiometric responses to predation risk indicate chronic stress and compensatory mechanisms.

    PubMed

    Van Dievel, Marie; Janssens, Lizanne; Stoks, Robby

    2016-06-01

    Prey organisms are expected to use different short- and long-term responses to predation risk to avoid excessive costs. Contrasting both types of responses is important to identify chronic stress responses and possible compensatory mechanisms in order to better understand the full impact of predators on prey life history and population dynamics. Using larvae of the damselfly Enallagma cyathigerum, we contrasted the effects of short- and long-term predation risk, with special focus on consequences for body stoichiometry. Under short-term predation risk, larvae reduced growth rate, which was associated with a reduced food intake, increased metabolic rate and reduced glucose content. Under long-term predation risk, larvae showed chronic predator stress as indicated by persistent increases in metabolic rate and reduced food intake. Despite this, larvae were able to compensate for the short-term growth reduction under long-term predation risk by relying on physiological compensatory mechanisms, including reduced energy storage. Only under long-term predation risk did we observe an increase in body C:N ratio, as predicted under the general stress paradigm (GSP). Although this was caused by a predator-induced decrease in N content, there was no associated increase in C content. These stoichiometric changes could not be explained by GSP responses because, under chronic predation risk, there was no decrease in N-rich proteins or increase in C-rich fat and sugars; instead glycogen decreased. Our results highlight the importance of compensatory mechanisms and the value of explicitly integrating physiological mechanisms to obtain insights into the temporal dynamics of non-consumptive effects, including effects on body stoichiometry.

  2. Micro electro-mechanical heater

    DOEpatents

    Oh, Yunje; Asif, Syed Amanulla Syed; Cyrankowski, Edward; Warren, Oden Lee

    2016-04-19

    A sub-micron scale property testing apparatus including a test subject holder and heating assembly. The assembly includes a holder base configured to couple with a sub-micron mechanical testing instrument and electro-mechanical transducer assembly. The assembly further includes a test subject stage coupled with the holder base. The test subject stage is thermally isolated from the holder base. The test subject stage includes a stage subject surface configured to receive a test subject, and a stage plate bracing the stage subject surface. The stage plate is under the stage subject surface. The test subject stage further includes a heating element adjacent to the stage subject surface, the heating element is configured to generate heat at the stage subject surface.

  3. Micro electro-mechanical heater

    DOEpatents

    Oh, Yunje; Asif, Syed Amanulla Syed; Cyrankowski, Edward; Warren, Oden Lee

    2017-09-12

    A sub-micron scale property testing apparatus including a test subject holder and heating assembly. The assembly includes a holder base configured to couple with a sub-micron mechanical testing instrument and electro-mechanical transducer assembly. The assembly further includes a test subject stage coupled with the holder base. The test subject stage is thermally isolated from the holder base. The test subject stage includes a stage subject surface configured to receive a test subject, and a stage plate bracing the stage subject surface. The stage plate is under the stage subject surface. The test subject stage further includes a heating element adjacent to the stage subject surface, the heating element is configured to generate heat at the stage subject surface.

  4. CRDM with separate SCRAM latch engagement and locking

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

    Dodd, Christopher D.; DeSantis, Paul K.; Stambaugh, Kevin J.

    A control rod drive mechanism (CRDM) configured to latch onto the lifting rod of a control rod assembly and including separate latch engagement and latch holding mechanisms. A CRDM configured to latch onto the lifting rod of a control rod assembly and including a four-bar linkage closing the latch, wherein the four-bar linkage biases the latch closed under force of gravity.

  5. GUIDES TO POLLUTION PREVENTION: THE MECHANICAL EQUIPMENT REPAIR INDUSTRY

    EPA Science Inventory

    Commercial mechanical equipment repair services are covered under SIC 76 and include activities such as repair of boilers, commercial appliances, lawn mowers, refrigerator and air conditioners, electric motors, generators and transformers, among others. This quide describes the ...

  6. 29 CFR Appendix A to Part 95 - Contract Provisions

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Construction”). Under this Act, contractors shall be required to pay wages to laborers and mechanics at a rate... contracts that involve the employment of mechanics or laborers shall include a provision for compliance with... shall be required to compute the wages of every mechanic and laborer on the basis of a standard work...

  7. 20 CFR Appendix A to Part 435 - Contract Provisions

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Assisted Construction”). Under this Act, contractors are required to pay wages to laborers and mechanics at... of mechanics or laborers must include a provision for compliance with Sections 102 and 107 of the... every mechanic and laborer on the basis of a standard workweek of 40 hours. Work in excess of the...

  8. 20 CFR Appendix A to Part 435 - Contract Provisions

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Assisted Construction”). Under this Act, contractors are required to pay wages to laborers and mechanics at... of mechanics or laborers must include a provision for compliance with Sections 102 and 107 of the... every mechanic and laborer on the basis of a standard workweek of 40 hours. Work in excess of the...

  9. 20 CFR Appendix A to Part 435 - Contract Provisions

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Assisted Construction”). Under this Act, contractors are required to pay wages to laborers and mechanics at... of mechanics or laborers must include a provision for compliance with Sections 102 and 107 of the... every mechanic and laborer on the basis of a standard workweek of 40 hours. Work in excess of the...

  10. 29 CFR Appendix A to Part 95 - Contract Provisions

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Construction”). Under this Act, contractors shall be required to pay wages to laborers and mechanics at a rate... contracts that involve the employment of mechanics or laborers shall include a provision for compliance with... shall be required to compute the wages of every mechanic and laborer on the basis of a standard work...

  11. 29 CFR Appendix A to Part 95 - Contract Provisions

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Construction”). Under this Act, contractors shall be required to pay wages to laborers and mechanics at a rate... contracts that involve the employment of mechanics or laborers shall include a provision for compliance with... shall be required to compute the wages of every mechanic and laborer on the basis of a standard work...

  12. 48 CFR 22.406-2 - Wages, fringe benefits, and overtime.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... to a laborer or mechanic, the contractor may include only the following items: (1) Amounts paid in cash to the laborer or mechanic, or deducted from payments under the conditions set forth in 29 CFR 3.5... determination for the classification of laborer or mechanic concerned. (2) Wages provided by the contractor and...

  13. 48 CFR 22.406-2 - Wages, fringe benefits, and overtime.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... to a laborer or mechanic, the contractor may include only the following items: (1) Amounts paid in cash to the laborer or mechanic, or deducted from payments under the conditions set forth in 29 CFR 3.5... determination for the classification of laborer or mechanic concerned. (2) Wages provided by the contractor and...

  14. 48 CFR 22.406-2 - Wages, fringe benefits, and overtime.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... to a laborer or mechanic, the contractor may include only the following items: (1) Amounts paid in cash to the laborer or mechanic, or deducted from payments under the conditions set forth in 29 CFR 3.5... prescribed in the wage determination for the classification of laborer or mechanic concerned. (2) Wages...

  15. 29 CFR 779.372 - Nonmanufacturing establishments with certain exempt employees under section 13(b)(10).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... salesman, partsman, or mechanic primarily engaged in selling or servicing automobiles, trucks, or farm... met by an establishment the exemption will be available for salesmen, partsmen and mechanics, employed... includes dealers in trailers, boats, and aircraft. (c) Salesman, partsman, or mechanic. (1) As used in...

  16. 26 CFR 301.6323(h)-1 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... financing security as a holder of a security interest, see § 301.6323(c)-1(e). (b) Mechanic's lienor—(1) In general. The term “mechanic's lienor” means any person who under local law has a lien on real property (or... in connection with the construction or improvement (including demolition) of the property. A mechanic...

  17. 26 CFR 301.6323(h)-1 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... financing security as a holder of a security interest, see § 301.6323(c)-1(e). (b) Mechanic's lienor—(1) In general. The term “mechanic's lienor” means any person who under local law has a lien on real property (or... in connection with the construction or improvement (including demolition) of the property. A mechanic...

  18. 29 CFR 779.372 - Nonmanufacturing establishments with certain exempt employees under section 13(b)(10).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... salesman, partsman, or mechanic primarily engaged in selling or servicing automobiles, trucks, or farm... met by an establishment the exemption will be available for salesmen, partsmen and mechanics, employed... includes dealers in trailers, boats, and aircraft. (c) Salesman, partsman, or mechanic. (1) As used in...

  19. 48 CFR 22.406-2 - Wages, fringe benefits, and overtime.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... to a laborer or mechanic, the contractor may include only the following items: (1) Amounts paid in cash to the laborer or mechanic, or deducted from payments under the conditions set forth in 29 CFR 3.5... determination for the classification of laborer or mechanic concerned. (2) Wages provided by the contractor and...

  20. 29 CFR 779.372 - Nonmanufacturing establishments with certain exempt employees under section 13(b)(10).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... salesman, partsman, or mechanic primarily engaged in selling or servicing automobiles, trucks, or farm... met by an establishment the exemption will be available for salesmen, partsmen and mechanics, employed... includes dealers in trailers, boats, and aircraft. (c) Salesman, partsman, or mechanic. (1) As used in...

  1. 29 CFR 779.372 - Nonmanufacturing establishments with certain exempt employees under section 13(b)(10).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... salesman, partsman, or mechanic primarily engaged in selling or servicing automobiles, trucks, or farm... met by an establishment the exemption will be available for salesmen, partsmen and mechanics, employed... includes dealers in trailers, boats, and aircraft. (c) Salesman, partsman, or mechanic. (1) As used in...

  2. 26 CFR 301.6323(h)-1 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... financing security as a holder of a security interest, see § 301.6323(c)-1(e). (b) Mechanic's lienor—(1) In general. The term “mechanic's lienor” means any person who under local law has a lien on real property (or... in connection with the construction or improvement (including demolition) of the property. A mechanic...

  3. Cellular Mechanosensing: Getting to the nucleus of it all

    PubMed Central

    Fedorchak, Gregory R.; Kaminski, Ashley; Lammerding, Jan

    2014-01-01

    Cells respond to mechanical forces by activating specific genes and signaling pathways that allow the cells to adapt to their physical environment. Examples include muscle growth in response to exercise, bone remodeling based on their mechanical load, or endothelial cells aligning under fluid shear stress. While the involved downstream signaling pathways and mechanoresponsive genes are generally well characterized, many of the molecular mechanisms of the initiating ‘mechanosensing’ remain still elusive. In this review, we discuss recent findings and accumulating evidence suggesting that the cell nucleus plays a crucial role in cellular mechanotransduction, including processing incoming mechanoresponsive signals and even directly responding to mechanical forces. Consequently, mutations in the involved proteins or changes in nuclear envelope composition can directly impact mechanotransduction signaling and contribute to the development and progression of a variety of human diseases, including muscular dystrophy, cancer, and the focus of this review, dilated cardiomyopathy. Improved insights into the molecular mechanisms underlying nuclear mechanotransduction, brought in part by the emergence of new technologies to study intracellular mechanics at high spatial and temporal resolution, will not only result in a better understanding of cellular mechanosensing in normal cells but may also lead to the development of novel therapies in the many diseases linked to defects in nuclear envelope proteins. PMID:25008017

  4. Dendritic Spines in Depression: What We Learned from Animal Models

    PubMed Central

    Qiao, Hui; Li, Ming-Xing; Xu, Chang; Chen, Hui-Bin; An, Shu-Cheng; Ma, Xin-Ming

    2016-01-01

    Depression, a severe psychiatric disorder, has been studied for decades, but the underlying mechanisms still remain largely unknown. Depression is closely associated with alterations in dendritic spine morphology and spine density. Therefore, understanding dendritic spines is vital for uncovering the mechanisms underlying depression. Several chronic stress models, including chronic restraint stress (CRS), chronic unpredictable mild stress (CUMS), and chronic social defeat stress (CSDS), have been used to recapitulate depression-like behaviors in rodents and study the underlying mechanisms. In comparison with CRS, CUMS overcomes the stress habituation and has been widely used to model depression-like behaviors. CSDS is one of the most frequently used models for depression, but it is limited to the study of male mice. Generally, chronic stress causes dendritic atrophy and spine loss in the neurons of the hippocampus and prefrontal cortex. Meanwhile, neurons of the amygdala and nucleus accumbens exhibit an increase in spine density. These alterations induced by chronic stress are often accompanied by depression-like behaviors. However, the underlying mechanisms are poorly understood. This review summarizes our current understanding of the chronic stress-induced remodeling of dendritic spines in the hippocampus, prefrontal cortex, orbitofrontal cortex, amygdala, and nucleus accumbens and also discusses the putative underlying mechanisms. PMID:26881133

  5. Systems and Methods for Implementing Bulk Metallic Glass-Based Macroscale Compliant Mechanisms

    NASA Technical Reports Server (NTRS)

    Hofmann, Douglas C. (Inventor); Agnes, Gregory (Inventor)

    2017-01-01

    Systems and methods in accordance with embodiments of the invention implement bulk metallic glass-based macroscale compliant mechanisms. In one embodiment, a bulk metallic glass-based macroscale compliant mechanism includes: a flexible member that is strained during the normal operation of the compliant mechanism; where the flexible member has a thickness of 0.5 mm; where the flexible member comprises a bulk metallic glass-based material; and where the bulk metallic glass-based material can survive a fatigue test that includes 1000 cycles under a bending loading mode at an applied stress to ultimate strength ratio of 0.25.

  6. The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features, epidemiology, and mechanisms.

    PubMed

    Andrade, Jason; Khairy, Paul; Dobrev, Dobromir; Nattel, Stanley

    2014-04-25

    Atrial fibrillation (AF) is the most common arrhythmia (estimated lifetime risk, 22%-26%). The aim of this article is to review the clinical epidemiological features of AF and to relate them to underlying mechanisms. Long-established risk factors for AF include aging, male sex, hypertension, valve disease, left ventricular dysfunction, obesity, and alcohol consumption. Emerging risk factors include prehypertension, increased pulse pressure, obstructive sleep apnea, high-level physical training, diastolic dysfunction, predisposing gene variants, hypertrophic cardiomyopathy, and congenital heart disease. Potential risk factors are coronary artery disease, kidney disease, systemic inflammation, pericardial fat, and tobacco use. AF has substantial population health consequences, including impaired quality of life, increased hospitalization rates, stroke occurrence, and increased medical costs. The pathophysiology of AF centers around 4 general types of disturbances that promote ectopic firing and reentrant mechanisms, and include the following: (1) ion channel dysfunction, (2) Ca(2+)-handling abnormalities, (3) structural remodeling, and (4) autonomic neural dysregulation. Aging, hypertension, valve disease, heart failure, myocardial infarction, obesity, smoking, diabetes mellitus, thyroid dysfunction, and endurance exercise training all cause structural remodeling. Heart failure and prior atrial infarction also cause Ca(2+)-handling abnormalities that lead to focal ectopic firing via delayed afterdepolarizations/triggered activity. Neural dysregulation is central to atrial arrhythmogenesis associated with endurance exercise training and occlusive coronary artery disease. Monogenic causes of AF typically promote the arrhythmia via ion channel dysfunction, but the mechanisms of the more common polygenic risk factors are still poorly understood and under intense investigation. Better recognition of the clinical epidemiology of AF, as well as an improved appreciation of the underlying mechanisms, is needed to develop improved methods for AF prevention and management.

  7. Quantifying the net economic benefits of mechanical wildfire hazard treatments on timberlands of the western United States

    Treesearch

    Jeffrey P. Prestemon; Karen L. Abt; James R. Barbour

    2012-01-01

    Mechanical treatment of vegetation is done on public and private lands for many possible reasons, including enhancing wildlife habitat, increasing timber growth of residual stands, and improving resistance to damaging pests. Few studies, however, have focused on the circumstances under which mechanical wildfire hazard reduction treatments can yield positive net...

  8. 14 CFR Appendix A to Part 152 - Contract and Labor Provisions

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... paragraph L need not be included in prime contracts of $2,000 or less. A. Minimum wages. (1) All mechanics... the contractor and such laborers and mechanics; and the wage determination decision(s) shall be posted... under section 1(b)(2) of the Davis-Bacon Act on behalf of laborers or mechanics are considered wages...

  9. 14 CFR Appendix A to Part 152 - Contract and Labor Provisions

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... paragraph L need not be included in prime contracts of $2,000 or less. A. Minimum wages. (1) All mechanics... the contractor and such laborers and mechanics; and the wage determination decision(s) shall be posted... under section 1(b)(2) of the Davis-Bacon Act on behalf of laborers or mechanics are considered wages...

  10. 14 CFR Appendix A to Part 152 - Contract and Labor Provisions

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... paragraph L need not be included in prime contracts of $2,000 or less. A. Minimum wages. (1) All mechanics... the contractor and such laborers and mechanics; and the wage determination decision(s) shall be posted... under section 1(b)(2) of the Davis-Bacon Act on behalf of laborers or mechanics are considered wages...

  11. 14 CFR Appendix A to Part 152 - Contract and Labor Provisions

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... paragraph L need not be included in prime contracts of $2,000 or less. A. Minimum wages. (1) All mechanics... the contractor and such laborers and mechanics; and the wage determination decision(s) shall be posted... under section 1(b)(2) of the Davis-Bacon Act on behalf of laborers or mechanics are considered wages...

  12. 14 CFR Appendix A to Part 152 - Contract and Labor Provisions

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... paragraph L need not be included in prime contracts of $2,000 or less. A. Minimum wages. (1) All mechanics... the contractor and such laborers and mechanics; and the wage determination decision(s) shall be posted... under section 1(b)(2) of the Davis-Bacon Act on behalf of laborers or mechanics are considered wages...

  13. Hydraulic fracture and resilience of epithelial monolayers under stretch

    NASA Astrophysics Data System (ADS)

    Arroyo, Marino; Lucantonio, Alessandro; Noselli, Giovanni; Casares, Laura; Desimone, Antonio; Trepat, Xavier

    Epithelial monolayers are very simple and prevalent tissues. Their functions include delimiting distinct physicochemical containers and protecting us from pathogens. Epithelial fracture disrupts the mechanical integrity of this barrier, and hence compromises these functions. Here, we show that in addition to the conventional fracture resulting from excessive tissue tension, epithelia can hydraulically fracture under stretch as a result of the poroelastic nature of the matrix. We will provide experimental evidence of this counterintuitive mechanism of fracture, in which cracks appear under compression. Intriguingly, unlike tensional fracture, which is localized and catastrophic, hydraulic epithelial fracture is distributed and reversible. We will also describe the active mechanisms responsible for crack healing, and the physical principles by which the poroelastic matrix contributes to this resilient behavior.

  14. Zinc finger proteins in cancer progression.

    PubMed

    Jen, Jayu; Wang, Yi-Ching

    2016-07-13

    Zinc finger proteins are the largest transcription factor family in human genome. The diverse combinations and functions of zinc finger motifs make zinc finger proteins versatile in biological processes, including development, differentiation, metabolism and autophagy. Over the last few decades, increasing evidence reveals the potential roles of zinc finger proteins in cancer progression. However, the underlying mechanisms of zinc finger proteins in cancer progression vary in different cancer types and even in the same cancer type under different types of stress. Here, we discuss general mechanisms of zinc finger proteins in transcription regulation and summarize recent studies on zinc finger proteins in cancer progression. In this review, we also emphasize the importance of further investigations in elucidating the underlying mechanisms of zinc finger proteins in cancer progression.

  15. Mechanical analysis of pipe-type cable under TMB

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

    Greenwood, A.N.; Levy, R.; Spillers, W.R.

    1982-07-01

    This paper summarizes recent work performed at Rensselaer Polytechnic Institute on the mechanical response of pipe-type cable to the TMB environment. It deals with both the internal stress distribution at a point and gross cable moduli. Typical experimental results are included.

  16. Turntable mechanism

    NASA Technical Reports Server (NTRS)

    Myers, William Neill (Inventor)

    1993-01-01

    In vacuum plasma spraying a turntable must be provided which not only makes it possible to rotate and tilt a heavy workpiece, but to operate at vacuum plasma temperatures to do so. In the vacuum plasma coating of large parts such as combustion chambers of rocket engines, the workpiece must not only be rotated, but it must be tilted. Hence, the turntable must be capable not only of supporting heavy parts, but of angulating such heavy workpieces. And this must be done without drive means failure due to extremely high temperatures under which the turntable mechanism is operated. A turntable mechanism is provided which is capable of operating under such conditions. For cooling the turntable drive mechanism, internal cooling means are included.

  17. Quiet Clean Short-haul Experimental Engine (QCSEE). Under-The-Wing (UTW) engine boilerplate nacelle test report. Volume 3: Mechanical performance

    NASA Technical Reports Server (NTRS)

    1977-01-01

    Results of initial tests of the under the wing experimental engine and boilerplate nacelle are presented. The mechanical performance of the engine is reported with emphasis on the advanced technology components. Technology elements of the propulsion system covered include: system dynamics, composite fan blades, reduction gear, lube and accessory drive system, fan frame, inlet, core cowl cooling, fan exhaust nozzle, and digital control system.

  18. Identification of Learning Mechanisms in a Wild Meerkat Population

    PubMed Central

    Hoppitt, Will; Samson, Jamie; Laland, Kevin N.; Thornton, Alex

    2012-01-01

    Vigorous debates as to the evolutionary origins of culture remain unresolved due to an absence of methods for identifying learning mechanisms in natural populations. While laboratory experiments on captive animals have revealed evidence for a number of mechanisms, these may not necessarily reflect the processes typically operating in nature. We developed a novel method that allows social and asocial learning mechanisms to be determined in animal groups from the patterns of interaction with, and solving of, a task. We deployed it to analyse learning in groups of wild meerkats (Suricata suricatta) presented with a novel foraging apparatus. We identify nine separate learning processes underlying the meerkats’ foraging behaviour, in each case precisely quantifying their strength and duration, including local enhancement, emulation, and a hitherto unrecognized form of social learning, which we term ‘observational perseverance’. Our analysis suggests a key factor underlying the stability of behavioural traditions is a high ratio of specific to generalized social learning effects. The approach has widespread potential as an ecologically valid tool to investigate learning mechanisms in natural groups of animals, including humans. PMID:22905113

  19. Plant responses to environmental stress: regulation and functions of the Arabidopsis TCH genes

    NASA Technical Reports Server (NTRS)

    Braam, J.; Sistrunk, M. L.; Polisensky, D. H.; Xu, W.; Purugganan, M. M.; Antosiewicz, D. M.; Campbell, P.; Johnson, K. A.; McIntire, L. V. (Principal Investigator)

    1997-01-01

    Expression of the Arabidopsis TCH genes is markedly upregulated in response to a variety of environmental stimuli including the seemingly innocuous stimulus of touch. Understanding the mechanism(s) and factors that control TCH gene regulation will shed light on the signaling pathways that enable plants to respond to environmental conditions. The TCH proteins include calmodulin, calmodulin-related proteins and a xyloglucan endotransglycosylase. Expression analyses and localization of protein accumulation indicates that the potential sites of TCH protein function include expanding cells and tissues under mechanical strain. We hypothesize that at least a subset of the TCH proteins may collaborate in cell wall biogenesis.

  20. Rapid microRNA changes in airways of human volunteers after controlled exposure to air pollutants

    EPA Science Inventory

    Introduction/Rationale: Exposure to air pollutants, including ozone and diesel exhaust (DE) are known to cause acute cardiopulmonary dysfunction; however, the molecular mechanisms underlying these changes remain elusive. One mechanism for rapid regulation of multiple genes is a...

  1. Transcriptome profiling reveals regulatory mechanisms underlying Corolla Senescence in Petunia

    USDA-ARS?s Scientific Manuscript database

    Genetic regulatory mechanisms that govern petal natural senescence in petunia is complicated and unclear. To identify key genes and pathways that regulate the process, we initiated a transcriptome analysis in petunia petals at four developmental time points, including petal opening without anthesis ...

  2. Evidence for transgenerational metabolic programming in Drosophila

    PubMed Central

    Buescher, Jessica L.; Musselman, Laura P.; Wilson, Christina A.; Lang, Tieming; Keleher, Madeline; Baranski, Thomas J.; Duncan, Jennifer G.

    2013-01-01

    SUMMARY Worldwide epidemiologic studies have repeatedly demonstrated an association between prenatal nutritional environment, birth weight and susceptibility to adult diseases including obesity, cardiovascular disease and type 2 diabetes. Despite advances in mammalian model systems, the molecular mechanisms underlying this phenomenon are unclear, but might involve programming mechanisms such as epigenetics. Here we describe a new system for evaluating metabolic programming mechanisms using a simple, genetically tractable Drosophila model. We examined the effect of maternal caloric excess on offspring and found that a high-sugar maternal diet alters body composition of larval offspring for at least two generations, augments an obese-like phenotype under suboptimal (high-calorie) feeding conditions in adult offspring, and modifies expression of metabolic genes. Our data indicate that nutritional programming mechanisms could be highly conserved and support the use of Drosophila as a model for evaluating the underlying genetic and epigenetic contributions to this phenomenon. PMID:23649823

  3. Elevated-CO2 Response of Stomata and Its Dependence on Environmental Factors

    PubMed Central

    Xu, Zhenzhu; Jiang, Yanling; Jia, Bingrui; Zhou, Guangsheng

    2016-01-01

    Stomata control the flow of gases between plants and the atmosphere. This review is centered on stomatal responses to elevated CO2 concentration and considers other key environmental factors and underlying mechanisms at multiple levels. First, an outline of general responses in stomatal conductance under elevated CO2 is presented. Second, stomatal density response, its development, and the trade-off with leaf growth under elevated CO2 conditions are depicted. Third, the molecular mechanism regulating guard cell movement at elevated CO2 is suggested. Finally, the interactive effects of elevated CO2 with other factors critical to stomatal behavior are reviewed. It may be useful to better understand how stomata respond to elevated CO2 levels while considering other key environmental factors and mechanisms, including molecular mechanism, biochemical processes, and ecophysiological regulation. This understanding may provide profound new insights into how plants cope with climate change. PMID:27242858

  4. First-principles predictions of structural, mechanical and electronic properties of βTiNb under high pressure

    NASA Astrophysics Data System (ADS)

    Wang, Z. P.; Fang, Q. H.; Li, J.; Liu, B.

    2018-04-01

    Structural, mechanical and electronic properties of βTiNb alloy under high pressure have been investigated based on the density functional theory (DFT). The dependences of dimensionless volume ratio, elastic constants, bulk modulus, Young's modulus, shear modulus, ductile/brittle, anisotropy and Poisson's ratio on applied pressure are all calculated successfully. The results reveal that βTiNb alloy is mechanically stable under pressure below 23.45 GPa, and the pressure-induced phase transformation could occur beyond this critical value. Meanwhile, the applied pressure can effectively promote the mechanical properties of βTiNb alloy, including the resistances to volume change, elastic deformation and shear deformation, as well as the material ductility and metallicity. Furthermore, the calculated electronic structures testify that βTiNb alloy performs the metallicity and the higher pressure reduces the structural stability of unit cell.

  5. Mechanical behavior of nanostructured and ultrafine-grained materials under shock wave loadings. experimental data and results of computer simulation

    NASA Astrophysics Data System (ADS)

    Skripnyak, Vladimir

    2012-03-01

    Features of mechanical behavior of nanostructured and ultrafine-grained metals under quasistatic and shock wave loadings are discussed. Features of mechanical behavior of nanostructured and ultrafine grained metals over a wide range of strain rates are discussed. A constitutive model for mechanical behavior of metal alloys under shock wave loading including a grain size distribution, a precipitate hardening, and physical mechanisms of shear stress relaxation is presented. Strain rate sensitivity of the yield stress of face-centered-cubic, hexagonal close-packed metal alloys depends on grain size, whereas the Hugoniot elastic limits of ultrafine-grained copper, aluminum, and titanium alloys are close to values of coarse-grained counterparts. At quasi-static loading the yield strength and the tensile strength of titanium alloys with grain size from 300 to 500 nm are twice higher than at coarse-grained counterparts. But the spall strength of the UFG titanium alloys exceeds the value of coarse-grained counterparts only for 10 percents.

  6. Electrostatic forces govern the binding mechanism of intrinsically disordered histone chaperones

    PubMed Central

    Liu, Chuanbo; Wang, Tianshu; Bai, Yawen; Wang, Jin

    2017-01-01

    A unified picture to understand the protein recognition and function must include the native binding complex structure ensembles and the underlying binding mechanisms involved in specific biological processes. However, quantifications of both binding complex structures and dynamical mechanisms are still challenging for IDP. In this study, we have investigated the underlying molecular mechanism of the chaperone Chz1 and histone H2A.Z-H2B association by equilibrium and kinetic stopped-flow fluorescence spectroscopy. The dependence of free energy and kinetic rate constant on electrolyte mean activity coefficient and urea concentration are uncovered. Our results indicate a previous unseen binding kinetic intermediate. An initial conformation selection step of Chz1 is also revealed before the formation of this intermediate state. Based on these observations, a mixed mechanism of three steps including both conformation selection and induced fit is proposed. By combination of the ion- and denaturant-induced experiments, we demonstrate that electrostatic forces play a dominant role in the recognition of bipolar charged intrinsically disordered protein Chz1 to its preferred partner H2A.Z-H2B. Both the intra-chain and inter-chain electrostatic interactions have direct impacts on the native collapsed structure and binding mechanism. PMID:28552960

  7. From cells to tissue: A continuum model of epithelial mechanics

    NASA Astrophysics Data System (ADS)

    Ishihara, Shuji; Marcq, Philippe; Sugimura, Kaoru

    2017-08-01

    A two-dimensional continuum model of epithelial tissue mechanics was formulated using cellular-level mechanical ingredients and cell morphogenetic processes, including cellular shape changes and cellular rearrangements. This model incorporates stress and deformation tensors, which can be compared with experimental data. Focusing on the interplay between cell shape changes and cell rearrangements, we elucidated dynamical behavior underlying passive relaxation, active contraction-elongation, and tissue shear flow, including a mechanism for contraction-elongation, whereby tissue flows perpendicularly to the axis of cell elongation. This study provides an integrated scheme for the understanding of the orchestration of morphogenetic processes in individual cells to achieve epithelial tissue morphogenesis.

  8. Transcriptome analysis reveals the role of glutaredoxin 3 in cardiac energy metabolism in obese mice

    USDA-ARS?s Scientific Manuscript database

    Obesity has been considered an independent risk factor for many cardiovascular diseases (CVD) including heart failure. Recent epidemiological studies; however, implicate that heart failure patients with mild obesity have a better prognosis than their leaner counterparts. The underlying mechanism(s) ...

  9. Computational Models and Emergent Properties of Respiratory Neural Networks

    PubMed Central

    Lindsey, Bruce G.; Rybak, Ilya A.; Smith, Jeffrey C.

    2012-01-01

    Computational models of the neural control system for breathing in mammals provide a theoretical and computational framework bringing together experimental data obtained from different animal preparations under various experimental conditions. Many of these models were developed in parallel and iteratively with experimental studies and provided predictions guiding new experiments. This data-driven modeling approach has advanced our understanding of respiratory network architecture and neural mechanisms underlying generation of the respiratory rhythm and pattern, including their functional reorganization under different physiological conditions. Models reviewed here vary in neurobiological details and computational complexity and span multiple spatiotemporal scales of respiratory control mechanisms. Recent models describe interacting populations of respiratory neurons spatially distributed within the Bötzinger and pre-Bötzinger complexes and rostral ventrolateral medulla that contain core circuits of the respiratory central pattern generator (CPG). Network interactions within these circuits along with intrinsic rhythmogenic properties of neurons form a hierarchy of multiple rhythm generation mechanisms. The functional expression of these mechanisms is controlled by input drives from other brainstem components, including the retrotrapezoid nucleus and pons, which regulate the dynamic behavior of the core circuitry. The emerging view is that the brainstem respiratory network has rhythmogenic capabilities at multiple levels of circuit organization. This allows flexible, state-dependent expression of different neural pattern-generation mechanisms under various physiological conditions, enabling a wide repertoire of respiratory behaviors. Some models consider control of the respiratory CPG by pulmonary feedback and network reconfiguration during defensive behaviors such as cough. Future directions in modeling of the respiratory CPG are considered. PMID:23687564

  10. Quiet Clean Short-haul Experimental Engine (QCSEE): The aerodynamic and mechanical design of the QCSEE under-the-wing fan

    NASA Technical Reports Server (NTRS)

    1977-01-01

    The design, fabrication, and testing of two experimental high bypass geared turbofan engines and propulsion systems for short haul passenger aircraft are described. The aerodynamic and mechanical design of a variable pitch 1.34 pressure ratio fan for the under the wing (UTW) engine are included. The UTW fan was designed to permit rotation of the 18 composite fan blades into the reverse thrust mode of operation through both flat pitch and stall pitch directions.

  11. Molecular mechanisms underlying formation of long-term reward memories and extinction memories in the honeybee (Apis mellifera)

    PubMed Central

    2014-01-01

    The honeybee (Apis mellifera) has long served as an invertebrate model organism for reward learning and memory research. Its capacity for learning and memory formation is rooted in the ecological need to efficiently collect nectar and pollen during summer to ensure survival of the hive during winter. Foraging bees learn to associate a flower's characteristic features with a reward in a way that resembles olfactory appetitive classical conditioning, a learning paradigm that is used to study mechanisms underlying learning and memory formation in the honeybee. Due to a plethora of studies on appetitive classical conditioning and phenomena related to it, the honeybee is one of the best characterized invertebrate model organisms from a learning psychological point of view. Moreover, classical conditioning and associated behavioral phenomena are surprisingly similar in honeybees and vertebrates, suggesting a convergence of underlying neuronal processes, including the molecular mechanisms that contribute to them. Here I review current thinking on the molecular mechanisms underlying long-term memory (LTM) formation in honeybees following classical conditioning and extinction, demonstrating that an in-depth analysis of the molecular mechanisms of classical conditioning in honeybees might add to our understanding of associative learning in honeybees and vertebrates. PMID:25225299

  12. 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…

  13. Suicide Clusters: A Review of Risk Factors and Mechanisms

    ERIC Educational Resources Information Center

    Haw, Camilla; Hawton, Keith; Niedzwiedz, Claire; Platt, Steve

    2013-01-01

    Suicide clusters, although uncommon, cause great concern in the communities in which they occur. We searched the world literature on suicide clusters and describe the risk factors and proposed psychological mechanisms underlying the spatio-temporal clustering of suicides (point clusters). Potential risk factors include male gender, being an…

  14. Emotion Dysregulation as a Mechanism Linking Stress Exposure to Adolescent Aggressive Behavior

    ERIC Educational Resources Information Center

    Herts, Kate L.; McLaughlin, Katie A.; Hatzenbuehler, Mark L.

    2012-01-01

    Exposure to stress is associated with a wide range of internalizing and externalizing problems in adolescents, including aggressive behavior. Extant research examining mechanisms underlying the associations between stress and youth aggression has consistently identified social information processing pathways that are disrupted by exposure to…

  15. Histological transformation after acquired resistance to epidermal growth factor tyrosine kinase inhibitors.

    PubMed

    Shao, Yi; Zhong, Dian-Sheng

    2018-04-01

    Non-small-cell lung cancer patients with sensitive epidermal growth factor receptor mutations generally respond well to tyrosine kinase inhibitors (TKIs). However, acquired resistance will eventually develop place after 8-16 months. Several mechanisms contribute to the resistance including T790M mutation, c-Met amplification, epithelial mesenchymal transformation and PIK3CA mutation; however, histological transformation is a rare mechanism. The patterns and mechanisms underlying histological transformation need to be explored. We searched PubMed, EMBASE and search engines Google Scholar, Medical Matrix for literature related to histological transformation. Case reports, cases series, and clinical and basic medical research articles were reviewed. Sixty-one articles were included in this review. Cases of transformation to small-cell lung cancer, squamous cell carcinoma, large-cell neuroendocrine carcinoma and sarcoma after TKI resistance have all been reported. As the clinical course differed dramatically between cases, a new treatment scheme needs to be recruited. The mechanisms underlying histological transformation have not been fully elucidated and probably relate to cancer stem cells, driver genetic alterations under selective pressure or the heterogeneity of the tumor. When TKI resistance develops, we recommend that patients undergo a second biopsy to determine the reason, guide the next treatment and predict the prognosis.

  16. 2 CFR Appendix II to Part 200 - Contract Provisions for Non-Federal Entity Contracts Under Federal Awards

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., contractors must be required to pay wages to laborers and mechanics at a rate not less than the prevailing...,000 that involve the employment of mechanics or laborers must include a provision for compliance with... U.S.C. 3702 of the Act, each contractor must be required to compute the wages of every mechanic and...

  17. Extreme mechanical properties of materials under extreme pressure and temperature conditions (Invited)

    NASA Astrophysics Data System (ADS)

    Kavner, A.; Armentrout, M. M.; Xie, M.; Weinberger, M.; Kaner, R. B.; Tolbert, S. H.

    2010-12-01

    A strong synergy ties together the high-pressure subfields of mineral physics, solid-state physics, and materials engineering. The catalog of studies measuring the mechanical properties of materials subjected to large differential stresses in the diamond anvil cell demonstrates a significant pressure-enhancement of strength across many classes of materials, including elemental solids, salts, oxides, silicates, and borides and nitrides. High pressure techniques—both radial diffraction and laser heating in the diamond anvil cell—can be used to characterize the behavior of ultrahard materials under extreme conditions, and help test hypotheses about how composition, structure, and bonding work together to govern the mechanical properties of materials. The principles that are elucidated by these studies can then be used to help design engineering materials to encourage desired properties. Understanding Earth and planetary interiors requires measuring equations of state of relevant materials, including oxides, silicates, and metals under extreme conditions. If these minerals in the diamond anvil cell have any ability to support a differential stress, the assumption of quasi-hydrostaticity no longer applies, with a resulting non-salubrious effect on attempts to measure equation of state. We illustrate these applications with the results of variety of studies from our laboratory and others’ that have used high-pressure radial diffraction techniques and also laser heating in the diamond anvil cell to characterize the mechanical properties of a variety of ultrahard materials, especially osmium metal, osmium diboride, rhenium diboride, and tungsten tetraboride. We compare ambient condition strength studies such as hardness testing with high-pressure studies, especially radial diffraction under differential stress. In addition, we outline criteria for evaluating mechanical properties of materials at combination high pressures and temperatures. Finally, we synthesize our understanding of mechanical properties and composite behavior to suggest new approaches to designing high-pressure experiments to target specific measurements of a wide variety of mechanical properties.

  18. Out with the old and in with the new: Synaptic mechanisms of extinction in the amygdala

    PubMed Central

    Maren, Stephen

    2014-01-01

    Considerable research indicates that long-term synaptic plasticity in the amygdala underlies the acquisition of emotional memories, including those learned during Pavlovian fear conditioning. Much less is known about the synaptic mechanisms involved in other forms of associative learning, including extinction, that update fear memories. Extinction learning might reverse conditioning-related changes (e.g., depotentiation) or induce plasticity at inhibitory synapses (e.g., long-term potentiation) to suppress conditioned fear responses. Either mechanism must account for fear recovery phenomena after extinction, as well as savings of extinction after fear recovery. PMID:25312830

  19. Mechanical Properties of Plasma-Sprayed ZrO2-8 wt% Y2O3 Thermal Barrier Coatings

    NASA Technical Reports Server (NTRS)

    Choi, Sung R.; Zhu, Dongming; Miller, Robert A.

    2004-01-01

    Mechanical behavior of free standing, plasma-sprayed ZrO2-8 wt% Y2O3 thermal barrier coatings, including strength, fracture toughness, fatigue, constitutive relation, elastic modulus, and directionality, has been determined under various loading-specimen configurations. This report presents and describes a summary of mechanical properties of the plasma-sprayed coating material to provide them as a design database.

  20. Contact force and mechanical loss of multistage cable under tension and bending

    NASA Astrophysics Data System (ADS)

    Ru, Yanyun; Yong, Huadong; Zhou, Youhe

    2016-10-01

    A theoretical model for calculating the stress and strain states of cabling structures with different loadings has been developed in this paper. We solve the problem for the first- and second-stage cable with tensile or bending strain. The contact and friction forces between the strands are presented by two-dimensional contact model. Several theoretical models have been proposed to verify the results when the triplet subjected to the tensile strain, including contact force, contact stresses, and mechanical loss. It is found that loadings will affect the friction force and the mechanical loss of the triplet. The results show that the contact force and mechanical loss are dependent on the twist pitch. A shorter twist pitch can lead to higher contact force, while the trend of mechanical loss with twist pitch is complicated. The mechanical loss may be reduced by adjusting the twist pitch reasonably. The present model provides a simple analysis method to investigate the mechanical behaviors in multistage-structures under different loads.

  1. 46 CFR 160.133-13 - Approval inspections and tests for prototype release mechanisms.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... plans of the release mechanism as built, in triplicate. The plans must include the instructions for... for Lifeboats and Rescue Boats (SOLAS) § 160.133-13 Approval inspections and tests for prototype... the prototype— (A) Conforms with the plans reviewed under § 160.133-9 of this subpart; (B) Is...

  2. 46 CFR 160.133-13 - Approval inspections and tests for prototype release mechanisms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... plans of the release mechanism as built, in triplicate. The plans must include the instructions for... for Lifeboats and Rescue Boats (SOLAS) § 160.133-13 Approval inspections and tests for prototype... the prototype— (A) Conforms with the plans reviewed under § 160.133-9 of this subpart; (B) Is...

  3. Exploring the evolutionary ecology of fungal endophyte in agricultural systems: using functional traits to reveal mechanisms in community processes

    USDA-ARS?s Scientific Manuscript database

    All plants, including crop species, harbor a community of fungal endophyte species, however, we know little about the biotic factors that are important in endophyte community assembly. We suggest that the most direct route to understanding the mechanisms underlying community assembly is through the...

  4. [Research advances of fluid bio-mechanics in bone].

    PubMed

    Chen, Zebin; Huo, Bo

    2017-04-01

    It has been found for more than one century that when experiencing mechanical loading, the structure of bone will adapt to the changing mechanical environment, which is called bone remodeling. Bone remodeling is charaterized as two processes of bone formation and bone resorption. A large number of studies have confirmed that the shear stress is resulted from interstitial fluid flow within bone cavities under mechanical loading and it is the key factor of stimulating the biological responses of bone cells. This review summarizes the major research progress during the past years, including the biological response of bone cells under fluid flow, the pressure within bone cavities, the theoretical modeling, numerical simulation and experiments about fluid flow within bone, and finally analyzes and predicts the possible tendency in this field in the future.

  5. Insights into Metabolic Mechanisms Underlying Folate-Responsive Neural Tube Defects: A Minireview

    PubMed Central

    Beaudin, Anna E.; Stover, Patrick J.

    2015-01-01

    Neural tube defects (NTDs), including anencephaly and spina bifida, arise from the failure of neurulation during early embryonic development. Neural tube defects are common birth defects with a heterogenous and multifactorial etiology with interacting genetic and environmental risk factors. Although the mechanisms resulting in failure of neural tube closure are unknown, up to 70% of NTDs can be prevented by maternal folic acid supplementation. However, the metabolic mechanisms underlying the association between folic acid and NTD pathogenesis have not been identified. This review summarizes our current understanding of the mechanisms by which impairments in folate metabolism might ultimately lead to failure of neural tube closure, with an emphasis on untangling the relative contributions of nutritional deficiency and genetic risk factors to NTD pathogenesis. PMID:19180567

  6. Insights into Protein–Ligand Interactions: Mechanisms, Models, and Methods

    PubMed Central

    Du, Xing; Li, Yi; Xia, Yuan-Ling; Ai, Shi-Meng; Liang, Jing; Sang, Peng; Ji, Xing-Lai; Liu, Shu-Qun

    2016-01-01

    Molecular recognition, which is the process of biological macromolecules interacting with each other or various small molecules with a high specificity and affinity to form a specific complex, constitutes the basis of all processes in living organisms. Proteins, an important class of biological macromolecules, realize their functions through binding to themselves or other molecules. A detailed understanding of the protein–ligand interactions is therefore central to understanding biology at the molecular level. Moreover, knowledge of the mechanisms responsible for the protein-ligand recognition and binding will also facilitate the discovery, design, and development of drugs. In the present review, first, the physicochemical mechanisms underlying protein–ligand binding, including the binding kinetics, thermodynamic concepts and relationships, and binding driving forces, are introduced and rationalized. Next, three currently existing protein-ligand binding models—the “lock-and-key”, “induced fit”, and “conformational selection”—are described and their underlying thermodynamic mechanisms are discussed. Finally, the methods available for investigating protein–ligand binding affinity, including experimental and theoretical/computational approaches, are introduced, and their advantages, disadvantages, and challenges are discussed. PMID:26821017

  7. Paradigms and mechanisms of inhalational anesthetics mediated neuroprotection against cerebral ischemic stroke.

    PubMed

    Wang, Hailian; Li, Peiying; Xu, Na; Zhu, Ling; Cai, Mengfei; Yu, Weifeng; Gao, Yanqin

    2016-01-01

    Cerebral ischemic stroke is a leading cause of serious long-term disability and cognitive dysfunction. The high mortality and disability of cerebral ischemic stroke is urging the health providers, including anesthesiologists and other perioperative professioners, to seek effective protective strategies, which are extremely limited, especially for those perioperative patients. Intriguingly, several commonly used inhalational anesthetics are recently suggested to possess neuroprotective effects against cerebral ischemia. This review introduces multiple paradigms of inhalational anesthetic treatments that have been investigated in the setting of cerebral ischemia, such as preconditioning, proconditioning and postconditioning with a variety of inhalational anesthetics. The pleiotropic mechanisms underlying these inhalational anesthetics-afforded neuroprotection against stroke are also discussed in detail, including the common pathways shared by most of the inhalational anesthetic paradigms, such as anti-excitotoxicity, anti-apoptosis and anti-inflammation. There are also distinct mechanisms involved in specific paradigms, such as preserving blood brain barrier integrity, regulating cerebral blood flow and catecholamine release. The ready availability of these inhalational anesthetics bedside and renders them a potentially translatable stroke therapy attracting great efforts for understanding of the underlying mechanisms.

  8. Paradigms and mechanisms of inhalational anesthetics mediated neuroprotection against cerebral ischemic stroke

    PubMed Central

    Wang, Hailian; Li, Peiying; Xu, Na; Zhu, Ling; Cai, Mengfei; Yu, Weifeng; Gao, Yanqin

    2016-01-01

    Cerebral ischemic stroke is a leading cause of serious long-term disability and cognitive dysfunction. The high mortality and disability of cerebral ischemic stroke is urging the health providers, including anesthesiologists and other perioperative professioners, to seek effective protective strategies, which are extremely limited, especially for those perioperative patients. Intriguingly, several commonly used inhalational anesthetics are recently suggested to possess neuroprotective effects against cerebral ischemia. This review introduces multiple paradigms of inhalational anesthetic treatments that have been investigated in the setting of cerebral ischemia, such as preconditioning, proconditioning and postconditioning with a variety of inhalational anesthetics. The pleiotropic mechanisms underlying these inhalational anesthetics-afforded neuroprotection against stroke are also discussed in detail, including the common pathways shared by most of the inhalational anesthetic paradigms, such as anti-excitotoxicity, anti-apoptosis and anti-inflammation. There are also distinct mechanisms involved in specific paradigms, such as preserving blood brain barrier integrity, regulating cerebral blood flow and catecholamine release. The ready availability of these inhalational anesthetics bedside and renders them a potentially translatable stroke therapy attracting great efforts for understanding of the underlying mechanisms. PMID:28217291

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

    Pesaran, Ahmad; Zhang, Chao; Santhanagopalan, Shriram

    Propagation of failure in lithium-ion batteries during field events or under abuse is a strong function of the mechanical response of the different components in the battery. Whereas thermal and electrochemical models that capture the abuse response of batteries have been developed and matured over the years, the interaction between the mechanical behavior and the thermal response of these batteries is not very well understood. With support from the Department of Energy, NREL has made progress in coupling mechanical, thermal, and electrochemical lithium-ion models to predict the initiation and propagation of short circuits under external crush in a cell. Themore » challenge with a cell crush simulation is to estimate the magnitude and location of the short. To address this, the model includes an explicit representation of each individual component such as the active material, current collector, separator, etc., and predicts their mechanical deformation under different crush scenarios. Initial results show reasonable agreement with experiments. In this presentation, the versatility of the approach for use with different design factors, cell formats and chemistries is explored using examples.« less

  10. Does modulation of selective attention to features reflect enhancement or suppression of neural activity?

    PubMed

    Daffner, Kirk R; Zhuravleva, Tatyana Y; Sun, Xue; Tarbi, Elise C; Haring, Anna E; Rentz, Dorene M; Holcomb, Phillip J

    2012-02-01

    Numerous studies have demonstrated that selective attention to color is associated with a larger neural response under attend than ignore conditions, but have not addressed whether this difference reflects enhanced activity under attend or suppressed activity under ignore. In this study, a color-neutral condition was included, which presented stimuli physically identical to those under attend and ignore conditions, but in which color was not task relevant. Attention to color did not modulate the early sensory-evoked P1 and N1 components. Traditional ERP markers of early selection (the anterior Selection Positivity and posterior Selection Negativity) did not differ between the attend and neutral conditions, arguing against a mechanism of enhanced activity. However, there were markedly reduced responses under the ignore relative to the neutral condition, consistent with the view that early selection mechanisms reflect suppression of neural activity under the ignore condition. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. TiN-Coating Effects on Stainless Steel Tribological Behavior Under Dry and Lubricated Conditions

    NASA Astrophysics Data System (ADS)

    Zhang, Liqiang; Yang, Huisheng; Pang, Xiaolu; Gao, Kewei; Tran, Hai T.; Volinsky, Alex A.

    2014-04-01

    The tribological properties of magnetron sputtered titanium nitride coating on 316L steel, sliding against Si3N4 ceramic ball under dry friction and synthetic perspiration lubrication, were investigated. The morphology of the worn surface and the elemental composition of the wear debris were examined by scanning electron microscopy and energy dispersive spectroscopy. TiN coatings and 316L stainless steel had better tribological properties under synthetic perspiration lubrication than under dry friction. Among the three tested materials (316L, 1.6 and 2.4 μm TiN coatings), 2.4 μm TiN coating exhibits the best wear resistance. The difference in wear damage of the three materials is essentially due to the wear mechanisms. For the TiN coating, the damage is attributed to abrasive wear under synthetic perspiration lubrication and the complex interactive mechanisms, including abrasive and adhesive wear, along with plastic deformation, under dry friction.

  12. Bidirectional Drive-And-Brake Mechanism

    NASA Technical Reports Server (NTRS)

    Swan, Scott A.

    1991-01-01

    Vehicle that crawls along monorail combines features of both bicycle and railroad handcar. Bidirectional drive-and-brake mechanism includes selectable-pawl-and-ratchet overrunning clutch (drive mechanism) and mating stationary and rotating conical surfaces pressing against each other (brake mechanism). Operates similarly to bicycle drive-and-brake mechanism except limits rotation of sprocket in both directions and brakes at both limits. Conceived for use by astronaut traveling along structure in outer space, concept also applied on Earth to make very small railraod handcars or crawling vehicles for use on large structures, in pipelines under construction, or underwater.

  13. Mechanisms Underlying Latent Disease Risk Associated with Early-Life Arsenic Exposure: Current Research Trends and Scientific Gaps

    PubMed Central

    Bailey, Kathryn A.; Smith, Allan H.; Tokar, Erik J.; Graziano, Joseph H.; Kim, Kyoung-Woong; Navasumrit, Panida; Ruchirawat, Mathuros; Thiantanawat, Apinya; Suk, William A.; Fry, Rebecca C.

    2015-01-01

    Background Millions of individuals worldwide, particularly those living in rural and developing areas, are exposed to harmful levels of inorganic arsenic (iAs) in their drinking water. Inorganic As exposure during key developmental periods is associated with a variety of adverse health effects, including those that are evident in adulthood. There is considerable interest in identifying the molecular mechanisms that relate early-life iAs exposure to the development of these latent diseases, particularly in relationship to cancer. Objectives This work summarizes research on the molecular mechanisms that underlie the increased risk of cancer development in adulthood that is associated with early-life iAs exposure. Discussion Epigenetic reprogramming that imparts functional changes in gene expression, the development of cancer stem cells, and immunomodulation are plausible underlying mechanisms by which early-life iAs exposure elicits latent carcinogenic effects. Conclusions Evidence is mounting that relates early-life iAs exposure and cancer development later in life. Future research should include animal studies that address mechanistic hypotheses and studies of human populations that integrate early-life exposure, molecular alterations, and latent disease outcomes. Citation Bailey KA, Smith AH, Tokar EJ, Graziano JH, Kim KW, Navasumrit P, Ruchirawat M, Thiantanawat A, Suk WA, Fry RC. 2016. Mechanisms underlying latent disease risk associated with early-life arsenic exposure: current research trends and scientific gaps. Environ Health Perspect 124:170–175; http://dx.doi.org/10.1289/ehp.1409360 PMID:26115410

  14. Design guide for predicting nonlinear random response (including snap-through) of buckled plates

    NASA Technical Reports Server (NTRS)

    Ng, Chung Fai

    1989-01-01

    This design guide describes a method for predicting the random response of flat and curved plates which is based on theoretical analyses and experimental results. The plate curvature can be due to postbuckling, in-plane mechanical or thermal stresses. Based on a single mode formula, root mean square values of the strain response to broadband excitation are evaluated for different static buckled configurations using the equivalent linearization technique. The effects on the overall strain response due to instability motion of snap-through are included. Panel parameters include clamped and simply-supported boundaries, aspect ratio, thickness and length. Analytical results are compared with experimental results from tests with 12 in. x 15 in. aluminum plates under thermal loading in a progressive wave facility. Comparisons are also made with results from tests with a 2 in. x 15 in. x 0.032 in. aluminum beam under base mechanical excitation. The comparisons help to assess the accuracy of the theory and the conditions under which deviations from the theory due to effects of imperfection and higher modes are significant.

  15. Identification of Nonlinear Micron-Level Mechanics for a Precision Deployable Joint

    NASA Technical Reports Server (NTRS)

    Bullock, S. J.; Peterson, L. D.

    1994-01-01

    The experimental identification of micron-level nonlinear joint mechanics and dynamics for a pin-clevis joint used in a precision, adaptive, deployable space structure are investigated. The force-state mapping method is used to identify the behavior of the joint under a preload. The results of applying a single tension-compression cycle to the joint under a tensile preload are presented. The observed micron-level behavior is highly nonlinear and involves all six rigid body motion degrees-of-freedom of the joint. it is also suggests that at micron levels of motion modelling of the joint mechanics and dynamics must include the interactions between all internal components, such as the pin, bushings, and the joint node.

  16. Genetics of Aggression in Voles

    PubMed Central

    Gobrogge, Kyle L.; Wang, Zuoxin

    2016-01-01

    Prairie voles (Microtus ochrogaster) are socially monogamous rodents that form pair bonds—a behavior composed of several social interactions including attachment with a familiar mate and aggression toward conspecific strangers. Therefore, this species has provided an excellent opportunity for the study of pair bonding behavior and its underlying neural mechanisms. In this chapter, we discuss the utility of this unique animal model in the study of aggression and review recent findings illustrating the neurochemical mechanisms underlying pair bonding-induced aggression. Implications of this research for our understanding of the neurobiology of human violence are also discussed. PMID:22078479

  17. Research advance on stable mechanism of endophytic fungi to red wine colour during the aging

    NASA Astrophysics Data System (ADS)

    Nan, Lijun; Li, Yashan; Cui, Changwei; Ning, Na; Huang, Jing; Xu, Chengdong; Tao, Fang; Zhang, Jinyong

    2018-04-01

    Based on the fact that persistent mutation of vinous color was not conducive to the stabilization of vinous quality during the aging, research advance on the stable mechanism of endophytic fungi to colour of red wine during the aging, including investigative status and developmental dynamic at home and abroad, endophytes and pigment of materials in wine, including effect of endophyte on vinaceous color, and even the application of tracer method in wine was summarized, respectively. The relationship between diversity of community the endophytic fungi and the main pigment material in wine was existent objectively, also included the response mechanism on colony dynamic of endophytic fungi to the various pigment as well as substance related to color, which laid the foundation for exploring the relationships between endophytic fungi and wine color, and the variational mechanism of the color under endophytic fungi during the aging period of wine. Color as an important reference index of wine quality influenced not only the sensory evaluation of consumer, but also the quality of wine because of the self-aggregation or combination of phenolic composition with other substances under the endophytic fungi during the storage. Only steady wine in the color could guarantee the security of quality.

  18. Classification and reduction of pilot error

    NASA Technical Reports Server (NTRS)

    Rogers, W. H.; Logan, A. L.; Boley, G. D.

    1989-01-01

    Human error is a primary or contributing factor in about two-thirds of commercial aviation accidents worldwide. With the ultimate goal of reducing pilot error accidents, this contract effort is aimed at understanding the factors underlying error events and reducing the probability of certain types of errors by modifying underlying factors such as flight deck design and procedures. A review of the literature relevant to error classification was conducted. Classification includes categorizing types of errors, the information processing mechanisms and factors underlying them, and identifying factor-mechanism-error relationships. The classification scheme developed by Jens Rasmussen was adopted because it provided a comprehensive yet basic error classification shell or structure that could easily accommodate addition of details on domain-specific factors. For these purposes, factors specific to the aviation environment were incorporated. Hypotheses concerning the relationship of a small number of underlying factors, information processing mechanisms, and error types types identified in the classification scheme were formulated. ASRS data were reviewed and a simulation experiment was performed to evaluate and quantify the hypotheses.

  19. Cerebellar learning mechanisms

    PubMed Central

    Freeman, John H.

    2014-01-01

    The mechanisms underlying cerebellar learning are reviewed with an emphasis on old arguments and new perspectives on eyeblink conditioning. Eyeblink conditioning has been used for decades a model system for elucidating cerebellar learning mechanisms. The standard model of the mechanisms underlying eyeblink conditioning is that there two synaptic plasticity processes within the cerebellum that are necessary for acquisition of the conditioned response: 1) long-term depression (LTD) at parallel fiber-Purkinje cell synapses and 2) long-term potentiation (LTP) at mossy fiber-interpositus nucleus synapses. Additional Purkinje cell plasticity mechanisms may also contribute to eyeblink conditioning including LTP, excitability, and entrainment of deep nucleus activity. Recent analyses of the sensory input pathways necessary for eyeblink conditioning indicate that the cerebellum regulates its inputs to facilitate learning and maintain plasticity. Cerebellar learning during eyeblink conditioning is therefore a dynamic interactive process which maximizes responding to significant stimuli and suppresses responding to irrelevant or redundant stimuli. PMID:25289586

  20. Phytoplankton defence mechanisms: traits and trade-offs.

    PubMed

    Pančić, Marina; Kiørboe, Thomas

    2018-05-01

    In aquatic ecosystems, unicellular algae form the basis of the food webs. Theoretical and experimental studies have demonstrated that one of the mechanisms that maintain high diversity of phytoplankton is through predation and the consequent evolution of defence mechanisms. Proposed defence mechanisms in phytoplankton are diverse and include physiological (e.g. toxicity, bioluminescence), morphological (e.g. silica shell, colony formation), and behavioural (e.g. escape response) traits. However, the function of many of the proposed defence mechanisms remains elusive, and the costs and benefits (trade-offs) are often unquantified or undocumented. Here, we provide an overview of suggested phytoplankton defensive traits and review their experimental support. Wherever possible we quantify the trade-offs from experimental evidence and theoretical considerations. In many instances, experimental evidence suggests that defences are costless. However, we argue that (i) some costs materialize only under natural conditions, for example, sinking losses, or dependency on the availability of specific nutrients, and (ii) other costs become evident only under resource-deficient conditions where a rivalry for limiting resources between growth and defence occurs. Based on these findings, we suggest two strategies for quantifying the costs of defence mechanisms in phytoplankton: (i) for the evaluation of defence costs that are realized under natural conditions, a mechanistic understanding of the hypothesized component processes is required; and (ii) the magnitude of the costs (i.e. growth reduction) must be assessed under conditions of resource limitation. © 2018 Cambridge Philosophical Society.

  1. Systems genetics: a paradigm to improve discovery of candidate genes and mechanisms underlying complex traits.

    PubMed

    Feltus, F Alex

    2014-06-01

    Understanding the control of any trait optimally requires the detection of causal genes, gene interaction, and mechanism of action to discover and model the biochemical pathways underlying the expressed phenotype. Functional genomics techniques, including RNA expression profiling via microarray and high-throughput DNA sequencing, allow for the precise genome localization of biological information. Powerful genetic approaches, including quantitative trait locus (QTL) and genome-wide association study mapping, link phenotype with genome positions, yet genetics is less precise in localizing the relevant mechanistic information encoded in DNA. The coupling of salient functional genomic signals with genetically mapped positions is an appealing approach to discover meaningful gene-phenotype relationships. Techniques used to define this genetic-genomic convergence comprise the field of systems genetics. This short review will address an application of systems genetics where RNA profiles are associated with genetically mapped genome positions of individual genes (eQTL mapping) or as gene sets (co-expression network modules). Both approaches can be applied for knowledge independent selection of candidate genes (and possible control mechanisms) underlying complex traits where multiple, likely unlinked, genomic regions might control specific complex traits. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. [Development of studies on bioeffects of ultrasound-acupuncture therapy and its underlying mechanism].

    PubMed

    Yang, Yu-Hua; Zhang, Di; Sa, Zhe-Yan; Huang, Meng; Ding, Guang-Hong

    2012-08-01

    The so-called ultrasound acupuncture is a therapeutic approach for clinical problems and health care by applying the ultrasound energy to the acupoints of the human body directly or indirectly. It has been applied in clinic for about 30 years since 1980s. In the present paper, the authors review the development of both experimental and clinical researches in the past 30 years. Its clinical application includes allergic rhinitis, local pain, mastitis, angina pectoris of coronary heart disease, stroke, etc. Regarding the researches on the underlying mechanism of ultrasound and ultrasound acupuncture, the authors make a summary from 1) bioeffects (thermal and nonthermal effects) of ultrasound intervention; 2) cell lysis and nonlysis effects of ultrasound intervention; and 3) effects of ultrasound acupuncture on the degranulation of mast cells. Based on the idea that "inflammatory reaction caused by mast cell degranulation is one of the initial factors of acupuncture for inducing therapeutic effects", bioeffects including cellular changes, especially mast cell degranulation caused by ultrasound stimulation, are thought to be the main possible mechanisms underlying the favorable efficacy of ultrasound acupuncture intervention. However, the ultrasound metrology and the specific superiority of ultrasound acupuncture remain unknown up to now.

  3. Endocrine Dysregulation in Anorexia Nervosa Update

    PubMed Central

    2011-01-01

    Context: Anorexia nervosa is a primary psychiatric disorder with serious endocrine consequences, including dysregulation of the gonadal, adrenal, and GH axes, and severe bone loss. This Update reviews recent advances in the understanding of the endocrine dysregulation observed in this state of chronic starvation, as well as the mechanisms underlying the disease itself. Evidence Acquisition: Findings of this update are based on a PubMed search and the author's knowledge of this field. Evidence Synthesis: Recent studies have provided insights into the mechanisms underlying endocrine dysregulation in states of chronic starvation as well as the etiology of anorexia nervosa itself. This includes a more complex understanding of the pathophysiologic bases of hypogonadism, hypercortisolemia, GH resistance, appetite regulation, and bone loss. Nevertheless, the etiology of the disease remains largely unknown, and effective therapies for the endocrine complications and for the disease itself are lacking. Conclusions: Despite significant progress in the field, further research is needed to elucidate the mechanisms underlying the development of anorexia nervosa and its endocrine complications. Such investigations promise to yield important advances in the therapeutic approach to this disease as well as to the understanding of the regulation of endocrine function, skeletal biology, and appetite regulation. PMID:21976742

  4. Plasma fibronectin stabilizes Borrelia burgdorferi–endothelial interactions under vascular shear stress by a catch-bond mechanism

    PubMed Central

    Niddam, Alexandra F.; Ebady, Rhodaba; Bansal, Anil; Koehler, Anne; Hinz, Boris

    2017-01-01

    Bacterial dissemination via the cardiovascular system is the most common cause of infection mortality. A key step in dissemination is bacterial interaction with endothelia lining blood vessels, which is physically challenging because of the shear stress generated by blood flow. Association of host cells such as leukocytes and platelets with endothelia under vascular shear stress requires mechanically specialized interaction mechanisms, including force-strengthened catch bonds. However, the biomechanical mechanisms supporting vascular interactions of most bacterial pathogens are undefined. Fibronectin (Fn), a ubiquitous host molecule targeted by many pathogens, promotes vascular interactions of the Lyme disease spirochete Borrelia burgdorferi. Here, we investigated how B. burgdorferi exploits Fn to interact with endothelia under physiological shear stress, using recently developed live cell imaging and particle-tracking methods for studying bacterial–endothelial interaction biomechanics. We found that B. burgdorferi does not primarily target insoluble matrix Fn deposited on endothelial surfaces but, instead, recruits and induces polymerization of soluble plasma Fn (pFn), an abundant protein in blood plasma that is normally soluble and nonadhesive. Under physiological shear stress, caps of polymerized pFn at bacterial poles formed part of mechanically loaded adhesion complexes, and pFn strengthened and stabilized interactions by a catch-bond mechanism. These results show that B. burgdorferi can transform a ubiquitous but normally nonadhesive blood constituent to increase the efficiency, strength, and stability of bacterial interactions with vascular surfaces. Similar mechanisms may promote dissemination of other Fn-binding pathogens. PMID:28396443

  5. Discovering Hematopoietic Mechanisms Through Genome-Wide Analysis of GATA Factor Chromatin Occupancy

    PubMed Central

    Fujiwara, Tohru; O'Geen, Henriette; Keles, Sunduz; Blahnik, Kimberly; Linnemann, Amelia K.; Kang, Yoon-A; Choi, Kyunghee; Farnham, Peggy J.; Bresnick, Emery H.

    2009-01-01

    SUMMARY GATA factors interact with simple DNA motifs (WGATAR) to regulate critical processes, including hematopoiesis, but very few WGATAR motifs are occupied in genomes. Given the rudimentary knowledge of mechanisms underlying this restriction, and how GATA factors establish genetic networks, we used ChIP-seq to define GATA-1 and GATA-2 occupancy genome-wide in erythroid cells. Coupled with genetic complementation analysis and transcriptional profiling, these studies revealed a rich collection of targets containing a characteristic binding motif of greater complexity than WGATAR. GATA factors occupied loci encoding multiple components of the Scl/TAL1 complex, a master regulator of hematopoiesis and leukemogenic target. Mechanistic analyses provided evidence for cross-regulatory and autoregulatory interactions among components of this complex, including GATA-2 induction of the hematopoietic corepressor ETO-2 and an ETO-2 negative autoregulatory loop. These results establish fundamental principles underlying GATA factor mechanisms in chromatin and illustrate a complex network of considerable importance for the control of hematopoiesis. PMID:19941826

  6. Collaborative Research Program on Advanced Metals and Ceramics for Armor and Anti-Armor Applications Dynamic Behavior of Non-Crystalline and Crystalline Metallic Systems

    DTIC Science & Technology

    2006-09-01

    compression, including real-time cinematography of failure under dynamic compression, was evaluated. The results (figure 10) clearly show that the failure... art of simulations of dynamic failure and damage mechanisms. An explicit dynamic parallel code has been developed to track damage mechanisms in the

  7. [From a Ph.D. Thesis: Understanding the Past, Predicting the Future].

    PubMed

    Watanabe, Kenichi

    2018-01-01

     Posey et al. have reported multiple molecular diagnoses in 4.5% of cases (101/2076) in which whole-exome sequencing was informative. Distinct disease phenotypes affect different organ systems, whereas overlapping disease phenotypes are more likely to be caused by two genes encoding proteins that interact within the same pathway. My research projects at the Niigata University of Pharmacy have investigated underlying mechanisms involved in human disease, including fatty acid metabolism, diabetic cardiomyopathy, atopic dermatitis, colitis, hepatitis, etc. Three students from abroad graduated this year from the Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences. These students reported on treatments for heart disease, non-alcoholic steatohepatitis and atopic dermatitis, as well as the underlying mechanisms involved in each. The titles of these reports are "Study of the role of cardiac 14-3-3η protein in cardiac inflammation and adverse cardiac remodeling during heart failure in mice", "Non-alcoholic steatohepatitis: onset of mechanisms under diabetic background and treatment strategies" and "The role of HMGB1 and its cascade signaling pathway in atopic dermatitis". It can be concluded from these three theses that oxidative stress and inflammation are among the principal mechanisms underlying these diseases.

  8. Dynamic Mechanical and Nanofibrous Topological Combinatory Cues Designed for Periodontal Ligament Engineering.

    PubMed

    Kim, Joong-Hyun; Kang, Min Sil; Eltohamy, Mohamed; Kim, Tae-Hyun; Kim, Hae-Won

    2016-01-01

    Complete reconstruction of damaged periodontal pockets, particularly regeneration of periodontal ligament (PDL) has been a significant challenge in dentistry. Tissue engineering approach utilizing PDL stem cells and scaffolding matrices offers great opportunity to this, and applying physical and mechanical cues mimicking native tissue conditions are of special importance. Here we approach to regenerate periodontal tissues by engineering PDL cells supported on a nanofibrous scaffold under a mechanical-stressed condition. PDL stem cells isolated from rats were seeded on an electrospun polycaprolactone/gelatin directionally-oriented nanofiber membrane and dynamic mechanical stress was applied to the cell/nanofiber construct, providing nanotopological and mechanical combined cues. Cells recognized the nanofiber orientation, aligning in parallel, and the mechanical stress increased the cell alignment. Importantly, the cells cultured on the oriented nanofiber combined with the mechanical stress produced significantly stimulated PDL specific markers, including periostin and tenascin with simultaneous down-regulation of osteogenesis, demonstrating the roles of topological and mechanical cues in altering phenotypic change in PDL cells. Tissue compatibility of the tissue-engineered constructs was confirmed in rat subcutaneous sites. Furthermore, in vivo regeneration of PDL and alveolar bone tissues was examined under the rat premaxillary periodontal defect models. The cell/nanofiber constructs engineered under mechanical stress showed sound integration into tissue defects and the regenerated bone volume and area were significantly improved. This study provides an effective tissue engineering approach for periodontal regeneration-culturing PDL stem cells with combinatory cues of oriented nanotopology and dynamic mechanical stretch.

  9. Dynamic Mechanical and Nanofibrous Topological Combinatory Cues Designed for Periodontal Ligament Engineering

    PubMed Central

    Kim, Joong-Hyun; Kang, Min Sil; Eltohamy, Mohamed; Kim, Tae-Hyun; Kim, Hae-Won

    2016-01-01

    Complete reconstruction of damaged periodontal pockets, particularly regeneration of periodontal ligament (PDL) has been a significant challenge in dentistry. Tissue engineering approach utilizing PDL stem cells and scaffolding matrices offers great opportunity to this, and applying physical and mechanical cues mimicking native tissue conditions are of special importance. Here we approach to regenerate periodontal tissues by engineering PDL cells supported on a nanofibrous scaffold under a mechanical-stressed condition. PDL stem cells isolated from rats were seeded on an electrospun polycaprolactone/gelatin directionally-oriented nanofiber membrane and dynamic mechanical stress was applied to the cell/nanofiber construct, providing nanotopological and mechanical combined cues. Cells recognized the nanofiber orientation, aligning in parallel, and the mechanical stress increased the cell alignment. Importantly, the cells cultured on the oriented nanofiber combined with the mechanical stress produced significantly stimulated PDL specific markers, including periostin and tenascin with simultaneous down-regulation of osteogenesis, demonstrating the roles of topological and mechanical cues in altering phenotypic change in PDL cells. Tissue compatibility of the tissue-engineered constructs was confirmed in rat subcutaneous sites. Furthermore, in vivo regeneration of PDL and alveolar bone tissues was examined under the rat premaxillary periodontal defect models. The cell/nanofiber constructs engineered under mechanical stress showed sound integration into tissue defects and the regenerated bone volume and area were significantly improved. This study provides an effective tissue engineering approach for periodontal regeneration—culturing PDL stem cells with combinatory cues of oriented nanotopology and dynamic mechanical stretch. PMID:26989897

  10. Stress, depression, and cardiovascular dysregulation: A review of neurobiological mechanisms and the integration of research from preclinical disease models

    PubMed Central

    Grippo, Angela J.; Johnson, Alan Kim

    2008-01-01

    A bidirectional association between mood disorders such as depression, and cardiovascular diseases such as myocardial infarction and congestive heart failure, has been described; however, the precise neurobiological mechanisms that underlie these associations have not been fully elucidated. This review is focused on the neurobiological processes and mediators that are common to both mood and cardiovascular disorders, with an emphasis on the role of exogenous stressors in addition to: (a) neuroendocrine and neurohumoral changes involving dysfunction of the hypothalamic-pituitary-adrenal axis and activation of the renin-angiotensin-aldosterone system, (b) immune alterations including activation of pro-inflammatory cytokines, (c) autonomic and cardiovascular dysregulation including increased sympathetic drive, withdrawal of parasympathetic tone, cardiac rate and rhythm disturbances, and altered baroreceptor reflex function, (d) central neurotransmitter system dysfunction including dopamine, norepinephrine and serotonin, and (e) behavioral changes including fatigue and physical inactivity. We also focus specifically on experimental investigations with preclinical disease models, conducted to elucidate the neurobiological mechanisms underlying the link between mood disorders and cardiovascular disease. These include: (a) the chronic mild stress model of depression, (b) a model of congestive heart failure, a model of cardiovascular deconditioning, (d) pharmacological manipulations of body fluid and sodium balance, and (e) pharmacological manipulations of the central serotonergic system. In combination with the extensive literature describing findings from human research, the investigation of mechanisms underlying mood and cardiovascular regulation using animal models will enhance our understanding of the association of depression and cardiovascular disease, and can promote the development of better treatments and interventions for individuals with these co-morbid conditions. PMID:19116888

  11. Biological mechanisms discriminating growth rate and adult body weight phenotypes in two Chinese indigenous chicken breeds.

    PubMed

    Dou, Tengfei; Zhao, Sumei; Rong, Hua; Gu, Dahai; Li, Qihua; Huang, Ying; Xu, Zhiqiang; Chu, Xiaohui; Tao, Linli; Liu, Lixian; Ge, Changrong; Te Pas, Marinus F W; Jia, Junjing

    2017-06-20

    Intensive selection has resulted in increased growth rates and muscularity in broiler chickens, in addition to adverse effects, including delayed organ development, sudden death syndrome, and altered metabolic rates. The biological mechanisms underlying selection responses remain largely unknown. Non-artificially-selected indigenous Chinese chicken breeds display a wide variety of phenotypes, including differential growth rate, body weight, and muscularity. The Wuding chicken breed is a fast growing large chicken breed, and the Daweishan mini chicken breed is a slow growing small chicken breed. Together they form an ideal model system to study the biological mechanisms underlying broiler chicken selection responses in a natural system. The objective of this study was to study the biological mechanisms underlying differential phenotypes between the two breeds in muscle and liver tissues, and relate these to the growth rate and body development phenotypes of the two breeds. The muscle tissue in the Wuding breed showed higher expression of muscle development genes than muscle tissue in the Daweishan chicken breed. This expression was accompanied by higher expression of acute inflammatory response genes in Wuding chicken than in Daweishan chicken. The muscle tissue of the Daweishan mini chicken breed showed higher expression of genes involved in several metabolic mechanisms including endoplasmic reticulum, protein and lipid metabolism, energy metabolism, as well as specific immune traits than in the Wuding chicken. The liver tissue showed fewer differences between the two breeds. Genes displaying higher expression in the Wuding breed than in the Daweishan breed were not associated with a specific gene network or biological mechanism. Genes highly expressed in the Daweishan mini chicken breed compared to the Wuding breed were enriched for protein metabolism, ABC receptors, signal transduction, and IL6-related mechanisms. We conclude that faster growth rates and larger body size are related to increased expression of genes involved in muscle development and immune response in muscle, while slower growth rates and smaller body size are related to increased general cellular metabolism. The liver of the Daweishan breed displayed increased expression of metabolic genes.

  12. Relationship between sleep duration and childhood obesity: Systematic review including the potential underlying mechanisms.

    PubMed

    Felső, R; Lohner, S; Hollódy, K; Erhardt, É; Molnár, D

    2017-09-01

    The prevalence of obesity is continually increasing worldwide. Determining risk factors for obesity may facilitate effective preventive programs. The present review focuses on sleep duration as a potential risk factor for childhood obesity. The aim is to summarize the evidence on the association of sleep duration and obesity and to discuss the underlying potential physiological and/or pathophysiological mechanisms. The Ovid MEDLINE, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for papers using text words with appropriate truncation and relevant indexing terms. All studies objectively measuring sleep duration and investigating the association between sleep duration and obesity or factors (lifestyle and hormonal) possibly associated with obesity were included, without making restrictions based on study design or language. Data from eligible studies were extracted in tabular form and summarized narratively. After removing duplicates, 3540 articles were obtained. Finally, 33 studies (including 3 randomized controlled trials and 30 observational studies) were included in the review. Sleep duration seems to influence weight gain in children, however, the underlying explanatory mechanisms are still uncertain. In our review only the link between short sleep duration and the development of insulin resistance, sedentarism and unhealthy dietary patterns could be verified, while the role of other mediators, such as physical activity, screen time, change in ghrelin and leptin levels, remained uncertain. There are numerous evidence gaps. To answer the remaining questions, there is a need for studies meeting high methodological standards and including a large number of children. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

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

    Smith, Kandler A; Santhanagopalan, Shriram; Yang, Chuanbo

    Computer models are helping to accelerate the design and validation of next generation batteries and provide valuable insights not possible through experimental testing alone. Validated 3-D physics-based models exist for predicting electrochemical performance, thermal and mechanical response of cells and packs under normal and abuse scenarios. The talk describes present efforts to make the models better suited for engineering design, including improving their computation speed, developing faster processes for model parameter identification including under aging, and predicting the performance of a proposed electrode material recipe a priori using microstructure models.

  14. Quasi-chemical theory of F-(aq): The "no split occupancies rule" revisited

    NASA Astrophysics Data System (ADS)

    Chaudhari, Mangesh I.; Rempe, Susan B.; Pratt, Lawrence R.

    2017-10-01

    We use ab initio molecular dynamics (AIMD) calculations and quasi-chemical theory (QCT) to study the inner-shell structure of F-(aq) and to evaluate that single-ion free energy under standard conditions. Following the "no split occupancies" rule, QCT calculations yield a free energy value of -101 kcal/mol under these conditions, in encouraging agreement with tabulated values (-111 kcal/mol). The AIMD calculations served only to guide the definition of an effective inner-shell constraint. QCT naturally includes quantum mechanical effects that can be concerning in more primitive calculations, including electronic polarizability and induction, electron density transfer, electron correlation, molecular/atomic cooperative interactions generally, molecular flexibility, and zero-point motion. No direct assessment of the contribution of dispersion contributions to the internal energies has been attempted here, however. We anticipate that other aqueous halide ions might be treated successfully with QCT, provided that the structure of the underlying statistical mechanical theory is absorbed, i.e., that the "no split occupancies" rule is recognized.

  15. Geometric charges in theories of elasticity and plasticity

    NASA Astrophysics Data System (ADS)

    Moshe, Michael

    The mechanics of many natural systems is governed by localized sources of stresses. Examples include ''plastic events'' that occur in amorphous solids under external stress, defects formation in crystalline material, and force-dipoles applied by cells adhered to an elastic substrate. Recent developments in a geometric formulation of elasticity theory paved the way for a unifying mathematical description of such singular sources of stress, as ''elastic charges''. In this talk I will review basic results in this emerging field, focusing on the geometry and mechanics of elastic charges in two-dimensional solid bodies. I will demonstrate the applicability of this new approach in three different problems: failure of an amorphous solid under load, mechanics of Kirigami, and wrinkle patterns in geometrically-incompatible elastic sheets.

  16. The dialectic of Hebb and homeostasis.

    PubMed

    Turrigiano, Gina G

    2017-03-05

    It has become widely accepted that homeostatic and Hebbian plasticity mechanisms work hand in glove to refine neural circuit function. Nonetheless, our understanding of how these fundamentally distinct forms of plasticity compliment (and under some circumstances interfere with) each other remains rudimentary. Here, I describe some of the recent progress of the field, as well as some of the deep puzzles that remain. These include unravelling the spatial and temporal scales of different homeostatic and Hebbian mechanisms, determining which aspects of network function are under homeostatic control, and understanding when and how homeostatic and Hebbian mechanisms must be segregated within neural circuits to prevent interference.This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity'. © 2017 The Author(s).

  17. Possible Mechanisms Underlying the Therapeutic Effects of Transcranial Magnetic Stimulation

    PubMed Central

    Chervyakov, Alexander V.; Chernyavsky, Andrey Yu.; Sinitsyn, Dmitry O.; Piradov, Michael A.

    2015-01-01

    Transcranial magnetic stimulation (TMS) is an effective method used to diagnose and treat many neurological disorders. Although repetitive TMS (rTMS) has been used to treat a variety of serious pathological conditions including stroke, depression, Parkinson’s disease, epilepsy, pain, and migraines, the pathophysiological mechanisms underlying the effects of long-term TMS remain unclear. In the present review, the effects of rTMS on neurotransmitters and synaptic plasticity are described, including the classic interpretations of TMS effects on synaptic plasticity via long-term potentiation and long-term depression. We also discuss the effects of rTMS on the genetic apparatus of neurons, glial cells, and the prevention of neuronal death. The neurotrophic effects of rTMS on dendritic growth and sprouting and neurotrophic factors are described, including change in brain-derived neurotrophic factor concentration under the influence of rTMS. Also, non-classical effects of TMS related to biophysical effects of magnetic fields are described, including the quantum effects, the magnetic spin effects, genetic magnetoreception, the macromolecular effects of TMS, and the electromagnetic theory of consciousness. Finally, we discuss possible interpretations of TMS effects according to dynamical systems theory. Evidence suggests that a rTMS-induced magnetic field should be considered a separate physical factor that can be impactful at the subatomic level and that rTMS is capable of significantly altering the reactivity of molecules (radicals). It is thought that these factors underlie the therapeutic benefits of therapy with TMS. Future research on these mechanisms will be instrumental to the development of more powerful and reliable TMS treatment protocols. PMID:26136672

  18. Possible Mechanisms Underlying the Therapeutic Effects of Transcranial Magnetic Stimulation.

    PubMed

    Chervyakov, Alexander V; Chernyavsky, Andrey Yu; Sinitsyn, Dmitry O; Piradov, Michael A

    2015-01-01

    Transcranial magnetic stimulation (TMS) is an effective method used to diagnose and treat many neurological disorders. Although repetitive TMS (rTMS) has been used to treat a variety of serious pathological conditions including stroke, depression, Parkinson's disease, epilepsy, pain, and migraines, the pathophysiological mechanisms underlying the effects of long-term TMS remain unclear. In the present review, the effects of rTMS on neurotransmitters and synaptic plasticity are described, including the classic interpretations of TMS effects on synaptic plasticity via long-term potentiation and long-term depression. We also discuss the effects of rTMS on the genetic apparatus of neurons, glial cells, and the prevention of neuronal death. The neurotrophic effects of rTMS on dendritic growth and sprouting and neurotrophic factors are described, including change in brain-derived neurotrophic factor concentration under the influence of rTMS. Also, non-classical effects of TMS related to biophysical effects of magnetic fields are described, including the quantum effects, the magnetic spin effects, genetic magnetoreception, the macromolecular effects of TMS, and the electromagnetic theory of consciousness. Finally, we discuss possible interpretations of TMS effects according to dynamical systems theory. Evidence suggests that a rTMS-induced magnetic field should be considered a separate physical factor that can be impactful at the subatomic level and that rTMS is capable of significantly altering the reactivity of molecules (radicals). It is thought that these factors underlie the therapeutic benefits of therapy with TMS. Future research on these mechanisms will be instrumental to the development of more powerful and reliable TMS treatment protocols.

  19. Mechanisms of crystalline silica-induced pulmonary toxicity revealed by global gene expression profiling

    PubMed Central

    Sellamuthu, Rajendran; Umbright, Christina; Li, Shengqiao; Kashon, Michael; Joseph, Pius

    2015-01-01

    A proper understanding of the mechanisms underlying crystalline silica-induced pulmonary toxicity has implications in the management and potential prevention of the adverse health effects associated with silica exposure including silicosis, cancer and several auto-immune diseases. Human lung type II epithelial cells and rat lungs exposed to crystalline silica were employed as experimental models to determine global gene expression changes in order to understand the molecular mechanisms underlying silica-induced pulmonary toxicity. The differential gene expression profile induced by silica correlated with its toxicity in the A549 cells. The biological processes perturbed by silica exposure in the A549 cells and rat lungs, as identified by the bioinformatics analysis of the differentially expressed genes, demonstrated significant similarity. Functional categorization of the differentially expressed genes identified cancer, cellular movement, cellular growth and proliferation, cell death, inflammatory response, cell cycle, cellular development, and genetic disorder as top ranking biological functions perturbed by silica exposure in A549 cells and rat lungs. Results of our study, in addition to confirming several previously identified molecular targets and mechanisms involved in silica toxicity, identified novel molecular targets and mechanisms potentially involved in silica-induced pulmonary toxicity. Further investigations, including those focused on the novel molecular targets and mechanisms identified in the current study may result in better management and, possibly, reduction and/or prevention of the potential adverse health effects associated with crystalline silica exposure. PMID:22087542

  20. Wearable, wireless gas sensors using highly stretchable and transparent structures of nanowires and graphene

    NASA Astrophysics Data System (ADS)

    Park, Jihun; Kim, Joohee; Kim, Kukjoo; Kim, So-Yun; Cheong, Woon Hyung; Park, Kyeongmin; Song, Joo Hyeb; Namgoong, Gyeongho; Kim, Jae Joon; Heo, Jaeyeong; Bien, Franklin; Park, Jang-Ung

    2016-05-01

    Herein, we report the fabrication of a highly stretchable, transparent gas sensor based on silver nanowire-graphene hybrid nanostructures. Due to its superb mechanical and optical characteristics, the fabricated sensor demonstrates outstanding and stable performances even under extreme mechanical deformation (stable until 20% of strain). The integration of a Bluetooth system or an inductive antenna enables the wireless operation of the sensor. In addition, the mechanical robustness of the materials allows the device to be transferred onto various nonplanar substrates, including a watch, a bicycle light, and the leaves of live plants, thereby achieving next-generation sensing electronics for the `Internet of Things' area.Herein, we report the fabrication of a highly stretchable, transparent gas sensor based on silver nanowire-graphene hybrid nanostructures. Due to its superb mechanical and optical characteristics, the fabricated sensor demonstrates outstanding and stable performances even under extreme mechanical deformation (stable until 20% of strain). The integration of a Bluetooth system or an inductive antenna enables the wireless operation of the sensor. In addition, the mechanical robustness of the materials allows the device to be transferred onto various nonplanar substrates, including a watch, a bicycle light, and the leaves of live plants, thereby achieving next-generation sensing electronics for the `Internet of Things' area. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr01468b

  1. Central sensitization as the mechanism underlying pain in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

    PubMed

    Di Stefano, G; Celletti, C; Baron, R; Castori, M; Di Franco, M; La Cesa, S; Leone, C; Pepe, A; Cruccu, G; Truini, A; Camerota, F

    2016-09-01

    Patients with joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT) commonly suffer from pain. How this hereditary connective tissue disorder causes pain remains unclear although previous studies suggested it shares similar mechanisms with neuropathic pain and fibromyalgia. In this prospective study seeking information on the mechanisms underlying pain in patients with JHS/EDS-HT, we enrolled 27 consecutive patients with this connective tissue disorder. Patients underwent a detailed clinical examination, including the neuropathic pain questionnaire DN4 and the fibromyalgia rapid screening tool. As quantitative sensory testing methods, we included thermal-pain perceptive thresholds and the wind-up ratio and recorded a standard nerve conduction study to assess non-nociceptive fibres and laser-evoked potentials, assessing nociceptive fibres. Clinical examination and diagnostic tests disclosed no somatosensory nervous system damage. Conversely, most patients suffered from widespread pain, the fibromyalgia rapid screening tool elicited positive findings, and quantitative sensory testing showed lowered cold and heat pain thresholds and an increased wind-up ratio. While the lack of somatosensory nervous system damage is incompatible with neuropathic pain as the mechanism underlying pain in JHS/EDS-HT, the lowered cold and heat pain thresholds and increased wind-up ratio imply that pain in JHS/EDS-HT might arise through central sensitization. Hence, this connective tissue disorder and fibromyalgia share similar pain mechanisms. WHAT DOES THIS STUDY ADD?: In patients with JHS/EDS-HT, the persistent nociceptive input due to joint abnormalities probably triggers central sensitization in the dorsal horn neurons and causes widespread pain. © 2016 European Pain Federation - EFIC®

  2. Thalidomide–A Notorious Sedative to a Wonder Anticancer Drug

    PubMed Central

    Zhou, Shuang; Wang, Fengfei; Hsieh, Tze-Chen; Wu, Joseph M.; Wu, Erxi

    2014-01-01

    In the past 50 years, thalidomide has undergone a remarkable metamorphosis from a notorious drug inducing birth defects into a highly effective therapy for treating leprosy and multiple myeloma. Today, most notably, thalidomide and its analogs have shown efficacy against a wide variety of diseases, including inflammation and cancer. The mechanism underlying its teratogenicity as well as its anticancer activities has been intensively studied. This review summarizes the biological effects and therapeutic uses of thalidomide and its analogs, and the underlying mechanisms of thalidomide’s action with a focus on its suppression of tumor growth. PMID:23931282

  3. Mechanics of Carbon Nanotubes and their Polymer Composites

    NASA Technical Reports Server (NTRS)

    Wei, Chenyu; Cho, K. J.; Srivastava, Deepak; Tang, Harry (Technical Monitor)

    2002-01-01

    Contents include the folloving: carbon nanotube (CNT): structures, application of carbon nanotubes, simulation method, Elastic properties of carbon nanotubes, yield strain of CNT, yielding under tensile stress, yielding: strain-rate and temperature dependence, yield strain under tension, yielding at realistic conditions, nano fibers, polymer CNT composite, force field, density dependency on temperature, diffusion coefficients, young modulus, and conclusions.

  4. Muscle-related side-effects of statins: from mechanisms to evidence-based solutions.

    PubMed

    Taylor, Beth A; Thompson, Paul D

    2015-06-01

    This article highlights the recent findings regarding statin-associated muscle side effects, including mechanisms and treatment as well as the need for more comprehensive clinical trials in statin myalgia. Statin myalgia is difficult to diagnose and treat, as major clinical trials have not routinely assessed muscle side-effects, there are few clinically relevant biomarkers and assessment tools for the symptoms, many apparent statin-related muscle symptoms may be nonspecific and related to other drugs or health conditions, and prevalence estimates vary widely. Data thus suggest that only 30-50% of patients with self-reported statin myalgia actually experience muscle pain on statins during blinded, placebo-controlled trials. In addition, evidence to date involving mechanisms underlying statin myalgia and its range of symptoms and presentations supports the hypothesis that there are multiple, interactive and potentially additive mechanisms underlying statin-associated muscle side-effects. There are likely multiple and interactive mechanisms underlying statin myalgia, and recent studies have produced equivocal data regarding prevalence of statin-associated muscle side-effects, contributing factors and effectiveness of common interventions. Therefore, more clinical trials on statin myalgia are critical to the field, as are systematic resources for quantifying, predicting and reporting statin-associated muscle side-effects.

  5. The evolved psychological mechanisms of fertility motivation: hunting for causation in a sea of correlation

    PubMed Central

    McAllister, Lisa S.; Pepper, Gillian V.; Virgo, Sandra

    2016-01-01

    Cultural, ecological, familial and physiological factors consistently influence fertility behaviours, however, the proximate psychological mechanisms underlying fertility decisions in humans are poorly understood. Understanding the psychological mechanisms underlying human fertility may illuminate the final processes by which some of these known predictors have their influence. To date, research into the psychological mechanisms underlying fertility has been fragmented. Aspects of reproductive psychology have been examined by researchers in a range of fields, but the findings have not been systematically integrated in one review. We provide such a review, examining current theories and research on psychological mechanisms of fertility. We examine the methods and populations used in the research, as well as the disciplines and theoretical perspectives from which the work has come. Much of the work that has been done to date is methodologically limited to examining correlations between ecological, social and economic factors and fertility. We propose, and support with examples, the use of experimental methods to differentiate causal factors from correlates. We also discuss weaknesses in the experimental research, including limited work with non-WEIRD (western, educated, industrialized, rich and democratic) populations. PMID:27022078

  6. Virtual Reality Rehabilitation from Social Cognitive and Motor Learning Theoretical Perspectives in Stroke Population

    PubMed Central

    Imam, Bita; Jarus, Tal

    2014-01-01

    Objectives. To identify the virtual reality (VR) interventions used for the lower extremity rehabilitation in stroke population and to explain their underlying training mechanisms using Social Cognitive (SCT) and Motor Learning (MLT) theoretical frameworks. Methods. Medline, Embase, Cinahl, and Cochrane databases were searched up to July 11, 2013. Randomized controlled trials that included a VR intervention for lower extremity rehabilitation in stroke population were included. The Physiotherapy Evidence Database (PEDro) scale was used to assess the quality of the included studies. The underlying training mechanisms involved in each VR intervention were explained according to the principles of SCT (vicarious learning, performance accomplishment, and verbal persuasion) and MLT (focus of attention, order and predictability of practice, augmented feedback, and feedback fading). Results. Eleven studies were included. PEDro scores varied from 3 to 7/10. All studies but one showed significant improvement in outcomes in favour of the VR group (P < 0.05). Ten VR interventions followed the principle of performance accomplishment. All the eleven VR interventions directed subject's attention externally, whereas nine provided training in an unpredictable and variable fashion. Conclusions. The results of this review suggest that VR applications used for lower extremity rehabilitation in stroke population predominantly mediate learning through providing a task-oriented and graduated learning under a variable and unpredictable practice. PMID:24523967

  7. Diet-induced obesity, gut microbiota and bone, including alveolar bone loss.

    PubMed

    Eaimworawuthikul, Sathima; Thiennimitr, Parameth; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2017-06-01

    Obesity is a major risk factor for several pathologies, including jaw bone resorption. The underlying mechanisms involved in pathological conditions resulting from obesity include chronic systemic inflammation and the development of insulin resistance. Although numerous studies have indicated the importance of the role of gut microbiota in the pathogenesis of inflammation and insulin resistance in obesity, only a few studies have established a relationship between obesity, gut microbiota and status of the jaw bone. This review aims to summarize current findings relating to these issues, focusing on the role of obesity and gut microbiota on jaw bone health, including possible mechanisms which can explain this link. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Finite Element Modeling of Multilayer Orthogonal Auxetic Composites under Low-Velocity Impact

    PubMed Central

    Jiang, Lili; Hu, Hong

    2017-01-01

    The multilayer orthogonal auxetic composites have been previously developed and tested to prove that they own excellent energy absorption and impact protection characteristics in a specific strain range under low-velocity impact. In this study, a three dimensional finite element (FE) model in ANSYS LS-DYNA was established to simulate the mechanical behavior of auxetic composites under low-velocity drop-weight impact. The simulation results including the Poisson’s ratio versus compressive strain curves and the contact stress versus compressive strain curves were compared with those in the experiments. The clear deformation pictures of the FE models have provided a simple and effective way for investigating the damage mechanism and optimizing the material, as well as structure design. PMID:28783054

  9. 78 FR 68714 - Medical Devices; Ophthalmic Devices; Classification of the Scleral Plug

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-15

    ... the device materials must be performed; (iv) Performance data must demonstrate acceptable mechanical properties under simulated clinical use conditions including insertion and removal of the device; (v...

  10. Direct in situ observation of ZnO nucleation and growth via transmission X-ray microscopy

    NASA Astrophysics Data System (ADS)

    Tay, S. E. R.; Goode, A. E.; Nelson Weker, J.; Cruickshank, A. A.; Heutz, S.; Porter, A. E.; Ryan, M. P.; Toney, M. F.

    2016-01-01

    The nucleation and growth of a nanostructure controls its size and morphology, and ultimately its functional properties. Hence it is crucial to investigate growth mechanisms under relevant growth conditions at the nanometer length scale. Here we image the nucleation and growth of electrodeposited ZnO nanostructures in situ, using a transmission X-ray microscope and specially designed electrochemical cell. We show that this imaging technique leads to new insights into the nucleation and growth mechanisms in electrodeposited ZnO including direct, in situ observations of instantaneous versus delayed nucleation.The nucleation and growth of a nanostructure controls its size and morphology, and ultimately its functional properties. Hence it is crucial to investigate growth mechanisms under relevant growth conditions at the nanometer length scale. Here we image the nucleation and growth of electrodeposited ZnO nanostructures in situ, using a transmission X-ray microscope and specially designed electrochemical cell. We show that this imaging technique leads to new insights into the nucleation and growth mechanisms in electrodeposited ZnO including direct, in situ observations of instantaneous versus delayed nucleation. Electronic supplementary information (ESI) available: Methods and videos of nanoparticle growth. See DOI: 10.1039/c5nr07019h

  11. Reduced Nucleus Pulposus Glycosaminoglycan Content Alters Intervertebral Disc Dynamic Viscoelastic Mechanics

    PubMed Central

    Boxberger, John I.; Orlansky, Amy S.; Sen, Sounok; Elliott, Dawn M.

    2009-01-01

    The intervertebral disc functions over a range of dynamic loading regimes including axial loads applied across a spectrum of frequencies at varying compressive loads. Biochemical changes occurring in early degeneration, including reduced nucleus pulposus glycosaminoglycan content, may alter disc mechanical behavior and thus may contribute to the progression of degeneration. The objective of this study was to determine disc dynamic viscoelastic properties under several equilibrium loads and loading frequencies, and further, to determine how reduced nucleus glycosaminglycan content alters dynamic mechanics. We hypothesized (1) that dynamic stiffness would be elevated with increasing equilibrium load and increasing frequency, (2) that the disc would behave more elastically at higher frequencies, and finally, (3) that dynamic stiffness would be reduced at low equilibrium loads under all frequencies due to nucleus glycosaminoglycan loss. We mechanically tested control and chondroitinase-ABC injected rat lumbar motion segments at several equilibrium loads using oscillatory loading at frequencies ranging from 0.05 to 5 Hz. The rat lumbar disc behaved non-linearly with higher dynamic stiffness at elevated compressive loads irrespective of frequency. Phase angle was not affected by equilibrium load, although it decreased as frequency was increased. Reduced glycosaminoglycan decreased dynamic stiffness at low loads but not at high equilibrium loads and led to increased phase angle at all loads and frequencies. The findings of this study demonstrate the effect of equilibrium load and loading frequencies on dynamic disc mechanics and indicate possible mechanical mechanisms through which disc degeneration can progress. PMID:19539936

  12. Energy evolution mechanism in process of Sandstone failure and energy strength criterion

    NASA Astrophysics Data System (ADS)

    Wang, Yunfei; Cui, Fang

    2018-07-01

    To reveal the inherent relation between energy change and confining pressure during the process of sandstone damage, and its characteristics of energy storage and energy dissipation in different deformation stage. Obtaining the mechanical parameters by testing the Sandstone of two1 coal seam roof under uniaxial compression in Zhaogu coalmine, using Particle Flow Code (PFC) and fish program to get the meso-mechanical parameters, studying Sandstone energy evolution mechanism under different confining pressures, and deducing energy strength criterion based on energy principle of rock failure, some main researching results are reached as follows: with the increasing of confining pressure, the Sandstone yield stage and ductility increases, but brittleness decreases; Under higher confining pressure, the elastic strain energy of Sandstone before peak approximately keeps constant in a certain strain range, and rock absorbs all the energy which converts into surface energy required for internal damage development; Under lower confining pressure, Sandstone no longer absorbs energy with increasing strain after peak under lower confining pressure, while it sequentially absorbs energy under higher confining pressure; Under lower confining pressure, the energy Sandstone before peak absorbed mainly converts into elastic strain energy, while under higher confining pressure, dissipation energy significantly increases before peak, which indicates that the degree rock strength loss is higher under higher confining pressure; with the increasing of confining pressure, the limit of elastic strain energy increases and there exists a favourable linear variation relationship; At the peak point, the ratio of elastic strain energy to total energy of Sandstone nonlinearly decreases, while the ratio of dissipation energy to total energy nonlinearly increases with the increasing of confining pressure; According to energy evolution mechanism of rock failure, an energy strength criterion is derived. The criterion equation includes lithology constants and three principal stresses, and its physical meaning is clear. This criterion has an evident advantage than Hoek-Brown and Drucker-Prager criterion in calculation accuracy and can commendably describe rock failure characteristics.

  13. Investigating the mechanism(s) underlying switching between states in bipolar disorder

    PubMed Central

    Young, Jared W.; Dulcis, Davide

    2015-01-01

    Bipolar Disorder (BD) is a unique disorder that transcends domains of function since the same patient can exhibit depression or mania, states with polar opposite mood symptoms. During depression, people feel helplessness, reduced energy, and risk aversion, while with mania behaviors include grandiosity, increased energy, less sleep, and risk preference. The neural mechanism(s) underlying each state are gaining clarity, with catecholaminergic disruption seen during mania, and cholinergic dysfunction during depression. The fact that the same patient cycles/switches between these states is the defining characteristic of BD however. Of greater importance therefore, is the mechanism(s) underlying cycling from one state - and its associated neural changes - to another, considered the ‘holy grail’ of BD research. Herein, we review studies investigating triggers that induce switching to these states. By identifying such triggers, researchers can study neural mechanisms underlying each state and importantly how such mechanistic changes can occur in the same subject. Current animal models of this switch are also discussed, from submissive- and dominant-behaviors to kindling effects. Focus however, is placed on how seasonal changes can induce manic and depressive states in BD sufferers. Importantly, changing photoperiod lengths can induce local switches in neurotransmitter expression in normal animals, from increased catecholaminergic expression during periods of high activity, to increased somatostatin and corticotrophin releasing factor during periods of low activity. Identifying susceptibilities to this switch would enable the development of targeted animal models. From animal models, targeted treatments could be developed and tested that would minimize the likelihood of switching. PMID:25814263

  14. The SEB-1 Transcription Factor Binds to the STRE Motif in Neurospora crassa and Regulates a Variety of Cellular Processes Including the Stress Response and Reserve Carbohydrate Metabolism.

    PubMed

    Freitas, Fernanda Zanolli; Virgilio, Stela; Cupertino, Fernanda Barbosa; Kowbel, David John; Fioramonte, Mariana; Gozzo, Fabio Cesar; Glass, N Louise; Bertolini, Maria Célia

    2016-05-03

    When exposed to stress conditions, all cells induce mechanisms resulting in an attempt to adapt to stress that involve proteins which, once activated, trigger cell responses by modulating specific signaling pathways. In this work, using a combination of pulldown assays and mass spectrometry analyses, we identified the Neurospora crassa SEB-1 transcription factor that binds to the Stress Response Element (STRE) under heat stress. Orthologs of SEB-1 have been functionally characterized in a few filamentous fungi as being involved in stress responses; however, the molecular mechanisms mediated by this transcription factor may not be conserved. Here, we provide evidences for the involvement of N. crassa SEB-1 in multiple cellular processes, including response to heat, as well as osmotic and oxidative stress. The Δseb-1 strain displayed reduced growth under these conditions, and genes encoding stress-responsive proteins were differentially regulated in the Δseb-1 strain grown under the same conditions. In addition, the SEB-1-GFP protein translocated from the cytosol to the nucleus under heat, osmotic, and oxidative stress conditions. SEB-1 also regulates the metabolism of the reserve carbohydrates glycogen and trehalose under heat stress, suggesting an interconnection between metabolism control and this environmental condition. We demonstrated that SEB-1 binds in vivo to the promoters of genes encoding glycogen metabolism enzymes and regulates their expression. A genome-wide transcriptional profile of the Δseb-1 strain under heat stress was determined by RNA-seq, and a broad range of cellular processes was identified that suggests a role for SEB-1 as a protein interconnecting these mechanisms. Copyright © 2016 Freitas et al.

  15. Global warming at the summit

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    During the recent summit meeting between Russian President Vladimir Putin and U.S. President Bill Clinton, the two leaders reaffirmed their concerns about global warming and the need to continue to take actions to try to reduce the threat.In a June 4 joint statement, they stressed the need to develop flexibility mechanisms, including international emissions trading, under the Kyoto Protocol to the United Nations Framework Convention on Climate Change. They also noted that initiatives to reduce the risk of greenhouse warming, including specific mechanisms of the Kyoto Protocol, could potentially promote economic growth.

  16. Composite materials research and education program: The NASA-Virginia Tech composites program

    NASA Technical Reports Server (NTRS)

    Herakovich, C. T.

    1980-01-01

    Major areas of study include: (1) edge effects in finite width laminated composites subjected to mechanical, thermal and hygroscopic loading with temperature dependent material properties and the influence of edge effects on the initiation of failure; (2) shear and compression testing of composite materials at room and elevated temperatures; (3) optical techniques for precise measurement of coefficients of thermal expansion of composites; (4) models for the nonlinear behavior of composites including material nonlinearity and damage accumulation and verification of the models under biaxial loading; (5) compressive failure of graphite/epoxy plates with circular holes and the buckling of composite cylinders under combined compression and torsion; (6) nonlinear mechanical properties of borsic/aluminum, graphite/polyimide and boron/aluminum; (7) the strength characteristics of spliced sandwich panels; and (8) curved graphite/epoxy panels subjected to internal pressure.

  17. Genes and signaling pathways involved in memory enhancement in mutant mice

    PubMed Central

    2014-01-01

    Mutant mice have been used successfully as a tool for investigating the mechanisms of memory at multiple levels, from genes to behavior. In most cases, manipulating a gene expressed in the brain impairs cognitive functions such as memory and their underlying cellular mechanisms, including synaptic plasticity. However, a remarkable number of mutations have been shown to enhance memory in mice. Understanding how to improve a system provides valuable insights into how the system works under normal conditions, because this involves understanding what the crucial components are. Therefore, more can be learned about the basic mechanisms of memory by studying mutant mice with enhanced memory. This review will summarize the genes and signaling pathways that are altered in the mutants with enhanced memory, as well as their roles in synaptic plasticity. Finally, I will discuss how knowledge of memory-enhancing mechanisms could be used to develop treatments for cognitive disorders associated with impaired plasticity. PMID:24894914

  18. Unilateral occipital nerve stimulation for bilateral occipital neuralgia: a case report and literature review

    PubMed Central

    Liu, Aijun; Jiao, Yongcheng; Ji, Huijun; Zhang, Zhiwen

    2017-01-01

    Objectives The aim of this study is to present a case of successful relief of bilateral occipital neuralgia (ON) using unilateral occipital nerve stimulation (ONS) and to discuss the possible underlying mechanisms. Materials and methods We present the case of a 59-year-old female patient with severe bilateral ON treated with unilateral ONS. We systematically reviewed previous studies of ONS for ON, discussing the possible mechanisms of ONS in the relief of ON. Results The patient reported complete pain relief after consistent unilateral ONS during the follow-up period. The underlying mechanisms may be linked to the relationship between pain and several brain regions, including the pons, midbrain, and periaqueductal gray. Conclusion ONS is an effective and safe option for treating ON. Future studies will be required to clarify the mechanisms by which unilateral occipital stimulation provided relief for bilateral neuralgia in this case. PMID:28176938

  19. Unilateral occipital nerve stimulation for bilateral occipital neuralgia: a case report and literature review.

    PubMed

    Liu, Aijun; Jiao, Yongcheng; Ji, Huijun; Zhang, Zhiwen

    2017-01-01

    The aim of this study is to present a case of successful relief of bilateral occipital neuralgia (ON) using unilateral occipital nerve stimulation (ONS) and to discuss the possible underlying mechanisms. We present the case of a 59-year-old female patient with severe bilateral ON treated with unilateral ONS. We systematically reviewed previous studies of ONS for ON, discussing the possible mechanisms of ONS in the relief of ON. The patient reported complete pain relief after consistent unilateral ONS during the follow-up period. The underlying mechanisms may be linked to the relationship between pain and several brain regions, including the pons, midbrain, and periaqueductal gray. ONS is an effective and safe option for treating ON. Future studies will be required to clarify the mechanisms by which unilateral occipital stimulation provided relief for bilateral neuralgia in this case.

  20. In Situ Observation of Failure Mechanisms Controlled by Rock Masses with Weak Interlayer Zones in Large Underground Cavern Excavations Under High Geostress

    NASA Astrophysics Data System (ADS)

    Duan, Shu-Qian; Feng, Xia-Ting; Jiang, Quan; Liu, Guo-Feng; Pei, Shu-Feng; Fan, Yi-Lin

    2017-09-01

    A weak interlayer zone (WIZ) is a poor rock mass system with loose structure, weak mechanical properties, variable thickness, random distribution, strong extension, and high risk due to the shear motion of rock masses under the action of tectonism, bringing many stability problems and geological hazards, especially representing a potential threat to the overall stability of rock masses with WIZs in large underground cavern excavations. Focusing on the deformation and failure problems encountered in the process of excavation unloading, this research proposes comprehensive in situ observation schemes for rock masses with WIZs in large underground cavern on the basis of the collection of geological, construction, monitoring, and testing data. The schemes have been fully applied in two valuable project cases of an underground cavern group under construction in the southwest of China, including the plastic squeezing-out tensile failure and the structural stress-induced collapse of rock masses with WIZs. In this way, the development of rock mass failure, affected by the step-by-step excavations along the cavern's axis and the subsequent excavation downward, could be observed thoroughly. Furthermore, this paper reveals the preliminary analyses of failure mechanism of rock masses with WIZs from several aspects, including rock mass structure, strength, high stress, ground water effects, and microfracture mechanisms. Finally, the failure particularities of rock masses with WIZs and rethink on prevention and control of failures are discussed. The research results could provide important guiding reference value for stability analysis, as well as for rethinking the excavation and support optimization of rock masses with WIZs in similar large underground cavern under high geostress.

  1. Mechanical obstacles to the movement of continent-bearing plates

    NASA Technical Reports Server (NTRS)

    Lowman, P. D., Jr.

    1985-01-01

    Selected geophysical problems associated with the concept of continental drift as an incidental corollary of plate movement are discussed. The problems include the absence of a suitable plate-driving mechanism for plates with continental leading edges, the absence of the low-velocity zone under shields, and continental roots of 400 to 700 km depths. It is shown that if continental drift occurs, it must use mechanisms not now understood, or that it may not occur at all, plate movement being confined to ocean basins.

  2. Antidepressant effects of ketamine and the roles of AMPA glutamate receptors and other mechanisms beyond NMDA receptor antagonism.

    PubMed

    Aleksandrova, Lily R; Phillips, Anthony G; Wang, Yu Tian

    2017-06-01

    The molecular mechanisms underlying major depressive disorder remain poorly understood, and current antidepressant treatments have many shortcomings. The recent discovery that a single intravenous infusion of ketamine at a subanesthetic dose had robust, rapid and sustained antidepressant effects in individuals with treatment-resistant depression inspired tremendous interest in investigating the molecular mechanisms mediating ketamine's clinical efficacy as well as increased efforts to identify new targets for antidepressant action. We review the clinical utility of ketamine and recent insights into its mechanism of action as an antidepressant, including the roles of N -methyl-D-aspartate receptor inhibition, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor upregulation, activation of downstream synaptogenic signalling pathways and the production of an active ketamine metabolite, hydroxynorketamine. Emerging knowledge of the molecular mechanisms underlying both ketamine's positive therapeutic and detrimental side effects will aid the development of a new generation of much-needed superior antidepressant agents.

  3. 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.

  4. Ultrasonographic measurement of the mechanical properties of the sole under the metatarsal heads.

    PubMed

    Wang, C L; Hsu, T C; Shau, Y W; Shieh, J Y; Hsu, K H

    1999-09-01

    The sole under the metatarsal heads functions as a shock absorber during walking and running. The mechanical properties of the sole provide the primary defense against the development of metatarsalgia and foot ulceration. However, limited information about these properties has been documented. In this study, we used ultrasonography to evaluate the mechanical properties, including unloaded thickness, compressibility index, elastic modulus, and energy dissipation ratio, of the sole in 20 healthy subjects. The unloaded thickness decreased progressively from the first to the fifth metatarsal heads, with values of 1.50, 1.36, 1.25, 1.14, and 1.04 cm. The sole under the first metatarsal head had the greatest values for the compressibility index and elastic modulus (55.9% and 1.39 kg/cm2), and the sole under the third metatarsal head had the smallest values (50.8% and 1.23 kg/cm2). The sole under the fifth metatarsal head had the greatest energy dissipation ratio (33.7%), followed by that under the third, second, first, and fourth metatarsal heads. Multivariate adjusted linear regression showed that the unloaded thickness, compressibility index, and elastic modulus values increased significantly with age and body weight (p < 0.05) and that the energy dissipation ratio increased significantly with body weight (p < 0.05)

  5. Robotic joint experiments under ultravacuum

    NASA Technical Reports Server (NTRS)

    Borrien, A.; Petitjean, L.

    1988-01-01

    First, various aspects of a robotic joint development program, including gearbox technology, electromechanical components, lubrication, and test results, are discussed. Secondly, a test prototype of the joint allowing simulation of robotic arm dynamic effects is presented. This prototype is tested under vacuum with different types of motors and sensors to characterize the functional parameters: angular position error, mechanical backlash, gearbox efficiency, and lifetime.

  6. 46 CFR 160.170-13 - Approval inspections and tests for prototype automatic release mechanisms.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... as built. The plans must include, in triplicate, the instructions for training and maintenance... determine that the prototype— (A) Conforms with the plans reviewed under § 160.170-9 of this subpart; (B) Is constructed by the methods and with the materials specified in the plans reviewed under § 160.170-9 of this...

  7. 46 CFR 160.170-13 - Approval inspections and tests for prototype automatic release mechanisms.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... as built. The plans must include, in triplicate, the instructions for training and maintenance... determine that the prototype— (A) Conforms with the plans reviewed under § 160.170-9 of this subpart; (B) Is constructed by the methods and with the materials specified in the plans reviewed under § 160.170-9 of this...

  8. 46 CFR 160.170-13 - Approval inspections and tests for prototype automatic release mechanisms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... as built. The plans must include, in triplicate, the instructions for training and maintenance... determine that the prototype— (A) Conforms with the plans reviewed under § 160.170-9 of this subpart; (B) Is constructed by the methods and with the materials specified in the plans reviewed under § 160.170-9 of this...

  9. The hazardous effects of tobacco smoking on male fertility

    PubMed Central

    Dai, Jing-Bo; Wang, Zhao-Xia; Qiao, Zhong-Dong

    2015-01-01

    The substantial harmful effects of tobacco smoking on fertility and reproduction have become apparent but are not generally appreciated. Tobacco smoke contains more than 4000 kinds of constituents, including nicotine, tar, carbonic monoxide, polycyclic aromatic hydrocarbons, and heavy metals. Because of the complexity of tobacco smoke components, the toxicological mechanism is notably complicated. Most studies have reported reduced semen quality, reproductive hormone system dysfunction and impaired spermatogenesis, sperm maturation, and spermatozoa function in smokers compared with nonsmokers. Underlying these effects, elevated oxidative stress, DNA damage, and cell apoptosis may play important roles collaboratively in the overall effect of tobacco smoking on male fertility. In this review, we strive to focus on both the phenotype of and the molecular mechanism underlying these harmful effects, although current studies regarding the mechanism remain insufficient. PMID:25851659

  10. The hazardous effects of tobacco smoking on male fertility.

    PubMed

    Dai, Jing-Bo; Wang, Zhao-Xia; Qiao, Zhong-Dong

    2015-01-01

    The substantial harmful effects of tobacco smoking on fertility and reproduction have become apparent but are not generally appreciated. Tobacco smoke contains more than 4000 kinds of constituents, including nicotine, tar, carbonic monoxide, polycyclic aromatic hydrocarbons, and heavy metals. Because of the complexity of tobacco smoke components, the toxicological mechanism is notably complicated. Most studies have reported reduced semen quality, reproductive hormone system dysfunction and impaired spermatogenesis, sperm maturation, and spermatozoa function in smokers compared with nonsmokers. Underlying these effects, elevated oxidative stress, DNA damage, and cell apoptosis may play important roles collaboratively in the overall effect of tobacco smoking on male fertility. In this review, we strive to focus on both the phenotype of and the molecular mechanism underlying these harmful effects, although current studies regarding the mechanism remain insufficient.

  11. Overshoot Convective Mixing in Nova Outbursts

    NASA Astrophysics Data System (ADS)

    Glasner, A. S.; Livne, E.; Truran, J. W.

    2014-12-01

    We present a 2D study of the overshoot convective mechanism in nova outbursts for a wide range of possible compositions of the layer underlying the accreted envelope. Previous surveys studied this mechanism only for solar composition matter accreted on top of carbon oxygen (CO) white dwarfs. Since, during the runaway, mixing with carbon enhances the hydrogen burning rates dramatically, one should question whether significant enrichment of the ejecta is possible also for other underlying compositions (He, O, Ne, Mg) predicted by stellar evolution models. When needed we upgraded our reaction network and simulated several non-carbon cases. Despite large differences in rates, time scales and energetics, our results show that the convective dredge up mechanism predicts significant enrichment in all cases, including that of helium enrichment in recurrent novae.

  12. The puzzle of immune phenotypes of childhood asthma.

    PubMed

    Landgraf-Rauf, Katja; Anselm, Bettina; Schaub, Bianca

    2016-12-01

    Asthma represents the most common chronic childhood disease worldwide. Whereas preschool children present with wheezing triggered by different factors (multitrigger and viral wheeze), clinical asthma manifestation in school children has previously been classified as allergic and non-allergic asthma. For both, the underlying immunological mechanisms are not yet understood in depth in children. Treatment is still prescribed regardless of underlying mechanisms, and children are not always treated successfully. This review summarizes recent key findings on the complex mechanisms of the development and manifestation of childhood asthma. Whereas traditional classification of childhood asthma is primarily based on clinical symptoms like wheezing and atopy, novel approaches to specify asthma phenotypes are under way and face challenges such as including the stability of phenotypes over time and transition into adulthood. Epidemiological studies enclose more information on the patient's disease history and environmental influences. Latest studies define endotypes based on molecular and cellular mechanisms, for example defining risk and protective single nucleotide polymorphisms (SNPs) and new immune phenotypes, showing promising results. Also, regulatory T cells and recently discovered T helper cell subtypes such as Th9 and Th17 cells were shown to be important for the development of asthma. Innate lymphoid cells (ILC) could play a critical role in asthma patients as they produce different cytokines associated with asthma. Epigenetic findings showed different acetylation and methylation patterns for children with allergic and non-allergic asthma. On a posttranscriptional level, miRNAs are regulating factors identified to differ between asthma patients and healthy controls and also indicate differences within asthma phenotypes. Metabolomics is another exciting chapter important for endotyping asthmatic children. Despite the development of new biomarkers and the discovery of new immunological molecules, the complex puzzle of childhood asthma is still far from being completed. Addressing the current challenges of distinct clinical asthma and wheeze phenotypes, including their stability and underlying endotypes, involves addressing the interplay of innate and adaptive immune regulatory mechanisms in large, interdisciplinary cohorts.

  13. Role of various hormones in photosynthetic responses of green plants under environmental stresses.

    PubMed

    Poonam; Bhardwaj, Renu; Kaur, Ravdeep; Bali, Shagun; Kaur, Parminder; Sirhindi, Geetika; Thukral, Ashwani K; Ohri, Puja; Vig, Adarsh P

    2015-01-01

    Environmental stress includes adverse factors like water deficit, high salinity, enhanced temperature and heavy metals etc. These stresses alter the normal growth and metabolic processes of plants including photosynthesis. Major photosynthetic responses under various stresses include inhibition of photosystems (I and II), changes in thylakoid complexes, decreased photosynthetic activity and modifications in structure and functions of chloroplasts etc. Various defense mechanisms are triggered inside the plants in response to these stresses that are regulated by plant hormones or plant growth regulators. These phytohormones include abscisic acid, auxins, cytokinins, ethylene, brassinosteroids, jasmonates and salicylic acid etc. The present review focuses on stress protective effects of plants hormones on the photosynthetic responses.

  14. Premature ejaculation: do we have effective therapy?

    PubMed

    Serefoglu, Ege Can; Saitz, Theodore R; Trost, Landon; Hellstrom, Wayne J G

    2013-03-01

    Premature ejaculation (PE) is the most common sexual dysfunction, with the majority of PE patients remaining undiagnosed and undertreated. Despite its prevalence, there is a current paucity of data regarding available treatment options and mechanisms. The objective of the current investigation is to review and summarize pertinent literature on therapeutic options for the treatment of PE, including behavioral/psychologic, oral pharmacotherapy, and surgery. A pubmed search was conducted on articles reporting data on available treatment options for PE. Articles describing potential mechanisms of action were additionally included for review. Preference was given towards randomized, controlled trials, when available. PE remains an underdiagnosed and undertreated disease process, with limited data available regarding potential underlying mechanisms and long-term outcomes of treatment options. Psychological/behavioral therapies, including the stop-start, squeeze, and pelvic floor rehabilitation techniques have demonstrated improvements in short-term series, with decreased efficacy with additional follow-up. Topical therapies, which are commonly utilized result in prolonged intravaginal ejaculatory latency time (IELT) at the expense of potential penile/vaginal Hypothesia. Oral therapies similarly demonstrate improved IELTs with variable side effect profiles and include selective serotonin reuptake inhibitors (daily or on demand), phosphodiesterase-5 inhibitors, alpha-1 adrenergic antagonists, and tramadol. Alternative therapies such as acupuncture have shown benefits in limited studies. Surgery is not commonly performed and is not recommended by available guidelines. PE is a common condition, with limited data available regarding its underlying pathophysiology and treatment. Available therapies include topical, oral, behavioral/psychologic modification, or a combination thereof. Additional research is required to assess the optimal treatment strategies and algorithms as well as to better define the mechanisms for PE and its management.

  15. Premature ejaculation: do we have effective therapy?

    PubMed Central

    Serefoglu, Ege Can; Saitz, Theodore R.; Trost, Landon

    2013-01-01

    Introduction Premature ejaculation (PE) is the most common sexual dysfunction, with the majority of PE patients remaining undiagnosed and undertreated. Despite its prevalence, there is a current paucity of data regarding available treatment options and mechanisms. The objective of the current investigation is to review and summarize pertinent literature on therapeutic options for the treatment of PE, including behavioral/psychologic, oral pharmacotherapy, and surgery. Methods A pubmed search was conducted on articles reporting data on available treatment options for PE. Articles describing potential mechanisms of action were additionally included for review. Preference was given towards randomized, controlled trials, when available. Results PE remains an underdiagnosed and undertreated disease process, with limited data available regarding potential underlying mechanisms and long-term outcomes of treatment options. Psychological/behavioral therapies, including the stop-start, squeeze, and pelvic floor rehabilitation techniques have demonstrated improvements in short-term series, with decreased efficacy with additional follow-up. Topical therapies, which are commonly utilized result in prolonged intravaginal ejaculatory latency time (IELT) at the expense of potential penile/vaginal Hypothesia. Oral therapies similarly demonstrate improved IELTs with variable side effect profiles and include selective serotonin reuptake inhibitors (daily or on demand), phosphodiesterase-5 inhibitors, alpha-1 adrenergic antagonists, and tramadol. Alternative therapies such as acupuncture have shown benefits in limited studies. Surgery is not commonly performed and is not recommended by available guidelines. Conclusions PE is a common condition, with limited data available regarding its underlying pathophysiology and treatment. Available therapies include topical, oral, behavioral/psychologic modification, or a combination thereof. Additional research is required to assess the optimal treatment strategies and algorithms as well as to better define the mechanisms for PE and its management. PMID:26816723

  16. Mechanism Design Principle for Optical-Precision, Deployable Instruments

    NASA Technical Reports Server (NTRS)

    Lake, Mark S.; Hachkowski, M. Roman

    2000-01-01

    The present paper is intended to be a guide for the design of 'microdynamically quiet' deployment mechanisms for optical-precision structures, such as deployable telescope mirrors and optical benches. Many of the guidelines included herein come directly from the field of optomechanical engineering, and are neither newly developed guidelines nor are they uniquely applicable to high-precision deployment mechanisms. However, the application of these guidelines to the design of deployment mechanisms is a rather new practice, so efforts are made herein to illustrate the process through the discussion of specific examples. The present paper summarizes a more extensive set of design guidelines for optical-precision mechanisms that are under development.

  17. Development and Use of Numerical and Factual Data Bases

    DTIC Science & Technology

    1983-10-01

    the quantitative description of what has been accomplished by their scientific and technical endeavors. 1-3 overhead charge to the national treasury... Molecular properties calculated with the aid of quantum mechanics or the prediction of solar eclipses using celestial mechanics are examples of theoretical...system under study. Examples include phase diagrams, molecular models, geological maps, metabolic pathways. Symbolic data (F3) are data presented in

  18. Detailed Kinetic Mechanism of the Combustion of Homogeneous Gaseous Mixtures with Participation of Oxygen-containing Oxidants

    NASA Astrophysics Data System (ADS)

    Baevich, V. Ya

    1987-05-01

    The kinetic mechanisms of the oxidation and combustion of hydrogen, methane, methyl alcohol, acetylene, ethylene, ethane, and methylamine, using oxygen as well as hydrogen peroxide and nitric acid as oxidants, are discussed. The calculated and experimental data obtained under static conditions, in a flow, during flame propagation, and in shock tubes are compared. The bibliography includes 184 references.

  19. Nitrergic Mechanisms for Management of Recurrent Priapism

    PubMed Central

    Anele, Uzoma A.; Burnett, Arthur L.

    2015-01-01

    Introduction Priapism is a condition involving prolonged penile erection unrelated to sexual interest or desire. The ischemic type, including its recurrent variant, is often associated with both physical and psychological complications. As such, management is of critical importance. Ideal therapies for recurrent priapism should address its underlying pathophysiology. Aim To review the available literature on priapism management approaches particularly related to nitrergic mechanisms. Methods A literature review of the pathophysiology and management of priapism was performed using PubMed. Main Outcome Measure Publications pertaining to mechanisms of the molecular pathophysiology of priapism. Results Nitrergic mechanisms are characterized as major players in the molecular pathophysiology of priapism. PDE5 inhibitors represent an available therapeutic option with demonstrated ability in attenuating these underlying nitrergic derangements. Several additional signaling pathways have been found to play a role in the molecular pathophysiology of priapism and have also been associated with these nitrergic mechanisms. Conclusion An increasing understanding of the molecular pathophysiology of priapism has led to the discovery of new potential targets. Several mechanism-based therapeutic approaches may become available in the future. PMID:26478814

  20. Biological Mechanisms Underlying the Relationship between Stress and Smoking: State of the Science and Directions for Future Work

    PubMed Central

    Richards, Jessica; Stipelman, Brooke A.; Bornovalova, Marina A.; Daughters, Stacey; Sinha, Rajita; Lejuez, C.W.

    2011-01-01

    Theories of addiction implicate stress as a crucial mechanism underlying initiation, maintenance, and relapse to cigarette smoking. Examinations of the biological stress systems, including functioning of the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS), have provided additional insights into the relationship between stress and smoking. To date, convergent data suggests that chronic cigarette smoking is associated with alterations in HPA and ANS functioning; however, less is known about the role of HPA and ANS functioning in smoking initiation and relapse following cessation. In order to organize existing findings and stimulate future research, the current paper summarizes the available literature on the roles of HPA axis and ANS functioning in the relationship between stress and cigarette smoking, highlights limitations within the existing literature, and suggests directions for future research to address unanswered questions in the extant literature on the biological mechanisms underlying the relationship between stress and smoking. PMID:21741435

  1. Neural mechanisms and personality correlates of the sunk cost effect

    PubMed Central

    Fujino, Junya; Fujimoto, Shinsuke; Kodaka, Fumitoshi; Camerer, Colin F.; Kawada, Ryosaku; Tsurumi, Kosuke; Tei, Shisei; Isobe, Masanori; Miyata, Jun; Sugihara, Genichi; Yamada, Makiko; Fukuyama, Hidenao; Murai, Toshiya; Takahashi, Hidehiko

    2016-01-01

    The sunk cost effect, an interesting and well-known maladaptive behavior, is pervasive in real life, and thus has been studied in various disciplines, including economics, psychology, organizational behavior, politics, and biology. However, the neural mechanisms underlying the sunk cost effect have not been clearly established, nor have their association with differences in individual susceptibility to the effect. Using functional magnetic resonance imaging, we investigated neural responses induced by sunk costs along with measures of core human personality. We found that individuals who tend to adhere to social rules and regulations (who are high in measured agreeableness and conscientiousness) are more susceptible to the sunk cost effect. Furthermore, this behavioral observation was strongly mediated by insula activity during sunk cost decision-making. Tight coupling between the insula and lateral prefrontal cortex was also observed during decision-making under sunk costs. Our findings reveal how individual differences can affect decision-making under sunk costs, thereby contributing to a better understanding of the psychological and neural mechanisms of the sunk cost effect. PMID:27611212

  2. Installing Mechanics of Granular Materials (MGM) Experiment Test Cell

    NASA Technical Reports Server (NTRS)

    1996-01-01

    Astronaut Carl Walz installs Mechanics of Granular Materials (MGM) test cell on STS-79. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditons that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: NASA/John Space Center

  3. Thymic function in the regulation of T cells, and molecular mechanisms underlying the modulation of cytokines and stress signaling (Review).

    PubMed

    Yan, Fenggen; Mo, Xiumei; Liu, Junfeng; Ye, Siqi; Zeng, Xing; Chen, Dacan

    2017-11-01

    The thymus is critical in establishing and maintaining the appropriate microenvironment for promoting the development and selection of T cells. The function and structure of the thymus gland has been extensively studied, particularly as the thymus serves an important physiological role in the lymphatic system. Numerous studies have investigated the morphological features of thymic involution. Recently, research attention has increasingly been focused on thymic proteins as targets for drug intervention. Omics approaches have yielded novel insights into the thymus and possible drug targets. The present review addresses the signaling and transcriptional functions of the thymus, including the molecular mechanisms underlying the regulatory functions of T cells and their role in the immune system. In addition, the levels of cytokines secreted in the thymus have a significant effect on thymic functions, including thymocyte migration and development, thymic atrophy and thymic recovery. Furthermore, the regulation and molecular mechanisms of stress‑mediated thymic atrophy and involution were investigated, with particular emphasis on thymic function as a potential target for drug development and discovery using proteomics.

  4. Universal Local Symmetries and Nonsuperposition in Classical Mechanics

    NASA Astrophysics Data System (ADS)

    Gozzi, Ennio; Pagani, Carlo

    2010-10-01

    In the Hilbert space formulation of classical mechanics, pioneered by Koopman and von Neumann, there are potentially more observables than in the standard approach to classical mechanics. In this Letter, we show that actually many of those extra observables are not invariant under a set of universal local symmetries which appear once the Koopman and von Neumann formulation is extended to include the evolution of differential forms. Because of their noninvariance, those extra observables have to be removed. This removal makes the superposition of states in the Koopman and von Neumann formulation, and as a consequence also in classical mechanics, impossible.

  5. Crack propagation of brittle rock under high geostress

    NASA Astrophysics Data System (ADS)

    Liu, Ning; Chu, Weijiang; Chen, Pingzhi

    2018-03-01

    Based on fracture mechanics and numerical methods, the characteristics and failure criterions of wall rock cracks including initiation, propagation, and coalescence are analyzed systematically under different conditions. In order to consider the interaction among cracks, adopt the sliding model of multi-cracks to simulate the splitting failure of rock in axial compress. The reinforcement of bolts and shotcrete supporting to rock mass can control the cracks propagation well. Adopt both theory analysis and simulation method to study the mechanism of controlling the propagation. The best fixed angle of bolts is calculated. Then use ansys to simulate the crack arrest function of bolt to crack. Analyze the influence of different factors on stress intensity factor. The method offer more scientific and rational criterion to evaluate the splitting failure of underground engineering under high geostress.

  6. The mechanical properties of polyimide films after exposure to high pH

    NASA Technical Reports Server (NTRS)

    Croall, Catharine I.; St.clair, Terry L.

    1992-01-01

    Wiring failures linked to insulation damage have drawn much attention in the aerospace industry and concerns have developed regarding the stability and safety of polyimide insulated electrical wire. Several polyimides were selected for evaluation for resistance to degradation by various aqueous alkaline solutions. The polyimides under evaluation include commercially available films such as Kapton (tk), Apical (tk), LaRC(tk)-TPI, and Upilex(tk)R and S, as well as a number of experimental films prepared by NASA Langley. Thermally imidized films were studied for their retention of mechanical properties after exposure to high pH solutions under stressed conditions.

  7. Preliminary Evaluation of Greases for Space Mechanisms Using a Vacuum Spiral Orbit Tribometer

    NASA Technical Reports Server (NTRS)

    Marchetti, Mario; Jones, William R., Jr.; Street, Kenneth W.; Pepper, Stephen V.; Jansen, Mark J.

    2001-01-01

    Most currently used greases for space applications are based on perfluoropolyalkylethers (PFPE) and multiply alkylated cyclopentane (MAC) oils. Evaluation of the greases includes outgassing properties, rheological behavior, and particularly the ability to create EHL films under conditions as close as possible to an actual application. A spiral orbit tribometer (SOT) has been developed to conduct accelerated tests under realistic conditions. The SOT was employed to evaluate two greases used in space mechanisms: a PFPE oil with polytetrafluoroethylene (PTFE) thickener, and a multiply alkylated cyclopentane oil with n-octadecylterephthalamate soap. The results from the greases are in agreement with results previously obtained with the base oils.

  8. Mechanical Stability of Fractured Rift Basin Mudstones: from lab to basin scale

    NASA Astrophysics Data System (ADS)

    Zakharova, N. V.; Goldberg, D.; Collins, D.; Swager, L.; Payne, W. G.

    2016-12-01

    Understanding petrophysical and mechanical properties of caprock mudstones is essential for ensuring good containment and mechanical formation stability at potential CO2 storage sites. Natural heterogeneity and presence of fractures, however, create challenges for accurate prediction of mudstone behavior under injection conditions and at reservoir scale. In this study, we present a multi-scale geomechanical analysis for Mesozoic mudstones from the Newark Rift basin, integrating petropyshical core and borehole data, in situ stress measurements, and caprock stability modeling. The project funded by the U.S. Department of Energy's National Energy Technology Laboratory (NETL) focuses on the Newark basin as a representative locality for a series of the Mesozoic rift basins in eastern North America considered as potential CO2 storage sites. An extensive core characterization program, which included laboratory CT scans, XRD, SEM, MICP, porosity, permeability, acoustic velocity measurements, and geomechanical testing under a range of confining pressures, revealed large variability and heterogeneity in both petrophysical and mechanical properties. Estimates of unconfined compressive strength for these predominantly lacustrine mudstones range from 5,000 to 50,000 psi, with only a weak correlation to clay content. Thinly bedded intervals exhibit up to 30% strength anisotropy. Mineralized fractures, abundant in most formations, are characterized by compressive strength as low as 10% of matrix strength. Upscaling these observations from core to reservoir scale is challenging. No simple one-to-one correlation between mechanical and petrophyscial properties exists, and therefore, we develop multivariate empirical relationships among these properties. A large suite of geophysical logs, including new measurements of the in situ stress field, is used to extrapolate these relationships to a basin-scale geomechanical model and predict mudstone behavior under injection conditions.

  9. Genetic architecture underlying convergent evolution of egg-laying behavior in a seed-feeding beetle.

    PubMed

    Fox, Charles W; Wagner, James D; Cline, Sara; Thomas, Frances Ann; Messina, Frank J

    2009-05-01

    Independent populations subjected to similar environments often exhibit convergent evolution. An unresolved question is the frequency with which such convergence reflects parallel genetic mechanisms. We examined the convergent evolution of egg-laying behavior in the seed-feeding beetle Callosobruchus maculatus. Females avoid ovipositing on seeds bearing conspecific eggs, but the degree of host discrimination varies among geographic populations. In a previous experiment, replicate lines switched from a small host to a large one evolved reduced discrimination after 40 generations. We used line crosses to determine the genetic architecture underlying this rapid response. The most parsimonious genetic models included dominance and/or epistasis for all crosses. The genetic architecture underlying reduced discrimination in two lines was not significantly different from the architecture underlying differences between geographic populations, but the architecture underlying the divergence of a third line differed from all others. We conclude that convergence of this complex trait may in some cases involve parallel genetic mechanisms.

  10. 78 FR 4856 - Extension of Agency Information Collection Activity Under OMB Review: Aviation Security...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-23

    ... screening passengers and property in calendar year 2000. DATES: Send your comments by February 22, 2013. A... those who are to respond, including using appropriate automated, electronic, mechanical, or other...

  11. Air pollution particles and iron homeostasis

    EPA Science Inventory

    Background: The mechanism underlying biological effects of particles deposited in the lung has not been defined. Major Conclusions: A disruption in iron homeostasis follows exposure of cells to all particulate matter including air pollution particles. Following endocytosis, fun...

  12. Seawater circulation in sediments driven by interactions between seabed topography and fluid density

    USGS Publications Warehouse

    Konikow, Leonard F.; Akhavan, M.; Langevin, C.D.; Michael, H.A.; Sawyer, A.H.

    2013-01-01

    Measurements of submarine groundwater discharge (SGD) in coastal areas often show that the saltwater discharge component is substantially greater than the freshwater discharge. Several mechanisms have been proposed to explain these high saltwater discharge values, including saltwater circulation driven by wave and tidal pumping, wave and tidal setup in intertidal areas, currents over bedforms, and density gradients resulting from mixing along the freshwater-saltwater interface. In this study, a new mechanism for saltwater circulation and discharge is proposed and evaluated. The process results from interaction between bedform topography and buoyancy forces, even without flow or current over the bedform. In this mechanism, an inverted salinity (and density) profile in the presence of both a bedform on the seafloor and an upward flow of fresher groundwater from depth induces a downward flow of saline pore water under the troughs and upward flow under the adjacent crest of the bedform. The magnitude and occurrence of the mechanism were tested using numerical methods. The results indicate that this mechanism could drive seawater circulation under a limited range of conditions and contribute 20%–30% of local SGD when and where the process is operative. Bedform shape, hydraulic conductivity, hydraulic head, and salinity at depth in the porous media, aquifer thickness, effective porosity, and hydrodynamic dispersion are among the factors that control the occurrence and magnitude of the circulation of seawater by this mechanism.

  13. Bioinspired model of mechanical energy harvesting based on flexoelectric membranes.

    PubMed

    Rey, Alejandro D; Servio, P; Herrera-Valencia, E E

    2013-02-01

    Membrane flexoelectricity is an electromechanical coupling process that describes membrane electrical polarization due to bending and membrane bending under electric fields. In this paper we propose, formulate, and characterize a mechanical energy harvesting system consisting of a deformable soft flexoelectric thin membrane subjected to harmonic forcing from contacting bulk fluids. The key elements of the energy harvester are formulated and characterized, including (i) the mechanical-to-electrical energy conversion efficiency, (ii) the electromechanical shape equation connecting fluid forces with membrane curvature and electric displacement, and (iii) the electric power generation and efficiency. The energy conversion efficiency is cast as the ratio of flexoelectric coupling to the product of electric and bending elasticity. The device is described by a second-order curvature dynamics coupled to the electric displacement equation and as such results in mechanical power absorption with a resonant peak whose amplitude decreases with bending viscosity. The electric power generation is proportional to the conversion factor and the power efficiency decreases with frequency. Under high bending viscosity, the power efficiency increases with the conversion factor and under low viscosities it decreases with the conversion factor. The theoretical results presented contribute to the ongoing experimental efforts to develop mechanical energy harvesting from fluid flow energy through solid-fluid interactions and electromechanical transduction.

  14. Characterization of interdigitated electrode piezoelectric fiber composites under high electrical and mechanical loading

    NASA Astrophysics Data System (ADS)

    Rodgers, John P.; Bent, Aaron A.; Hagood, Nesbitt W.

    1996-05-01

    The primary objective of this work is to develop a standard methodology for characterizing structural actuation systems intended for operation in high electrical and mechanical loading environments. The designed set of tests evaluates the performance of the active materials system under realistic operating conditions. The tests are also used to characterize piezoelectric fiber composites which have been developed as an alternative to monolithic piezoceramic wafers for structural actuation applications. The performance of this actuator system has been improved using an interdigitated electrode pattern, which orients the primary component of the electric field into the plane of the structure, enabling the use of the primary piezoelectric effect along the active fibers. One possible application of this technology is in the integral twist actuation of helicopter rotor blades for higher harmonic control. This application requires actuators which can withstand the harsh rotor blade operating environment. This includes large numbers of electrical and mechanical cycles with considerable centripetal and bending loads. The characterization tests include standard active material tests as well as application-driven tests which evaluate the performance of the actuators during simulated operation. Test results for several actuator configurations are provided, including S2 glass- reinforced and E-glass laminated actuators. The study concludes that the interdigitated electrode piezoelectric fiber composite actuator has great potential for high loading applications.

  15. Control rod drive

    DOEpatents

    Hawke, Basil C.

    1986-01-01

    A control rod drive uses gravitational forces to insert one or more control rods upwardly into a reactor core from beneath the reactor core under emergency conditions. The preferred control rod drive includes a vertically movable weight and a mechanism operatively associating the weight with the control rod so that downward movement of the weight is translated into upward movement of the control rod. The preferred control rod drive further includes an electric motor for driving the control rods under normal conditions, an electrically actuated clutch which automatically disengages the motor during a power failure and a decelerator for bringing the control rod to a controlled stop when it is inserted under emergency conditions into a reactor core.

  16. Berberine Regulated Lipid Metabolism in the Presence of C75, Compound C, and TOFA in Breast Cancer Cell Line MCF-7.

    PubMed

    Tan, Wen; Zhong, Zhangfeng; Wang, Shengpeng; Suo, Zhanwei; Yang, Xian; Hu, Xiaodong; Wang, Yitao

    2015-01-01

    Berberine interfering with cancer reprogramming metabolism was confirmed in our previous study. Lipid metabolism and mitochondrial function were also the core parts in reprogramming metabolism. In the presence of some energy-related inhibitors, including C75, compound C, and TOFA, the discrete roles of berberine in lipid metabolism and mitochondrial function were elucidated. An altered lipid metabolism induced by berberine was observed under the inhibition of FASN, AMPK, and ACC in breast cancer cell MCF-7. And the reversion of berberine-induced lipid suppression indicated that ACC inhibition might be involved in that process instead of FASN inhibition. A robust apoptosis induced by berberine even under the inhibition of AMPK and lipid synthesis was also indicated. Finally, mitochondrial function regulation under the inhibition of AMPK and ACC might be in an ACL-independent manner. Undoubtedly, the detailed mechanisms of berberine interfering with lipid metabolism and mitochondrial function combined with energy-related inhibitors need further investigation, including the potential compensatory mechanisms for ATP production and the upregulation of ACL.

  17. Berberine Regulated Lipid Metabolism in the Presence of C75, Compound C, and TOFA in Breast Cancer Cell Line MCF-7

    PubMed Central

    Tan, Wen; Zhong, Zhangfeng; Suo, Zhanwei; Yang, Xian; Hu, Xiaodong; Wang, Yitao

    2015-01-01

    Berberine interfering with cancer reprogramming metabolism was confirmed in our previous study. Lipid metabolism and mitochondrial function were also the core parts in reprogramming metabolism. In the presence of some energy-related inhibitors, including C75, compound C, and TOFA, the discrete roles of berberine in lipid metabolism and mitochondrial function were elucidated. An altered lipid metabolism induced by berberine was observed under the inhibition of FASN, AMPK, and ACC in breast cancer cell MCF-7. And the reversion of berberine-induced lipid suppression indicated that ACC inhibition might be involved in that process instead of FASN inhibition. A robust apoptosis induced by berberine even under the inhibition of AMPK and lipid synthesis was also indicated. Finally, mitochondrial function regulation under the inhibition of AMPK and ACC might be in an ACL-independent manner. Undoubtedly, the detailed mechanisms of berberine interfering with lipid metabolism and mitochondrial function combined with energy-related inhibitors need further investigation, including the potential compensatory mechanisms for ATP production and the upregulation of ACL. PMID:26351511

  18. Mechanics of Granular Materials (MGM) Investigators

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Key persornel in the Mechanics of Granular Materials (MGM) experiment at the University of Colorado at Boulder include Tawnya Ferbiak (software engineer), Susan Batiste (research assistant), and Christina Winkler (graduate research assistant). Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. MGM experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditions that cannot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. (Credit: University of Colorado at Boulder).

  19. Shading Contributes to the Reduction of Stem Mechanical Strength by Decreasing Cell Wall Synthesis in Japonica Rice (Oryza sativa L.).

    PubMed

    Wu, Longmei; Zhang, Wujun; Ding, Yanfeng; Zhang, Jianwei; Cambula, Elidio D; Weng, Fei; Liu, Zhenghui; Ding, Chengqiang; Tang, She; Chen, Lin; Wang, Shaohua; Li, Ganghua

    2017-01-01

    Low solar radiation caused by industrial development and solar dimming has become a limitation in crop production in China. It is widely accepted that low solar radiation influences many aspects of plant development, including slender, weak stems and susceptibility to lodging. However, the underlying mechanisms are not well understood. To clarify how low solar radiation affects stem mechanical strength formation and lodging resistance, the japonica rice cultivars Wuyunjing23 (lodging-resistant) and W3668 (lodging-susceptible) were grown under field conditions with normal light (Control) and shading (the incident light was reduced by 60%) with a black nylon net. The yield and yield components, plant morphological characteristics, the stem mechanical strength, cell wall components, culm microstructure, gene expression correlated with cellulose and lignin biosynthesis were measured. The results showed that shading significantly reduced grain yield attributed to reduction of spikelets per panicles and grain weight. The stem-breaking strength decreased significantly under shading treatment; consequently, resulting in higher lodging index in rice plant in both varieties, as revealed by decreased by culm diameter, culm wall thickness and increased plant height, gravity center height. Compared with control, cell wall components including non-structural carbohydrate, sucrose, cellulose, and lignin reduced quite higher. With histochemical straining, shading largely reduced lignin deposition in the sclerenchyma cells and vascular bundle cells compared with control, and decreased cellulose deposition in the parenchyma cells of culm tissue in both Wuyunjing23 and W3668. And under shading condition, gene expression involved in secondary cell wall synthesis, OsPAL, OsCOMT, OsCCoAOMT, OsCCR , and OsCAD2 , and primary cell wall synthesis, OsCesA1, OsCesA3 , and OsCesA8 were decreased significantly. These results suggest that gene expression involved in the reduction of lignin and cellulose in both sclerenchyma and parenchyma cells, which attribute to lignin and cellulose in culm tissue and weak mechanical tissue, consequently, result in poor stem strength and higher lodging risks. Highlights : (1) Shading decreases the stem mechanical strength of japonica rice by decreasing non-structural carbohydrate, sucrose, lignin, and cellulose accumulation in culms. (2) The decrease of carbon source under shading condition is the cause for the lower lignin and cellulose accumulation in culm. (3) The expression of genes involved in lignin and primarily cell wall cellulose biosynthesis ( OsCesA1, OsCesA3 , and OsCesA8 ) at the stem formation stage are down-regulated under shading condition, inducing defective cell wall development and poor lodging resistance.

  20. Cardiac Dysfunction and Oxidative Stress in the Metabolic Syndrome: an Update on Antioxidant Therapies

    PubMed Central

    Ilkun, Olesya; Boudina, Sihem

    2013-01-01

    The metabolic syndrome (MetS) is a cluster of risk factors including obesity, insulin resistance, dyslipidemia, elevated blood pressure and glucose intolerance. The MetS increases the risk for cardiovascular disease (CVD) and type 2 diabetes. Each component of the MetS causes cardiac dysfunction and their combination carries additional risk. The mechanisms underlying cardiac dysfunction in the MetS are complex and might include lipid accumulation, increased fibrosis and stiffness, altered calcium homeostasis, abnormal autophagy, altered substrate utilization, mitochondrial dysfunction and increased oxidative stress. Mitochondrial and extra-mitochondrial sources of reactive oxygen species (ROS) and reduced antioxidant defense mechanisms characterize the myocardium of humans and animals with the MetS. The mechanisms for increased cardiac oxidative stress in the MetS are not fully understood but include increased fatty acid oxidation, mitochondrial dysfunction and enhanced NADPH oxidase activity. Therapies aimed to reduce oxidative stress and enhance antioxidant defense have been employed to reduce cardiac dysfunction in the MetS in animals. In contrast, large scale clinical trials using antioxidants therapies for the treatment of CVD have been disappointing because of the lack of efficacy and undesired side effects. The focus of this review is to summarize the current knowledge about the mechanisms underlying cardiac dysfunction in the MetS with a special interest in the role of oxidative stress. Finally, we will update the reader on the results obtained with natural antioxidant and mitochondria-targeted antioxidant therapies for the treatment of CVD in the MetS. PMID:23323621

  1. Grained composite materials prepared by combustion synthesis under mechanical pressure

    DOEpatents

    Dunmead, Stephen D.; Holt, Joseph B.; Kingman, Donald D.; Munir, Zuhair A.

    1990-01-01

    Dense, finely grained composite materials comprising one or more ceramic phase or phase and one or more metallic and/or intermetallic phase or phases are produced by combustion synthesis. Spherical ceramic grains are homogeneously dispersed within the matrix. Methods are provided, which include the step of applying mechanical pressure during or immediately after ignition, by which the microstructures in the resulting composites can be controllably selected.

  2. Genetic alterations in hepatocellular carcinoma: An update

    PubMed Central

    Niu, Zhao-Shan; Niu, Xiao-Jun; Wang, Wen-Hong

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although recent advances in therapeutic approaches for treating HCC have improved the prognoses of patients with HCC, this cancer is still associated with a poor survival rate mainly due to late diagnosis. Therefore, a diagnosis must be made sufficiently early to perform curative and effective treatments. There is a need for a deeper understanding of the molecular mechanisms underlying the initiation and progression of HCC because these mechanisms are critical for making early diagnoses and developing novel therapeutic strategies. Over the past decade, much progress has been made in elucidating the molecular mechanisms underlying hepatocarcinogenesis. In particular, recent advances in next-generation sequencing technologies have revealed numerous genetic alterations, including recurrently mutated genes and dysregulated signaling pathways in HCC. A better understanding of the genetic alterations in HCC could contribute to identifying potential driver mutations and discovering novel therapeutic targets in the future. In this article, we summarize the current advances in research on the genetic alterations, including genomic instability, single-nucleotide polymorphisms, somatic mutations and deregulated signaling pathways, implicated in the initiation and progression of HCC. We also attempt to elucidate some of the genetic mechanisms that contribute to making early diagnoses of and developing molecularly targeted therapies for HCC. PMID:27895396

  3. The Utilization of Plant Facilities on the International Space Station—The Composition, Growth, and Development of Plant Cell Walls under Microgravity Conditions

    PubMed Central

    Jost, Ann-Iren Kittang; Hoson, Takayuki; Iversen, Tor-Henning

    2015-01-01

    In the preparation for missions to Mars, basic knowledge of the mechanisms of growth and development of living plants under microgravity (micro-g) conditions is essential. Focus has centered on the g-effects on rigidity, including mechanisms of signal perception, transduction, and response in gravity resistance. These components of gravity resistance are linked to the evolution and acquisition of responses to various mechanical stresses. An overview is given both on the basic effect of hypergravity as well as of micro-g conditions in the cell wall changes. The review includes plant experiments in the US Space Shuttle and the effect of short space stays (8–14 days) on single cells (plant protoplasts). Regeneration of protoplasts is dependent on cortical microtubules to orient the nascent cellulose microfibrils in the cell wall. The space protoplast experiments demonstrated that the regeneration capacity of protoplasts was retarded. Two critical factors are the basis for longer space experiments: a. the effects of gravity on the molecular mechanisms for cell wall development, b. the availability of facilities and hardware for performing cell wall experiments in space and return of RNA/DNA back to the Earth. Linked to these aspects is a description of existing hardware functioning on the International Space Station. PMID:27135317

  4. Dietary protein intake and quality in early life: impact on growth and obesity.

    PubMed

    Lind, Mads V; Larnkjær, Anni; Mølgaard, Christian; Michaelsen, Kim F

    2017-01-01

    Obesity is an increasing problem and high-protein intake early in life seems to increase later risk of obesity. This review summarizes recent publications in the area including observational and intervention studies and publications on underlying mechanisms. Recent observational and randomized controlled trials confirmed that high-protein intake in early life seems to increase early weight gain and the risk of later overweight and obesity. Recent studies have looked at the effect of different sources of protein, and especially high-animal protein intake seems to have an effect on obesity. Specific amino acids, such as leucine, have also been implicated in increasing later obesity risk maybe via specific actions on insulin-like growth factor I. Furthermore, additional underlying mechanisms including epigenetics have been linked to long-term obesogenic programming. Finally, infants with catch-up growth or specific genotypes might be particularly vulnerable to high-protein intake. Recent studies confirm the associations between high-protein intake during the first 2 years and later obesity. Furthermore, knowledge of the mechanisms involved and the role of different dietary protein sources and amino acids has increased, but intervention studies are needed to confirm the mechanisms. Avoiding high-protein intake in early life holds promise as a preventive strategy for childhood obesity.

  5. The Utilization of Plant Facilities on the International Space Station-The Composition, Growth, and Development of Plant Cell Walls under Microgravity Conditions.

    PubMed

    Jost, Ann-Iren Kittang; Hoson, Takayuki; Iversen, Tor-Henning

    2015-01-20

    In the preparation for missions to Mars, basic knowledge of the mechanisms of growth and development of living plants under microgravity (micro-g) conditions is essential. Focus has centered on the g-effects on rigidity, including mechanisms of signal perception, transduction, and response in gravity resistance. These components of gravity resistance are linked to the evolution and acquisition of responses to various mechanical stresses. An overview is given both on the basic effect of hypergravity as well as of micro-g conditions in the cell wall changes. The review includes plant experiments in the US Space Shuttle and the effect of short space stays (8-14 days) on single cells (plant protoplasts). Regeneration of protoplasts is dependent on cortical microtubules to orient the nascent cellulose microfibrils in the cell wall. The space protoplast experiments demonstrated that the regeneration capacity of protoplasts was retarded. Two critical factors are the basis for longer space experiments: a. the effects of gravity on the molecular mechanisms for cell wall development, b. the availability of facilities and hardware for performing cell wall experiments in space and return of RNA/DNA back to the Earth. Linked to these aspects is a description of existing hardware functioning on the International Space Station.

  6. Experimental Investigation on the Fatigue Mechanical Properties of Intermittently Jointed Rock Models Under Cyclic Uniaxial Compression with Different Loading Parameters

    NASA Astrophysics Data System (ADS)

    Liu, Yi; Dai, Feng; Dong, Lu; Xu, Nuwen; Feng, Peng

    2018-01-01

    Intermittently jointed rocks, widely existing in many mining and civil engineering structures, are quite susceptible to cyclic loading. Understanding the fatigue mechanism of jointed rocks is vital to the rational design and the long-term stability analysis of rock structures. In this study, the fatigue mechanical properties of synthetic jointed rock models under different cyclic conditions are systematically investigated in the laboratory, including four loading frequencies, four maximum stresses, and four amplitudes. Our experimental results reveal the influence of the three cyclic loading parameters on the mechanical properties of jointed rock models, regarding the fatigue deformation characteristics, the fatigue energy and damage evolution, and the fatigue failure and progressive failure behavior. Under lower loading frequency or higher maximum stress and amplitude, the jointed specimen is characterized by higher fatigue deformation moduli and higher dissipated hysteresis energy, resulting in higher cumulative damage and lower fatigue life. However, the fatigue failure modes of jointed specimens are independent of cyclic loading parameters; all tested jointed specimens exhibit a prominent tensile splitting failure mode. Three different crack coalescence patterns are classified between two adjacent joints. Furthermore, different from the progressive failure under static monotonic loading, the jointed rock specimens under cyclic compression fail more abruptly without evident preceding signs. The tensile cracks on the front surface of jointed specimens always initiate from the joint tips and then propagate at a certain angle with the joints toward the direction of maximum compression.

  7. Neutrophilic inflammation in asthma: mechanisms and therapeutic considerations.

    PubMed

    Chang, Hun Soo; Lee, Tae-Hyeong; Jun, Ji Ae; Baek, Ae Rin; Park, Jong-Sook; Koo, So-My; Kim, Yang-Ki; Lee, Ho Sung; Park, Choon-Sik

    2017-01-01

    Neutrophilic airway inflammation represents a pathologically distinct form of asthma and frequently appears in symptomatic adulthood asthmatics. However, clinical impacts and mechanisms of the neutrophilic inflammation have not been thoroughly evaluated up to date. Areas covered: Currently, distinct clinical manifestations, triggers, and molecular mechanisms of the neutrophilic inflammation (namely Toll-like receptor, Th1, Th17, inflammasome) are under investigation in asthma. Furthermore, possible role of the neutrophilic inflammation is being investigated in respect to the airway remodeling. We searched the related literatures published during the past 10 years on the website of Pub Med under the title of asthma and neutrophilic inflammation in human. Expert commentary: Epidemiologic and experimental studies have revealed that the neutrophilic airway inflammation is induced by a wide variety of stimuli including ozone, particulate matters, cigarette smoke, occupational irritants, endotoxins, microbial infection and colonization, and aeroallergens. These triggers provoke diverse immune and inflammatory responses leading to progressive and sometimes irreversible airway obstruction. Clinically, neutrophilic airway inflammation is frequently associated with severe asthma and poor response to glucocorticoid therapy, indicating the need for other treatment strategies. Accordingly, therapeutics will be targeted against the main mediators behind the underlying molecular mechanisms of the neutrophilic inflammation.

  8. The short-term stress response - Mother nature's mechanism for enhancing protection and performance under conditions of threat, challenge, and opportunity.

    PubMed

    Dhabhar, Firdaus S

    2018-03-26

    Our group has proposed that in contrast to chronic stress that can have harmful effects, the short-term (fight-or-flight) stress response (lasting for minutes to hours) is nature's fundamental survival mechanism that enhances protection and performance under conditions involving threat/challenge/opportunity. Short-term stress enhances innate/primary, adaptive/secondary, vaccine-induced, and anti-tumor immune responses, and post-surgical recovery. Mechanisms and mediators include stress hormones, dendritic cell, neutrophil, macrophage, and lymphocyte trafficking/function and local/systemic chemokine and cytokine production. Short-term stress may also enhance mental/cognitive and physical performance through effects on brain, musculo-skeletal, and cardiovascular function, reappraisal of threat/anxiety, and training-induced stress-optimization. Therefore, short-term stress psychology/physiology could be harnessed to enhance immuno-protection, as well as mental and physical performance. This review aims to provide a conceptual framework and targets for further investigation of mechanisms and conditions under which the protective/adaptive aspects of short-term stress/exercise can be optimized/harnessed, and for developing pharmacological/biobehavioral interventions to enhance health/healing, and mental/cognitive/physical performance. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Control of optical properties of YAG crystals by thermal annealing

    NASA Astrophysics Data System (ADS)

    Tkachenko, S.; Arhipov, P.; Gerasymov, I.; Kurtsev, D.; Vasyukov, S.; Nesterkina, V.; Shiran, N.; Mateichenko, P.; Sidletskiy, O.

    2018-02-01

    Optical properties of YAG crystals grown and annealed under different atmosphere conditions have been compared. Simultaneously we have registered the surface composition of crystals and content of basic admixtures in the crystals grown under the reducing conditions. Unlike YAG grown under weakly oxidizing conditions in Ir crucibles and bleached under oxidizing annealing, YAGMo crystals grown in Mo crucibles under reducing Ar + CO atmosphere can be bleached by both oxidizing and reducing thermal annealing. The bleaching of YAGMo is not reversed by further annealing under any available conditions. Mechanisms of this phenomenon have been discussed, including a possible role of admixtures in elimination of color centers in YAG grown under the reducing conditions.

  10. Cellular and Molecular Mechanisms of Sexual Differentiation in the Mammalian Nervous System

    PubMed Central

    Forger, Nancy G.; Strahan, J. Alex; Castillo-Ruiz, Alexandra

    2016-01-01

    Neuroscientists are likely to discover new sex differences in the coming years, spurred by the National Institutes of Health initiative to include both sexes in preclinical studies. This review summarizes the current state of knowledge of the cellular and molecular mechanisms underlying sex differences in the mammalian nervous system, based primarily on work in rodents. Cellular mechanisms examined include neurogenesis, migration, the differentiation of neurochemical and morphological cell phenotype, and cell death. At the molecular level we discuss evolving roles for epigenetics, sex chromosome complement, the immune system, and newly identified cell signaling pathways. We review recent findings on the role of the environment, as well as genome-wide studies with some surprising results, causing us to rethink often-used models of sexual differentiation. We end by pointing to future directions, including an increased awareness of the important contributions of tissues outside of the nervous system to sexual differentiation of the brain. PMID:26790970

  11. A mechanical adapter for installing mission equipment on large space structures

    NASA Technical Reports Server (NTRS)

    Lefever, A. E.; Totah, R. S.

    1980-01-01

    A mechanical attachment adapter was designed, constructed, and tested. The adapter was was included in a simulation program that investigated techniques for assembling erectable structures under simulated zero-g conditions by pressure-suited subjects in a simulated EVA mode. The adapter was utilized as an interface attachment between a simulated equipment module and one node point of a tetrahedral structural cell. The mating performance of the adapter, a self-energized mechanism, was easily and quickly demonstrated and required little effort on the part of the test subjects.

  12. Revealing Slip Bands In A Metal-Matrix/Fiber Composite

    NASA Technical Reports Server (NTRS)

    Lerch, Bradley A.

    1995-01-01

    Experimental procedure includes heat treatments and metallographic techniques developed to facilitate studies of deformation of metal-matrix/fiber composite under stress. Reveals slip bands, indicative of plastic flow occurring in matrix during mechanical tests of specimens of composite.

  13. Stability-Augmentation Devices for Miniature Aircraft

    NASA Technical Reports Server (NTRS)

    Wood, RIchard M.

    2005-01-01

    Non-aerodynamic mechanical devices are under consideration as means to augment the stability of miniature autonomous and remotely controlled aircraft. Such aircraft can be used for diverse purposes, including military reconnaissance, radio communications, and safety-related monitoring of wide areas. The need for stability-augmentation devices arises because adverse meteorological conditions generally affect smaller aircraft more strongly than they affect larger aircraft: Miniature aircraft often become uncontrollable under conditions that would not be considered severe enough to warrant grounding of larger aircraft. The need for the stability-augmentation devices to be non-aerodynamic arises because there is no known way to create controlled aerodynamic forces sufficient to counteract the uncontrollable meteorological forces on miniature aircraft. A stability-augmentation device of the type under consideration includes a mass pod (a counterweight) at the outer end of a telescoping shaft, plus associated equipment to support the operation of the aircraft. The telescoping shaft and mass pod are stowed in the rear of the aircraft. When deployed, they extend below the aircraft. Optionally, an antenna for radio communication can be integrated into the shaft. At the time of writing this article, the deployment of the telescoping shaft and mass pod was characterized as passive and automatic, but information about the deployment mechanism(s) was not available. The feasibility of this stability-augmentation concept was demonstrated in flights of hand-launched prototype aircraft.

  14. Genetic Diversity of Salt Tolerance in Miscanthus

    PubMed Central

    Chen, Chang-Lin; van der Schoot, Hanneke; Dehghan, Shiva; Alvim Kamei, Claire L.; Schwarz, Kai-Uwe; Meyer, Heike; Visser, Richard G. F.; van der Linden, C. Gerard

    2017-01-01

    Miscanthus is a woody rhizomatous C4 grass that can be used as a CO2 neutral biofuel resource. It has potential to grow in marginal areas such as saline soils, avoiding competition for arable lands with food crops. This study explored genetic diversity for salt tolerance in Miscanthus and discovered mechanisms and traits that can be used to improve the yield under salt stress. Seventy genotypes of Miscanthus (including 57 M. sinensis, 5 M. sacchariflorus, and 8 hybrids) were evaluated for salt tolerance under saline (150 mM NaCl) and normal growing conditions using a hydroponic system. Analyses of shoot growth traits and ion concentrations revealed the existence of large variation for salt tolerance in the genotypes. We identified genotypes with potential for high biomass production both under control and saline conditions that may be utilized for growth under marginal, saline conditions. Several relatively salt tolerant genotypes had clearly lower Na+ concentrations and showed relatively high K+/Na+ ratios in the shoots under salt stress, indicating that a Na+ exclusion mechanism was utilized to prevent Na+ accumulation in the leaves. Other genotypes showed limited reduction in leaf expansion and growth rate under saline conditions, which may be indicative of osmotic stress tolerance. The genotypes demonstrating potentially different salt tolerance mechanisms can serve as starting material for breeding programs aimed at improving salinity tolerance of Miscanthus. PMID:28261243

  15. Epinephrine Enhances the Response of Macrophages under LPS Stimulation

    PubMed Central

    Zhou, Jianyun; Liang, Huaping; Jiang, Jianxin

    2014-01-01

    Trauma associated with infection may directly trigger a neuroendocrine reaction in vivo while the hormone epinephrine is known to mediate immune responses to inflammation after injury. However, the role of epinephrine during the earliest stage of trauma still remains unclear. We therefore explored the role of epinephrine on activated macrophages under LPS stimulation in vitro as well as the mechanisms underlying its effect. Dose- and time-dependent effects of epinephrine on macrophage immune function were assessed after LPS activation. We also employed CD14 siRNA interference to investigate whether CD14 played a role in the mechanism underlying the effect of epinephrine on LPS-induced macrophage responses. Our results showed that epinephrine pretreatment (10 ng/mL) significantly promoted immune responses from LPS stimulated macrophages, including phagocytic rate, phagocytic index, TNFα/IL-1β/IL-10 secretion, and CD14 expression (P < 0.05). Moreover, TNFα/IL-1β/IL-10 levels attained their peak value 1 hour after incubation with 10 ng/mL epinephrine (P < 0.05), and CD14 siRNA transfection dramatically decreased phagocytosis and cytokine secretion by LPS-activated macrophages (P < 0.05). We therefore conclude that 10 ng/mL epinephrine enhances immune responses from macrophages under LPS stimulation and that the underlying mechanism may relate to CD14 upregulation on the surface of macrophages. PMID:25243125

  16. Auditory motion-specific mechanisms in the primate brain

    PubMed Central

    Baumann, Simon; Dheerendra, Pradeep; Joly, Olivier; Hunter, David; Balezeau, Fabien; Sun, Li; Rees, Adrian; Petkov, Christopher I.; Thiele, Alexander; Griffiths, Timothy D.

    2017-01-01

    This work examined the mechanisms underlying auditory motion processing in the auditory cortex of awake monkeys using functional magnetic resonance imaging (fMRI). We tested to what extent auditory motion analysis can be explained by the linear combination of static spatial mechanisms, spectrotemporal processes, and their interaction. We found that the posterior auditory cortex, including A1 and the surrounding caudal belt and parabelt, is involved in auditory motion analysis. Static spatial and spectrotemporal processes were able to fully explain motion-induced activation in most parts of the auditory cortex, including A1, but not in circumscribed regions of the posterior belt and parabelt cortex. We show that in these regions motion-specific processes contribute to the activation, providing the first demonstration that auditory motion is not simply deduced from changes in static spatial location. These results demonstrate that parallel mechanisms for motion and static spatial analysis coexist within the auditory dorsal stream. PMID:28472038

  17. A Drosophila model for developmental nicotine exposure

    PubMed Central

    2017-01-01

    Despite the known health risks of tobacco smoking, many people including pregnant women continue smoking. The effects of developmental nicotine exposure are known, but the underlying mechanisms are not well understood. Drosophila melanogaster is a model organism that can be used for uncovering genetic and molecular mechanisms for drugs of abuse. Here I show that Drosophila can be a model to elucidate the mechanisms for nicotine’s effects on a developing organism. Drosophila reared on nicotine food display developmental and behavioral effects similar to those in mammals including decreased survival and weight, increased developmental time, and decreased sensitivity to acute nicotine and ethanol. The Drosophila nicotinic acetylcholine receptor subunit alpha 7 (Dα7) mediates some of these effects. A novel role for Dα7 on ethanol sedation in Drosophila is also shown. Future research taking advantage of the genetic and molecular tools for Drosophila will allow additional discovery of the mechanisms behind the effects of nicotine during development. PMID:28498868

  18. The over-pruning hypothesis of autism.

    PubMed

    Thomas, Michael S C; Davis, Rachael; Karmiloff-Smith, Annette; Knowland, Victoria C P; Charman, Tony

    2016-03-01

    This article outlines the over-pruning hypothesis of autism. The hypothesis originates in a neurocomputational model of the regressive sub-type (Thomas, Knowland & Karmiloff-Smith, 2011a, 2011b). Here we develop a more general version of the over-pruning hypothesis to address heterogeneity in the timing of manifestation of ASD, including new computer simulations which reconcile the different observed developmental trajectories (early onset, late onset, regression) via a single underlying atypical mechanism; and which show how unaffected siblings of individuals with ASD may differ from controls either by inheriting a milder version of the pathological mechanism or by co-inheriting the risk factors without the pathological mechanism. The proposed atypical mechanism involves overly aggressive synaptic pruning in infancy and early childhood, an exaggeration of a normal phase of brain development. We show how the hypothesis generates novel predictions that differ from existing theories of ASD including that (1) the first few months of development in ASD will be indistinguishable from typical, and (2) the earliest atypicalities in ASD will be sensory and motor rather than social. Both predictions gain cautious support from emerging longitudinal studies of infants at-risk of ASD. We review evidence consistent with the over-pruning hypothesis, its relation to other current theories (including C. Frith's under-pruning proposal; C. Frith, 2003, 2004), as well as inconsistent data and current limitations. The hypothesis situates causal accounts of ASD within a framework of protective and risk factors (Newschaffer et al., 2012); clarifies different versions of the broader autism phenotype (i.e. the implication of observed similarities between individuals with autism and their family members); and integrates data from multiple disciplines, including behavioural studies, neuroscience studies, genetics, and intervention studies. © 2015 John Wiley & Sons Ltd.

  19. Matrix viscoplasticity and its shielding by active mechanics in microtissue models: experiments and mathematical modeling

    NASA Astrophysics Data System (ADS)

    Liu, Alan S.; Wang, Hailong; Copeland, Craig R.; Chen, Christopher S.; Shenoy, Vivek B.; Reich, Daniel H.

    2016-09-01

    The biomechanical behavior of tissues under mechanical stimulation is critically important to physiological function. We report a combined experimental and modeling study of bioengineered 3D smooth muscle microtissues that reveals a previously unappreciated interaction between active cell mechanics and the viscoplastic properties of the extracellular matrix. The microtissues’ response to stretch/unstretch actuations, as probed by microcantilever force sensors, was dominated by cellular actomyosin dynamics. However, cell lysis revealed a viscoplastic response of the underlying model collagen/fibrin matrix. A model coupling Hill-type actomyosin dynamics with a plastic perfectly viscoplastic description of the matrix quantitatively accounts for the microtissue dynamics, including notably the cells’ shielding of the matrix plasticity. Stretch measurements of single cells confirmed the active cell dynamics, and were well described by a single-cell version of our model. These results reveal the need for new focus on matrix plasticity and its interactions with active cell mechanics in describing tissue dynamics.

  20. Molecular Mechanisms Underlying Occult Hepatitis B Virus Infection

    PubMed Central

    Samal, Jasmine; Kandpal, Manish

    2012-01-01

    Summary: Chronic hepatitis B virus (HBV) infection is a complex clinical entity frequently associated with cirrhosis and hepatocellular carcinoma (HCC). The persistence of HBV genomes in the absence of detectable surface antigenemia is termed occult HBV infection. Mutations in the surface gene rendering HBsAg undetectable by commercial assays and inhibition of HBV by suppression of viral replication and viral proteins represent two fundamentally different mechanisms that lead to occult HBV infections. The molecular mechanisms underlying occult HBV infections, including recently identified mechanisms associated with the suppression of HBV replication and inhibition of HBV proteins, are reviewed in detail. The availability of highly sensitive molecular methods has led to increased detection of occult HBV infections in various clinical settings. The clinical relevance of occult HBV infection and the utility of appropriate diagnostic methods to detect occult HBV infection are discussed. The need for specific guidelines on the diagnosis and management of occult HBV infection is being increasingly recognized; the aspects of mechanistic studies that warrant further investigation are discussed in the final section. PMID:22232374

  1. Matrix viscoplasticity and its shielding by active mechanics in microtissue models: experiments and mathematical modeling

    PubMed Central

    Liu, Alan S.; Wang, Hailong; Copeland, Craig R.; Chen, Christopher S.; Shenoy, Vivek B.; Reich, Daniel H.

    2016-01-01

    The biomechanical behavior of tissues under mechanical stimulation is critically important to physiological function. We report a combined experimental and modeling study of bioengineered 3D smooth muscle microtissues that reveals a previously unappreciated interaction between active cell mechanics and the viscoplastic properties of the extracellular matrix. The microtissues’ response to stretch/unstretch actuations, as probed by microcantilever force sensors, was dominated by cellular actomyosin dynamics. However, cell lysis revealed a viscoplastic response of the underlying model collagen/fibrin matrix. A model coupling Hill-type actomyosin dynamics with a plastic perfectly viscoplastic description of the matrix quantitatively accounts for the microtissue dynamics, including notably the cells’ shielding of the matrix plasticity. Stretch measurements of single cells confirmed the active cell dynamics, and were well described by a single-cell version of our model. These results reveal the need for new focus on matrix plasticity and its interactions with active cell mechanics in describing tissue dynamics. PMID:27671239

  2. Mechanisms Underlying Tolerance after Long-Term Benzodiazepine Use: A Future for Subtype-Selective GABAA Receptor Modulators?

    PubMed Central

    Vinkers, Christiaan H.; Olivier, Berend

    2012-01-01

    Despite decades of basic and clinical research, our understanding of how benzodiazepines tend to lose their efficacy over time (tolerance) is at least incomplete. In appears that tolerance develops relatively quickly for the sedative and anticonvulsant actions of benzodiazepines, whereas tolerance to anxiolytic and amnesic effects probably does not develop at all. In light of this evidence, we review the current evidence for the neuroadaptive mechanisms underlying benzodiazepine tolerance, including changes of (i) the GABAA receptor (subunit expression and receptor coupling), (ii) intracellular changes stemming from transcriptional and neurotrophic factors, (iii) ionotropic glutamate receptors, (iv) other neurotransmitters (serotonin, dopamine, and acetylcholine systems), and (v) the neurosteroid system. From the large variance in the studies, it appears that either different (simultaneous) tolerance mechanisms occur depending on the benzodiazepine effect, or that the tolerance-inducing mechanism depends on the activated GABAA receptor subtypes. Importantly, there is no convincing evidence that tolerance occurs with α subunit subtype-selective compounds acting at the benzodiazepine site. PMID:22536226

  3. Eucalyptus tolerance mechanisms to lanthanum and cerium: subcellular distribution, antioxidant system and thiol pools.

    PubMed

    Shen, Yichang; Zhang, Shirong; Li, Sen; Xu, Xiaoxun; Jia, Yongxia; Gong, Guoshu

    2014-12-01

    Guanglin 9 (Eucalyptus grandis × Eucalyptus urophlla) and Eucalyptus grandis 5 are two eucalyptus species which have been found to grow normally in soils contaminated with lanthanum and cerium, but the tolerance mechanisms are not clear yet. In this study, a pot experiment was conducted to investigate the tolerance mechanisms of the eucalyptus to lanthanum and cerium. Cell walls stored 45.40-63.44% of the metals under lanthanum or cerium stress. Peroxidase and catalase activities enhanced with increasing soil La or Ce concentrations up to 200 mg kg(-1), while there were no obvious changes in glutathione and ascorbate concentrations. Non-protein thiols concentrations increased with increasing treatment levels up to 200 mg kg(-1), and then decreased. Phytochelatins concentrations continued to increase under La or Ce stress. Therefore, the two eucalyptus species are La and Ce tolerant plants, and the tolerance mechanisms include cell wall deposition, antioxidant system response, and thiol compound synthesis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Microgravity inhibition of lipopolysaccharide-induced tumor necrosis factor-α expression in macrophage cells.

    PubMed

    Wang, Chongzhen; Luo, Haiying; Zhu, Linnan; Yang, Fan; Chu, Zhulang; Tian, Hongling; Feng, Meifu; Zhao, Yong; Shang, Peng

    2014-01-01

    Microgravity environments in space can cause major abnormalities in human physiology, including decreased immunity. The underlying mechanisms of microgravity-induced inflammatory defects in macrophages are unclear. RAW264.7 cells and primary mouse macrophages were used in the present study. Lipopolysaccharide (LPS)-induced cytokine expression in mouse macrophages was detected under either simulated microgravity or 1g control. Freshly isolated primary mouse macrophages and RAW264.7 cells were cultured in a standard simulated microgravity situation using a rotary cell culture system (RCCS-1) and 1g control conditions. The cytokine expression was determined by real-time PCR and ELISA assays. Western blots were used to investigate the related intracellular signals. LPS-induced tumor necrosis factor-α (TNF-α) expression, but not interleukin-1β expression, in mouse macrophages was significantly suppressed under simulated microgravity. The molecular mechanism studies showed that LPS-induced intracellular signal transduction including phosphorylation of IKK and JNK and nuclear translocation of NF-κB in macrophages was identical under normal gravity and simulated microgravity. Furthermore, TNF-α mRNA stability did not decrease under simulated microgravity. Finally, we found that heat shock factor-1 (HSF1), a known repressor of TNF-α promoter, was markedly activated under simulated microgravity. Short-term treatment with microgravity caused significantly decreased TNF-α production. Microgravity-activated HSF1 may contribute to the decreased TNF-α expression in macrophages directly caused by microgravity, while the LPS-induced NF-κB pathway is resistant to microgravity.

  5. QM/MM MD and Free Energy Simulation Study of Methyl Transfer Processes Catalyzed by PKMTs and PRMTs.

    PubMed

    Chu, Yuzhuo; Guo, Hong

    2015-09-01

    Methyl transfer processes catalyzed by protein lysine methyltransferases (PKMTs) and protein arginine methyltransferases (PRMTs) control important biological events including transcriptional regulation and cell signaling. One important property of these enzymes is that different PKMTs and PRMTs catalyze the formation of different methylated product (product specificity). These different methylation states lead to different biological outcomes. Here, we review the results of quantum mechanics/molecular mechanics molecular dynamics and free energy simulations that have been performed to study the reaction mechanism of PKMTs and PRMTs and the mechanism underlying the product specificity of the methyl transfer processes.

  6. QM/MM MD and free energy simulation study of methyl transfer processes catalyzed by PKMTs and PRMTs.

    PubMed

    Chu, Yuzhuo; Guo, Hong

    2015-01-16

    Methyl transfer processes catalyzed by protein lysine methyltransferases (PKMTs) and protein arginine methyltransferases (PRMTs) control important biological events including transcriptional regulation and cell signaling. One important property of these enzymes is that different PKMTs and PRMTs catalyze the formation of different methylated product (product specificity). These different methylation states lead to different biological outcomes. Here we review the results of quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) and free energy simulations that have been performed to study the reaction mechanism of PKMTs and PRMTs and the mechanism underlying the product specificity of the methyl transfer processes.

  7. Contribution of facet joints, axial compression, and composition to human lumbar disc torsion mechanics.

    PubMed

    Bezci, Semih E; Eleswarapu, Ananth; Klineberg, Eric O; O'Connell, Grace D

    2018-02-12

    Stresses applied to the spinal column are distributed between the intervertebral disc and facet joints. Structural and compositional changes alter stress distributions within the disc and between the disc and facet joints. These changes influence the mechanical properties of the disc joint, including its stiffness, range of motion, and energy absorption under quasi-static and dynamic loads. There have been few studies evaluating the role of facet joints in torsion. Furthermore, the relationship between biochemical composition and torsion mechanics is not well understood. Therefore, the first objective of this study was to investigate the role of facet joints in torsion mechanics of healthy and degenerated human lumbar discs under a wide range of compressive preloads. To achieve this, each disc was tested under four different compressive preloads (300-1200 N) with and without facet joints. The second objective was to develop a quantitative structure-function relationship between tissue composition and torsion mechanics. Facet joints have a significant contribution to disc torsional stiffness (∼60%) and viscoelasticity, regardless of the magnitude of axial compression. The findings from this study demonstrate that annulus fibrosus GAG content plays an important role in disc torsion mechanics. A decrease in GAG content with degeneration reduced torsion mechanics by more than an order of magnitude, while collagen content did not significantly influence disc torsion mechanics. The biochemical-mechanical and compression-torsion relationships reported in this study allow for better comparison between studies that use discs of varying levels of degeneration or testing protocols and provide important design criteria for biological repair strategies. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  8. Numerical Analysis of Solids at Failure

    DTIC Science & Technology

    2011-08-20

    failure analyses include the formulation of invariant finite elements for thin Kirchhoff rods, and preliminary initial studies of growth in...analysis of the failure of other structural/mechanical systems, including the finite element modeling of thin Kirchhoff rods and the constitutive...algorithm based on the connectivity graph of the underlying finite element mesh. In this setting, the discontinuities are defined by fronts propagating

  9. Alternative Polyadenylation in Human Diseases

    PubMed Central

    Chang, Jae-Woong; Yeh, Hsin-Sung

    2017-01-01

    Varying length of messenger RNA (mRNA) 3′-untranslated region is generated by alternating the usage of polyadenylation sites during pre-mRNA processing. It is prevalent through all eukaryotes and has emerged as a key mechanism for controlling gene expression. Alternative polyadenylation (APA) plays an important role for cell growth, proliferation, and differentiation. In this review, we discuss the functions of APA related with various physiological conditions including cellular metabolism, mRNA processing, and protein diversity in a variety of disease models. We also discuss the molecular mechanisms underlying APA regulation, such as variations in the concentration of mRNA processing factors and RNA-binding proteins, as well as global transcriptome changes under cellular signaling pathway. PMID:29271615

  10. 75 FR 27980 - Request for Extension and Revision of a Currently Approved Information Collection Under the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-19

    ... livestock, meat packing and poultry industries. The purpose of this notice is to solicit comments from the... on those who are to respond, including the use of appropriate automated, electronic, mechanical, or...

  11. Nutritional epigenomics

    USDA-ARS?s Scientific Manuscript database

    The last decade of discoveries and technological advances has taken the epigenomics field to a completely new level. The modern version of epigenomics includes the molecular mechanisms that influence the phenotypic outcome of a gene or genome, in the absence of changes to the underlying DNA sequence...

  12. Epigenetics and the Developmental Origins of Health and Disease#

    EPA Science Inventory

    Epigenetic programming is likely to be an important mechanism underlying the lasting influence of the reproductive and developmental environment on lifelong health, a concept known as the Developmental Origins of Health and Disease (DOHaD). Environmental exposures including paren...

  13. Maternal Cadmium, Iron and Zinc Levels, DNA Methylation and Birth Weight

    EPA Science Inventory

    BACKGROUND:Cadmium (Cd) is a ubiquitous and environmentally persistent toxic metal that has been implicated in neurotoxicity, carcinogenesis and obesity and essential metals including zinc (Zn) and iron (Fe) may alter these outcomes. However mechanisms underlying these relationsh...

  14. Consensus Paper: Pathological Role of the Cerebellum in Autism

    PubMed Central

    Fatemi, S. Hossein; Aldinger, Kimberly A.; Ashwood, Paul; Bauman, Margaret L.; Blaha, Charles D.; Blatt, Gene J.; Chauhan, Abha; Chauhan, Ved; Dager, Stephen R.; Dickson, Price E.; Estes, Annette M.; Goldowitz, Dan; Heck, Detlef H.; Kemper, Thomas L.; King, Bryan H.; Martin, Loren A.; Millen, Kathleen J.; Mittleman, Guy; Mosconi, Matthew W.; Persico, Antonio M.; Sweeney, John A.; Webb, Sara J.; Welsh, John P.

    2013-01-01

    There has been significant advancement in various aspects of scientific knowledge concerning the role of cerebellum in the etiopathogenesis of autism. In the current consensus paper, we will observe the diversity of opinions regarding the involvement of this important site in the pathology of autism. Recent emergent findings in literature related to cerebellar involvement in autism are discussed, including: cerebellar pathology, cerebellar imaging and symptom expression in autism, cerebellar genetics, cerebellar immune function, oxidative stress and mitochondrial dysfunction, GABAergic and glutamatergic systems, cholinergic, dopaminergic, serotonergic, and oxytocin related changes in autism, motor control and cognitive deficits, cerebellar coordination of movements and cognition, gene-environment interactions, therapeutics in autism and relevant animal models of autism. Points of consensus include presence of abnormal cerebellar anatomy, abnormal neurotransmitter systems, oxidative stress, cerebellar motor and cognitive deficits, and neuroinflammation in subjects with autism. Undefined areas or areas requiring further investigation include lack of treatment options for core symptoms of autism, vermal hypoplasia and other vermal abnormalities as a consistent feature of autism, mechanisms underlying cerebellar contributions to cognition, and unknown mechanisms underlying neuroinflammation. PMID:22370873

  15. Consensus paper: pathological role of the cerebellum in autism.

    PubMed

    Fatemi, S Hossein; Aldinger, Kimberly A; Ashwood, Paul; Bauman, Margaret L; Blaha, Charles D; Blatt, Gene J; Chauhan, Abha; Chauhan, Ved; Dager, Stephen R; Dickson, Price E; Estes, Annette M; Goldowitz, Dan; Heck, Detlef H; Kemper, Thomas L; King, Bryan H; Martin, Loren A; Millen, Kathleen J; Mittleman, Guy; Mosconi, Matthew W; Persico, Antonio M; Sweeney, John A; Webb, Sara J; Welsh, John P

    2012-09-01

    There has been significant advancement in various aspects of scientific knowledge concerning the role of cerebellum in the etiopathogenesis of autism. In the current consensus paper, we will observe the diversity of opinions regarding the involvement of this important site in the pathology of autism. Recent emergent findings in literature related to cerebellar involvement in autism are discussed, including: cerebellar pathology, cerebellar imaging and symptom expression in autism, cerebellar genetics, cerebellar immune function, oxidative stress and mitochondrial dysfunction, GABAergic and glutamatergic systems, cholinergic, dopaminergic, serotonergic, and oxytocin-related changes in autism, motor control and cognitive deficits, cerebellar coordination of movements and cognition, gene-environment interactions, therapeutics in autism, and relevant animal models of autism. Points of consensus include presence of abnormal cerebellar anatomy, abnormal neurotransmitter systems, oxidative stress, cerebellar motor and cognitive deficits, and neuroinflammation in subjects with autism. Undefined areas or areas requiring further investigation include lack of treatment options for core symptoms of autism, vermal hypoplasia, and other vermal abnormalities as a consistent feature of autism, mechanisms underlying cerebellar contributions to cognition, and unknown mechanisms underlying neuroinflammation.

  16. Stress-mediated translational control in cancer cells.

    PubMed

    Leprivier, Gabriel; Rotblat, Barak; Khan, Debjit; Jan, Eric; Sorensen, Poul H

    2015-07-01

    Tumor cells are continually subjected to diverse stress conditions of the tumor microenvironment, including hypoxia, nutrient deprivation, and oxidative or genotoxic stress. Tumor cells must evolve adaptive mechanisms to survive these conditions to ultimately drive tumor progression. Tight control of mRNA translation is critical for this response and the adaptation of tumor cells to such stress forms. This proceeds though a translational reprogramming process which restrains overall translation activity to preserve energy and nutrients, but which also stimulates the selective synthesis of major stress adaptor proteins. Here we present the different regulatory signaling pathways which coordinate mRNA translation in the response to different stress forms, including those regulating eIF2α, mTORC1 and eEF2K, and we explain how tumor cells hijack these pathways for survival under stress. Finally, mechanisms for selective mRNA translation under stress, including the utilization of upstream open reading frames (uORFs) and internal ribosome entry sites (IRESes) are discussed in the context of cell stress. This article is part of a Special Issue entitled: Translation and Cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Comparing Risk- and Non-Risk-Groups Is a Favored Approach in Developmental Psychopathology. Commentary on: "Variations in Early Attachment Mechanisms Contribute to Attachment Quality: Case Studies Including Babies Born Preterm"

    ERIC Educational Resources Information Center

    Suess, Gerhard J.

    2016-01-01

    In this commentary, Suess opines that comparing risk- and non-risk-groups, as is done in the study by Witting, Ruiz, and Ahnert (2016), is a favored approach in developmental psychopathology in order to learn more about underlying mechanisms of normal development, as well as developmental deviations. Witting and colleagues followed up this…

  18. Functional connectivity arises from a slow rhythmic mechanism

    PubMed Central

    Li, Jingfeng M.; Bentley, William J.; Snyder, Lawrence H.

    2015-01-01

    The mechanism underlying temporal correlations among blood oxygen level-dependent signals is unclear. We used oxygen polarography to better characterize oxygen fluctuations and their correlation and to gain insight into the driving mechanism. The power spectrum of local oxygen fluctuations is inversely proportional to frequency raised to a power (1/f) raised to the beta, with an additional positive band-limited component centered at 0.06 Hz. In contrast, the power of the correlated oxygen signal is band limited from ∼0.01 Hz to 0.4 Hz with a peak at 0.06 Hz. These results suggest that there is a band-limited mechanism (or mechanisms) driving interregional oxygen correlation that is distinct from the mechanism(s) driving local (1/f) oxygen fluctuations. Candidates for driving interregional oxygen correlation include rhythmic or pseudo-oscillatory mechanisms. PMID:25918427

  19. Computational mechanics research and support for aerodynamics and hydraulics at TFHRC. Quarterly report January through March 2011. Year 1 Quarter 2 progress report.

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

    Lottes, S. A.; Kulak, R. F.; Bojanowski, C.

    2011-05-19

    This project was established with a new interagency agreement between the Department of Energy and the Department of Transportation to provide collaborative research, development, and benchmarking of advanced three-dimensional computational mechanics analysis methods to the aerodynamics and hydraulics laboratories at the Turner-Fairbank Highway Research Center for a period of five years, beginning in October 2010. The analysis methods employ well-benchmarked and supported commercial computational mechanics software. Computational mechanics encompasses the areas of Computational Fluid Dynamics (CFD), Computational Wind Engineering (CWE), Computational Structural Mechanics (CSM), and Computational Multiphysics Mechanics (CMM) applied in Fluid-Structure Interaction (FSI) problems. The major areas of focusmore » of the project are wind and water loads on bridges - superstructure, deck, cables, and substructure (including soil), primarily during storms and flood events - and the risks that these loads pose to structural failure. For flood events at bridges, another major focus of the work is assessment of the risk to bridges caused by scour of stream and riverbed material away from the foundations of a bridge. Other areas of current research include modeling of flow through culverts to assess them for fish passage, modeling of the salt spray transport into bridge girders to address suitability of using weathering steel in bridges, vehicle stability under high wind loading, and the use of electromagnetic shock absorbers to improve vehicle stability under high wind conditions. This quarterly report documents technical progress on the project tasks for the period of January through March 2011.« less

  20. Nootropic potential of Ashwagandha leaves: Beyond traditional root extracts.

    PubMed

    Wadhwa, Renu; Konar, Arpita; Kaul, Sunil C

    2016-05-01

    Rapidly increasing aging population and environmental stressors are the two main global concerns of the modern society. These have brought in light rapidly increasing incidence of a variety of pathological conditions including brain tumors, neurodegenerative & neuropsychiatric disorders, and new challenges for their treatment. The overlapping symptoms, complex etiology and lack of full understanding of the brain structure and function to-date further complicate these tasks. On the other hand, several herbal reagents with a long history of their use have been asserted to possess neurodifferentiation, neuroregenerative and neuroprotective potentials, and hence been recommended as supplement to enhance and maintain brain health and function. Although they have been claimed to function by holistic approach resulting in maintaining body homeostasis and brain health, there are not enough laboratory studies in support to these and mechanism(s) of such beneficial activities remain largely undefined. One such herb is Ashwagandha, also called "Queen of Ayurveda" for its popular use in Indian traditional home medicine because of its extensive benefits including anticancer, anti-stress and remedial potential for aging and neurodegenerative pathologies. However, active principles and underlying mechanism(s) of action remain largely unknown. Here we provide a review on the effects of Ashwagandha extracts and active principles, and underlying molecular mechanism(s) for brain pathologies. We highlight our findings on the nootropic potential of Ashwagandha leaves. The effects of Ashwagandha leaf extracts are multidimensional ranging from differentiation of neuroblastoma and glioma cells, reversal of Alzheimer and Parkinson's pathologies, protection against environmental neurotoxins and enhancement of memory. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Interfacial characteristics and leakage current transfer mechanisms in organometal trihalide perovskite gate-controlled devices via doping of PCBM

    NASA Astrophysics Data System (ADS)

    Wang, Yucheng; Zhang, Yuming; Liu, Yintao; Pang, Tiqiang; Hu, Ziyang; Zhu, Yuejin; Luan, Suzhen; Jia, Renxu

    2017-11-01

    Two types of perovskite (with and without doping of PCBM) based metal-oxide-semiconductor (MOS) gate-controlled devices were fabricated and characterized. The study of the interfacial characteristics and charge transfer mechanisms by doping of PCBM were analyzed by material and electrical measurements. Doping of PCBM does not affect the size and crystallinity of perovskite films, but has an impact on carrier extraction in perovskite MOS devices. The electrical hysteresis observed in capacitance-voltage and current-voltage measurements can be alleviated by doping of PCBM. Experimental results demonstrate that extremely low trap densities are found for the perovskite device without doping, while the doped sample leads to higher density of interface state. Three mechanisms including Ohm’s law, trap-filled-limit (TFL) emission, and child’s law were used to analyze possible charge transfer mechanisms. Ohm’s law mechanism is well suitable for charge transfer of both the perovskite MOS devices under light condition at large voltage, while TFL emission well addresses the behavior of charge transfer under dark at small voltage. This change of charge transfer mechanism is attributed to the impact of the ion drift within perovskites.

  2. Cachexia.

    PubMed

    Graul, A I; Stringer, M; Sorbera, L

    2016-09-01

    Cachexia is a multiorgan, multifactorial and often irreversible wasting syndrome associated with cancer and other serious, chronic illnesses including AIDS, chronic heart failure, chronic kidney disease and chronic obstructive pulmonary disease. Treatment of the patient with cachexia is currently targeted to correcting the two underlying features of the condition: anorexia and metabolic disturbances. Greater understanding of the mechanisms behind cachexia and muscle wasting have led to new therapeutic possibilities, however. Several classes of drugs are under active development for cachexia including drugs acting on hormone receptors or cytokine receptors, myostatin/activin pathway antagonists, beta-adrenoceptor agonists and cannabinoids. This review will cover the pathophysiology, epidemiology, diagnosis, treatment, drug candidates under active development and targets for therapeutic intervention of cachexia. Copyright 2016 Prous Science, S.A.U. or its licensors. All rights reserved.

  3. Computational mechanics research and support for aerodynamics and hydraulics at TFHRC, year 1 quarter 3 progress report.

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

    Lottes, S.A.; Kulak, R.F.; Bojanowski, C.

    2011-08-26

    The computational fluid dynamics (CFD) and computational structural mechanics (CSM) focus areas at Argonne's Transportation Research and Analysis Computing Center (TRACC) initiated a project to support and compliment the experimental programs at the Turner-Fairbank Highway Research Center (TFHRC) with high performance computing based analysis capabilities in August 2010. The project was established with a new interagency agreement between the Department of Energy and the Department of Transportation to provide collaborative research, development, and benchmarking of advanced three-dimensional computational mechanics analysis methods to the aerodynamics and hydraulics laboratories at TFHRC for a period of five years, beginning in October 2010. Themore » analysis methods employ well-benchmarked and supported commercial computational mechanics software. Computational mechanics encompasses the areas of Computational Fluid Dynamics (CFD), Computational Wind Engineering (CWE), Computational Structural Mechanics (CSM), and Computational Multiphysics Mechanics (CMM) applied in Fluid-Structure Interaction (FSI) problems. The major areas of focus of the project are wind and water loads on bridges - superstructure, deck, cables, and substructure (including soil), primarily during storms and flood events - and the risks that these loads pose to structural failure. For flood events at bridges, another major focus of the work is assessment of the risk to bridges caused by scour of stream and riverbed material away from the foundations of a bridge. Other areas of current research include modeling of flow through culverts to assess them for fish passage, modeling of the salt spray transport into bridge girders to address suitability of using weathering steel in bridges, vehicle stability under high wind loading, and the use of electromagnetic shock absorbers to improve vehicle stability under high wind conditions. This quarterly report documents technical progress on the project tasks for the period of April through June 2011.« less

  4. Mechanical stress and network structure drive protein dynamics during cytokinesis.

    PubMed

    Srivastava, Vasudha; Robinson, Douglas N

    2015-03-02

    Cell-shape changes associated with processes like cytokinesis and motility proceed on several-second timescales but are derived from molecular events, including protein-protein interactions, filament assembly, and force generation by molecular motors, all of which occur much faster [1-4]. Therefore, defining the dynamics of such molecular machinery is critical for understanding cell-shape regulation. In addition to signaling pathways, mechanical stresses also direct cytoskeletal protein accumulation [5-7]. A myosin-II-based mechanosensory system controls cellular contractility and shape during cytokinesis and under applied stress [6, 8]. In Dictyostelium, this system tunes myosin II accumulation by feedback through the actin network, particularly through the crosslinker cortexillin I. Cortexillin-binding IQGAPs are major regulators of this system. Here, we defined the short timescale dynamics of key cytoskeletal proteins during cytokinesis and under mechanical stress, using fluorescence recovery after photobleaching and fluorescence correlation spectroscopy, to examine the dynamic interplay between these proteins. Equatorially enriched proteins including cortexillin I, IQGAP2, and myosin II recovered much more slowly than actin and polar crosslinkers. The mobility of equatorial proteins was greatly reduced at the furrow compared to the interphase cortex, suggesting their stabilization during cytokinesis. This mobility shift did not arise from a single biochemical event, but rather from a global inhibition of protein dynamics by mechanical-stress-associated changes in the cytoskeletal structure. Mechanical tuning of contractile protein dynamics provides robustness to the cytoskeletal framework responsible for regulating cell shape and contributes to cytokinesis fidelity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Progressive Damage Analysis of Bonded Composite Joints

    NASA Technical Reports Server (NTRS)

    Leone, Frank A., Jr.; Girolamo, Donato; Davila, Carlos G.

    2012-01-01

    The present work is related to the development and application of progressive damage modeling techniques to bonded joint technology. The joint designs studied in this work include a conventional composite splice joint and a NASA-patented durable redundant joint. Both designs involve honeycomb sandwich structures with carbon/epoxy facesheets joined using adhesively bonded doublers.Progressive damage modeling allows for the prediction of the initiation and evolution of damage within a structure. For structures that include multiple material systems, such as the joint designs under consideration, the number of potential failure mechanisms that must be accounted for drastically increases the complexity of the analyses. Potential failure mechanisms include fiber fracture, intraply matrix cracking, delamination, core crushing, adhesive failure, and their interactions. The bonded joints were modeled using highly parametric, explicitly solved finite element models, with damage modeling implemented via custom user-written subroutines. Each ply was discretely meshed using three-dimensional solid elements. Layers of cohesive elements were included between each ply to account for the possibility of delaminations and were used to model the adhesive layers forming the joint. Good correlation with experimental results was achieved both in terms of load-displacement history and the predicted failure mechanism(s).

  6. The development and maintenance of mental toughness: perceptions of elite performers.

    PubMed

    Connaughton, Declan; Wadey, Ross; Hanton, Sheldon; Jones, Graham

    2008-01-01

    Seven participants from a previous study (Jones, Hanton, & Connaughton, 2002) agreed to be interviewed about the development of mental toughness. We also aimed to determine whether mental toughness requires maintenance. Semistructured interviews were conducted to elicit the participants' perceptions of how mental toughness is cultivated and retained. Findings indicated that the development of mental toughness is a long-term process that encompasses a multitude of underlying mechanisms that operate in a combined, rather than independent, fashion. In general, these perceived underlying mechanisms related to many features associated with a motivational climate (e.g. enjoyment, mastery), various individuals (i.e. coaches, peers, parents, grandparents, siblings, senior athletes, sport psychologists, team-mates), experiences in and outside sport, psychological skills and strategies, and an insatiable desire and internalized motives to succeed. It was also reported that once mental toughness had been developed, three perceived underlying mechanisms were required to maintain this construct: a desire and motivation to succeed that was insatiable and internalized, a support network that included sporting and non-sporting personnel, and effective use of basic and advanced psychological skills. Practical implications and future avenues of research are discussed.

  7. Temperature dependent electrical characterization of organic Schottky diode based on thick MgPc films

    NASA Astrophysics Data System (ADS)

    Singh, J.; Sharma, R. K.; Sule, U. S.; Goutam, U. K.; Gupta, Jagannath; Gadkari, S. C.

    2017-07-01

    Magnesium phthalocyanine (MgPc) based Schottky diode on indium tin oxide (ITO) substrate was fabricated by thermal evaporation method. The dark current voltage characteristics of the prepared ITO-MgPc-Al heterojunction Schottky diode were measured at different temperatures. The diode showed the non-ideal rectification behavior under forward and reverse bias conditions with a rectification ratio (RR) of 56 at  ±1 V at room temperature. Under forward bias, thermionic emission and space charge limited conduction (SCLC) were found to be the dominant conduction mechanisms at low (below 0.6 V) and high voltages (above 0.6 V) respectively. Under reverse bias conditions, Poole-Frenkel (field assisted thermal detrapping of carriers) was the dominant conduction mechanism. Three different approaches namely, I-V plots, Norde and Cheung methods were used to determine the diode parameters including ideality factor (n), barrier height (Φb), series resistance (R s) and were compared. SCLC mechanism showed that the trap concentration is 5.52  ×  1022 m-3 and it lies at 0.46 eV above the valence band edge.

  8. Critical realism: a practical ontology to explain the complexities of smoking and tobacco control in different resource settings

    PubMed Central

    Oladele, Dunsi; Clark, Alexander M.; Richter, Solina; Laing, Lory

    2013-01-01

    Background This paper presents critical realism (CR) as an innovative system for research in tobacco prevention and control. CR argues that underlying mechanisms are considered and explored to ensure effective implementation of any program/policy or intervention. Any intervention or program/policy that is transposed from one country to another or one setting to another is complex. Methods The research was undertaken and analyzed through a critical ethnography lens using CR as a philosophical underpinning. The study relied upon the following components: original fieldwork in Nigeria including participant observation of smokers, in-depth interviews and focus groups with smokers, and in-depth interviews with health professionals working in the area of tobacco control in Nigeria. Results Findings from this small ethnographic study in Nigeria, suggest that Critical Realism holds promise for addressing underlying mechanism that links complex influences on smoking. Conclusion This paper argues that understanding the underlying mechanisms associated with smoking in different societies will enable a platform for effective implementation of tobacco control policies that work in various settings. PMID:23561029

  9. Mechanics of Granular Materials (MGM) Test Cell

    NASA Technical Reports Server (NTRS)

    1998-01-01

    A test cell for Mechanics of Granular Materials (MGM) experiment is shown approximately 20 and 60 minutes after the start of an experiment on STS-89. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditons that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: NASA/Marshall Space Flight Center (MSFC)

  10. Mechanics of Granular Materials Test Cell

    NASA Technical Reports Server (NTRS)

    1998-01-01

    A test cell for Mechanics of Granular Materials (MGM) experiment is shown from all three sides by its video camera during STS-89. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditons that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: NASA/Marshall Space Flight Center (MSFC)

  11. Genetic control of postnatal human brain growth

    PubMed Central

    van Dyck, Laura I.; Morrow, Eric M.

    2017-01-01

    Purpose of review Studies investigating postnatal brain growth disorders inform the biology underlying the development of human brain circuitry. This research is becoming increasingly important for the diagnosis and treatment of childhood neurodevelopmental disorders, including autism and related disorders. Here we review recent research on typical and abnormal postnatal brain growth and examine potential biological mechanisms. Recent findings Clinically, brain growth disorders are heralded by diverging head size for a given age and sex, but are more precisely characterized by brain imaging, postmortem analysis, and animal model studies. Recent neuroimaging and molecular biological studies on postnatal brain growth disorders have broadened our view of both typical and pathological postnatal neurodevelopment. Correlating gene and protein function with brain growth trajectories uncovers postnatal biological mechanisms, including neuronal arborization, synaptogenesis and pruning, and gliogenesis and myelination. Recent investigations of childhood neurodevelopmental and neurodegenerative disorders highlight the underlying genetic programming and experience-dependent remodeling of neural circuitry. Summary In order to understand typical and abnormal postnatal brain development, clinicians and researchers should characterize brain growth trajectories in the context of neurogenetic syndromes. Understanding mechanisms and trajectories of postnatal brain growth will aid in differentiating, diagnosing, and potentially treating neurodevelopmental disorders. PMID:27898583

  12. Modulation of Brain Activity with Noninvasive Transcranial Direct Current Stimulation (tDCS): Clinical Applications and Safety Concerns

    PubMed Central

    Zhao, Haichao; Qiao, Lei; Fan, Dongqiong; Zhang, Shuyue; Turel, Ofir; Li, Yonghui; Li, Jun; Xue, Gui; Chen, Antao; He, Qinghua

    2017-01-01

    Transcranial direct current stimulation (tDCS) is a widely-used tool to induce neuroplasticity and modulate cortical function by applying weak direct current over the scalp. In this review, we first introduce the underlying mechanism of action, the brief history from discovery to clinical scientific research, electrode positioning and montages, and parameter setup of tDCS. Then, we review tDCS application in clinical samples including people with drug addiction, major depression disorder, Alzheimer's disease, as well as in children. This review covers the typical characteristics and the underlying neural mechanisms of tDCS treatment in such studies. This is followed by a discussion of safety, especially when the current intensity is increased or the stimulation duration is prolonged. Given such concerns, we provide detailed suggestions regarding safety procedures for tDCS operation. Lastly, future research directions are discussed. They include foci on the development of multi-tech combination with tDCS such as with TMS and fMRI; long-term behavioral and morphological changes; possible applications in other research domains, and more animal research to deepen the understanding of the biological and physiological mechanisms of tDCS stimulation. PMID:28539894

  13. New Physical Mechanism for Lightning

    NASA Astrophysics Data System (ADS)

    Artekha, Sergey N.; Belyan, Andrey V.

    2018-02-01

    The article is devoted to electromagnetic phenomena in the atmosphere. The set of experimental data on the thunderstorm activity is analyzed. It helps to identify a possible physical mechanism of lightning flashes. This mechanism can involve the formation of metallic bonds in thunderclouds. The analysis of the problem is performed at a microphysical level within the framework of quantum mechanics. The mechanism of appearance of metallic conductivity includes the resonant tunneling of electrons along resonance-percolation trajectories. Such bonds allow the charges from the vast cloud charged subsystems concentrate quickly in lightning channel. The formation of metal bonds in the thunderstorm cloudiness is described as the second-order phase transition. A successive mechanism for the process of formation and development of the lightning channel is suggested. This mechanism is associated with the change in the orientation of crystals in growing electric field. Possible consequences of the quantum-mechanical mechanism under discussion are compared with the results of observations.

  14. Role of exercise in maintaining the integrity of the neuromuscular junction

    PubMed Central

    Nishimune, Hiroshi; Stanford, John A.; Mori, Yasuo

    2014-01-01

    Physical activity plays an important role in preventing chronic disease in adults and the elderly. Exercise has beneficial effects on the nervous system, including at the neuromuscular junction (NMJ). Exercise causes hypertrophy of NMJs and improves recovery from peripheral nerve injuries, whereas decreased physical activity causes degenerative changes in NMJs. Recent studies have begun to elucidate molecular mechanisms underlying the beneficial effects of exercise. These mechanisms involve Bassoon, neuregulin-1, peroxisome proliferator-activated receptor gamma coactivator 1α, Insulin-like growth factor-1, glial cell line-derived neurotrophic factor, neurotrophin 4, Homer, and nuclear factor of activated T cells c1. For example, NMJ denervation and active zone decreases have been observed in aged NMJs, but these age-dependent degenerative changes can be ameliorated by exercise. This review will discuss the effects of exercise on the maintenance and regeneration of NMJs and will highlight recent insights into the molecular mechanisms underlying these exercise effects. PMID:24122772

  15. A Hypothesis Regarding the Molecular Mechanism Underlying Dietary Soy-Induced Effects on Seizure Propensity

    PubMed Central

    Westmark, Cara Jean

    2014-01-01

    Numerous neurological disorders including fragile X syndrome, Down syndrome, autism, and Alzheimer’s disease are co-morbid with epilepsy. We have observed elevated seizure propensity in mouse models of these disorders dependent on diet. Specifically, soy-based diets exacerbate audiogenic-induced seizures in juvenile mice. We have also found potential associations between the consumption of soy-based infant formula and seizure incidence, epilepsy comorbidity, and autism diagnostic scores in autistic children by retrospective analyses of medical record data. In total, these data suggest that consumption of high levels of soy protein during postnatal development may affect neuronal excitability. Herein, we present our theory regarding the molecular mechanism underlying soy-induced effects on seizure propensity. We hypothesize that soy phytoestrogens interfere with metabotropic glutamate receptor signaling through an estrogen receptor-dependent mechanism, which results in elevated production of key synaptic proteins and decreased seizure threshold. PMID:25232349

  16. Mechanisms of antibiotic resistance in enterococci

    PubMed Central

    Miller, William R; Munita, Jose M; Arias, Cesar A

    2015-01-01

    Multidrug-resistant (MDR) enterococci are important nosocomial pathogens and a growing clinical challenge. These organisms have developed resistance to virtually all antimicrobials currently used in clinical practice using a diverse number of genetic strategies. Due to this ability to recruit antibiotic resistance determinants, MDR enterococci display a wide repertoire of antibiotic resistance mechanisms including modification of drug targets, inactivation of therapeutic agents, overexpression of efflux pumps and a sophisticated cell envelope adaptive response that promotes survival in the human host and the nosocomial environment. MDR enterococci are well adapted to survive in the gastrointestinal tract and can become the dominant flora under antibiotic pressure, predisposing the severely ill and immunocompromised patient to invasive infections. A thorough understanding of the mechanisms underlying antibiotic resistance in enterococci is the first step for devising strategies to control the spread of these organisms and potentially establish novel therapeutic approaches. PMID:25199988

  17. Quantitative sensory testing of neuropathic pain patients: potential mechanistic and therapeutic implications.

    PubMed

    Pfau, Doreen B; Geber, Christian; Birklein, Frank; Treede, Rolf-Detlef

    2012-06-01

    Quantitative sensory testing (QST) is a widely accepted tool to investigate somatosensory changes in pain patients. Many different protocols have been developed in clinical pain research within recent years. In this review, we provide an overview of QST and tested neuroanatomical pathways, including peripheral and central structures. Based on research studies using animal and human surrogate models of neuropathic pain, possible underlying mechanisms of chronic pain are discussed. Clinically, QST may be useful for 1) the identification of subgroups of patients with different underlying pain mechanisms; 2) prediction of therapeutic outcomes; and 3) quantification of therapeutic interventions in pain therapy. Combined with sensory mapping, QST may provide useful information on the site of neural damage and on mechanisms of positive and negative somatosensory abnormalities. The use of QST in individual patients for diagnostic purposes leading to individualized therapy is an interesting concept, but needs further validation.

  18. Static and yawed-rolling mechanical properties of two type 7 aircraft tires

    NASA Technical Reports Server (NTRS)

    Tanner, J. A.; Stubbs, S. M.; Mccarty, J. L.

    1981-01-01

    Selected mechanical properties of 18 x 5.5 and 49 x 17 size, type 7 aircraft tires were evaluated. The tires were subjected to pure vertical loads and to combined vertical and lateral loads under both static and rolling conditions. Parameters for the static tests consisted of tire load in the vertical and lateral directions, and parameters for the rolling tests included tire vertical load, yaw angle, and ground speed. Effects of each of these parameters on the measured tire characteristics are discussed and, where possible, compared with previous work. Results indicate that dynamic tire properties under investigation were generally insensitive to speed variations and therefore tend to support the conclusion that many tire dynamic characteristics can be obtained from static and low speed rolling tests. Furthermore, many of the tire mechanical properties are in good agreement with empirical predictions based on earlier research.

  19. Mechanisms of rotator cuff tendinopathy: intrinsic, extrinsic, or both?

    PubMed

    Seitz, Amee L; McClure, Philip W; Finucane, Sheryl; Boardman, N Douglas; Michener, Lori A

    2011-01-01

    The etiology of rotator cuff tendinopathy is multi-factorial, and has been attributed to both extrinsic and intrinsic mechanisms. Extrinsic factors that encroach upon the subacromial space and contribute to bursal side compression of the rotator cuff tendons include anatomical variants of the acromion, alterations in scapular or humeral kinematics, postural abnormalities, rotator cuff and scapular muscle performance deficits, and decreased extensibility of pectoralis minor or posterior shoulder. A unique extrinsic mechanism, internal impingement, is attributed to compression of the posterior articular surface of the tendons between the humeral head and glenoid and is not related to subacromial space narrowing. Intrinsic factors that contribute to rotator cuff tendon degradation with tensile/shear overload include alterations in biology, mechanical properties, morphology, and vascularity. The varied nature of these mechanisms indicates that rotator cuff tendinopathy is not a homogenous entity, and thus may require different treatment interventions. Treatment aimed at addressing mechanistic factors appears to be beneficial for patients with rotator cuff tendinopathy, however, not for all patients. Classification of rotator cuff tendinopathy into subgroups based on underlying mechanism may improve treatment outcomes. 2010 Elsevier Ltd. All rights reserved.

  20. The structure-mechanical relationship of palm vascular tissue.

    PubMed

    Wang, Ningling; Liu, Wangyu; Huang, Jiale; Ma, Ke

    2014-08-01

    The structure-mechanical relationship of palm sheath is studied with numerical and experimental methods. The cellular structure of the vascular tissue is rebuilt with an image-based reconstruction method and used to create finite element models. The validity of the models is firstly verified with the results from the tensile tests. Then, the cell walls inside each of the specific regions (fiber cap, vessel, xylem, etc.) are randomly removed to obtain virtually imperfect structures. By comparing the magnitudes of performance degradation in the different imperfect structures, the influences of each region on the overall mechanical performances of the vascular tissue are discussed. The longitudinal stiffness and yield strength are sensitive to the defects in the vessel regions. While in the transverse directions (including the radial and tangential directions), the parenchymatous tissue determines the mechanical properties of the vascular tissue. Moreover, the hydraulic, dynamic response and energy absorption behavior of the vascular tissue are numerically explored. The flexibility of natural palm tissue enhances its impact resistance. Under the quasi-static compression, the cell walls connecting the fiber cap and the vessel dissipate more energy. The dominant role of the fiber cap in the plastic energy dissipation under high-speed impact is observed. And the radially-arranged fiber cap also allows the palm tissue to improve its tangential mechanical performances under hydraulic pressure. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Plastic Faulting in Ice: Shear Localization under Elevated Pressure

    NASA Astrophysics Data System (ADS)

    Golding, N.; Durham, W. B.

    2013-12-01

    Ice exhibits, at least, two distinct kinds of shear faults when loaded triaxially under compression. Under moderate levels of confinement, brittle failure follows crack growth, crack coalescence and the development of a fault oriented about 30 degrees from the direction of maximum compression. The mechanism governing this mode of failure, termed frictional or Coulombic faulting, has previously been discussed for ice and rocks in connection with the comb-crack model. Under higher levels of confinement, where frictional sliding is suppressed by confining pressure, failure is characterized by sudden brittle-like loss in load bearing capacity and the development of a narrow shear band, comprised of recrystallized grains, oriented about 45 degrees from the direction of maximum compression, i.e. along the direction of maximum shear. This mode of failure, referred to here as plastic faulting, has previously been discussed for warm ice, T = 233 - 263 K, in connection with adiabatic shear heating and has been discussed for cold ice, T = 77 - 163 K, in connection with phase transformation. Here, new results are presented that examine the mechanical behavior and microstructural properties of plastic faulting in polycrystalline ice loaded at temperatures from T = 175 - 210 K and confining pressures up to P = 200 MPa. The results are reviewed in context of previous work and possible mechanisms to account for shear localization in ice under high pressure, including 1) adiabatic shear heating, 2) grain refinement and 3) phase transformation, are discussed. The present observations highlight the similarities in the behavior of plastic faulting under both warm and cold conditions and suggest adiabatic shear heating as a possible mechanism to account for shear instability and plastic faulting at temperatures ranging from T = 77 - 263 K.

  2. Development of a mathematical model for mechanical transmission of trypanosomes and other pathogens of cattle transmitted by tabanids.

    PubMed

    Desquesnes, Marc; Biteau-Coroller, Fabienne; Bouyer, Jérémy; Dia, Mamadou Lamine; Foil, Lane

    2009-02-01

    Mechanical transmission of pathogens by biting insects is a non-specific phenomenon in which pathogens are transmitted from the blood of an infected host to another host during interrupted feeding of the insects. A large range of pathogens can be mechanically transmitted, e.g. hemoparasites, bacteria and viruses. Some pathogens are almost exclusively mechanically transmitted, while others are also cyclically transmitted. For agents transmitted both cyclically and mechanically (mixed transmission), such as certain African pathogenic trypanosomes, the relative impact of mechanical versus cyclical transmission is essentially unknown. We have developed a mathematical model of pathogen transmission by a defined insect population to evaluate the importance of mechanical transmission. Based on a series of experiments aimed at demonstrating mechanical transmission of African trypanosomes by tabanids, the main parameters of the model were either quantified (host parasitaemia, mean individual insect burden, initial prevalence of infection) or estimated (unknown parameters). This model allows us to simulate the evolution of pathogen prevalence under various predictive circumstances, including control measures and could be used to assess the risk of mechanical transmission under field conditions. If adjustments of parameters are provided, this model could be generalized to other pathogenic agents present in the blood of their hosts (Bovine Leukemia virus, Anaplasma, etc.) or other biting insects such as biting muscids (stomoxyines) and hippoboscids.

  3. Refractory chronic cough due to gastroesophageal reflux: Definition, mechanism and management

    PubMed Central

    Lv, Han-Jing; Qiu, Zhong-Min

    2015-01-01

    Refractory chronic cough due to gastroesophageal reflux is a troublesome condition unresponsive to the standard medical anti-reflux therapy. Its underlying mechanisms may include incomplete acid suppression, non-acid reflux, transient lower esophageal sphincter relaxations and esophageal hypersensitivity. The diagnosis of this disorder depends on both the findings of multi-channel intraluminal impedance-pH monitoring and the subsequent intensified anti-reflux therapy. The strategies of pharmacological treatment for refractory chronic cough due to reflux include the optimization of proton pump inhibitors and add-on therapies with histamine H2 receptor antagonists, baclofen and gabapentin. However, the further study is needed to satisfy its management. PMID:26413488

  4. DISSECTING COLONY DEVELOPMENT OF NEUROSPORA CRASSA USING mRNA PROFILING AND COMPARTATIVE GENOMICS APPROACHES

    USDA-ARS?s Scientific Manuscript database

    Colony development, which includes hyphal extension, branching, anastomosis and asexual sporulation are fundamental aspects of the lifecycle of filamentous fungi; genetic mechanisms underlying these phenomena are poorly understood. We conducted transcriptional profiling during colony development of...

  5. Nutrients and bioactives in green leafy vegetables and cognitive decline: prospective study

    USDA-ARS?s Scientific Manuscript database

    Objective: To increase understanding of the biological mechanisms underlying this association, we investigated the individual relations to cognitive decline of the primary nutrients and bioactives in green leafy vegetables, including vitamin K (phylloquinone), lutein, beta-carotene, nitrate, folate,...

  6. The Biomarkers of Exposure and Effect in Agriculture (BEEA) Study: Rationale, design, methods, and participant characteristics

    EPA Science Inventory

    Agricultural exposures including pesticides, endotoxin, and allergens have been associated with risk of various cancers and other chronic diseases, although the biological mechanisms underlying these associations are generally unclear. To facilitate future molecular epidemiologic...

  7. Mechanisms and pharmacogenetic signals underlying thiazide diuretics blood pressure response

    PubMed Central

    Shahin, Mohamed H; Johnson, Julie A

    2016-01-01

    Thiazide (TZD) diuretics are among the most commonly prescribed antihypertensives globally; however their chronic blood pressure (BP) lowering mechanism remains unclear. Herein we discuss the current evidence regarding specific mechanisms regulating the antihypertensive effects of TZDs, suggesting that TZDs act via multiple complex and interacting mechanisms, including natriuresis with short term use and direct vasodilatory effects chronically. Additionally, we review pharmacogenomics signals that have been associated with TZDs BP-response in several cohorts (i.e. NEDD4L, PRKCA, EDNRA-GNAS, and YEATS4) and discuss how these genes might be related to TZD BP-response mechanism. Understanding the association between these genes and TZD BP mechanism might facilitate the development of new drugs and therapeutic approaches based on a deeper understanding of the determinants of BP-response. PMID:26874237

  8. Gratitude influences sleep through the mechanism of pre-sleep cognitions.

    PubMed

    Wood, Alex M; Joseph, Stephen; Lloyd, Joanna; Atkins, Samuel

    2009-01-01

    To test whether individual differences in gratitude are related to sleep after controlling for neuroticism and other traits. To test whether pre-sleep cognitions are the mechanism underlying this relationship. A cross-sectional questionnaire study was conducted with a large (186 males, 215 females) community sample (ages=18-68 years, mean=24.89, S.D.=9.02), including 161 people (40%) scoring above 5 on the Pittsburgh Sleep Quality Index, indicating clinically impaired sleep. Measures included gratitude, the Pittsburgh Sleep Quality Index (PSQI), self-statement test of pre-sleep cognitions, the Mini-IPIP scales of Big Five personality traits, and the Social Desirability Scale. Gratitude predicted greater subjective sleep quality and sleep duration, and less sleep latency and daytime dysfunction. The relationship between gratitude and each of the sleep variables was mediated by more positive pre-sleep cognitions and less negative pre-sleep cognitions. All of the results were independent of the effect of the Big Five personality traits (including neuroticism) and social desirability. This is the first study to show that a positive trait is related to good sleep quality above the effect of other personality traits, and to test whether pre-sleep cognitions are the mechanism underlying the relationship between any personality trait and sleep. The study is also the first to show that trait gratitude is related to sleep and to explain why this occurs, suggesting future directions for research, and novel clinical implications.

  9. Reliability Issues and Solutions in Flexible Electronics Under Mechanical Fatigue

    NASA Astrophysics Data System (ADS)

    Yi, Seol-Min; Choi, In-Suk; Kim, Byoung-Joon; Joo, Young-Chang

    2018-07-01

    Flexible devices are of significant interest due to their potential expansion of the application of smart devices into various fields, such as energy harvesting, biological applications and consumer electronics. Due to the mechanically dynamic operations of flexible electronics, their mechanical reliability must be thoroughly investigated to understand their failure mechanisms and lifetimes. Reliability issue caused by bending fatigue, one of the typical operational limitations of flexible electronics, has been studied using various test methodologies; however, electromechanical evaluations which are essential to assess the reliability of electronic devices for flexible applications had not been investigated because the testing method was not established. By employing the in situ bending fatigue test, we has studied the failure mechanism for various conditions and parameters, such as bending strain, fatigue area, film thickness, and lateral dimensions. Moreover, various methods for improving the bending reliability have been developed based on the failure mechanism. Nanostructures such as holes, pores, wires and composites of nanoparticles and nanotubes have been suggested for better reliability. Flexible devices were also investigated to find the potential failures initiated by complex structures under bending fatigue strain. In this review, the recent advances in test methodology, mechanism studies, and practical applications are introduced. Additionally, perspectives including the future advance to stretchable electronics are discussed based on the current achievements in research.

  10. Reliability Issues and Solutions in Flexible Electronics Under Mechanical Fatigue

    NASA Astrophysics Data System (ADS)

    Yi, Seol-Min; Choi, In-Suk; Kim, Byoung-Joon; Joo, Young-Chang

    2018-03-01

    Flexible devices are of significant interest due to their potential expansion of the application of smart devices into various fields, such as energy harvesting, biological applications and consumer electronics. Due to the mechanically dynamic operations of flexible electronics, their mechanical reliability must be thoroughly investigated to understand their failure mechanisms and lifetimes. Reliability issue caused by bending fatigue, one of the typical operational limitations of flexible electronics, has been studied using various test methodologies; however, electromechanical evaluations which are essential to assess the reliability of electronic devices for flexible applications had not been investigated because the testing method was not established. By employing the in situ bending fatigue test, we has studied the failure mechanism for various conditions and parameters, such as bending strain, fatigue area, film thickness, and lateral dimensions. Moreover, various methods for improving the bending reliability have been developed based on the failure mechanism. Nanostructures such as holes, pores, wires and composites of nanoparticles and nanotubes have been suggested for better reliability. Flexible devices were also investigated to find the potential failures initiated by complex structures under bending fatigue strain. In this review, the recent advances in test methodology, mechanism studies, and practical applications are introduced. Additionally, perspectives including the future advance to stretchable electronics are discussed based on the current achievements in research.

  11. Finite Element Implementation of Mechanochemical Phenomena in Neutral Deformable Porous Media Under Finite Deformation

    PubMed Central

    Ateshian, Gerard A.; Albro, Michael B.; Maas, Steve; Weiss, Jeffrey A.

    2011-01-01

    Biological soft tissues and cells may be subjected to mechanical as well as chemical (osmotic) loading under their natural physiological environment or various experimental conditions. The interaction of mechanical and chemical effects may be very significant under some of these conditions, yet the highly nonlinear nature of the set of governing equations describing these mechanisms poses a challenge for the modeling of such phenomena. This study formulated and implemented a finite element algorithm for analyzing mechanochemical events in neutral deformable porous media under finite deformation. The algorithm employed the framework of mixture theory to model the porous permeable solid matrix and interstitial fluid, where the fluid consists of a mixture of solvent and solute. A special emphasis was placed on solute-solid matrix interactions, such as solute exclusion from a fraction of the matrix pore space (solubility) and frictional momentum exchange that produces solute hindrance and pumping under certain dynamic loading conditions. The finite element formulation implemented full coupling of mechanical and chemical effects, providing a framework where material properties and response functions may depend on solid matrix strain as well as solute concentration. The implementation was validated using selected canonical problems for which analytical or alternative numerical solutions exist. This finite element code includes a number of unique features that enhance the modeling of mechanochemical phenomena in biological tissues. The code is available in the public domain, open source finite element program FEBio (http://mrl.sci.utah.edu/software). PMID:21950898

  12. Tactical STOL moment balance through innovative configuration technology

    NASA Technical Reports Server (NTRS)

    Eckard, G. J.; Sutton, R. C.; Poth, G. E.

    1981-01-01

    Innovative and conventional thrust vectoring moment balance mechanisms, as applied to advanced tactical fighters, are examined. The innovative mechanisms include thrust line translation, life line translation, and auxiliary power control; the conventional mechanisms under investigation are horizontal tails, canards, and variable sweep wings. These mechanisms are tested for their ability to provide negative static margins for landing approach or relocation of the vectored thrust line nearer the aircraft's center of gravity. The net pitching moment due to wing, flaps, and vectored thrust lift would then be small, making possible beneficial trim forces from small trimming devices. These innovative mechanisms are, however, possibly heavy and must be evaluated on their complexity, reliability, maintainability, and STOL capabilities. Several candidate fighter configurations are compared and evaluated.

  13. Significant weight loss following clozapine use, how is it possible? A case report and review of published cases and literature relevant to the subject.

    PubMed

    Tungaraza, Tongeji E

    2016-10-01

    It has been repeatedly shown that clozapine is more efficacious than other antipsychotics in the management of treatment-resistant schizophrenia. However, clozapine is associated with a number of side effects including weight gain. Antipsychotic-induced weight gain has been linked with a number of untoward events including psychological factors such as stigma and low self-esteem, and physical factors such as metabolic syndromes and untimely death. The mechanism underlying antipsychotic (including clozapine)-induced weight gain is not clearly understood, although it is said to involve several brain areas, several neurotransmitters, neuropeptides and genetic factors. To some individuals however, clozapine use is associated with significant weight loss (13.5-50% of body weight). The observed weight loss in these groups of patients has not been attributed to any underlying diagnosable physical disorders. There have been a handful cases published with this phenomenon, which seems to be contrary to what is expected when clozapine is prescribed. From the currently published cases three groups emerge - those who lost weight simply by taking clozapine, those who lost weight due to improved mental state, engaging in diet and increased exercise, and those for whom weight loss was a sign of a poor response to clozapine. A case of JX who has a diagnosis of schizoaffective disorder is presented. JX lost over 26% of her body weight when she was prescribed clozapine. A detailed review of other published cases is undertaken. The underlying mechanisms involving weight loss are discussed and the implications to clinicians are highlighted. Coordinated studies to examine these groups of patients may provide some insight, not only in the mechanism of clozapine-induced weight loss, but also in the better management of patients with treatment-resistant schizophrenia involving clozapine use.

  14. Woody-Herbaceous Species Coexistence in Mulga Hillslopes: Modelling Structure and Function

    NASA Astrophysics Data System (ADS)

    Soltanjalili, M. J.; Saco, P. M.; Willgoose, G. R.

    2016-12-01

    The fundamental processes underlying the coexistence of woody and herbaceous species in arid and semi-arid areas have been a topic of intense research during the last few decades. Experimental and modelling studies have both supported and disputed alternative hypotheses explaining this phenomenon. Vegetation models including the key processes that drive coexistence can be used to understand vegetation pattern dynamics and structure under current climate conditions, and to predict changes under future conditions. Here we present work done towards linking the observations to modelling. The model captures woody-herbaceous coexistence along a rainfall gradient characteristic of typical conditions on Mulga ecosystems in Australia. The dynamic vegetation model simulates the spatial dynamics of overland flow, soil moisture and vegetation growth of two species. It incorporates key mechanisms for coexistence and pattern formation, including facilitation by evaporation reduction through shading, and infiltration feedbacks, local and non-local seed dispersal, competition for water uptake. Model outcomes, obtained including diflerent mechanisms, are qualitatively compared to typical vegetation cover patterns in the Australian Mulga bioregion where bush fire is very infrequent and the fate of vegetation cover is mostly determined by intra- and interspecies interactions. Through these comparisons, and by drawing on the large number of recent studies that have delivered new insights into the dynamics of such ecosystems, we identify main mechanisms that need an improved representation in the dynamic vegetation models. We show that a realistic parameterization of the model leads to results which are aligned with the observations reported in the literature. At the lower end of the rainfall gradient woody species coexist with herbaceous species within a sparse banded pattern, while at higher rainfall woody species tend to dominate the landscape.

  15. Proteases in cardiometabolic diseases: Pathophysiology, molecular mechanisms and clinical applications

    PubMed Central

    Hua, Yinan; Nair, Sreejayan

    2014-01-01

    Cardiovascular disease is the leading cause of death in the U.S. and other developed country. Metabolic syndrome, including obesity, diabetes/insulin resistance, hypertension and dyslipidemia is major threat for public health in the modern society. It is well established that metabolic syndrome contributes to the development of cardiovascular disease collective called as cardiometabolic disease. Despite documented studies in the research field of cardiometabolic disease, the underlying mechanisms are far from clear. Proteases are enzymes that break down proteins, many of which have been implicated in various diseases including cardiac disease. Matrix metalloproteinase (MMP), calpain, cathepsin and caspase are among the major proteases involved in cardiac remodeling. Recent studies have also implicated proteases in the pathogenesis of cardiometabolic disease. Elevated expression and activities of proteases in atherosclerosis, coronary heart disease, obesity/insulin-associated heart disease as well as hypertensive heart disease have been documented. Furthermore, transgenic animals that are deficient in or overexpress proteases allow scientists to understand the causal relationship between proteases and cardiometabolic disease. Mechanistically, MMPs and cathepsins exert their effect on cardiometabolic diseases mainly through modifying the extracellular matrix. However, MMP and cathepsin are also reported to affect intracellular proteins, by which they contribute to the development of cardiometabolic diseases. On the other hand, activation of calpain and caspases has been shown to influence intracellular signaling cascade including the NF-κB and apoptosis pathways. Clinically, proteases are reported to function as biomarkers of cardiometabolic diseases. More importantly, the inhibitors of proteases are credited with beneficial cardiometabolic profile, although the exact molecular mechanisms underlying these salutary effects are still under investigation. A better understanding of the role of MMPs, cathepsins, calpains and caspases in cardiometabolic diseases process may yield novel therapeutic targets for threating or controlling these diseases. PMID:24815358

  16. 609th Iraqi National Guard Battalion Garrison, Thi Qar Governorate, Iraq

    DTIC Science & Technology

    2006-07-25

    views of structural members (reinforced concrete footers, columns , beams , floor, and roof slabs). Mechanical drawings included plumbing plans and...well as reinforced concrete columns and beams . The exterior walls were constructed with sand lime block. Although the assessment team did not...foundation support for the perimeter wall included reinforced concrete footers to support the columns and a reinforced concrete tie beam under the wall

  17. European Scientific Notes. Volume 34, Number 7,

    DTIC Science & Technology

    1980-07-31

    fatigue , the effect of patient during the fitting, but which moisture on mechanical properties, could still be bent 900 without delamin- and creep...behavior. In the fatigue ating the composite or debonding the work; different reinforcing fibers composite from the aluminum . Once (including glass-carbon... fatigue work sulting structure has better properties Sturgeon has under way includes the than steel and weighs a good deal less, effect of

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

    PubMed

    Chen, Lianguo; Qian, Pei-Yuan

    2017-08-28

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

  19. Analysis of Gene Expression and Physiological Responses in Three Mexican Maize Landraces under Drought Stress and Recovery Irrigation

    PubMed Central

    Hayano-Kanashiro, Corina; Calderón-Vázquez, Carlos; Ibarra-Laclette, Enrique; Herrera-Estrella, Luis; Simpson, June

    2009-01-01

    Background Drought is one of the major constraints for plant productivity worldwide. Different mechanisms of drought-tolerance have been reported for several plant species including maize. However, the differences in global gene expression between drought-tolerant and susceptible genotypes and their relationship to physiological adaptations to drought are largely unknown. The study of the differences in global gene expression between tolerant and susceptible genotypes could provide important information to design more efficient breeding programs to produce maize varieties better adapted to water limiting conditions. Methodology/Principal Findings Changes in physiological responses and gene expression patterns were studied under drought stress and recovery in three Mexican maize landraces which included two drought tolerant (Cajete criollo and Michoacán 21) and one susceptible (85-2) genotypes. Photosynthesis, stomatal conductance, soil and leaf water potentials were monitored throughout the experiment and microarray analysis was carried out on transcripts obtained at 10 and 17 days following application of stress and after recovery irrigation. The two tolerant genotypes show more drastic changes in global gene expression which correlate with different physiological mechanisms of adaptation to drought. Differences in the kinetics and number of up- and down-regulated genes were observed between the tolerant and susceptible maize genotypes, as well as differences between the two tolerant genotypes. Interestingly, the most dramatic differences between the tolerant and susceptible genotypes were observed during recovery irrigation, suggesting that the tolerant genotypes activate mechanisms that allow more efficient recovery after a severe drought. Conclusions/Significance A correlation between levels of photosynthesis and transcription under stress was observed and differences in the number, type and expression levels of transcription factor families were also identified under drought and recovery between the three maize landraces. Gene expression analysis suggests that the drought tolerant landraces have a greater capacity to rapidly modulate more genes under drought and recovery in comparison to the susceptible landrace. Modulation of a greater number of differentially expressed genes of different TF gene families is an important characteristic of the tolerant genotypes. Finally, important differences were also noted between the tolerant landraces that underlie different mechanisms of achieving tolerance. PMID:19888455

  20. Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit

    PubMed Central

    Arima, Yasunobu; Ohki, Takuto; Nishikawa, Naoki; Higuchi, Kotaro; Ota, Mitsutoshi; Tanaka, Yuki; Nio-Kobayashi, Junko; Elfeky, Mohamed; Sakai, Ryota; Mori, Yuki; Kawamoto, Tadafumi; Stofkova, Andrea; Sakashita, Yukihiro; Morimoto, Yuji; Kuwatani, Masaki; Iwanaga, Toshihiko; Yoshioka, Yoshichika; Sakamoto, Naoya; Yoshimura, Akihiko; Takiguchi, Mitsuyoshi; Sakoda, Saburo; Prinz, Marco; Kamimura, Daisuke; Murakami, Masaaki

    2017-01-01

    Impact of stress on diseases including gastrointestinal failure is well-known, but molecular mechanism is not understood. Here we show underlying molecular mechanism using EAE mice. Under stress conditions, EAE caused severe gastrointestinal failure with high-mortality. Mechanistically, autoreactive-pathogenic CD4+ T cells accumulated at specific vessels of boundary area of third-ventricle, thalamus, and dentate-gyrus to establish brain micro-inflammation via stress-gateway reflex. Importantly, induction of brain micro-inflammation at specific vessels by cytokine injection was sufficient to establish fatal gastrointestinal failure. Resulting micro-inflammation activated new neural pathway including neurons in paraventricular-nucleus, dorsomedial-nucleus-of-hypothalamus, and also vagal neurons to cause fatal gastrointestinal failure. Suppression of the brain micro-inflammation or blockage of these neural pathways inhibited the gastrointestinal failure. These results demonstrate direct link between brain micro-inflammation and fatal gastrointestinal disease via establishment of a new neural pathway under stress. They further suggest that brain micro-inflammation around specific vessels could be switch to activate new neural pathway(s) to regulate organ homeostasis. DOI: http://dx.doi.org/10.7554/eLife.25517.001 PMID:28809157

  1. Motor Priming in Neurorehabilitation

    PubMed Central

    Stoykov, Mary Ellen; Madhavan, Sangeetha

    2014-01-01

    Priming is a type of implicit learning wherein a stimulus prompts a change in behavior. Priming has been long studied in the field of psychology. More recently, rehabilitation researchers have studied motor priming as a possible way to facilitate motor learning. For example, priming of the motor cortex is associated with changes in neuroplasticity that are associated with improvements in motor performance. Of the numerous motor priming paradigms under investigation, only a few are practical for the current clinical environment, and the optimal priming modalities for specific clinical presentations are not known. Accordingly, developing an understanding of the various types of motor priming paradigms and their underlying neural mechanisms is an important step for therapists in neurorehabilitation. Most importantly, an understanding of the methods and their underlying mechanisms is essential for optimizing rehabilitation outcomes. The future of neurorehabilitation is likely to include these priming methods, which are delivered prior to or in conjunction with primary neurorehabilitation therapies. In this Special Interest article we discuss those priming paradigms that are supported by the greatest amount of evidence including: (i) stimulation-based priming, (ii) motor imagery and action observation, (iii) sensory priming, (iv) movement-based priming, and (v) pharmacological priming. PMID:25415551

  2. Dammarane Sapogenins Ameliorates Neurocognitive Functional Impairment Induced by Simulated Long-Duration Spaceflight.

    PubMed

    Wu, Xiaorui; Li, Dong; Liu, Junlian; Diao, Lihong; Ling, Shukuan; Li, Yuheng; Gao, Jianyi; Fan, Quanchun; Sun, Weijia; Li, Qi; Zhao, Dingsheng; Zhong, Guohui; Cao, Dengchao; Liu, Min; Wang, Jiaping; Zhao, Shuang; Liu, Yu; Bai, Guie; Shi, Hongzhi; Xu, Zi; Wang, Jing; Xue, Chunmei; Jin, Xiaoyan; Yuan, Xinxin; Li, Hongxing; Liu, Caizhi; Sun, Huiyuan; Li, Jianwei; Li, Yongzhi; Li, Yingxian

    2017-01-01

    Increasing evidence indicates the occurrence of cognitive impairment in astronauts under spaceflight compound conditions, but the underlying mechanisms and countermeasures need to be explored. In this study, we found that learning and memory abilities were significantly reduced in rats under a simulated long-duration spaceflight environment (SLSE), which includes microgravity, isolation confinement, noises, and altered circadian rhythms. Dammarane sapogenins (DS), alkaline hydrolyzed products of ginsenosides, can enhance cognition function by regulating brain neurotransmitter levels and inhibiting SLSE-induced neuronal injury. Bioinformatics combined with experimental verification identified that the PI3K-Akt-mTOR pathway was inhibited and the MAPK pathway was activated during SLSE-induced cognition dysfunction, whereas DS substantially ameliorated the changes in brain. These findings defined the characteristics of SLSE-induced cognitive decline and the mechanisms by which DS improves it. The results provide an effective candidate for improving cognitive function in spaceflight missions.

  3. Dammarane Sapogenins Ameliorates Neurocognitive Functional Impairment Induced by Simulated Long-Duration Spaceflight

    PubMed Central

    Wu, Xiaorui; Li, Dong; Liu, Junlian; Diao, Lihong; Ling, Shukuan; Li, Yuheng; Gao, Jianyi; Fan, Quanchun; Sun, Weijia; Li, Qi; Zhao, Dingsheng; Zhong, Guohui; Cao, Dengchao; Liu, Min; Wang, Jiaping; Zhao, Shuang; Liu, Yu; Bai, Guie; Shi, Hongzhi; Xu, Zi; Wang, Jing; Xue, Chunmei; Jin, Xiaoyan; Yuan, Xinxin; Li, Hongxing; Liu, Caizhi; Sun, Huiyuan; Li, Jianwei; Li, Yongzhi; Li, Yingxian

    2017-01-01

    Increasing evidence indicates the occurrence of cognitive impairment in astronauts under spaceflight compound conditions, but the underlying mechanisms and countermeasures need to be explored. In this study, we found that learning and memory abilities were significantly reduced in rats under a simulated long-duration spaceflight environment (SLSE), which includes microgravity, isolation confinement, noises, and altered circadian rhythms. Dammarane sapogenins (DS), alkaline hydrolyzed products of ginsenosides, can enhance cognition function by regulating brain neurotransmitter levels and inhibiting SLSE-induced neuronal injury. Bioinformatics combined with experimental verification identified that the PI3K-Akt-mTOR pathway was inhibited and the MAPK pathway was activated during SLSE-induced cognition dysfunction, whereas DS substantially ameliorated the changes in brain. These findings defined the characteristics of SLSE-induced cognitive decline and the mechanisms by which DS improves it. The results provide an effective candidate for improving cognitive function in spaceflight missions. PMID:28611667

  4. Studies of the structure-antioxidant activity relationships and antioxidant activity mechanism of iridoid valepotriates and their degradation products

    PubMed Central

    Wang, Feifei; Zhang, Yumei; Wu, Shouhai; He, Yi; Dai, Zhong; Liu, Bin

    2017-01-01

    Oxidative stress has been associated with diverse diseases, including obesity, cancer and neurodegeneration. In fact, Valeriana jatamansi Jones (valerian) and its extracts possess strong antioxidant activities that extend their application in clinical practice to the treatment of these illnesses, even though the underlying mechanisms are not well understood. Iridoid valepotriate, a characteristic iridoid ester in valerian with poor chemical stability, possesses considerable antioxidant components. The original compounds and their degradation products have been found to exhibit strong antioxidant activities. However, the relationship between their structure and antioxidant effects and the mechanism underlying their oxidation resistance remain unclear. A forced degradation study using three iridoid valepotriates (valtrate, acevaltrate and 1-β acevaltrate) was performed in this work, and the structures of their degradation products were estimated by TLC-MS and LC-MS. Comparison of the antioxidant activities of the iridoid valepotriates before and after forced degradation revealed that degradation reduced the activities of the iridoid valepotriates in free radical scavenging and cytotoxic and cell apoptosis tests. The results suggested that the oxirane nucleus is important for defining the antioxidant profile of iridoid valepotriate. We uncovered possible mechanisms that could explain the antioxidant activities, including the generation of two hydroxyl groups through intramolecular transfer of an H• from an oxirane ring and a reduction in ROS levels through interactions with GABAergic signalling pathways. PMID:29232391

  5. An Experimental Study to Measure the Mechanical Properties of the Human Liver.

    PubMed

    Karimi, Alireza; Shojaei, Ahmad

    2018-01-01

    Since the liver is one of the most important organs of the body that can be injured during trauma, that is, during accidents like car crashes, understanding its mechanical properties is of great interest. Experimental data is needed to address the mechanical properties of the liver to be used for a variety of applications, such as the numerical simulations for medical purposes, including the virtual reality simulators, trauma research, diagnosis objectives, as well as injury biomechanics. However, the data on the mechanical properties of the liver capsule is limited to the animal models or confined to the tensile/compressive loading under single direction. Therefore, this study was aimed at experimentally measuring the axial and transversal mechanical properties of the human liver capsule under both the tensile and compressive loadings. To do that, 20 human cadavers were autopsied and their liver capsules were excised and histologically analyzed to extract the mean angle of a large fibers population (bundle of the fine collagen fibers). Thereafter, the samples were cut and subjected to a series of axial and transversal tensile/compressive loadings. The results revealed the tensile elastic modulus of 12.16 ± 1.20 (mean ± SD) and 7.17 ± 0.85 kPa under the axial and transversal loadings respectively. Correspondingly, the compressive elastic modulus of 196.54 ± 13.15 and 112.41 ± 8.98 kPa were observed under the axial and transversal loadings respectively. The compressive axial and transversal maximum/failure stress of the capsule were 32.54 and 37.30 times higher than that of the tensile ones respectively. The capsule showed a stiffer behavior under the compressive load compared to the tensile one. In addition, the axial elastic modulus of the capsule was found to be higher than that of the transversal one. The findings of the current study have implications not only for understanding the mechanical properties of the human capsule tissue under tensile/compressive loading, but also for providing unprocessed data for both the doctors and engineers to be used for diagnosis and simulation purposes. © 2017 S. Karger AG, Basel.

  6. Osteoporosis and alzheimer pathology: Role of cellular stress response and hormetic redox signaling in aging and bone remodeling

    PubMed Central

    Cornelius, Carolin; Koverech, Guido; Crupi, Rosalia; Di Paola, Rosanna; Koverech, Angela; Lodato, Francesca; Scuto, Maria; Salinaro, Angela T.; Cuzzocrea, Salvatore; Calabrese, Edward J.; Calabrese, Vittorio

    2014-01-01

    Alzheimer’s disease (AD) and osteoporosis are multifactorial progressive degenerative disorders. Increasing evidence shows that osteoporosis and hip fracture are common complication observed in AD patients, although the mechanisms underlying this association remain poorly understood. Reactive oxygen species (ROS) are emerging as intracellular redox signaling molecules involved in the regulation of bone metabolism, including receptor activator of nuclear factor-κB ligand-dependent osteoclast differentiation, but they also have cytotoxic effects that include lipoperoxidation and oxidative damage to proteins and DNA. ROS generation, which is implicated in the regulation of cellular stress response mechanisms, is an integrated, highly regulated, process under control of redox sensitive genes coding for redox proteins called vitagenes. Vitagenes, encoding for proteins such as heat shock proteins (Hsps) Hsp32, Hsp70, the thioredoxin, and the sirtuin protein, represent a systems controlling a complex network of intracellular signaling pathways relevant to life span and involved in the preservation of cellular homeostasis under stress conditions. Consistently, nutritional anti-oxidants have demonstrated their neuroprotective potential through a hormetic-dependent activation of vitagenes. The biological relevance of dose–response affects those strategies pointing to the optimal dosing to patients in the treatment of numerous diseases. Thus, the heat shock response has become an important hormetic target for novel cytoprotective strategies focusing on the pharmacological development of compounds capable of modulating stress response mechanisms. Here we discuss possible signaling mechanisms involved in the activation of vitagenes which, relevant to bone remodeling and through enhancement of cellular stress resistance provide a rationale to limit the deleterious consequences associated to homeostasis disruption with consequent impact on the aging process. PMID:24959146

  7. New Insights into the Explosion Source from SPE

    NASA Astrophysics Data System (ADS)

    Patton, H. J.

    2015-12-01

    Phase I of the Source Physics Experiments (SPE) is a series of chemical explosions at varying depths and yields detonated in the same emplacement hole on Climax stock, a granitic pluton located on the Nevada National Security Site. To date, four of the seven planned tests have been conducted, the last in May 2015, called SPE-4P, with a scaled depth of burial of 1549 m/kt1/3 in order to localize the source in time and space. Surface ground motions validated that the source medium did not undergo spallation, and a key experimental objective was achieved where SPE-4P is the closest of all tests in the series to a pure monopole source and will serve as an empirical Green's function for analysis against other SPE tests. A scientific objective of SPE is to understand mechanisms of rock damage for generating seismic waves, particularly surface and S waves, including prompt damage under compressive stresses and "late-time" damage under tensile stresses. Studies have shown that prompt damage can explain ~75% of the seismic moment for some SPE tests. Spallation is a form of late-time damage and a facilitator of damage mechanisms under tensile stresses including inelastic brittle deformation and shear dilatancy on pre-existing faults or joints. As an empirical Green's function, SPE-4P allows the study of late-time damage mechanisms on other SPE tests that induce spallation and late-time damage, and I'll discuss these studies. The importance for nuclear monitoring cannot be overstated because new research shows that damage mechanisms can affect surface wave magnitude Ms more than tectonic release, and are a likely factor related to anomalous mb-Ms behavior for North Korean tests.

  8. Regulatory domain phosphorylation to distinguish the mechanistic basis underlying acute CFTR modulators

    PubMed Central

    Pyle, Louise C.; Ehrhardt, Annette; Mitchell, Lisa High; Fan, LiJuan; Ren, Aixia; Naren, Anjaparavanda P.; Li, Yao; Clancy, J. P.; Bolger, Graeme B.; Sorscher, Eric J.

    2011-01-01

    Modulator compounds intended to overcome disease-causing mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) show significant promise in clinical testing for cystic fibrosis. However, the mechanism(s) of action underlying these compounds are not fully understood. Activation of CFTR ion transport requires PKA-regulated phosphorylation of the regulatory domain (R-D) and dimerization of the nucleotide binding domains. Using a newly developed assay, we evaluated nine compounds including both CFTR potentatiators and activators discovered via various high-throughput screening strategies to acutely augment CFTR activity. We found considerable differences in the effects on R-D phosphorylation. Some (including UCCF-152) stimulated robust phosphorylation, and others had little effect (e.g., VRT-532 and VX-770). We then compared CFTR activation by UCCF-152 and VRT-532 in Ussing chamber studies using two epithelial models, CFBE41o− and Fischer rat thyroid cells, expressing various CFTR forms. UCCF-152 activated wild-type-, G551D-, and rescued F508del-CFTR currents but did not potentiate cAMP-mediated CFTR activation. In contrast, VRT-532 moderately activated CFTR short-circuit current and strongly potentiated forskolin-mediated current. Combined with the result that UCCF-152, but not VRT-532 or VX-770, acts by increasing CFTR R-D phosphorylation, these findings indicate that potentiation of endogenous cAMP-mediated activation of mutant CFTR is not due to a pathway involving augmented R-D phosphorylation. This study presents an assay useful to distinguish preclinical compounds by a crucial mechanism underlying CFTR activation, delineates two types of compound able to acutely augment CFTR activity (e.g., activators and potentiators), and demonstrates that a number of different mechanisms can be successfully employed to activate mutant CFTR. PMID:21724857

  9. Synergism and Antagonism of Proximate Mechanisms Enable and Constrain the Response to Simultaneous Selection on Body Size and Development Time: An Empirical Test Using Experimental Evolution.

    PubMed

    Davidowitz, Goggy; Roff, Derek; Nijhout, H Frederik

    2016-11-01

    Natural selection acts on multiple traits simultaneously. How mechanisms underlying such traits enable or constrain their response to simultaneous selection is poorly understood. We show how antagonism and synergism among three traits at the developmental level enable or constrain evolutionary change in response to simultaneous selection on two focal traits at the phenotypic level. After 10 generations of 25% simultaneous directional selection on all four combinations of body size and development time in Manduca sexta (Sphingidae), the changes in the three developmental traits predict 93% of the response of development time and 100% of the response of body size. When the two focal traits were under synergistic selection, the response to simultaneous selection was enabled by juvenile hormone and ecdysteroids and constrained by growth rate. When the two focal traits were under antagonistic selection, the response to selection was due primarily to change in growth rate and constrained by the two hormonal traits. The approach used here reduces the complexity of the developmental and endocrine mechanisms to three proxy traits. This generates explicit predictions for the evolutionary response to selection that are based on biologically informed mechanisms. This approach has broad applicability to a diverse range of taxa, including algae, plants, amphibians, mammals, and insects.

  10. Clozapine-induced agranulocytosis: Evidence for an immune-mediated mechanism from a patient-specific in-vitro approach

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

    Regen, Francesca; Herzog, Irmelin; Hahn, Eric

    2017-02-01

    Use of the atypical antipsychotic clozapine (CZP) is compromised by the risk of potentially fatal agranulocytosis/granulocytopenia (CIAG). To address this, we have established a simple, personalized cell culture-based strategy to identify CIAG-susceptible patients, hypothesizing that an immunogenic and possibly haptene-based mechanism underlies CIAG pathophysiology. To detect a putative haptene-induced response to CZP in vitro exposure, a traditional lymphocyte stimulation assay was adapted and applied to patient-specific peripheral blood-derived mononuclear cells (PBMC). 6 patients with a history of CIAG, 6 patients under CZP treatment (without CIAG) and 12 matched healthy controls were studied. In vitro CZP exposure, even at strikingly lowmore » levels, resulted in significantly increased proliferation rates only in CIAG patients' PBMC. Other parameters including cell viability and mitogen-induced proliferation were also affected by in vitro CZP exposure, yet there was no significant difference between the groups. This personalized approach is a starting point for further investigations into a putative haptene-based mechanism underlying CIAG development, and may facilitate the future development of predictive testing. - Highlights: • Clozapine induces proliferation in PBMCs from patients with a history of CIAG. • Simple, PBMC-based assay results in robust effects of physiological clozapine levels. • Haptene-based mechanisms discussed to underlie clozapine-induced proliferation.« less

  11. Comparison of data analysis strategies for intent-to-treat analysis in pre-test-post-test designs with substantial dropout rates.

    PubMed

    Salim, Agus; Mackinnon, Andrew; Christensen, Helen; Griffiths, Kathleen

    2008-09-30

    The pre-test-post-test design (PPD) is predominant in trials of psychotherapeutic treatments. Missing data due to withdrawals present an even bigger challenge in assessing treatment effectiveness under the PPD than under designs with more observations since dropout implies an absence of information about response to treatment. When confronted with missing data, often it is reasonable to assume that the mechanism underlying missingness is related to observed but not to unobserved outcomes (missing at random, MAR). Previous simulation and theoretical studies have shown that, under MAR, modern techniques such as maximum-likelihood (ML) based methods and multiple imputation (MI) can be used to produce unbiased estimates of treatment effects. In practice, however, ad hoc methods such as last observation carried forward (LOCF) imputation and complete-case (CC) analysis continue to be used. In order to better understand the behaviour of these methods in the PPD, we compare the performance of traditional approaches (LOCF, CC) and theoretically sound techniques (MI, ML), under various MAR mechanisms. We show that the LOCF method is seriously biased and conclude that its use should be abandoned. Complete-case analysis produces unbiased estimates only when the dropout mechanism does not depend on pre-test values even when dropout is related to fixed covariates including treatment group (covariate-dependent: CD). However, CC analysis is generally biased under MAR. The magnitude of the bias is largest when the correlation of post- and pre-test is relatively low.

  12. Fast and stable redox reactions of MnO2/CNT hybrid electrodes for dynamically stretchable pseudocapacitors

    NASA Astrophysics Data System (ADS)

    Gu, Taoli; Wei, Bingqing

    2015-07-01

    Pseudocapacitors, which are energy storage devices that take advantage of redox reactions to store electricity, have a different charge storage mechanism compared to lithium-ion batteries (LIBs) and electric double-layer capacitors (EDLCs), and they could realize further gains if they were used as stretchable power sources. The realization of dynamically stretchable pseudocapacitors and understanding of the underlying fundamentals of their mechanical-electrochemical relationship have become indispensable. We report herein the electrochemical performance of dynamically stretchable pseudocapacitors using buckled MnO2/CNT hybrid electrodes. The extremely small relaxation time constant of less than 0.15 s indicates a fast redox reaction at the MnO2/CNT hybrid electrodes, securing a stable electrochemical performance for the dynamically stretchable pseudocapacitors. This finding and the fundamental understanding gained from the pseudo-capacitive behavior coupled with mechanical deformation under a dynamic stretching mode would provide guidance to further improve their overall performance including a higher power density than LIBs, a higher energy density than EDLCs, and a long-life cycling stability. Most importantly, these results will potentially accelerate the applications of stretchable pseudocapacitors for flexible and biomedical electronics.Pseudocapacitors, which are energy storage devices that take advantage of redox reactions to store electricity, have a different charge storage mechanism compared to lithium-ion batteries (LIBs) and electric double-layer capacitors (EDLCs), and they could realize further gains if they were used as stretchable power sources. The realization of dynamically stretchable pseudocapacitors and understanding of the underlying fundamentals of their mechanical-electrochemical relationship have become indispensable. We report herein the electrochemical performance of dynamically stretchable pseudocapacitors using buckled MnO2/CNT hybrid electrodes. The extremely small relaxation time constant of less than 0.15 s indicates a fast redox reaction at the MnO2/CNT hybrid electrodes, securing a stable electrochemical performance for the dynamically stretchable pseudocapacitors. This finding and the fundamental understanding gained from the pseudo-capacitive behavior coupled with mechanical deformation under a dynamic stretching mode would provide guidance to further improve their overall performance including a higher power density than LIBs, a higher energy density than EDLCs, and a long-life cycling stability. Most importantly, these results will potentially accelerate the applications of stretchable pseudocapacitors for flexible and biomedical electronics. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr02310f

  13. In vitro total antioxidant capacity and anti-flammatory activity of three common avenanthramides

    USDA-ARS?s Scientific Manuscript database

    Oats possess numerous beneficial properties, including anti-inflammatory, antiatherogenic, antiproliferative, anticancer, and anti-itch effects. To better understand mechanisms underlying the health benefits of oats, we evaluated the free radical scavenging abilities of oat avenanthramides 2c, 2f, a...

  14. Air toxics and epigenetic effects: ozone altered microRNAs in the sputum of human subjects

    EPA Science Inventory

    Ozone (03) is a criteria air pollutant that is associated with numerous adverse health effects, including altered respiratory immune responses. Despite its deleterious health effects, possible epigenetic mechanisms underlying 03-induced health effects remain understudied. MicroRN...

  15. Whitewater Kayaking Instruction: Skills and Techniques.

    ERIC Educational Resources Information Center

    Poff, Raymond; Stuessy, Tom

    This paper briefly presents ideas and techniques that can facilitate effective whitewater kayaking instruction. Instructors often focus so much on the mechanics of specific skills that they overlook less obvious, but equally important, aspects of instruction. These aspects include the underlying purposes and guiding principles of kayaking…

  16. Metals in airpollution particles decrease whole blood coagulation time

    EPA Science Inventory

    The mechanism underlying the pro-coagulative effect of air pollution particle exposure is not known. We tested the postulate that 1) the soluble fraction ofan air pollution particle can affect whole blood coagulation time and 2) metals included in the soluble fraction are respons...

  17. REDUCING UNCERTAINTIES IN CHEMICAL MECHANISMS OF AROMATIC AND BIOGENIC HYDROCARBONS

    EPA Science Inventory

    The state of science in ozone chemistry was reviewed recently in a series of journal reports published under the auspices of the North American Research Strategy for Tropospheric Ozone (NARSTO) in Atmospheric Environment. Included in the NARSTO reports are research gaps that ne...

  18. Underlying molecular and cellular mechanisms in childhood irritable bowel syndrome

    USDA-ARS?s Scientific Manuscript database

    Irritable bowel syndrome (IBS) affects a large number of children throughout the world. The symptom expression of IBS is heterogeneous, and several factors which may be interrelated within the IBS biopsychosocial model play a role. These factors include visceral hyperalgesia, intestinal permeability...

  19. The menstrual cycle and the skin.

    PubMed

    Raghunath, R S; Venables, Z C; Millington, G W M

    2015-03-01

    Perimenstrual exacerbations of dermatoses are commonly recognized, yet our knowledge of the underlying pathophysiological mechanisms remains imperfect. Research into the effects of oestrogen on the skin has provided evidence to suggest that oestrogen is associated with increases in skin thickness and dermal water content, improved barrier function, and enhanced wound healing. Research into the effects of progesterone suggests that the presence of various dermatoses correlates with peak levels of progesterone. Dermatoses that are exacerbated perimenstrually include acne, psoriasis, atopic eczema and irritant dermatitis, and possibly also erythema multiforme. Exacerbations occur at the peak levels of progesterone in the menstrual cycle. Underlying mechanisms include reduced immune and barrier functions as a result of cyclical fluctuations in oestrogen and/or progesterone. Autoimmune progesterone and oestrogen dermatitis are the best-characterized examples of perimenstrual cutaneous reactions to hormones produced during the menstrual cycle. In this review, we describe the current understanding of the menstrual cycle, and its effect on the skin and cutaneous disorders. © 2015 British Association of Dermatologists.

  20. The mouse F3/contactin glycoprotein

    PubMed Central

    Bizzoca, Antonella; Corsi, Patrizia

    2009-01-01

    F3/Contactin is an immunoglobulin superfamily component expressed in the nervous tissue of several species. Here we focus on the structural and functional properties of its mouse relative, on the mechanisms driving its regulated expression and on its developmental role. F3/Contactin is differentially expressed in distinct populations of central and peripheral neurons and in some non-neuronal cells. Accordingly, the regulatory region of the underlying gene includes promoter elements undergoing differential activation, associated with an intricate splicing profile, indicating that transcriptional and posttranscriptional mechanisms contribute to its expression. Transgenic models allowed to follow F3/Contactin promoter activation in vivo and to modify F3/Contactin gene expression under a heterologous promoter, which resulted in morphological and functional phenotypes. Besides axonal growth and pathfinding, these concerned earlier events, including precursor proliferation and commitment. This wide role in neural ontogenesis is consistent with the recognized interaction of F3/Contactin with developmental control genes belonging to the Notch pathway. PMID:19372728

  1. Laser Doppler vibrometry measurement of the mechanical myogram

    NASA Astrophysics Data System (ADS)

    Rohrbaugh, John W.; Sirevaag, Erik J.; Richter, Edward J.

    2013-12-01

    Contracting muscles show complex dimensional changes that include lateral expansion. Because this expansion process is intrinsically vibrational, driven by repetitive actions of multiple motor units, it can be sensed and quantified using the method of Laser Doppler Vibrometry (LDV). LDV has a number of advantages over more traditional mechanical methods based on microphones and accelerometers. The LDV mechanical myogram from a small hand muscle (the first dorsal interosseous) was studied under conditions of elastic loading applied to the tip of the abducted index finger. The LDV signal was shown to be related systematically to the level of force production, and to compare favorably with conventional methods for sensing the mechanical and electrical aspects of muscle contraction.

  2. Lunar surface engineering properties experiment definition. Volume 2: Mechanics of rolling sphere-soil slope interaction

    NASA Technical Reports Server (NTRS)

    Hovland, H. J.; Mitchell, J. K.

    1971-01-01

    The soil deformation mode under the action of a rolling sphere (boulder) was determined, and a theory based on actual soil failure mechanism was developed which provides a remote reconnaissance technique for study of soil conditions using boulder track observations. The failure mechanism was investigated by using models and by testing an instrumented spherical wheel. The wheel was specifically designed to measure contact pressure, but it also provided information on the failure mechanism. Further tests included rolling some 200 spheres down sand slopes. Films were taken of the rolling spheres, and the tracks were measured. Implications of the results and reevaluation of the lunar boulder tracks are discussed.

  3. Plants Used in the Management of Diabetic Complications

    PubMed Central

    Dodda, D.; Ciddi, V.

    2014-01-01

    Diabetes is a disease, which has assumed vital public health importance because of the complications associated with it. Various mechanisms including polyol pathway along with a complex integrating paradigm have been implicated in glucose-mediated complications. Though polyol pathway was established as a major mechanism, precise pathogenesis of these complications is not yet completely elucidated. Thus research focus was shifted towards key enzyme, aldose reductase in the pathway. Even though various compounds with aldose reductase inhibitory activity were synthesised, a very few compounds are under clinical use. However, studies on these compounds were always under conflicting results and an attempt has been made to review various natural substances with aldose reductase inhibitory activity and their role in management of diabetic complications. PMID:24843182

  4. Rapid adaptive responses to climate change in corals

    NASA Astrophysics Data System (ADS)

    Torda, Gergely; Donelson, Jennifer M.; Aranda, Manuel; Barshis, Daniel J.; Bay, Line; Berumen, Michael L.; Bourne, David G.; Cantin, Neal; Foret, Sylvain; Matz, Mikhail; Miller, David J.; Moya, Aurelie; Putnam, Hollie M.; Ravasi, Timothy; van Oppen, Madeleine J. H.; Thurber, Rebecca Vega; Vidal-Dupiol, Jeremie; Voolstra, Christian R.; Watson, Sue-Ann; Whitelaw, Emma; Willis, Bette L.; Munday, Philip L.

    2017-09-01

    Pivotal to projecting the fate of coral reefs is the capacity of reef-building corals to acclimatize and adapt to climate change. Transgenerational plasticity may enable some marine organisms to acclimatize over several generations and it has been hypothesized that epigenetic processes and microbial associations might facilitate adaptive responses. However, current evidence is equivocal and understanding of the underlying processes is limited. Here, we discuss prospects for observing transgenerational plasticity in corals and the mechanisms that could enable adaptive plasticity in the coral holobiont, including the potential role of epigenetics and coral-associated microbes. Well-designed and strictly controlled experiments are needed to distinguish transgenerational plasticity from other forms of plasticity, and to elucidate the underlying mechanisms and their relative importance compared with genetic adaptation.

  5. Chromatin and lamin A determine two different mechanical response regimes of the cell nucleus.

    PubMed

    Stephens, Andrew D; Banigan, Edward J; Adam, Stephen A; Goldman, Robert D; Marko, John F

    2017-07-07

    The cell nucleus must continually resist and respond to intercellular and intracellular mechanical forces to transduce mechanical signals and maintain proper genome organization and expression. Altered nuclear mechanics is associated with many human diseases, including heart disease, progeria, and cancer. Chromatin and nuclear envelope A-type lamin proteins are known to be key nuclear mechanical components perturbed in these diseases, but their distinct mechanical contributions are not known. Here we directly establish the separate roles of chromatin and lamin A/C and show that they determine two distinct mechanical regimes via micromanipulation of single isolated nuclei. Chromatin governs response to small extensions (<3 μm), and euchromatin/heterochromatin levels modulate the stiffness. In contrast, lamin A/C levels control nuclear strain stiffening at large extensions. These results can be understood through simulations of a polymeric shell and cross-linked polymer interior. Our results provide a framework for understanding the differential effects of chromatin and lamin A/C in cell nuclear mechanics and their alterations in disease. © 2017 Stephens 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).

  6. Influence of thermodynamic mechanism of inter- facial adsorption on purifying air-conditioning engineering under intensification of electric field

    NASA Astrophysics Data System (ADS)

    Chen, Yun-Yu

    2016-12-01

    As a kind of mass transfer process as well as the basis of separating and purifying mixtures, interfacial adsorption has been widely applied to fields like chemical industry, medical industry and purification engineering in recent years. Influencing factors of interfacial adsorption, in addition to the traditional temperature, intensity of pressure, amount of substance and concentration, also include external fields, such as magnetic field, electric field and electromagnetic field, etc. Starting from the point of thermodynamics and taking the Gibbs adsorption as the model, the combination of energy axiom and the first law of thermodynamics was applied to boundary phase, and thus the theoretical expression for the volume of interface absorption under electric field as well as the mathematical relationship between surface tension and electric field intensity was obtained. In addition, according to the obtained theoretical expression, the volume of interface absorption of ethanol solution under different electric field intensities and concentrations was calculated. Moreover, the mechanism of interfacial adsorption was described from the perspective of thermodynamics and the influence of electric field on interfacial adsorption was explained reasonably, aiming to further discuss the influence of thermodynamic mechanism of interfacial adsorption on purifying air-conditioning engineering under intensification of electric field.

  7. Mechanisms and pathways of growth failure in primordial dwarfism.

    PubMed

    Klingseisen, Anna; Jackson, Andrew P

    2011-10-01

    The greatest difference between species is size; however, the developmental mechanisms determining organism growth remain poorly understood. Primordial dwarfism is a group of human single-gene disorders with extreme global growth failure (which includes Seckel syndrome, microcephalic osteodysplastic primordial dwarfism I [MOPD] types I and II, and Meier-Gorlin syndrome). Ten genes have now been identified for microcephalic primordial dwarfism, encoding proteins involved in fundamental cellular processes including genome replication (ORC1 [origin recognition complex 1], ORC4, ORC6, CDT1, and CDC6), DNA damage response (ATR [ataxia-telangiectasia and Rad3-related]), mRNA splicing (U4atac), and centrosome function (CEP152, PCNT, and CPAP). Here, we review the cellular and developmental mechanisms underlying the pathogenesis of these conditions and address whether further study of these genes could provide novel insight into the physiological regulation of organism growth.

  8. Splanchnic vein thrombosis in myeloproliferative neoplasms: pathophysiology and molecular mechanisms of disease

    PubMed Central

    How, Joan; Zhou, Amy; Oh, Stephen T.

    2016-01-01

    Myeloproliferative neoplasms (MPNs) are the most common underlying prothrombotic disorder found in patients with splanchnic vein thrombosis (SVT). Clinical risk factors for MPN-associated SVTs include younger age, female sex, concomitant hypercoagulable disorders, and the JAK2 V617F mutation. These risk factors are distinct from those associated with arterial or deep venous thrombosis (DVT) in MPN patients, suggesting disparate disease mechanisms. The pathophysiology of SVT is thought to derive from local interactions between activated blood cells and the unique splanchnic endothelial environment. Other mutations commonly found in MPNs, including CALR and MPL, are rare in MPN-associated SVT. The purpose of this article is to review the clinical and molecular risk factors for MPN-associated SVT, with particular focus on the possible mechanisms of SVT formation in MPN patients. PMID:28246554

  9. Responds of Bone Cells to Microgravity: Ground-Based Research

    NASA Astrophysics Data System (ADS)

    Zhang, Jian; Li, Jingbao; Xu, Huiyun; Yang, Pengfei; Xie, Li; Qian, Airong; Zhao, Yong; Shang, Peng

    2015-11-01

    Severe loss of bone occurs due to long-duration spaceflight. Mechanical loading stimulates bone formation, while bone degradation happens under mechanical unloading. Bone remodeling is a dynamic process in which bone formation and bone resorption are tightly coupled. Increased bone resorption and decreased bone formation caused by reduced mechanical loading, generally result in disrupted bone remodeling. Bone remodeling is orchestrated by multiple bone cells including osteoblast, osteocyte, osteoclast and mesenchymal stem cell. It is yet not clear that how these bone cells sense altered gravity, translate physical stimulus into biochemical signals, and then regulate themselves structurally and functionally. In this paper, studies elucidating the bioeffects of microgravity on bone cells (osteoblast, osteocyte, osteoclast, mesenchymal stem cell) using various platforms including spaceflight and ground-based simulated microgravity were summarized. Promising gravity-sensitive signaling pathways and protein molecules were proposed.

  10. Structure of the TRPA1 ion channel suggests regulatory mechanisms.

    PubMed

    Paulsen, Candice E; Armache, Jean-Paul; Gao, Yuan; Cheng, Yifan; Julius, David

    2015-04-23

    The TRPA1 ion channel (also known as the wasabi receptor) is a detector of noxious chemical agents encountered in our environment or produced endogenously during tissue injury or drug metabolism. These include a broad class of electrophiles that activate the channel through covalent protein modification. TRPA1 antagonists hold potential for treating neurogenic inflammatory conditions provoked or exacerbated by irritant exposure. Despite compelling reasons to understand TRPA1 function, structural mechanisms underlying channel regulation remain obscure. Here we use single-particle electron cryo- microscopy to determine the structure of full-length human TRPA1 to ∼4 Å resolution in the presence of pharmacophores, including a potent antagonist. Several unexpected features are revealed, including an extensive coiled-coil assembly domain stabilized by polyphosphate co-factors and a highly integrated nexus that converges on an unpredicted transient receptor potential (TRP)-like allosteric domain. These findings provide new insights into the mechanisms of TRPA1 regulation, and establish a blueprint for structure-based design of analgesic and anti-inflammatory agents.

  11. Structure of the TRPA1 ion channel suggests regulatory mechanisms

    PubMed Central

    Paulsen, Candice E.; Armache, Jean-Paul; Gao, Yuan; Cheng, Yifan; Julius, David

    2015-01-01

    The TRPA1 ion channel (a.k.a the ‘wasabi receptor’) is a detector of noxious chemical agents encountered in our environment or produced endogenously during tissue injury or drug metabolism. These include a broad class of electrophiles that activate the channel through covalent protein modification. TRPA1 antagonists hold potential for treating neurogenic inflammatory conditions provoked or exacerbated by irritant exposure. Despite compelling reasons to understand TRPA1 function, structural mechanisms underlying channel regulation remain obscure. Here, we use single-particle electron cryo-microscopy to determine the structure of full-length human TRPA1 to ~4Å resolution in the presence of pharmacophores, including a potent antagonist. A number of unexpected features are revealed, including an extensive coiled-coil assembly domain stabilized by polyphosphate co-factors and a highly integrated nexus that converges on an unpredicted TRP-like allosteric domain. These findings provide novel insights into mechanisms of TRPA1 regulation, and establish a blueprint for structure-based design of analgesic and anti-inflammatory agents. PMID:25855297

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

    PubMed Central

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

    2017-01-01

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

  13. 78 FR 50453 - Notice of Permit Applications Received Under the Antarctic Conservation Act of 1978 (Pub. L. 95-541)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-19

    ... would remain deployed for 5 years and would be completely removed (including bolts and power sources) at... knowledge on the mechanics and pace of glacial retreat. Images gained from the cameras would also be used in...

  14. Two Arabidopsis AGC kinases are critical for the polarized growth of pollen tubes

    USDA-ARS?s Scientific Manuscript database

    Reproduction of flowering plants requires the growth of pollen tubes to deliver immotile sperm for fertilization. Pollen tube growth resembles that of polarized metazoan cells, in that some molecular mechanisms underlying cell polarization and growth are evolutionarily conserved, including the funct...

  15. The Role of Antimatter in Big-Bang Cosmology

    ERIC Educational Resources Information Center

    Stecker, Floyd W.

    1974-01-01

    Discusses theories underlying man's conceptions of the universe, including Omnes' repulsive separation mechanism, the turbulence theory of galaxy formation, and the author's idea about gamma ray spectra in cosmological matter-antimatter annihilation. Indicates that the Apollo data provide encouraging evidence by fitting well with his theoretical…

  16. Omics, microbial modeling, and food safety information infrastructure: a food safety perspective

    USDA-ARS?s Scientific Manuscript database

    Over the last three decades, advances in a variety of cutting-edge “omics” technologies, including genomics, proteomics, and metabolomics, as well as in molecular and mathematical modeling approaches have provided the ability to more easily determine and interpret the mechanisms underlying pathogene...

  17. Photocatalytic disinfection of spoilage bacteria Pseudomonas fluorescens and Macrococcus caseolyticus by nano-TiO2

    USDA-ARS?s Scientific Manuscript database

    Photocatalytic disinfection of spoilage bacteria gram-negative (G-) P. fluorescens and gram-positive (G+) M. caseolyticus by nano-TiO2 under different experimental conditions and the disinfection mechanism were investigated. The experimental conditions included the initial bacterial populations, nan...

  18. Method to study cell migration under uniaxial compression

    PubMed Central

    Srivastava, Nishit; Kay, Robert R.; Kabla, Alexandre J.

    2017-01-01

    The chemical, physical, and mechanical properties of the extracellular environment have a strong effect on cell migration. Aspects such as pore size or stiffness of the matrix influence the selection of the mechanism used by cells to propel themselves, including by pseudopods or blebbing. How a cell perceives its environment and how such a cue triggers a change in behavior are largely unknown, but mechanics is likely to be involved. Because mechanical conditions are often controlled by modifying the composition of the environment, separating chemical and physical contributions is difficult and requires multiple controls. Here we propose a simple method to impose a mechanical compression on individual cells without altering the composition of the matrix. Live imaging during compression provides accurate information about the cell's morphology and migratory phenotype. Using Dictyostelium as a model, we observe that a compression of the order of 500 Pa flattens the cells under gel by up to 50%. This uniaxial compression directly triggers a transition in the mode of migration from primarily pseudopodial to bleb driven in <30 s. This novel device is therefore capable of influencing cell migration in real time and offers a convenient approach with which to systematically study mechanotransduction in confined environments. PMID:28122819

  19. Mechanisms and Modifiers of Methylmercury-Induced Neurotoxicity

    PubMed Central

    Fretham, Stephanie JB; Caito, Samuel; Martinez-Finley, Ebany J; Aschner, Michael

    2016-01-01

    The neurotoxic consequences of methylmercury (MeHg) exposure have long been known, however a complete understanding of the mechanisms underlying this toxicity is elusive. Recent epidemiological and experimental studies have provided many mechanistic insights, particularly into the contribution of genetic and environmental factors that interact with MeHg to modify toxicity. This review will outline cellular processes directly and indirectly affected by MeHg, including oxidative stress, cellular signaling and gene expression, and discuss genetic, environmental and nutritional factors capable of modifying MeHg toxicity. PMID:27795823

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

    Xie, Miao; Mohammadi, Reza; Turner, Christopher L.

    In this paper, we explore the hardening mechanisms in WB4-based solid solutions upon addition of Ta, Mn, and Cr using in situ radial X-ray diffraction techniques under nonhydrostatic pressure. By examining the lattice-supported differential strain, we provide insights into the mechanism for hardness increase in binary solid solutions at low dopant concentrations. Speculations on the combined effects of electronic structure and atomic size in ternary WB 4 solid solutions containing Ta with Mn or Cr are also included to understand the extremely high hardness of these materials.

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

    Xie, Miao; Turner, Christopher L.; Mohammadi, Reza

    In this work, we explore the hardening mechanisms in WB{sub 4}-based solid solutions upon addition of Ta, Mn, and Cr using in situ radial X-ray diffraction techniques under non-hydrostatic pressure. By examining the lattice-supported differential strain, we provide insights into the mechanism for hardness increase in binary solid solutions at low dopant concentrations. Speculations on the combined effects of electronic structure and atomic size in ternary WB{sub 4} solid solutions containing Ta with Mn or Cr are also included to understand the extremely high hardness of these materials.

  2. Lunar drill and test apparatus

    NASA Technical Reports Server (NTRS)

    Norrington, David W.; Ardoin, Didier C.; Alexander, Stephen G.; Rowland, Philip N.; Vastakis, Frank N.; Linsey, Steven L.

    1988-01-01

    The design of an experimental lunar drill and a facility to test the drill under simulated lunar conditions is described. The drill utilizes a polycrystalline diamond compact drag bit and an auger to mechanically remove cuttings from the hole. The drill will be tested in a vacuum chamber and powered through a vacuum seal by a drive mechanism located above the chamber. A general description of the design is provided followed by a detailed description and analysis of each component. Recommendations for the further development of the design are included.

  3. Pyrolytic graphite collector development program

    NASA Technical Reports Server (NTRS)

    Wilkins, W. J.

    1982-01-01

    Pyrolytic graphite promises to have significant advantages as a material for multistage depressed collector electrodes. Among these advantages are lighter weight, improved mechanical stiffness under shock and vibration, reduced secondary electron back-streaming for higher efficiency, and reduced outgassing at higher operating temperatures. The essential properties of pyrolytic graphite and the necessary design criteria are discussed. This includes the study of suitable electrode geometries and methods of attachment to other metal and ceramic collector components consistent with typical electrical, thermal, and mechanical requirements.

  4. The pathophysiology of heart failure.

    PubMed

    Kemp, Clinton D; Conte, John V

    2012-01-01

    Heart failure is a clinical syndrome that results when the heart is unable to provide sufficient blood flow to meet metabolic requirements or accommodate systemic venous return. This common condition affects over 5 million people in the United States at a cost of $10-38 billion per year. Heart failure results from injury to the myocardium from a variety of causes including ischemic heart disease, hypertension, and diabetes. Less common etiologies include cardiomyopathies, valvular disease, myocarditis, infections, systemic toxins, and cardiotoxic drugs. As the heart fails, patients develop symptoms which include dyspnea from pulmonary congestion, and peripheral edema and ascites from impaired venous return. Constitutional symptoms such as nausea, lack of appetite, and fatigue are also common. There are several compensatory mechanisms that occur as the failing heart attempts to maintain adequate function. These include increasing cardiac output via the Frank-Starling mechanism, increasing ventricular volume and wall thickness through ventricular remodeling, and maintaining tissue perfusion with augmented mean arterial pressure through activation of neurohormonal systems. Although initially beneficial in the early stages of heart failure, all of these compensatory mechanisms eventually lead to a vicious cycle of worsening heart failure. Treatment strategies have been developed based upon the understanding of these compensatory mechanisms. Medical therapy includes diuresis, suppression of the overactive neurohormonal systems, and augmentation of contractility. Surgical options include ventricular resynchronization therapy, surgical ventricular remodeling, ventricular assist device implantation, and heart transplantation. Despite significant understanding of the underlying pathophysiological mechanisms in heart failure, this disease causes significant morbidity and carries a 50% 5-year mortality. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Mechanisms and pharmacogenetic signals underlying thiazide diuretics blood pressure response.

    PubMed

    Shahin, Mohamed H; Johnson, Julie A

    2016-04-01

    Thiazide (TZD) diuretics are among the most commonly prescribed antihypertensives globally; however their chronic blood pressure (BP) lowering mechanism remains unclear. Herein we discuss the current evidence regarding specific mechanisms regulating the antihypertensive effects of TZDs, suggesting that TZDs act via multiple complex and interacting mechanisms, including natriuresis with short term use and direct vasodilatory effects chronically. Additionally, we review pharmacogenomics signals that have been associated with TZDs BP-response in several cohorts (i.e. NEDD4L, PRKCA, EDNRA-GNAS, and YEATS4) and discuss how these genes might be related to TZD BP-response mechanism. Understanding the association between these genes and TZD BP mechanism might facilitate the development of new drugs and therapeutic approaches based on a deeper understanding of the determinants of BP-response. Copyright © 2016. Published by Elsevier Ltd.

  6. Elucidate the Mechanism of Telomere Maintenance in STAG2 Mutated Tumor Cells

    DTIC Science & Technology

    2017-12-01

    recent analysis identified the cohesin subunit STAG2 as one of twelve genes mutated in four or more tumor types including melanoma, pancreatic...conferences, seminars, study groups , and individual study. Include participation in conferences, workshops, and seminars not listed under major...only 12 genes found to be significantly mutated in four or more cancer types (18). Approximately 85% of STAG2 mutations are truncating and often result

  7. Baseline Description and Analysis of the Operations Related to Warehouse Controlled Documents at the Navy Publications and Forms Center, Philadelphia, Pennsylvania. Volume I. Phase I.

    DTIC Science & Technology

    1980-03-06

    performing the present NPFC tasks. Potential automation technologies may include order processing mechanization, demand printing from micrographic or...effort and documented in this volume included the following: a. Functional description of the order processing activities as they currently operate. b...covered under each analysis area. i It is obvious from the exhibit that the functional description of order processing operations was to include COG I

  8. Elongated Nanoparticle Aggregates in Cancer Cells for Mechanical Destruction with Low Frequency Rotating Magnetic Field.

    PubMed

    Shen, Yajing; Wu, Congyu; Uyeda, Taro Q P; Plaza, Gustavo R; Liu, Bin; Han, Yu; Lesniak, Maciej S; Cheng, Yu

    2017-01-01

    Magnetic nanoparticles (MNPs) functionalized with targeting moieties can recognize specific cell components and induce mechanical actuation under magnetic field. Their size is adequate for reaching tumors and targeting cancer cells. However, due to the nanometric size, the force generated by MNPs is smaller than the force required for largely disrupting key components of cells. Here, we show the magnetic assembly process of the nanoparticles inside the cells, to form elongated aggregates with the size required to produce elevated mechanical forces. We synthesized iron oxide nanoparticles doped with zinc, to obtain high magnetization, and functionalized with the epidermal growth factor (EGF) peptide for targeting cancer cells. Under a low frequency rotating magnetic field at 15 Hz and 40 mT, the internalized EGF-MNPs formed elongated aggregates and generated hundreds of pN to dramatically damage the plasma and lysosomal membranes. The physical disruption, including leakage of lysosomal hydrolases into the cytosol, led to programmed cell death and necrosis. Our work provides a novel strategy of designing magnetic nanomedicines for mechanical destruction of cancer cells.

  9. Mitochondrial Ca2+ overload underlies Abeta oligomers neurotoxicity providing an unexpected mechanism of neuroprotection by NSAIDs.

    PubMed

    Sanz-Blasco, Sara; Valero, Ruth A; Rodríguez-Crespo, Ignacio; Villalobos, Carlos; Núñez, Lucía

    2008-07-23

    Dysregulation of intracellular Ca(2+) homeostasis may underlie amyloid beta peptide (Abeta) toxicity in Alzheimer's Disease (AD) but the mechanism is unknown. In search for this mechanism we found that Abeta(1-42) oligomers, the assembly state correlating best with cognitive decline in AD, but not Abeta fibrils, induce a massive entry of Ca(2+) in neurons and promote mitochondrial Ca(2+) overload as shown by bioluminescence imaging of targeted aequorin in individual neurons. Abeta oligomers induce also mitochondrial permeability transition, cytochrome c release, apoptosis and cell death. Mitochondrial depolarization prevents mitochondrial Ca(2+) overload, cytochrome c release and cell death. In addition, we found that a series of non-steroidal anti-inflammatory drugs (NSAIDs) including salicylate, sulindac sulfide, indomethacin, ibuprofen and R-flurbiprofen depolarize mitochondria and inhibit mitochondrial Ca(2+) overload, cytochrome c release and cell death induced by Abeta oligomers. Our results indicate that i) mitochondrial Ca(2+) overload underlies the neurotoxicity induced by Abeta oligomers and ii) inhibition of mitochondrial Ca(2+) overload provides a novel mechanism of neuroprotection by NSAIDs against Abeta oligomers and AD.

  10. Fatigue crack initiation of magnesium alloys under elastic stress amplitudes: A review

    NASA Astrophysics Data System (ADS)

    Wang, B. J.; Xu, D. K.; Wang, S. D.; Han, E. H.

    2017-12-01

    The most advantageous property of magnesium (Mg) alloys is their density, which is lower compared with traditional metallic materials. Mg alloys, considered the lightest metallic structural material among others, have great potential for applications as secondary load components in the transportation and aerospace industries. The fatigue evaluation of Mg alloys under elastic stress amplitudes is very important in ensuring their service safety and reliability. Given their hexagonal close packed structure, the fatigue crack initiation of Mg and its alloys is closely related to the deformation mechanisms of twinning and basal slips. However, for Mg alloys with shrinkage porosities and inclusions, fatigue cracks will preferentially initiate at these defects, remarkably reducing the fatigue lifetime. In this paper, some fundamental aspects about the fatigue crack initiation mechanisms of Mg alloys are reviewed, including the 3 followings: 1) Fatigue crack initiation of as-cast Mg alloys, 2) influence of microstructure on fatigue crack initiation of wrought Mg alloys, and 3) the effect of heat treatment on fatigue initiation mechanisms. Moreover, some unresolved issues and future target on the fatigue crack initiation mechanism of Mg alloys are also described.

  11. Elongated Nanoparticle Aggregates in Cancer Cells for Mechanical Destruction with Low Frequency Rotating Magnetic Field

    PubMed Central

    Shen, Yajing; Wu, Congyu; Uyeda, Taro Q. P.; Plaza, Gustavo R.; Liu, Bin; Han, Yu; Lesniak, Maciej S.; Cheng, Yu

    2017-01-01

    Magnetic nanoparticles (MNPs) functionalized with targeting moieties can recognize specific cell components and induce mechanical actuation under magnetic field. Their size is adequate for reaching tumors and targeting cancer cells. However, due to the nanometric size, the force generated by MNPs is smaller than the force required for largely disrupting key components of cells. Here, we show the magnetic assembly process of the nanoparticles inside the cells, to form elongated aggregates with the size required to produce elevated mechanical forces. We synthesized iron oxide nanoparticles doped with zinc, to obtain high magnetization, and functionalized with the epidermal growth factor (EGF) peptide for targeting cancer cells. Under a low frequency rotating magnetic field at 15 Hz and 40 mT, the internalized EGF-MNPs formed elongated aggregates and generated hundreds of pN to dramatically damage the plasma and lysosomal membranes. The physical disruption, including leakage of lysosomal hydrolases into the cytosol, led to programmed cell death and necrosis. Our work provides a novel strategy of designing magnetic nanomedicines for mechanical destruction of cancer cells. PMID:28529648

  12. Leigh syndrome: neuropathology and pathogenesis.

    PubMed

    Lake, Nicole J; Bird, Matthew J; Isohanni, Pirjo; Paetau, Anders

    2015-06-01

    Leigh syndrome (LS) is the most common pediatric presentation of a defined mitochondrial disease. This progressive encephalopathy is characterized pathologically by the development of bilateral symmetrical lesions in the brainstem and basal ganglia that show gliosis, vacuolation, capillary proliferation, relative neuronal preservation, and by hyperlacticacidemia in the blood and/or cerebrospinal fluid. Understanding the molecular mechanisms underlying this unique pathology has been challenging, particularly in view of the heterogeneous and not yet fully determined genetic basis of LS. Moreover, animal models that mimic features of LS have only been created relatively recently. Here, we review the pathology of LS and consider what might be the molecular mechanisms underlying its pathogenesis. Data from a wide range of sources, including patient samples, animal models, and studies of hypoxic-ischemic encephalopathy (a condition that shares features with LS), were used to provide insight into the pathogenic mechanisms that may drive lesion development. Based on current data, we suggest that severe ATP depletion, gliosis, hyperlacticacidemia, reactive oxygen species, and potentially excitotoxicity cumulatively contribute to the neuropathogenesis of LS. An intimate understanding of the molecular mechanisms causing LS is required to accelerate the development of LS treatments.

  13. Mechanical Properties and Failure of Biopolymers: Atomistic Reactions to Macroscale Response

    PubMed Central

    Jung, GangSeob; Qin, Zhao

    2017-01-01

    The behavior of chemical bonding under various mechanical loadings is an intriguing mechanochemical property of biological materials, and the property plays a critical role in determining their deformation and failure mechanisms. Because of their astonishing mechanical properties and roles in constituting the basis of a variety of physiologically relevant materials, biological protein materials have been intensively studied. Understanding the relation between chemical bond networks (structures) and their mechanical properties offers great possibilities to enable new materials design in nanotechnology and new medical treatments for human diseases. Here we focus on how the chemical bonds in biological systems affect mechanical properties and how they change during mechanical deformation and failure. Three representative cases of biomaterials related to the human diseases are discussed in case studies, including: amyloids, intermediate filaments, and collagen, each describing mechanochemical features and how they relate to the pathological conditions at multiple scales. PMID:26108895

  14. 3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response

    DOE PAGES

    Maiti, A.; Small, W.; Lewicki, J.; ...

    2016-04-27

    3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curvesmore » predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. As a result, this indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter’s improved long-term stability and mechanical performance.« less

  15. 3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response

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

    Maiti, A.; Small, W.; Lewicki, J.

    3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curvesmore » predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. As a result, this indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter’s improved long-term stability and mechanical performance.« less

  16. 3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response

    NASA Astrophysics Data System (ADS)

    Maiti, A.; Small, W.; Lewicki, J. P.; Weisgraber, T. H.; Duoss, E. B.; Chinn, S. C.; Pearson, M. A.; Spadaccini, C. M.; Maxwell, R. S.; Wilson, T. S.

    2016-04-01

    3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curves predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. This indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter’s improved long-term stability and mechanical performance.

  17. 3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response

    PubMed Central

    Maiti, A.; Small, W.; Lewicki, J. P.; Weisgraber, T. H.; Duoss, E. B.; Chinn, S. C.; Pearson, M. A.; Spadaccini, C. M.; Maxwell, R. S.; Wilson, T. S.

    2016-01-01

    3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curves predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. This indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter’s improved long-term stability and mechanical performance. PMID:27117858

  18. Controlled growth factor release from synthetic extracellular matrices

    NASA Astrophysics Data System (ADS)

    Lee, Kuen Yong; Peters, Martin C.; Anderson, Kenneth W.; Mooney, David J.

    2000-12-01

    Polymeric matrices can be used to grow new tissues and organs, and the delivery of growth factors from these matrices is one method to regenerate tissues. A problem with engineering tissues that exist in a mechanically dynamic environment, such as bone, muscle and blood vessels, is that most drug delivery systems have been designed to operate under static conditions. We thought that polymeric matrices, which release growth factors in response to mechanical signals, might provide a new approach to guide tissue formation in mechanically stressed environments. Critical design features for this type of system include the ability to undergo repeated deformation, and a reversible binding of the protein growth factors to polymeric matrices to allow for responses to repeated stimuli. Here we report a model delivery system that can respond to mechanical signalling and upregulate the release of a growth factor to promote blood vessel formation. This approach may find a number of applications, including regeneration and engineering of new tissues and more general drug-delivery applications.

  19. Space Mechanisms Lessons Learned Study. Volume 2: Literature Review

    NASA Technical Reports Server (NTRS)

    Shapiro, Wilbur; Murray, Frank; Howarth, Roy; Fusaro, Robert

    1995-01-01

    Hundreds of satellites have been launched to date. Some have operated extremely well and others have not. In order to learn from past operating experiences, a study was conducted to determine the conditions under which space mechanisms (mechanically moving components) have previously worked or failed. The study consisted of an extensive literature review that included both government contractor reports and technical journals, communication and visits (when necessary) to the various NASA and DOD centers and their designated contractors (this included contact with project managers of current and prior NASA satellite programs as well as their industry counterparts), requests for unpublished information to NASA and industry, and a mail survey designed to acquire specific mechanism experience. The information obtained has been organized into two volumes. Volume 1 provides a summary of the lesson learned, the results of a needs analysis, responses to the mail survey, a listing of experts, a description of some available facilities, and a compilation of references. Volume 2 contains a compilation of the literature review synopsis.

  20. Mechanical design of translocating motor proteins.

    PubMed

    Hwang, Wonmuk; Lang, Matthew J

    2009-01-01

    Translocating motors generate force and move along a biofilament track to achieve diverse functions including gene transcription, translation, intracellular cargo transport, protein degradation, and muscle contraction. Advances in single molecule manipulation experiments, structural biology, and computational analysis are making it possible to consider common mechanical design principles of these diverse families of motors. Here, we propose a mechanical parts list that include track, energy conversion machinery, and moving parts. Energy is supplied not just by burning of a fuel molecule, but there are other sources or sinks of free energy, by binding and release of a fuel or products, or similarly between the motor and the track. Dynamic conformational changes of the motor domain can be regarded as controlling the flow of free energy to and from the surrounding heat reservoir. Multiple motor domains are organized in distinct ways to achieve motility under imposed physical constraints. Transcending amino acid sequence and structure, physically and functionally similar mechanical parts may have evolved as nature's design strategy for these molecular engines.

  1. Mechanical Design of Translocating Motor Proteins

    PubMed Central

    Lang, Matthew J.

    2013-01-01

    Translocating motors generate force and move along a biofilament track to achieve diverse functions including gene transcription, translation, intracellular cargo transport, protein degradation, and muscle contraction. Advances in single molecule manipulation experiments, structural biology, and computational analysis are making it possible to consider common mechanical design principles of these diverse families of motors. Here, we propose a mechanical parts list that include track, energy conversion machinery, and moving parts. Energy is supplied not just by burning of a fuel molecule, but there are other sources or sinks of free energy, by binding and release of a fuel or products, or similarly between the motor and the track. Dynamic conformational changes of the motor domain can be regarded as controlling the flow of free energy to and from the surrounding heat reservoir. Multiple motor domains are organized in distinct ways to achieve motility under imposed physical constraints. Transcending amino acid sequence and structure, physically and functionally similar mechanical parts may have evolved as nature’s design strategy for these molecular engines. PMID:19452133

  2. Mechanisms of Memory Enhancement

    PubMed Central

    Stern, Sarah A.

    2012-01-01

    The ongoing quest for memory enhancement is one that grows necessary as the global population increasingly ages. The extraordinary progress that has been made in the past few decades elucidating the underlying mechanisms of how long-term memories are formed has provided insight into how memories might also be enhanced. Capitalizing on this knowledge, it has been postulated that targeting many of the same mechanisms, including CREB activation, AMPA/NMDA receptor trafficking, neuromodulation (e.g. via dopamine, adrenaline, cortisol or acetylcholine) and metabolic processes (e.g. via glucose and insulin) may all lead to the enhancement of memory. These and other mechanisms and/or approaches have been tested via genetic or pharmacological methods in animal models, and several have been investigated in humans as well. In addition, a number of behavioral methods, including exercise and reconsolidation, may also serve to strengthen and enhance memories. By capitalizing on this knowledge and continuing to investigate these promising avenues, memory enhancement may indeed be achieved in the future. PMID:23151999

  3. The role of redox mechanisms in hepatic chronic wound healing and fibrogenesis

    PubMed Central

    2012-01-01

    Under physiological conditions, intracellular and tissue levels of reactive oxygen species (ROS) are carefully controlled and employed as fine modulators of signal transduction, gene expression and cell functional responses (redox signaling). A significant derangement in redox homeostasis, resulting in sustained levels of oxidative stress and related mediators, plays a role in the pathogenesis of human diseases characterized by chronic inflammation, chronic activation of wound healing and tissue fibrogenesis, including chronic liver diseases. In this chapter major concepts and mechanisms in redox signaling will be briefly recalled to introduce a number of selected examples of redox-related mechanisms that can actively contribute to critical events in the natural history of a chronic liver diseases, including induction of cell death, perpetuation of chronic inflammatory responses and fibrogenesis. A major focus will be on redox-dependent mechanisms involved in the modulation of phenotypic responses of activated, myofibroblast-like, hepatic stellate cells (HSC/MFs), still considered as the most relevant pro-fibrogenic cells operating in chronic liver diseases. PMID:23259696

  4. Space Mechanisms Lessons Learned Study. Volume 1: Summary

    NASA Technical Reports Server (NTRS)

    Shapiro, Wilbur; Murray, Frank; Howarth, Roy; Fusaro, Robert

    1995-01-01

    Hundreds of satellites have been launched to date. Some have operated extremely well and others have not. In order to learn from past operating experiences, a study was conducted to determine the conditions under which space mechanisms (mechanically moving components) have previously worked or failed. The study consisted of: (1) an extensive literature review that included both government contractor reports and technical journals; (2) communication and visits (when necessary) to the various NASA and DOD centers and their designated contractors (this included contact with project managers of current and prior NASA satellite programs as well as their industry counterparts); (3) requests for unpublished information to NASA and industry; and (4) a mail survey designed to acquire specific mechanism experience. The information obtained has been organized into two volumes. Volume 1 provides a summary of the lessons learned, the results of a needs analysis, responses to the mail survey, a listing of experts, a description of some available facilities and a compilation of references. Volume 2 contains a compilation of the literature review synopsis.

  5. Mechanical Anisotropy and Pressure Induced Structural Changes in Piroxicam Crystals Probed by In Situ Indentation and Raman Spectroscopy

    NASA Astrophysics Data System (ADS)

    Manimunda, Praveena; Hintsala, Eric; Asif, Syed; Mishra, Manish Kumar

    2017-01-01

    The ability to correlate mechanical and chemical characterization techniques in real time is both lacking and powerful tool for gaining insights into material behavior. This is demonstrated through use of a novel nanoindentation device equipped with Raman spectroscopy to explore the deformation-induced structural changes in piroxicam crystals. Mechanical anisotropy was observed in two major faces ( 0bar{1}1 ) and (011), which are correlated to changes in the interlayer interaction from in situ Raman spectra recorded during indentation. The results of this study demonstrate the considerable potential of an in situ Raman nanoindentation instrument for studying a variety of topics, including stress-induced phase transformation mechanisms, mechanochemistry, and solid state reactivity under mechanical forces that occur in molecular and pharmaceutical solids.

  6. Cargo-Positioning System for Next-Generation Spacecraft

    NASA Technical Reports Server (NTRS)

    Holladay, Jon; Colton, Jonathan

    2006-01-01

    A report discusses a proposed system for mounting loaded pallets in the cargo bay of a next-generation space-shuttle-like spacecraft, such that the center of mass of the cargo would lie within a 1-in. (2.54-cm) cube that would also contain the center of mass of the spacecraft. The system would include (1) an algorithm for planning the locations of the pallets, given the geometric and weight properties of the pallets, and the geometric restrictions of the cargo bay; (2) quick-connect/quick-disconnect mounting mechanisms similar to those now used on air hoses; (3) other mounting mechanisms, comprising mostly spring-loaded pins, in a locking subsystem that would prevent shifting of the pallets under load; and (4) mechanisms for performing fine position adjustments to satisfy the center-of-mass requirement. The position- adjusting mechanisms would be motor-driven lead-screw mechanisms in groups of three - one for positioning each pin of the locking subsystem along each of three mutually perpendicular coordinate axes. The system also would include a triple-threaded screw that would provide compensation for thermal expansion or contraction of the spacecraft.

  7. Biological versus nonbiological older brothers and men's sexual orientation.

    PubMed

    Bogaert, Anthony F

    2006-07-11

    The most consistent biodemographic correlate of sexual orientation in men is the number of older brothers (fraternal birth order). The mechanism underlying this effect remains unknown. In this article, I provide a direct test pitting prenatal against postnatal (e.g., social/rearing) mechanisms. Four samples of homosexual and heterosexual men (total n = 944), including one sample of men raised in nonbiological and blended families (e.g., raised with half- or step-siblings or as adoptees) were studied. Only biological older brothers, and not any other sibling characteristic, including nonbiological older brothers, predicted men's sexual orientation, regardless of the amount of time reared with these siblings. These results strongly suggest a prenatal origin to the fraternal birth-order effect.

  8. Sexual arousal in men: a review and conceptual analysis.

    PubMed

    Janssen, Erick

    2011-05-01

    Sexual arousal is an emotional/motivational state that can be triggered by internal and external stimuli and that can be inferred from central (including verbal), peripheral (including genital), and behavioral (including action tendencies and motor preparation) responses. This article, while focusing on sexual arousal in men, provides a conceptual analysis of this construct, reviews models of sexual arousal, and discusses the usefulness of perspectives derived from motivation and emotion research in improving our understanding of its determinants and behavioral correlates. In this, it considers the role of genital feedback in men's subjective sexual arousal and the connections between sexual arousal and sexual desire. Future research and definitions may increasingly focus on its central integrative functions (as opposed to its input and output characteristics). Yet, the study of sexual arousal can be expected to continue to benefit from the measurement of its genital, verbal, and behavioral components. Instances of discordance between response components suggest that they are, at least in part, under the control of different mechanisms, and it is proposed that a better understanding of sexual arousal will prove contingent on a better understanding of such mechanisms and the conditions under which they converge and diverge. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. The role of chemistry in under-predictions of NO2 in the upper troposphere

    NASA Astrophysics Data System (ADS)

    Henderson, B. H.; Pinder, R. W.; Goliff, W. S.; Stockwell, W. R.; Fahr, A.; Sarwar, G.; Hutzell, W. T.; Mathur, R.; Vizuete, W.; Cohen, R. C.

    2009-12-01

    Global and regional atmospheric models under-predict upper troposphere NO2 compared to satellite and aircraft observations. The upper tropospheric under-prediction of NO2 could be a function of emissions, transport, chemistry or some combination. Previous researchers have linked poor performance in the model to over-prediction of the OH and under-prediction of the HO2 by chemistry (Olson et al. 2006, Bertram et al. 2007). This study isolates upper tropospheric chemistry to evaluate the chemical contribution to NO2 under-predictions and to diagnose OH and HO2 discrepancies.

    We use a 0-dimensional time dependent model to evaluate seven chemical mechanisms. Because chamber data representing upper tropospheric conditions does not exist, we evaluate the predictions based against an observation-based aging model. Following Bertram et al (2007), we use the NOx:HNO3 ratio to categorize the chemical age of thousands of 10 second average observations between 8 and 10km. Measurements of 10 inorganics and 32 hydrocarbons are translated to model species for each of seven chemical mechanisms. We chose mechanisms ranging from condensed to semi-explicit. The seven mechanisms' design scopes range from urban to global scale. Results include simulations from Model for OZone And Related chemical Tracers (MOZART), Carbon Bond 05 (CB05), State Air Pollution Research Center (SAPRC) 99, SAPRC 07, GEOS-Chem, Regional Atmospheric Chemical Mechanism version 2, and the LEEDS Master Chemical Mechanism.

    Results from each chemical mechanism are compared to aircraft observations and to those obtained with other chemical mechanisms. Each mechanism is then further evaluated using integrated reaction rate analysis to identify sources of NO2 bias. We find that the largest contributors to the NO2 bias are over-predictions of PAN and HNO3. The formation of PAN is sensitive to the acetone photolysis rate. The conversion of NOx to HNO3 is most sensitive to hydroxyl radical concentrations. Hydroxyl radical sources and sinks have been quantified for each chemical mechanism using IRR analysis. Based on our modeling experience and results, we make recommendations for better simulating upper tropospheric photochemistry and we identify future research needs.

    Bertram et al. Direct Measurements of the Convective Recycling of the Upper Troposphere. Science (2007)
    Olson et al. A reevaluation of airborne HOx observations from NASA field campaigns. J Geophys Res-Atmos (2006) vol. 111 pp. D10301

  10. A dual closed-loop control system for mechanical ventilation.

    PubMed

    Tehrani, Fleur; Rogers, Mark; Lo, Takkin; Malinowski, Thomas; Afuwape, Samuel; Lum, Michael; Grundl, Brett; Terry, Michael

    2004-04-01

    Closed-loop mechanical ventilation has the potential to provide more effective ventilatory support to patients with less complexity than conventional ventilation. The purpose of this study was to investigate the effectiveness of an automatic technique for mechanical ventilation. Two closed-loop control systems for mechanical ventilation are combined in this study. In one of the control systems several physiological data are used to automatically adjust the frequency and tidal volume of breaths of a patient. This method, which is patented under US Patent number 4986268, uses the criterion of minimal respiratory work rate to provide the patient with a natural pattern of breathing. The inputs to the system include data representing CO2 and O2 levels of the patient as well as respiratory compliance and airway resistance. The I:E ratio is adjusted on the basis of the respiratory time constant to allow for effective emptying of the lungs in expiration and to avoid intrinsic positive end expiratory pressure (PEEP). This system is combined with another closed-loop control system for automatic adjustment of the inspired fraction of oxygen of the patient. This controller uses the feedback of arterial oxygen saturation of the patient and combines a rapid stepwise control procedure with a proportional-integral-derivative (PID) control algorithm to automatically adjust the oxygen concentration in the patient's inspired gas. The dual closed-loop control system has been examined by using mechanical lung studies, computer simulations and animal experiments. In the mechanical lung studies, the ventilation controller adjusted the breathing frequency and tidal volume in a clinically appropriate manner in response to changes in respiratory mechanics. The results of computer simulations and animal studies under induced disturbances showed that blood gases were returned to the normal physiologic range in less than 25 s by the control system. In the animal experiments understeady-state conditions, the maximum standard deviations of arterial oxygen saturation and the end-tidal partial pressure of CO2 were +/- 1.76% and +/- 1.78 mmHg, respectively. The controller maintained the arterial blood gases within normal limits under steady-state conditions and the transient response of the system was robust under various disturbances. The results of the study have showed that the proposed dual closed-loop technique has effectively controlled mechanical ventilation under different test conditions.

  11. Cardiac Mechano-Gated Ion Channels and Arrhythmias

    PubMed Central

    Peyronnet, Remi; Nerbonne, Jeanne M.; Kohl, Peter

    2015-01-01

    Mechanical forces will have been omnipresent since the origin of life, and living organisms have evolved mechanisms to sense, interpret and respond to mechanical stimuli. The cardiovascular system in general, and the heart in particular, are exposed to constantly changing mechanical signals, including stretch, compression, bending, and shear. The heart adjusts its performance to the mechanical environment, modifying electrical, mechanical, metabolic, and structural properties over a range of time scales. Many of the underlying regulatory processes are encoded intra-cardially, and are thus maintained even in heart transplant recipients. Although mechano-sensitivity of heart rhythm has been described in the medical literature for over a century, its molecular mechanisms are incompletely understood. Thanks to modern biophysical and molecular technologies, the roles of mechanical forces in cardiac biology are being explored in more detail, and detailed mechanisms of mechano-transduction have started to emerge. Mechano-gated ion channels are cardiac mechano-receptors. They give rise to mechano-electric feedback, thought to contribute to normal function, disease development, and, potentially, therapeutic interventions. In this review, we focus on acute mechanical effects on cardiac electrophysiology, explore molecular candidates underlying observed responses, and discuss their pharmaceutical regulation. From this, we identify open research questions and highlight emerging technologies that may help in addressing them. Cardiac electrophysiology is acutely affected by the heart’s mechanical environment. Mechano-electric feedback affects excitability, conduction, and electrical load, and remains an underestimated player in arrhythmogenesis. The utility of therapeutic interventions targeting acute mechano-electrical transduction is an open field worthy of further study. PMID:26838316

  12. Damage mechanisms in bithermal and thermomechanical fatigue of Haynes 188

    NASA Technical Reports Server (NTRS)

    Kalluri, Sreeramesh; Halford, Gary R.

    1992-01-01

    Post failure fractographic and metallographic studies were conducted on Haynes 188 specimens fatigued under bithermal and thermomechanical loading conditions between 316 and 760 C. Bithermal fatigue specimens examined included those tested under high strain rate in-phase and out-phase, tensile creep in-phase, and compressive creep out-of-phase loading conditions. Specimens tested under in-phase and out-of-phase thermomechanical fatigue were also examined. The nature of failure mode (transgrandular versus intergranular), the topography of the fracture surface, and the roles of oxidation and metallurgical changes were studied for each type of bithermal and thermomechanical test.

  13. Effect of contact barrier on electron transport in graphene.

    PubMed

    Zhou, Yang-Bo; Han, Bing-Hong; Liao, Zhi-Min; Zhao, Qing; Xu, Jun; Yu, Da-Peng

    2010-01-14

    The influence of the barrier between metal electrodes and graphene on the electrical properties was studied on a two-electrode device. A classical barrier model was used to analyze the current-voltage characteristics. Primary parameters including barrier height and effective resistance were achieved. The electron transport properties under magnetic field were further investigated. An abnormal peak-valley-peak shape of voltage-magnetoresistance curve was observed. The underlying mechanisms were discussed under the consideration of the important influence of the contact barrier. Our results indicate electrical properties of graphene based devices are sensitive to the contact interface.

  14. Cross-generational influences on childhood anxiety disorders: pathways and mechanisms

    PubMed Central

    Leckman, James F.; Silverman, Wendy K.; Feldman, Ruth

    2016-01-01

    Anxiety disorders are common across the lifespan, cause severe distress and impairment, and usually have their onset in childhood. Substantial clinical and epidemiological research has demonstrated the existence of links between anxiety and its disorders in children and parents. Research on the pathways and mechanisms underlying these links has pointed to both behavioral and biological systems. This review synthesizes and summarizes several major aspects of this research. Behavioral systems include vicarious learning, social referencing, and modeling of parental anxiety; overly protective or critical parenting styles; and aspects of parental responses to child anxiety including family accommodation of the child’s symptoms. Biological systems include aspects of the prenatal environment affected by maternal anxiety, development and functioning of the oxytocinergic system, and genetic and epigenetic transmission. Implications for the prevention and treatment of child anxiety disorders are discussed, including the potential to enhance child anxiety treatment outcomes through biologically informed parent-based interventions. PMID:27145763

  15. Cross-generational influences on childhood anxiety disorders: pathways and mechanisms.

    PubMed

    Lebowitz, Eli R; Leckman, James F; Silverman, Wendy K; Feldman, Ruth

    2016-09-01

    Anxiety disorders are common across the lifespan, cause severe distress and impairment, and usually have their onset in childhood. Substantial clinical and epidemiological research has demonstrated the existence of links between anxiety and its disorders in children and parents. Research on the pathways and mechanisms underlying these links has pointed to both behavioral and biological systems. This review synthesizes and summarizes several major aspects of this research. Behavioral systems include vicarious learning, social referencing, and modeling of parental anxiety; overly protective or critical parenting styles; and aspects of parental responses to child anxiety including family accommodation of the child's symptoms. Biological systems include aspects of the prenatal environment affected by maternal anxiety, development and functioning of the oxytocinergic system, and genetic and epigenetic transmission. Implications for the prevention and treatment of child anxiety disorders are discussed, including the potential to enhance child anxiety treatment outcomes through biologically informed parent-based interventions.

  16. High fidelity computational characterization of the mechanical response of thermally aged polycarbonate

    NASA Astrophysics Data System (ADS)

    Zhang, Zesheng; Zhang, Lili; Jasa, John; Li, Wenlong; Gazonas, George; Negahban, Mehrdad

    2017-07-01

    A representative all-atom molecular dynamics (MD) system of polycarbonate (PC) is built and conditioned to capture and predict the behaviours of PC in response to a broad range of thermo-mechanical loadings for various thermal aging. The PC system is constructed to have a distribution of molecular weights comparable to a widely used commercial PC (LEXAN 9034), and thermally conditioned to produce models for aged and unaged PC. The MD responses of these models are evaluated through comparisons to existing experimental results carried out at much lower loading rates, but done over a broad range of temperatures and loading modes. These experiments include monotonic extension/compression/shear, unilaterally and bilaterally confined compression, and load-reversal during shear. It is shown that the MD simulations show both qualitative and quantitative similarity with the experimental response. The quantitative similarity is evaluated by comparing the dilatational response under bilaterally confined compression, the shear flow viscosity and the equivalent yield stress. The consistency of the in silico response to real laboratory experiments strongly suggests that the current PC models are physically and mechanically relevant and potentially can be used to investigate thermo-mechanical response to loading conditions that would not easily be possible. These MD models may provide valuable insight into the molecular sources of certain observations, and could possibly offer new perspectives on how to develop constitutive models that are based on better understanding the response of PC under complex loadings. To this latter end, the models are used to predict the response of PC to complex loading modes that would normally be difficult to do or that include characteristics that would be difficult to measure. These include the responses of unaged and aged PC to unilaterally confined extension/compression, cyclic uniaxial/shear loadings, and saw-tooth extension/compression/shear.

  17. Octopamine and tyramine modulate the thermoregulatory fanning response in honey bees (Apis mellifera L.)

    USDA-ARS?s Scientific Manuscript database

    Biogenic amines regulate the proximate mechanisms underlying most behavior, including those that contribute to the overall success of complex societies. For honey bees one critical set of behaviors contributing to the welfare of a colony are involved with nest thermoregulation. Worker honey bees co...

  18. Dietary substitution of whole grains for refined grains favorably effects fiber intake and energy metabolism in adults

    USDA-ARS?s Scientific Manuscript database

    Whole grain-rich diets are consistently associated with lower adiposity in observational studies. However, clinical trials have failed to substantiate this association or identify underlying mechanisms. The inconsistency has been suggested to be due to trial methodology including suboptimal dietary ...

  19. Hybrid Macro-Micro Fluidics System for a Chip-Based Biosensor

    DTIC Science & Technology

    2002-02-18

    fluids, including elements based on acoustic, centrifugal and electromagnetic forces; electroosmotic and electrophoretic effects; micro- mechanical and... mixed then degassed in a desiccator under vacuum for 30 min. The mixture was poured into the mold and allowed to stand for 5 min to self-level. The PDMS

  20. Accelerated microbial turnover but constant growth efficiency with warming in soil

    Treesearch

    Shannon B. Hagerty; Kees Jan van Groenigen; Steven D. Allison; Bruce A. Hungate; Egbert Schwartz; George W. Koch; Randall K. Kolka; Paul Dijkstra

    2014-01-01

    Rising temperatures are expected to reduce global soil carbon (C) stocks, driving a positive feedback to climate change1-3. However, the mechanisms underlying this prediction are not well understood, including how temperature affects microbial enzyme kinetics, growth effiency (MGE), and turnover4,5. Here, in a laboratory...

  1. The application of elastohydrodynamic lubrication in gear tooth contacts

    NASA Technical Reports Server (NTRS)

    Townsend, D. P.

    1972-01-01

    An analytical method is presented for determining elastohydrodynamic film thickness in gears from theory and how the film affects gear failure and life. The practical aspects of gear lubrication are presented, including mechanical and service variables which must be considered to obtain optimum gear performance under severe operating conditions.

  2. A substrate-specific cytochrome P450 monoxygenase, CYP6AB11, from the polyphagous navel orangeworm

    USDA-ARS?s Scientific Manuscript database

    The navel orangeworm, Amyelois transitella (Walker)is a serious pest of many tree crops in California, including almonds, pistachios, walnuts and figs. In order to understand the molecular mechanisms underlying detoxification of phytochemicals, insecticides, and mycotoxins by this species, full leng...

  3. Using Online Measures to Determine How Learners Process Instructional Explanations

    ERIC Educational Resources Information Center

    Sanchez, Emilio; Garcia-Rodicio, Hector

    2013-01-01

    The goal of the present study was to examine the mechanisms underlying a strategy that we developed to make instructional explanations effective. In two experiments participants learned about plate tectonics from a multimedia material, including adjunct explanations that revised common misunderstandings. These explanations were either marked…

  4. Age Differences in Emotion Perception: The Effects of the Social Environment

    ERIC Educational Resources Information Center

    Murry, Matthew W. E.; Isaacowitz, Derek M.

    2017-01-01

    Older adults tend to have lower emotion-perception accuracy compared to younger adults. Previous studies have centered on individual characteristics, including cognitive decline and positive attentional preferences, as possible mechanisms underlying these age differences in emotion perception; however, thus far, no perceiver-focused factor has…

  5. 78 FR 66865 - Acquisition Regulation: Patents, Data, and Copyrights

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ... obligations under current law. The proposed changes include policy revisions for computer software developed.... Computer Software DOE's existing Rights in Technical Data-Technology Transfer clause at 970.5227-2 provides mechanisms by which computer software first produced by a DOE contractor may be made available to the public...

  6. An ethylene-induced regulatory module delays rose flower senescence by regulating cytokinin content

    USDA-ARS?s Scientific Manuscript database

    In many plant species, including rose (Rosa hybrida), flower senescence is promoted by the gaseous hormone, ethylene, and inhibited by cytokinin (CTK) class of hormones. However, the molecular mechanisms underlying these antagonistic effects are not well understood. In this current study, we charact...

  7. Comparative transcriptome and lipidome analyses reveal molecular systems underlying chilling response in chilling-tolerant sorghums

    USDA-ARS?s Scientific Manuscript database

    Chilling temperatures are a major constraint for temperate cultivation of tropical-origin crops, including the cereal crop sorghum (Sorghum bicolor [L.] Moench). Northern Chinese sorghums have adapted to early-season chilling, but molecular mechanisms of chilling tolerance are unknown. We used RNA ...

  8. Oxidation-induced water-solubilization and chemical functionalization of fullerenes C60, Gd@C60 and Gd@C82: atomistic insights into the formation mechanisms and structures of fullerenols synthesized by different methods.

    PubMed

    Wang, Zhenzhen; Lu, Zhanghui; Zhao, Yuliang; Gao, Xingfa

    2015-02-21

    Water-solubilization is the prerequisite to endow the pristinely hydrophobic fullerenes with biocompatibility and biofunctionality, which has been widely applied to derive fullerene-based nanomaterials for biomedical applications. Oxidation reactions using O2 and H2O2 are the most commonly used approaches to this end, through which fullerenols with different structural features can be obtained. Despite the progress in the syntheses and bioapplications of fullerenols, their formation mechanisms and structures at the atomic level, which substantialize their physical properties and biofunctions, have been little understood. Using density functional theory calculations, we comparatively study the mechanisms and product structures for the oxidations of C60, Gd@C60 and Gd@C82 using both O2 and H2O2 as oxidizing agents under both neutral and alkaline aqueous conditions. We predict the formation mechanisms and product structures corresponding to the different synthetic conditions. Briefly, the H2O2 oxidations of C60, Gd@C60 and Gd@C82 under neutral conditions do not occur readily at room temperature because of the high energy barriers, whereas the H2O2 oxidations can readily proceed under alkaline conditions. The oxygen-containing groups of the fullerenols obtained under these conditions include hydroxyl, carbonyl, hemiacetal and deprotonated vic-diol. In contrast, through O2 oxidation under alkaline conditions, the most probable oxygen-containing groups for C60 fullerenols are epoxide and deprotonated vic-diol, and those for Gd@C60 and Gd@C82 fullerenols are hydroxyls and carbonyls. The results explain a wide range of experimental findings reported before. More importantly, they provide atomistic-level insights into the formation mechanisms and structures for various fullerenols, which are of fundamental interest for understanding their biomedical applications in the future.

  9. Damage mechanisms in PBT-GF30 under thermo-mechanical cyclic loading

    NASA Astrophysics Data System (ADS)

    Schaaf, A.; De Monte, M.; Hoffmann, C.; Vormwald, M.; Quaresimin, M.

    2014-05-01

    The scope of this paper is the investigation of damage mechanisms at microscopic scale on a short glass fiber reinforced polybutylene terephthalate (PBT-GF30) under thermo-mechanical cyclic loading. In addition the principal mechanisms are verified through micro mechanical FE models. In order to investigate the fatigue behavior of the material both isothermal strain controlled fatigue (ISCF) tests at three different temperatures and thermo-mechanical fatigue (TMF) tests were conducted on plain and notched specimens, manufactured by injection molding. The goal of the work is to determine the damage mechanisms occurring under TMF conditions and to compare them with the mechanisms occurring under ISCF. For this reason fracture surfaces of TMF and ISCF samples loaded at different temperature levels were analyzed using scanning electron microscopy. Furthermore, specimens that failed under TMF were examined on microsections revealing insight into both crack initiation and crack propagation. The findings of this investigation give valuable information about the main damage mechanisms of PBT-GF30 under TMF loading and serve as basis for the development of a TMF life estimation methodology.

  10. Effects of Carbon Black and the Presence of Static Mechanical Strain on the Swelling of Elastomers in Solvent

    PubMed Central

    Ch’ng, Shiau Ying; Andriyana, Andri; Tee, Yun Lu; Verron, Erwan

    2015-01-01

    The effect of carbon black on the mechanical properties of elastomers is of great interest, because the filler is one of principal ingredients for the manufacturing of rubber products. While fillers can be used to enhance the properties of elastomers, including stress-free swelling resistance in solvent, it is widely known that the introduction of fillers yields significant inelastic responses of elastomers under cyclic mechanical loading, such as stress-softening, hysteresis and permanent set. When a filled elastomer is under mechanical deformation, the filler acts as a strain amplifier in the rubber matrix. Since the matrix local strain has a profound effect on the material’s ability to absorb solvent, the study of the effect of carbon black content on the swelling characteristics of elastomeric components exposed to solvent in the presence of mechanical deformation is a prerequisite for durability analysis. The aim of this study is to investigate the effect of carbon black content on the swelling of elastomers in solvent in the presence of static mechanical strains: simple extension and simple torsion. Three different types of elastomers are considered: unfilled, filled with 33 phr (parts per hundred) and 66 phr of carbon black. The peculiar role of carbon black on the swelling characteristics of elastomers in solvent in the presence of mechanical strain is explored. PMID:28787977

  11. Colchicine--Update on mechanisms of action and therapeutic uses.

    PubMed

    Leung, Ying Ying; Yao Hui, Laura Li; Kraus, Virginia B

    2015-12-01

    To review the literature and provide an update on the mechanisms of action and therapeutic uses of oral colchicine in arthritis and inflammatory conditions. We performed PubMed database searches through June 2014 for relevant studies in the English literature published since the last update of colchicine in 2008. Searches encompassed colchicine mechanisms of action and clinical applications in medical conditions. A total of 381 articles were reviewed. The primary mechanism of action of colchicine is tubulin disruption. This leads to subsequent down regulation of multiple inflammatory pathways and modulation of innate immunity. Newly described mechanisms include various inhibitory effects on macrophages including the inhibition of the NACHT-LRRPYD-containing protein 3 (NALP3) inflammasome, inhibition of pore formation activated by purinergic receptors P2X7 and P2X2, and stimulation of dendritic cell maturation and antigen presentation. Colchicine also has anti-fibrotic activities and various effects on endothelial function. The therapeutic use of colchicine has extended beyond gouty arthritis and familial Mediterranean fever, to osteoarthritis, pericarditis, and atherosclerosis. Further understanding of the mechanisms of action underlying the therapeutic efficacy of colchicine will lead to its potential use in a variety of conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Alternative polyadenylation of mRNA precursors

    PubMed Central

    Tian, Bin; Manley, James L.

    2017-01-01

    Alternative polyadenylation (APA) is an RNA-processing mechanism that generates distinct 3′ termini on mRNAs and other RNA polymerase II transcripts. It is widespread across all eukaryotic species and is recognized as a major mechanism of gene regulation. APA exhibits tissue specificity and is important for cell proliferation and differentiation. In this Review, we discuss the roles of APA in diverse cellular processes, including mRNA metabolism, protein diversification and protein localization, and more generally in gene regulation. We also discuss the molecular mechanisms underlying APA, such as variation in the concentration of core processing factors and RNA-binding proteins, as well as transcription-based regulation. PMID:27677860

  13. How Does It Work? Mechanisms of Action in an In-Prison Restorative Justice Program.

    PubMed

    Armour, Marilyn; Sliva, Shannon

    2018-02-01

    Research is limited on mechanisms of action in restorative justice interventions. This multimethods study delineates the change processes underlying a successful in-prison group treatment program by (a) examining shifts in offenders' self-schemas and (b) identifying key program components that influence this movement. Researchers assigned to small groups as "co-facilitators" gathered data using participant observation, semi-structured interviews, and psychological assessments at three time points. Mechanisms of action include group norms and behaviors that contrast with prior experiences and uncover offenders' self-schemas through intrapsychic processes, which prompt them to test and act upon new possible selves through the group process.

  14. Assessment of allowance mechanism China's carbon trading pilots

    DOE PAGES

    Xiong, Ling; Shen, Bo; Qi, Shaozhou; ...

    2015-08-28

    The allowance mechanism is one of the core and sensitive aspects in design of a carbon trading scheme and affects the compliance cost for each company covered under the scheme. By examining China's allowance mechanism from two aspects including allowance allocation and allowance distribution, this paper compares China's carbon trading pilots with the EU Emissions Trading System and California Cap-and-Trade Program, and through the comparison identify issues that affect the efficiency of the pilots. The paper also recommends course of actions to strengthen China's existing pilots and build valuable experiences for the establishment of the national cap-and-trade system in China.

  15. Final technical report

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

    Loveland, Walter David

    2016-08-27

    This report describes the research carried out under this grant for the period from 1997 to 2014. This work has been previously described in annual progress reports and renewal applications. As a result of this project, ~100 papers were published in open refereed journals and 107 invited talks were given by the PI. The research subjects covered by this project included the synthesis and characterization of super-heavy nuclei, the critical study of the reaction mechanisms used in these synthesis reactions, the mechanism(s) of intermediate energy and relativistic nuclear collisions, the study of reactions induced by radioactive nuclear beams, and generalmore » properties of the heaviest elements.« less

  16. mRNA localization: an orchestration of assembly, traffic and synthesis.

    PubMed

    Xing, Lei; Bassell, Gary J

    2013-01-01

    Asymmetrical mRNA localization and subsequent local translation provide efficient mechanisms for protein sorting in polarized cells. Defects in mRNA localization have been linked to developmental abnormalities and neurological diseases. Thus, it is critical to understand the machineries mediating and mechanisms underlying the asymmetrical distribution of mRNA and its regulation. The goal of this review is to summarize recent advances in the understanding of mRNA transport and localization, including the assembly and sorting of transport messenger ribonucleic protein (mRNP) granules, molecular mechanisms of active mRNP transport, cytoskeletal interactions and regulation of these events by extracellular signals. © 2012 John Wiley & Sons A/S.

  17. Wearable, wireless gas sensors using highly stretchable and transparent structures of nanowires and graphene.

    PubMed

    Park, Jihun; Kim, Joohee; Kim, Kukjoo; Kim, So-Yun; Cheong, Woon Hyung; Park, Kyeongmin; Song, Joo Hyeb; Namgoong, GyeongHo; Kim, Jae Joon; Heo, Jaeyeong; Bien, Franklin; Park, Jang-Ung

    2016-05-19

    Herein, we report the fabrication of a highly stretchable, transparent gas sensor based on silver nanowire-graphene hybrid nanostructures. Due to its superb mechanical and optical characteristics, the fabricated sensor demonstrates outstanding and stable performances even under extreme mechanical deformation (stable until 20% of strain). The integration of a Bluetooth system or an inductive antenna enables the wireless operation of the sensor. In addition, the mechanical robustness of the materials allows the device to be transferred onto various nonplanar substrates, including a watch, a bicycle light, and the leaves of live plants, thereby achieving next-generation sensing electronics for the 'Internet of Things' area.

  18. Triplex molecular layers with nonlinear nanomechanical response

    NASA Astrophysics Data System (ADS)

    Tsukruk, V. V.; Ahn, H.-S.; Kim, D.; Sidorenko, A.

    2002-06-01

    The molecular design of surface structures with built-in mechanisms for mechanical energy dissipation under nanomechanical deformation and compression resistance provided superior nanoscale wear stability. We designed robust, well-defined trilayer surface nanostructures chemically grafted to a silicon oxide surface with an effective composite modulus of about 1 GPa. The total thickness was within 20-30 nm and included an 8 nm rubber layer sandwiched between two hard layers. The rubber layer provides an effective mechanism for energy dissipation, facilitated by nonlinear, giant, reversible elastic deformations of the rubber matrix, restoring the initial status due to the presence of an effective nanodomain network and chemical grafting within the rubber matrix.

  19. Interpersonal Factors in Understanding and Treating Posttraumatic Stress Disorder

    PubMed Central

    Markowitz, John C.; Milrod, Barbara; Bleiberg, Kathryn; Marshall, Randall D.

    2010-01-01

    Exposure to reminders of trauma underlies the theory and practice of most treatments for posttraumatic stress disorder (PTSD), yet exposure may not be the sole important treatment mechanism. Interpersonal features of PTSD influence its onset, chronicity, and possibly its treatment. The authors review interpersonal factors in PTSD, including the critical but underrecognized role of social support as both protective posttrauma and as a mechanism of recovery. They discuss interpersonal psychotherapy (IPT) as an alternative treatment for PTSD and present encouraging findings from two initial studies. Highlighting the potential importance of attachment and interpersonal relationships, the authors propose a mechanism to explain why improving relationships may ameliorate PTSD symptoms. PMID:19339847

  20. A Model for Sustainable Building Energy Efficiency Retrofit (BEER) Using Energy Performance Contracting (EPC) Mechanism for Hotel Buildings in China

    NASA Astrophysics Data System (ADS)

    Xu, Pengpeng

    Hotel building is one of the high-energy-consuming building types, and retrofitting hotel buildings is an untapped solution to help cut carbon emissions contributing towards sustainable development. Energy Performance Contracting (EPC) has been promulgated as a market mechanism for the delivery of energy efficiency projects. EPC mechanism has been introduced into China relatively recently, and it has not been implemented successfully in building energy efficiency retrofit projects. The aim of this research is to develop a model for achieving the sustainability of Building Energy Efficiency Retrofit (BEER) in hotel buildings under the Energy Performance Contracting (EPC) mechanism. The objectives include: • To identify a set of Key Performance Indicators (KPIs) for measuring the sustainability of BEER in hotel buildings; • To identify Critical Success Factors (CSFs) under EPC mechanism that have a strong correlation with sustainable BEER project; • To develop a model explaining the relationships between the CSFs and the sustainability performance of BEER in hotel building. Literature reviews revealed the essence of sustainable BEER and EPC, which help to develop a conceptual framework for analyzing sustainable BEER under EPC mechanism in hotel buildings. 11 potential KPIs for sustainable BEER and 28 success factors of EPC were selected based on the developed framework. A questionnaire survey was conducted to ascertain the importance of selected performance indicators and success factors. Fuzzy set theory was adopted in identifying the KPIs. Six KPIs were identified from the 11 selected performance indicators. Through a questionnaire survey, out of the 28 success factors, 21 Critical Success Factors (CSFs) were also indentified. Using the factor analysis technique, the 21 identified CSFs in this study were grouped into six clusters to help explain project success of sustainable BEER. Finally, AHP/ANP approach was used in this research to develop a model to examine the interrelationships among the identified CSFs, KPIs, and sustainable dimensions of BEER. The findings indicate that the success of sustainable BEER in hotel buildings under the EPC mechanism is mainly decided by project objectives control mechanism, available technology, organizing capacity of team leader, trust among partners, accurate M&V, and team workers' technical skills.

  1. Molecular Mechanism of Betaine on Hepatic Lipid Metabolism: Inhibition of Forkhead Box O1 (FoxO1) Binding to Peroxisome Proliferator-Activated Receptor Gamma (PPARγ).

    PubMed

    Kim, Dae Hyun; Lee, Bonggi; Kim, Min Jo; Park, Min Hi; An, Hye Jin; Lee, Eun Kyeong; Chung, Ki Wung; Park, June Whoun; Yu, Byung Pal; Choi, Jae Sue; Chung, Hae Young

    2016-09-14

    Betaine is a major water-soluble component of Lycium chinensis. Although there are reports about the protective effects of betaine on hepatic steatosis, the underlying mechanisms are unclear. We used db/db mice and HepG2 cells to examine the mechanism underlying betaine-mediated protection against hepatic steatosis. Here, we showed increased hepatic lipid accumulation in db/db mice, which is associated with increased activation of lipogenic transcription factors including forkhead box O1 (FoxO1) and peroxisome proliferator-activated receptor gamma (PPARγ), whereas betaine administration by oral gavage reversed these characteristics. We investigated whether betaine ameliorates hepatic steatosis by inhibiting FoxO1/PPARγ signaling in HepG2 cells. Although adenovirus-mediated FoxO1 overexpression notably increased mRNA expression levels of PPARγ and its target genes including FAS and ACC, betaine treatment reversed them. Furthermore, betaine inhibited FoxO1 binding to the PPARγ promoter and PPARγ transcriptional activity in HepG2 cells, which was previously shown to induce hepatic steatosis. We concluded that betaine ameliorates hepatic steatosis, at least in part, by inhibiting the FoxO1 binding to PPARγ and their downstream lipogenic signaling cascade.

  2. Biomarkers of anhedonic-like behavior, antidepressant drug refraction, and stress resilience in a rat model of depression.

    PubMed

    Christensen, T; Bisgaard, C F; Wiborg, O

    2011-11-24

    The aim of the present study was to identify potential biomarkers for depression in the search for novel disease targets and treatment regimens. Furthermore, the study includes a search for biomarkers involved in treatment resistance and stress resilience in order to investigate mechanisms underlying antidepressant drug refraction and stress-coping strategies. Depression-related transcriptomic changes in gene expression profiles were investigated in laser-captured microdissected (LCM) rat hippocampal granular cell layers (GCL) using the chronic mild stress (CMS) rat model of depression and chronic administration of two selective serotonin reuptake inhibitors (SSRIs), escitalopram and sertraline. CMS rats were segregated into diverging groups according to behavioral readouts, and under stringent constraints, the associated differential gene regulations were analyzed. Accordingly, we identified four genes associated with recovery, two genes implicated in treatment resistance, and three genes involved in stress resilience. The identified genes associated with mechanisms of cellular plasticity, including signal transduction, cell proliferation, cell differentiation, and synaptic release. Hierarchical clustering analysis confirmed the subgroup segregation pattern in the CMS model. Thus antidepressant treatment refractors cluster with anhedonic-like rats, and, interestingly, stress-resilient rats cluster with rats undergoing antidepressant-mediated recovery from anhedonia, suggesting antidepressant mechanisms of action to emulate endogenous stress-coping strategies. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. The impact of Polycomb group (PcG) and Trithorax group (TrxG) epigenetic factors in plant plasticity.

    PubMed

    de la Paz Sanchez, Maria; Aceves-García, Pamela; Petrone, Emilio; Steckenborn, Stefan; Vega-León, Rosario; Álvarez-Buylla, Elena R; Garay-Arroyo, Adriana; García-Ponce, Berenice

    2015-11-01

    Current advances indicate that epigenetic mechanisms play important roles in the regulatory networks involved in plant developmental responses to environmental conditions. Hence, understanding the role of such components becomes crucial to understanding the mechanisms underlying the plasticity and variability of plant traits, and thus the ecology and evolution of plant development. We now know that important components of phenotypic variation may result from heritable and reversible epigenetic mechanisms without genetic alterations. The epigenetic factors Polycomb group (PcG) and Trithorax group (TrxG) are involved in developmental processes that respond to environmental signals, playing important roles in plant plasticity. In this review, we discuss current knowledge of TrxG and PcG functions in different developmental processes in response to internal and environmental cues and we also integrate the emerging evidence concerning their function in plant plasticity. Many such plastic responses rely on meristematic cell behavior, including stem cell niche maintenance, cellular reprogramming, flowering and dormancy as well as stress memory. This information will help to determine how to integrate the role of epigenetic regulation into models of gene regulatory networks, which have mostly included transcriptional interactions underlying various aspects of plant development and its plastic response to environmental conditions. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  4. Preterm Infant Massage Therapy Research: A Review

    PubMed Central

    Field, Tiffany; Diego, Miguel; Hernandez-Reif, Maria

    2010-01-01

    In this paper, preterm infant massage therapy studies are reviewed. Massage therapy has led to weight gain in preterm infants when moderate pressure massage was provided. In studies on passive movement of the limbs, preterm infants also gained significantly more weight, and their bone density also increased. Research on ways of delivering the massage is also explored including using mothers versus therapists and the added effects of using oils. The use of mothers as therapists was effective in at least one study. The use of oils including coconut oil and safflower oil enhanced the average weight gain, and the transcutaneous absorption of oil also increased triglycerides. In addition, the use of synthetic oil increased vagal activity, which may indirectly contribute to weight gain. The weight gain was associated with shorter hospital stays and, thereby, significant hospital cost savings. Despite these benefits, preterm infant massage is only practiced in 38% of neonatal intensive care units. This may relate to the underlying mechanisms not being well understood. The increases noted in vagal activity, gastric motility, insulin and IGF-1 levels following moderate pressure massage are potential underlying mechanisms. However, those variables combined do not explain all of the variance in weight gain, highlighting the need for additional mechanism studies. PMID:20137814

  5. Detoxification strategies and regulation of oxygen production and flowering of Platanus acerifolia under lead (Pb) stress by transcriptome analysis.

    PubMed

    Wang, Limin; Yang, Haijiao; Liu, Rongning; Fan, Guoqiang

    2015-08-01

    Toxic metal pollution is a major environmental problem that has received wide attention. Platanus acerifolia (London plane tree) is an important greening tree species that can adapt to environmental pollution. The genetic basis and molecular mechanisms associated with the ability of P. acerifolia to respond lead (Pb) stress have not been reported so far. In this study, 16,246 unigenes differentially expressed unigenes that were obtained from P. acerifolia under Pb stress using next-generation sequencing. Essential pathways such as photosynthesis, and gibberellins and glutathione metabolism were enriched among the differentially expressed unigenes. Furthermore, many important unigenes, including antioxidant enzymes, plants chelate compounds, and metal transporters involved in defense and detoxification mechanisms, were differentially expressed in response to Pb stress. The unigenes encoding the oxygen-evolving enhancer Psb and OEE protein families were downregulated in Pb-stressed plants, implying that oxygen production might decrease in plants under Pb stress. The relationship between gibberellin and P. acerifolia flowering is also discussed. The information and new insights obtained in this study will contribute to further investigations into the molecular regulation mechanisms of Pb accumulation and tolerance in greening tree species.

  6. INSULIN RESISTANCE POST-BURN: UNDERLYING MECHANISMS AND CURRENT THERAPEUTIC STRATEGIES

    PubMed Central

    Gauglitz, Gerd G.; Herndon, David N.; Jeschke, Marc G.

    2014-01-01

    The profound hypermetabolic response to burn injury is associated with insulin resistance and hyperglycemia, significantly contributing to the incidence of morbidity and mortality in this patient population. These responses are present in all trauma, surgical, or critically ill patients, but the severity, length, and magnitude is unique for burn patients. Although advances in therapeutic strategies to attenuate the post-burn hypermetabolic response have significantly improved the clinical outcome of these patients over the past years, therapeutic approaches to overcome stress-induced hyperglycemia have remained challenging. Intensive insulin therapy has been shown to significantly reduce morbidity and mortality in critically ill patients. High incidence of hypoglycemic events and difficult blood glucose titrations have led to investigation of alternative strategies, including the use of metformin, a biguanide, or fenofibrate, a PPAR-γ agonist. Nevertheless, weaknesses and potential side affects of these drugs reinforces the need for better understanding of the molecular mechanisms underlying insulin resistance post-burn that may lead to novel therapeutic strategies further improving the prognosis of these patients. This review aims to discuss the mechanisms underlying insulin resistance induced hyperglycemia post-burn and outlines current therapeutic strategies that are being used to modulate hyperglycemia following thermal trauma. PMID:18695610

  7. A comparative study of the mechanical behaviour of thermally oxidised commercially pure titanium and zirconium.

    PubMed

    Alansari, A; Sun, Y

    2017-10-01

    The objective of this study is to compare the mechanical behaviour of thermally oxidised commercially pure titanium (CP-Ti) and commercially pure zirconium (CP-Zr). For this purpose, these two bio-metals were thermally oxidised under the same condition (650°C for 6h) and the oxidised specimens were characterised using various analytical and experimental techniques, including oxygen uptake analysis, layer thickness and hardness measurements, scratch tests, dry sliding friction and wear tests and tribocorrosion tests in Ringer's solution. The results show that under the present thermal oxidation condition, 4 times more oxygen is introduced into CP-Zr than into CP-Ti and the oxide layer produced on CP-Zr is nearly 6 times thicker than that on CP-Ti. Thermally oxidised CP-Zr possesses a higher hardness, a deeper hardening depth and better scratch resistance than thermally oxidised CP-Ti. Under dry sliding and tribocorrosion conditions, thermally oxidised CP-Zr also possesses much better resistance to material removal and a higher load bearing capacity than thermally oxidised CP-Ti. Thus, thermally oxidised Zr possesses much better mechanical behaviour than thermally oxidised Ti. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Mechanics of Granular Materials (MGM) Test Cell

    NASA Technical Reports Server (NTRS)

    2000-01-01

    A test cell for Mechanics of Granular Materials (MGM) experiment is tested for long-term storage with water in the system as plarned for STS-107. This view shows the compressed sand column with the protective water jacket removed. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditons that cannot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: University of Colorado at Boulder

  9. Mechanics of Granular Materials (MGM) Cell

    NASA Technical Reports Server (NTRS)

    1996-01-01

    One of three Mechanics of Granular Materials (MGM) test cells after flight on STS-79 and before impregnation with resin. Note that the sand column has bulged in the middle, and that the top of the column is several inches lower than the top of the plastic enclosure. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditons that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: University of Colorado at Boulder

  10. Mechanics of Granular Materials (MGM) Test Cell

    NASA Technical Reports Server (NTRS)

    2000-01-01

    A test cell for Mechanics of Granular Materials (MGM) experiment is tested for long-term storage with water in the system as plarned for STS-107. This view shows the top of the sand column with the metal platten removed. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditons that cannot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: University of Colorado at Boulder

  11. Zinc as a Gatekeeper of Immune Function

    PubMed Central

    Wessels, Inga; Maywald, Martina; Rink, Lothar

    2017-01-01

    After the discovery of zinc deficiency in the 1960s, it soon became clear that zinc is essential for the function of the immune system. Zinc ions are involved in regulating intracellular signaling pathways in innate and adaptive immune cells. Zinc homeostasis is largely controlled via the expression and action of zinc “importers” (ZIP 1–14), zinc “exporters” (ZnT 1–10), and zinc-binding proteins. Anti-inflammatory and anti-oxidant properties of zinc have long been documented, however, underlying mechanisms are still not entirely clear. Here, we report molecular mechanisms underlying the development of a pro-inflammatory phenotype during zinc deficiency. Furthermore, we describe links between altered zinc homeostasis and disease development. Consequently, the benefits of zinc supplementation for a malfunctioning immune system become clear. This article will focus on underlying mechanisms responsible for the regulation of cellular signaling by alterations in zinc homeostasis. Effects of fast zinc flux, intermediate “zinc waves”, and late homeostatic zinc signals will be discriminated. Description of zinc homeostasis-related effects on the activation of key signaling molecules, as well as on epigenetic modifications, are included to emphasize the role of zinc as a gatekeeper of immune function. PMID:29186856

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

    PubMed Central

    Chen, Lianguo; Qian, Pei-Yuan

    2017-01-01

    Better understanding of the mechanisms of antifouling compounds is recognized to be of high value in establishing sensitive biomarkers, allowing the targeted optimization of antifouling compounds and guaranteeing environmental safety. Despite vigorous efforts to find new antifouling compounds, information about the mechanisms of antifouling is still scarce. This review summarizes the progress into understanding the molecular mechanisms underlying antifouling activity since 2012. Non-toxic mechanisms aimed at specific targets, including inhibitors of transmembrane transport, quorum sensing inhibitors, neurotransmission blockers, adhesive production/release inhibitors and enzyme/protein inhibitors, are put forward for natural antifouling products or shelf-stable chemicals. Several molecular targets show good potential for use as biomarkers in future mechanistic screening, such as acetylcholine esterase for neurotransmission, phenoloxidase/tyrosinase for the formation of adhesive plaques, N-acyl homoserine lactone for quorum sensing and intracellular Ca2+ levels as second messenger. The studies on overall responses to challenges by antifoulants can be categorized as general targets, including protein expression/metabolic activity regulators, oxidative stress inducers, neurotransmission blockers, surface modifiers, biofilm inhibitors, adhesive production/release inhibitors and toxic killing. Given the current situation and the knowledge gaps regarding the development of alternative antifoulants, a basic workflow is proposed that covers the indispensable steps, including preliminary mechanism- or bioassay-guided screening, evaluation of environmental risks, field antifouling performance, clarification of antifouling mechanisms and the establishment of sensitive biomarkers, which are combined to construct a positive feedback loop. PMID:28846624

  13. Stress and tension-type headache mechanisms.

    PubMed

    Cathcart, Stuart; Winefield, Anthony H; Lushington, Kurt; Rolan, Paul

    2010-10-01

    Stress is widely demonstrated as a contributing factor in tension-type headache (TTH). The mechanisms underlying this remain unclear at present. Recent research indicates the importance of central pain processes in tension-type headache (TTH) pathophysiology. Concurrently, research with animals and healthy humans has begun to elucidate the relationship between stress and pain processing in the central nervous system, including central pain processes putatively dysfunctional in TTH. Combined, these two fields of research present new insights and hypotheses into possible mechanisms by which stress may contribute to TTH. To date, however, there has been no comprehensive review of this literature. The present paper provides such a review, which may be valuable in facilitating a broader understanding of the central mechanisms by which stress may contribute to TTH.

  14. Stretch-induced prostaglandins and protein turnover in cultured skeletal muscle

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman H.; Hatfaludy, Sophia; Sohar, Istvan; Shansky, Janet

    1990-01-01

    The purpose of the study is to determine whether mechanical stimulation of cultured muscle cells influences prostaglandin efflux rates and whether they are related to stretch-induced alterations in protein turnover rates. The materials and methods of the experiment, including cell cultures, mechanical stimulation, protein synthesis, and degradation assays are outlined, and emphasis is placed on the effect of short-term mechanical stimulation in basal medium prostaglandin efflux from cultured skeletal muscle and stretch-induced alterations in prostaglandins efflux in complete medium. The major finding of the study is that mechanical stimulation of tissue-cultured skeletal-muscle cells under conditions inducing skeletal-muscle hypertropy increases the efflux of PGE(2) and PGE(2-alpha) but not 6-keto-PGF(1-alpha), the prostacyclin product.

  15. The Effects of Glucosamine Sulfate on Intervertebral Disc Annulus Fibrosus Cells in Vitro

    PubMed Central

    Sowa, Gwendolyn; Coelho, J. Paulo; Jacobs, Lloydine; Komperda, Kasey; Sherry, Nora; Vo, Nam; Preuss, Harry; Balk, Judith; Kang, Jame

    2014-01-01

    Background context Glucosamine has gained widespread use among patients, despite inconclusive efficacy data. Inconsistency in the clinical literature may be related to lack of understanding of the effects of glucosamine on the intervertebral disc, and therefore, improper patient selection. Purpose The goal of our study was to investigate the effects of glucosamine on intervertebral disc cells in vitro under the physiological conditions of inflammation and mechanical loading. Study Design Controlled in vitro laboratory setting Methods Intervertebral disc cells isolated from the rabbit annulus fibrosus were exposed to glucosamine sulfate in the presence and absence of interleukin-1beta and tensile strain. Outcome measures included gene expression, measurement of total glycosaminoglycans, new proteoglycan synthesis, prostaglandin E2 production, and matrix metalloproteinase activity. The study was funded by NIH/NCCAM and the authors have no conflicts of interest. Results Under conditions of inflammatory stimulation alone, glucosamine demonstrated a dose dependent effect in decreasing inflammatory and catabolic mediators and increasing anabolic genes. However, under conditions of mechanical stimulation, although inflammatory gene expression was decreased, PGE2 was not. In addition, MMP-3 gene expression was increased and aggrecan expression decreased, both of which would have a detrimental effect on matrix homeostasis. Consistent with this, measurement of total glycosaminoglycans and new proteoglycan synthesis demonstrated detrimental effects of glucosamine under all conditions tested. Conclusions These results may in part help to explain the conflicting reports of efficacy, as there is biological plausibility for a therapeutic effect under conditions of predominate inflammation, but not under conditions where mechanical loading is present or in which matrix synthesis is needed. PMID:24361347

  16. Intercellular and systemic spread of RNA and RNAi in plants.

    PubMed

    Nazim Uddin, Mohammad; Kim, Jae-Yean

    2013-01-01

    Plants possess dynamic networks of intercellular communication that are crucial for plant development and physiology. In plants, intercellular communication involves a combination of ligand-receptor-based apoplasmic signaling, and plasmodesmata and phloem-mediated symplasmic signaling. The intercellular trafficking of macromolecules, including RNAs and proteins, has emerged as a novel mechanism of intercellular communication in plants. Various forms of regulatory RNAs move over distinct cellular boundaries through plasmodesmata and phloem. This plant-specific, non-cell-autonomous RNA trafficking network is also involved in development, nutrient homeostasis, gene silencing, pathogen defense, and many other physiological processes. However, the mechanism underlying macromolecular trafficking in plants remains poorly understood. Current progress made in RNA trafficking research and its biological relevance to plant development will be summarized. Diverse plant regulatory mechanisms of cell-to-cell and systemic long-distance transport of RNAs, including mRNAs, viral RNAs, and small RNAs, will also be discussed. Copyright © 2013 John Wiley & Sons, Ltd.

  17. Adaptive support ventilation: State of the art review

    PubMed Central

    Fernández, Jaime; Miguelena, Dayra; Mulett, Hernando; Godoy, Javier; Martinón-Torres, Federico

    2013-01-01

    Mechanical ventilation is one of the most commonly applied interventions in intensive care units. Despite its life-saving role, it can be a risky procedure for the patient if not applied appropriately. To decrease risks, new ventilator modes continue to be developed in an attempt to improve patient outcomes. Advances in ventilator modes include closed-loop systems that facilitate ventilator manipulation of variables based on measured respiratory parameters. Adaptive support ventilation (ASV) is a positive pressure mode of mechanical ventilation that is closed-loop controlled, and automatically adjust based on the patient's requirements. In order to deliver safe and appropriate patient care, clinicians need to achieve a thorough understanding of this mode, including its effects on underlying respiratory mechanics. This article will discuss ASV while emphasizing appropriate ventilator settings, their advantages and disadvantages, their particular effects on oxygenation and ventilation, and the monitoring priorities for clinicians. PMID:23833471

  18. Myasthenia gravis and related disorders: Pathology and molecular pathogenesis.

    PubMed

    Ha, James C; Richman, David P

    2015-04-01

    Disorders affecting the presynaptic, synaptic, and postsynaptic portions of the neuromuscular junction arise from various mechanisms in children and adults, including acquired autoimmune or toxic processes as well as genetic mutations. Disorders include autoimmune myasthenia gravis associated with acetylcholine receptor, muscle specific kinase or Lrp4 antibodies, Lambert-Eaton myasthenic syndrome, nerve terminal hyperexcitability syndromes, Guillain Barré syndrome, botulism, organophosphate poisoning and a number of congenital myasthenic syndromes. This review focuses on the various molecular and pathophysiological mechanisms of these disorders, characterization of which has been crucial to the development of treatment strategies specific for each pathogenic mechanism. In the future, further understanding of the underlying processes may lead to more effective and targeted therapies of these disorders. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Mental Imagery in Depression: Phenomenology, Potential Mechanisms, and Treatment Implications.

    PubMed

    Holmes, Emily A; Blackwell, Simon E; Burnett Heyes, Stephanie; Renner, Fritz; Raes, Filip

    2016-01-01

    Mental imagery is an experience like perception in the absence of a percept. It is a ubiquitous feature of human cognition, yet it has been relatively neglected in the etiology, maintenance, and treatment of depression. Imagery abnormalities in depression include an excess of intrusive negative mental imagery; impoverished positive imagery; bias for observer perspective imagery; and overgeneral memory, in which specific imagery is lacking. We consider the contribution of imagery dysfunctions to depressive psychopathology and implications for cognitive behavioral interventions. Treatment advances capitalizing on the representational format of imagery (as opposed to its content) are reviewed, including imagery rescripting, positive imagery generation, and memory specificity training. Consideration of mental imagery can contribute to clinical assessment and imagery-focused psychological therapeutic techniques and promote investigation of underlying mechanisms for treatment innovation. Research into mental imagery in depression is at an early stage. Work that bridges clinical psychology and neuroscience in the investigation of imagery-related mechanisms is recommended.

  20. Mechanisms and pathways of growth failure in primordial dwarfism

    PubMed Central

    Klingseisen, Anna; Jackson, Andrew P.

    2011-01-01

    The greatest difference between species is size; however, the developmental mechanisms determining organism growth remain poorly understood. Primordial dwarfism is a group of human single-gene disorders with extreme global growth failure (which includes Seckel syndrome, microcephalic osteodysplastic primordial dwarfism I [MOPD] types I and II, and Meier-Gorlin syndrome). Ten genes have now been identified for microcephalic primordial dwarfism, encoding proteins involved in fundamental cellular processes including genome replication (ORC1 [origin recognition complex 1], ORC4, ORC6, CDT1, and CDC6), DNA damage response (ATR [ataxia-telangiectasia and Rad3-related]), mRNA splicing (U4atac), and centrosome function (CEP152, PCNT, and CPAP). Here, we review the cellular and developmental mechanisms underlying the pathogenesis of these conditions and address whether further study of these genes could provide novel insight into the physiological regulation of organism growth. PMID:21979914

  1. Exertional Dyspnoea in Chronic Respiratory Diseases: From Physiology to Clinical Application.

    PubMed

    Dubé, Bruno-Pierre; Vermeulen, François; Laveneziana, Pierantonio

    2017-02-01

    Dyspnoea is a complex, highly personalized and multidimensional sensory experience, and its underlying cause and mechanisms are still being investigated. Exertional dyspnoea is one of the most frequently encountered symptoms of patients with cardiopulmonary diseases, and is a common reason for seeking medical help. As the symptom usually progresses with the underlying disease, it can lead to an avoidance of physical activity, peripheral muscle deconditioning and decreased quality of life. Dyspnoea is closely associated with quality of life, exercise (in)tolerance and prognosis in various conditions, including chronic obstructive pulmonary disease, heart failure, interstitial lung disease and pulmonary hypertension, and is therefore an important therapeutic target. Effective management and treatment of dyspnoea is an important challenge for caregivers, and therapeutic options that attempt to reverse its underlying cause have been only partially successful This "review" will attempt to shed light on the physiological mechanisms underlying dyspnoea during exercise and to translate/apply them to a broad clinical spectrum of cardio-respiratory disorders. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Effects of state recovery on creep buckling under variable loading

    NASA Technical Reports Server (NTRS)

    Robinson, D. N.; Arnold, S. M.

    1986-01-01

    Structural alloys embody internal mechanisms that allow recovery of state with varying stress and elevated temperature, i.e., they can return to a softer state following periods of hardening. Such material behavior is known to strongly influence structural response under some important thermomechanical loadings, for example, that involving thermal ratchetting. The influence of dynamic and thermal recovery on the creep buckling of a column under variable loading is investigated. The column is taken as the idealized (Shanley) sandwich column. The constitutive model, unlike the commonly employed Norton creep model, incorporates a representation of both dynamic and thermal (state) recovery. The material parameters of the constitutive model are chosen to characterize Narloy Z, a representative copper alloy used in thrust nozzle liners of reusable rocket engines. Variable loading histories include rapid cyclic unloading/reloading sequences and intermittent reductions of load for extended periods of time; these are superimposed on a constant load. The calculated results show that state recovery significantly affects creep buckling under variable loading. Structural alloys embody internal mechanisms that allow recovery of state with varying stress and time.

  3. Lymphoid cell kinetics under continuous low dose-rate gamma irradiation: A comparison study

    NASA Technical Reports Server (NTRS)

    Foster, B. R.

    1975-01-01

    A comparison study was conducted of the effects of continuous low dose-rate gamma irradiation on cell population kinetics of lymphoid tissue (white pulp) of the mouse spleen with findings as they relate to the mouse thymus. Experimental techniques employed included autoradiography and specific labeling with tritiated thymidine (TdR-(h-3)). The problem studied involved the mechanism of cell proliferation of lymphoid tissue of the mouse spleen and thymus under the stress of continuous irradiation at a dose rate of 10 roentgens (R) per day for 105 days (15 weeks). The aim was to determine whether or not a steady state or near-steady state of cell population could be established for this period of time, and what compensatory mechanisms of cell population were involved.

  4. Brain nuclear receptors and body weight regulation

    PubMed Central

    O’Malley, Bert W.; Elmquist, Joel K.

    2017-01-01

    Neural pathways, especially those in the hypothalamus, integrate multiple nutritional, hormonal, and neural signals, resulting in the coordinated control of body weight balance and glucose homeostasis. Nuclear receptors (NRs) sense changing levels of nutrients and hormones, and therefore play essential roles in the regulation of energy homeostasis. Understanding the role and the underlying mechanisms of NRs in the context of energy balance control may facilitate the identification of novel targets to treat obesity. Notably, NRs are abundantly expressed in the brain, and emerging evidence indicates that a number of these brain NRs regulate multiple aspects of energy balance, including feeding, energy expenditure and physical activity. In this Review we summarize some of the recent literature regarding effects of brain NRs on body weight regulation and discuss mechanisms underlying these effects. PMID:28218618

  5. Anomalous Nonlocal Resistance and Spin-Charge Conversion Mechanisms in Two-Dimensional Metals

    NASA Astrophysics Data System (ADS)

    Huang, Chunli; Chong, Y. D.; Cazalilla, Miguel A.

    2017-09-01

    We uncover two anomalous features in the nonlocal transport behavior of two-dimensional metallic materials with spin-orbit coupling. First, the nonlocal resistance can have negative values and oscillate with distance, even in the absence of a magnetic field. Second, the oscillations of the nonlocal resistance under an applied in-plane magnetic field (the Hanle effect) can be asymmetric under field reversal. Both features are produced by direct magnetoelectric coupling, which is possible in materials with broken inversion symmetry but was not included in previous spin-diffusion theories of nonlocal transport. These effects can be used to identify the relative contributions of different spin-charge conversion mechanisms. They should be observable in adatom-functionalized graphene, and they may provide the reason for discrepancies in recent nonlocal transport experiments on graphene.

  6. Impact of lifestyle and technology developments on sleep

    PubMed Central

    Shochat, Tamar

    2012-01-01

    Although the physiological and psychological mechanisms involved in the development of sleep disorders remain similar throughout history, factors that potentiate these mechanisms are closely related to the “zeitgeist”, ie, the sociocultural, technological and lifestyle trends which characterize an era. Technological advancements have afforded modern society with 24-hour work operations, transmeridian travel and exposure to a myriad of electronic devices such as televisions, computers and cellular phones. Growing evidence suggests that these advancements take their toll on human functioning and health via their damaging effects on sleep quality, quantity and timing. Additional behavioral lifestyle factors associated with poor sleep include weight gain, insufficient physical exercise and consumption of substances such as caffeine, alcohol and nicotine. Some of these factors have been implicated as self-help aids used to combat daytime sleepiness and impaired daytime functioning. This review aims to highlight current lifestyle trends that have been shown in scientific investigations to be associated with sleep patterns, sleep duration and sleep quality. Current understanding of the underlying mechanisms of these associations will be presented, as well as some of the reported consequences. Available therapies used to treat some lifestyle related sleep disorders will be discussed. Perspectives will be provided for further investigation of lifestyle factors that are associated with poor sleep, including developing theoretical frameworks, identifying underlying mechanisms, and establishing appropriate therapies and public health interventions aimed to improve sleep behaviors in order to enhance functioning and health in modern society. PMID:23616726

  7. The Clementine mechanisms

    NASA Technical Reports Server (NTRS)

    Purdy, William; Hurley, Michael

    1995-01-01

    The Clementine spacecraft was developed under the 'faster, better, cheaper' theme. The constraints of a low budget coupled with an unusually tight schedule forced many departures from the normal spacecraft development methods. This paper discusses technical lessons learned about several of the mechanisms on the Clementine spacecraft as well as managerial lessons learned for the entire mechanisms subsystem. A quick overview of the Clementine mission is included; the mission schedule and environment during the mechanisms releases and deployment are highlighted. This paper then describes the entire mechanisms subsystem. The design and test approach and key philosophies for a fast-track program are discussed during the description of the mechanisms subsystem. The mechanism subsystem included a marman clamp separation system, a separation nut separation system, a solar panel deployment and pointing system, a high gain antenna feed deployment system, and two separate sensor cover systems. Each mechanism is briefly discussed. Additional technical discussion is given on the marman clamp design, the sensor cover designs, and the design and testing practices for systems driven by heated actuators (specifically paraffin actuators and frangibolts). All of the other mechanisms were of conventional designs and will receive less emphasis. Lessons learned are discussed throughout the paper as they applied to the systems being discussed. Since there is information on many different systems, this paper is organized so that information on a particular topic can be quickly referenced.

  8. Photoperiodic responses of depression-like behavior, the brain serotonergic system, and peripheral metabolism in laboratory mice.

    PubMed

    Otsuka, Tsuyoshi; Kawai, Misato; Togo, Yuki; Goda, Ryosei; Kawase, Takahiro; Matsuo, Haruka; Iwamoto, Ayaka; Nagasawa, Mao; Furuse, Mitsuhiro; Yasuo, Shinobu

    2014-02-01

    Seasonal affective disorder (SAD) is characterized by depression during specific seasons, generally winter. The pathophysiological mechanisms underlying SAD remain elusive due to a limited number of animal models with high availability and validity. Here we show that laboratory C57BL/6J mice display photoperiodic changes in depression-like behavior and brain serotonin content. C57BL/6J mice maintained under short-day conditions, as compared to those under long-day conditions, demonstrated prolonged immobility times in the forced swimming test with lower brain levels of serotonin and its precursor l-tryptophan. Furthermore, photoperiod altered multiple parameters reflective of peripheral metabolism, including the ratio of plasma l-tryptophan to the sum of other large neutral amino acids that compete for transport across the blood-brain barrier, responses of circulating glucose and insulin to glucose load, sucrose intake under restricted feeding condition, and sensitivity of the brain serotonergic system to peripherally administered glucose. These data suggest that the mechanisms underlying SAD involve the brain-peripheral tissue network, and C57BL/6J mice can serve as a powerful tool for investigating the link between seasons and mood. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Activation of respiratory muscles during weaning from mechanical ventilation.

    PubMed

    Walterspacher, Stephan; Gückler, Julia; Pietsch, Fabian; Walker, David Johannes; Kabitz, Hans-Joachim; Dreher, Michael

    2017-04-01

    Respiratory muscle dysfunction is a key component of weaning failure. Balancing respiratory muscle loading and unloading by applying different ventilation modes along with spontaneous breathing episodes are established weaning strategies. However, the effects of body positioning on the respiratory muscles during weaning remains unclear. This study aimed at assessing respiratory drive by surface electromyography (EMG) of the diaphragm (EMG dia ) and parasternal muscles (EMG para ) in tracheotomized patients during prolonged weaning in 3 randomized body positions-supine, 30° semirecumbent, and 80° sitting-during mechanical ventilation and spontaneous breathing. Nine patients were included for analysis. Cardiorespiratory parameters (heart rate, blood pressure, arterial oxygen saturation, dyspnea) did not change under each condition (all P>.05). EMG para and EMG dia did not change under mechanical ventilation (both P>.05). EMG dia changed under spontaneous breathing from supine to sitting (0.45±0.26 vs 0.32±0.19; P=.012) and between semirecumbent to sitting (0.41±0.23 vs 0.32±0.19; P=.039), whereas EMG para did not change. This is the first study to show that body positioning influences respiratory drive to the diaphragm in tracheotomized patients with prolonged weaning from mechanical ventilation during unassisted breathing. Sitting position reduces respiratory drive compared with semirecumbent and supine positioning and might therefore be favored during spontaneous breathing trials. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Technetium incorporation into goethite (α-FeOOH): An atomic-scale investigation

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

    Smith, Frances N.; Taylor, Christopher D.; Um, Wooyong

    2015-11-17

    During the processing of low-activity radioactive waste to generate solid waste forms (e.g., glass), technetium-99 (Tc) is of concern because of its volatility. A variety of materials are under consideration to capture Tc from waste streams, including the iron oxyhydroxide, goethite (α-FeOOH), which was experimentally shown to sequester Tc(IV). This material could ultimately be incorporated into glass or other low-temperature waste form matrices. However, questions remain regarding the incorporation mechanism for Tc(IV) in goethite, which has implications for predicting the long-term stability of Tc in waste forms under changing conditions. Here, quantum-mechanical calculations were used to evaluate the energy ofmore » five different charge-compensated Tc(IV) incorporation scenarios in goethite. The two most stable incorporation mechanisms involve direct substitution of Tc(IV) onto Fe(III) lattice sites and charge balancing either by removing one nearby H+ (i.e., within 5 Å), or by creating an Fe(III) vacancy when substituting 3 Tc(IV) for 4 Fe(III), with the former being preferred over the latter relative to gas-phase ions. When corrections for hydrated references phases are applied, the Fe(III)-vacancy mechanism becomes more energetically competitive. Calculated incorporation energies and optimized bond-lengths are presented. Proton movement is observed to satisfy under-coordinated bonds surrounding vacancies in the goethite structure.« less

  11. Curcumin-mediated regulation of intestinal barrier function: The mechanism underlying its beneficial effects.

    PubMed

    Ghosh, Siddhartha S; He, Hongliang; Wang, Jing; Gehr, Todd W; Ghosh, Shobha

    2018-01-02

    Curcumin has anti-inflammatory, anti-oxidant and anti-proliferative properties established largely by in vitro studies. Accordingly, oral administration of curcumin beneficially modulates many diseases including diabetes, fatty-liver disease, atherosclerosis, arthritis, cancer and neurological disorders such as depression, Alzheimer's or Parkinson's disease. However, limited bioavailability and inability to detect curcumin in circulation or target tissues has hindered the validation of a causal role. We established curcumin-mediated decrease in the release of gut bacteria-derived lipopolysaccharide (LPS) into circulation by maintaining the integrity of the intestinal barrier function as the mechanism underlying the attenuation of metabolic diseases (diabetes, atherosclerosis, kidney disease) by curcumin supplementation precluding the need for curcumin absorption. In view of the causative role of circulating LPS and resulting chronic inflammation in the development of diseases listed above, this review summarizes the mechanism by which curcumin affects the several layers of the intestinal barrier and, despite negligible absorption, can beneficially modulate these diseases.

  12. (Per)chlorate in Biology on Earth and Beyond.

    PubMed

    Youngblut, Matthew D; Wang, Ouwei; Barnum, Tyler P; Coates, John D

    2016-09-08

    Respiration of perchlorate and chlorate [collectively, (per)chlorate] was only recognized in the last 20 years, yet substantial advances have been made in our understanding of the underlying metabolisms. Although it was once considered solely anthropogenic, pervasive natural sources, both terrestrial and extraterrestrial, indicate an ancient (per)chlorate presence across our solar system. These discoveries stimulated interest in (per)chlorate microbiology, and the application of advanced approaches highlights exciting new facets. Forward and reverse genetics revealed new information regarding underlying molecular biology and associated regulatory mechanisms. Structural and functional analysis characterized core enzymes and identified novel reaction sequences. Comparative genomics elucidated evolutionary aspects, and stress analysis identified novel response mechanisms to reactive chlorine species. Finally, systems biology identified unique metabolic versatility and novel mechanisms of (per)chlorate respiration, including symbiosis and a hybrid enzymatic-abiotic metabolism. While many published studies focus on (per)chlorate and their basic metabolism, this review highlights seminal advances made over the last decade and identifies new directions and potential novel applications.

  13. Role of exercise in maintaining the integrity of the neuromuscular junction.

    PubMed

    Nishimune, Hiroshi; Stanford, John A; Mori, Yasuo

    2014-03-01

    Physical activity plays an important role in preventing chronic disease in adults and the elderly. Exercise has beneficial effects on the nervous system, including at the neuromuscular junction (NMJ). Exercise causes hypertrophy of NMJs and improves recovery from peripheral nerve injuries, whereas decreased physical activity causes degenerative changes in NMJs. Recent studies have begun to elucidate molecular mechanisms underlying the beneficial effects of exercise. These mechanisms involve Bassoon, neuregulin-1, peroxisome proliferator-activated receptor gamma coactivator 1α, insulin-like growth factor-1, glial cell line-derived neurotrophic factor, neurotrophin 4, Homer, and nuclear factor of activated T cells c1. For example, NMJ denervation and active zone decreases have been observed in aged NMJs, but these age-dependent degenerative changes can be ameliorated by exercise. In this review we assess the effects of exercise on the maintenance and regeneration of NMJs and highlight recent insights into the molecular mechanisms underlying these exercise effects. Copyright © 2013 Wiley Periodicals, Inc.

  14. ON THE BIOMECHANICS OF HEART VALVE FUNCTION

    PubMed Central

    Sacks, Michael S.; Merryman, W. David; Schmidt, David E.

    2009-01-01

    Heart valves (HVs) are fluidic control components of the heart that ensure unidirectional blood flow during the cardiac cycle. However, this description does not adequately describe the biomechanical ramifications of their function in that their mechanics are multi-modal. Moreover, they must replicate their cyclic function over an entire lifetime, with an estimated total functional demand of least 3×109 cycles. The focus of the present review is on the functional biomechanics of heart valves. Thus, the focus of the present review is on functional biomechanics, referring primarily to biosolid as well as several key biofluid mechanical aspects underlying heart valve physiological function. Specifically, we refer to the mechanical behaviors of the extra-cellular matrix structural proteins, underlying cellular function, and their integrated relation to the major aspects of valvular hemodynamic function. While we focus on the work from the author’s laboratories, relevant works of other investigators have been included whenever appropriate. We conclude with a summary of important future trends. PMID:19540499

  15. Combination of Universal Mechanical Testing Machine with Atomic Force Microscope for Materials Research

    PubMed Central

    Zhong, Jian; He, Dannong

    2015-01-01

    Surface deformation and fracture processes of materials under external force are important for understanding and developing materials. Here, a combined horizontal universal mechanical testing machine (HUMTM)-atomic force microscope (AFM) system is developed by modifying UMTM to combine with AFM and designing a height-adjustable stabilizing apparatus. Then the combined HUMTM-AFM system is evaluated. Finally, as initial demonstrations, it is applied to analyze the relationship among macroscopic mechanical properties, surface nanomorphological changes under external force, and fracture processes of two kinds of representative large scale thin film materials: polymer material with high strain rate (Parafilm) and metal material with low strain rate (aluminum foil). All the results demonstrate the combined HUMTM-AFM system overcomes several disadvantages of current AFM-combined tensile/compression devices including small load force, incapability for large scale specimens, disability for materials with high strain rate, and etc. Therefore, the combined HUMTM-AFM system is a promising tool for materials research in the future. PMID:26265357

  16. Combination of Universal Mechanical Testing Machine with Atomic Force Microscope for Materials Research.

    PubMed

    Zhong, Jian; He, Dannong

    2015-08-12

    Surface deformation and fracture processes of materials under external force are important for understanding and developing materials. Here, a combined horizontal universal mechanical testing machine (HUMTM)-atomic force microscope (AFM) system is developed by modifying UMTM to combine with AFM and designing a height-adjustable stabilizing apparatus. Then the combined HUMTM-AFM system is evaluated. Finally, as initial demonstrations, it is applied to analyze the relationship among macroscopic mechanical properties, surface nanomorphological changes under external force, and fracture processes of two kinds of representative large scale thin film materials: polymer material with high strain rate (Parafilm) and metal material with low strain rate (aluminum foil). All the results demonstrate the combined HUMTM-AFM system overcomes several disadvantages of current AFM-combined tensile/compression devices including small load force, incapability for large scale specimens, disability for materials with high strain rate, and etc. Therefore, the combined HUMTM-AFM system is a promising tool for materials research in the future.

  17. Fatigue responses of lead zirconate titanate stacks under semibipolar electric cycling with mechanical preload

    NASA Astrophysics Data System (ADS)

    Wang, Hong; Cooper, Thomas A.; Lin, Hua-Tay; Wereszczak, Andrew A.

    2010-10-01

    Lead zirconate titanate (PZT) stacks that had an interdigital internal electrode configuration were tested to more than 108 cycles. A 100 Hz semibipolar sine wave with a field range of +4.5/-0.9 kV/mm was used in cycling with a concurrently-applied 20 MPa preload. Significant reductions in piezoelectric and dielectric responses were observed during the cycling depending on the measuring condition. Extensive partial discharges were also observed. These surface events resulted in the erosion of external electrode and the exposure of internal electrodes. Sections prepared by sequential polishing technique revealed a variety of damage mechanisms including delaminations, pores, and etch grooves. The scale of damage was correlated with the degree of fatigue-induced reduction in piezoelectric and dielectric responses. The results from this study demonstrate the feasibility of using a semibipolar mode to drive a PZT stack under a mechanical preload and illustrate the potential fatigue and damages of the stack in service.

  18. Nanoarchitectured materials composed of fullerene-like spheroids and disordered graphene layers with tunable mechanical properties.

    PubMed

    Zhao, Zhisheng; Wang, Erik F; Yan, Hongping; Kono, Yoshio; Wen, Bin; Bai, Ligang; Shi, Feng; Zhang, Junfeng; Kenney-Benson, Curtis; Park, Changyong; Wang, Yanbin; Shen, Guoyin

    2015-02-04

    Type-II glass-like carbon is a widely used material with a unique combination of properties including low density, high strength, extreme impermeability to gas and liquid and resistance to chemical corrosion. It can be considered as a carbon-based nanoarchitectured material, consisting of a disordered multilayer graphene matrix encasing numerous randomly distributed nanosized fullerene-like spheroids. Here we show that under both hydrostatic compression and triaxial deformation, this high-strength material is highly compressible and exhibits a superelastic ability to recover from large strains. Under hydrostatic compression, bulk, shear and Young's moduli decrease anomalously with pressure, reaching minima around 1-2 GPa, where Poisson's ratio approaches zero, and then revert to normal behaviour with positive pressure dependences. Controlling the concentration, size and shape of fullerene-like spheroids with tailored topological connectivity to graphene layers is expected to yield exceptional and tunable mechanical properties, similar to mechanical metamaterials, with potentially wide applications.

  19. Nanoarchitectured materials composed of fullerene-like spheroids and disordered graphene layers with tunable mechanical properties

    NASA Astrophysics Data System (ADS)

    Zhao, Zhisheng; Wang, Erik F.; Yan, Hongping; Kono, Yoshio; Wen, Bin; Bai, Ligang; Shi, Feng; Zhang, Junfeng; Kenney-Benson, Curtis; Park, Changyong; Wang, Yanbin; Shen, Guoyin

    2015-02-01

    Type-II glass-like carbon is a widely used material with a unique combination of properties including low density, high strength, extreme impermeability to gas and liquid and resistance to chemical corrosion. It can be considered as a carbon-based nanoarchitectured material, consisting of a disordered multilayer graphene matrix encasing numerous randomly distributed nanosized fullerene-like spheroids. Here we show that under both hydrostatic compression and triaxial deformation, this high-strength material is highly compressible and exhibits a superelastic ability to recover from large strains. Under hydrostatic compression, bulk, shear and Young’s moduli decrease anomalously with pressure, reaching minima around 1-2 GPa, where Poisson’s ratio approaches zero, and then revert to normal behaviour with positive pressure dependences. Controlling the concentration, size and shape of fullerene-like spheroids with tailored topological connectivity to graphene layers is expected to yield exceptional and tunable mechanical properties, similar to mechanical metamaterials, with potentially wide applications.

  20. Rosaceae Fruit Development, Ripening and Post-harvest: An Epigenetic Perspective

    PubMed Central

    Farinati, Silvia; Rasori, Angela; Varotto, Serena; Bonghi, Claudio

    2017-01-01

    Rosaceae is a family with an extraordinary spectrum of fruit types, including fleshy peach, apple, and strawberry that provide unique contributions to a healthy diet for consumers, and represent an excellent model for studying fruit patterning and development. In recent years, many efforts have been made to unravel regulatory mechanism underlying the hormonal, transcriptomic, proteomic and metabolomic changes occurring during Rosaceae fruit development. More recently, several studies on fleshy (tomato) and dry (Arabidopsis) fruit model have contributed to a better understanding of epigenetic mechanisms underlying important heritable crop traits, such as ripening and stress response. In this context and summing up the results obtained so far, this review aims to collect the available information on epigenetic mechanisms that may provide an additional level in gene transcription regulation, thus influencing and driving the entire Rosaceae fruit developmental process. The whole body of information suggests that Rosaceae fruit could become also a model for studying the epigenetic basis of economically important phenotypes, allowing for their more efficient exploitation in plant breeding. PMID:28769956

  1. Immunoglobulin class-switch recombination deficiencies.

    PubMed

    Durandy, Anne; Kracker, Sven

    2012-07-30

    Immunoglobulin class-switch recombination deficiencies (Ig-CSR-Ds) are rare primary immunodeficiencies characterized by defective switched isotype (IgG/IgA/IgE) production. Depending on the molecular defect in question, the Ig-CSR-D may be combined with an impairment in somatic hypermutation (SHM). Some of the mechanisms underlying Ig-CSR and SHM have been described by studying natural mutants in humans. This approach has revealed that T cell-B cell interaction (resulting in CD40-mediated signaling), intrinsic B-cell mechanisms (activation-induced cytidine deaminase-induced DNA damage), and complex DNA repair machineries (including uracil-N-glycosylase and mismatch repair pathways) are all involved in class-switch recombination and SHM. However, several of the mechanisms required for full antibody maturation have yet to be defined. Elucidation of the molecular defects underlying the diverse set of Ig-CSR-Ds is essential for understanding Ig diversification and has prompted better definition of the clinical spectrum of diseases and the development of increasingly accurate diagnostic and therapeutic approaches.

  2. Immunoglobulin class-switch recombination deficiencies

    PubMed Central

    2012-01-01

    Immunoglobulin class-switch recombination deficiencies (Ig-CSR-Ds) are rare primary immunodeficiencies characterized by defective switched isotype (IgG/IgA/IgE) production. Depending on the molecular defect in question, the Ig-CSR-D may be combined with an impairment in somatic hypermutation (SHM). Some of the mechanisms underlying Ig-CSR and SHM have been described by studying natural mutants in humans. This approach has revealed that T cell-B cell interaction (resulting in CD40-mediated signaling), intrinsic B-cell mechanisms (activation-induced cytidine deaminase-induced DNA damage), and complex DNA repair machineries (including uracil-N-glycosylase and mismatch repair pathways) are all involved in class-switch recombination and SHM. However, several of the mechanisms required for full antibody maturation have yet to be defined. Elucidation of the molecular defects underlying the diverse set of Ig-CSR-Ds is essential for understanding Ig diversification and has prompted better definition of the clinical spectrum of diseases and the development of increasingly accurate diagnostic and therapeutic approaches. PMID:22894609

  3. Five year magnetic tape for unattended satellite tape recorders

    NASA Technical Reports Server (NTRS)

    Benn, G. S. L.; Gutfreund, K.

    1972-01-01

    The development and fabrication of a quantity of long life magnetic tape with properties selected specifically for unattended operation in spacecraft tape recorders was studied. A detailed analytical consideration of various binder systems was undertaken. This included the chemical aspects of the binders, cohesion and adhesion effects, stability and the mechanical and physical properties. The ability to form free films of these polymers and their combination with various oxide loadings and other additives allowed a rapid selection of four polymer candidates for a five year magnetic tape. Samples were evaluated under actual running conditions which included physical, magnetic, and extensive life testing. These sample tapes withstood 50,000 bidirectional tape passes under fairly harsh operating conditions.

  4. Photoconductivity in Dirac materials

    NASA Astrophysics Data System (ADS)

    Shao, J. M.; Yang, G. W.

    2015-11-01

    Two-dimensional (2D) Dirac materials including graphene and the surface of a three-dimensional (3D) topological insulator, and 3D Dirac materials including 3D Dirac semimetal and Weyl semimetal have attracted great attention due to their linear Dirac nodes and exotic properties. Here, we use the Fermi's golden rule and Boltzmann equation within the relaxation time approximation to study and compare the photoconductivity of Dirac materials under different far- or mid-infrared irradiation. Theoretical results show that the photoconductivity exhibits the anisotropic property under the polarized irradiation, but the anisotropic strength is different between 2D and 3D Dirac materials. The photoconductivity depends strongly on the relaxation time for different scattering mechanism, just like the dark conductivity.

  5. A comparative integrated transcript analysis and functional characterization of differential mechanisms for induction of liver hypertrophy in the rat

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

    Boitier, Eric, E-mail: eric.boitier@sanofi-aventis.com; Amberg, Alexander; Barbie, Valerie

    2011-04-15

    The main goal of the present work was to better understand the molecular mechanisms underlying liver hypertrophy (LH), a recurrent finding observed following acute or repeated drug administration to animals, using transcriptomic technologies together with the results from conventional toxicology methods. Administration of 5 terminated proprietary drug candidates from participating companies involved in the EU Innomed PredTox Project or the reference hepatotoxicant troglitazone to rats for up to a 14-day duration induced LH as the main liver phenotypic toxicity outcome. The integrated analysis of transcriptomic liver expression data across studies turned out to be the most informative approach for themore » generation of mechanistic models of LH. In response to a xenobiotic stimulus, a marked increase in the expression of xenobiotic metabolizing enzymes (XME) was observed in a subset of 4 studies. Accumulation of these newly-synthesized proteins within the smooth endoplasmic reticulum (SER) would suggest proliferation of this organelle, which most likely is the main molecular process underlying the LH observed in XME studies. In another subset of 2 studies (including troglitazone), a marked up-regulation of genes involved in peroxisomal fatty acid {beta}-oxidation was noted, associated with induction of genes involved in peroxisome proliferation. Therefore, an increase in peroxisome abundance would be the main mechanism underlying LH noted in this second study subset. Together, the use of transcript profiling provides a means to generate putative mechanistic models underlying the pathogenesis of liver hypertrophy, to distinguish between subtle variations in subcellular organelle proliferation and creates opportunities for improved mechanism-based risk assessment.« less

  6. Cracks dynamics under tensional stress - a DEM approach

    NASA Astrophysics Data System (ADS)

    Debski, Wojciech; Klejment, Piotr; Kosmala, Alicja; Foltyn, Natalia; Szpindler, Maciej

    2017-04-01

    Breaking and fragmentation of solid materials is an extremely complex process involving scales ranging from an atomic scale (breaking inter-atomic bounds) up to thousands of kilometers in case of catastrophic earthquakes (in energy scale it ranges from single eV up to 1024 J). Such a large scale span of breaking processes opens lot of questions like, for example, scaling of breaking processes, existence of factors controlling final size of broken area, existence of precursors, dynamics of fragmentation, to name a few. The classical approach to study breaking process at seismological scales, i.e., physical processes in earthquake foci, is essentially based on two factors: seismic data (mostly) and the continuum mechanics (including the linear fracture mechanics). Such approach has been gratefully successful in developing kinematic (first) and dynamic (recently) models of seismic rupture and explaining many of earthquake features observed all around the globe. However, such approach will sooner or latter face a limitation due to a limited information content of seismic data and inherit limitations of the fracture mechanics principles. A way of avoiding this expected limitation is turning an attention towards a well established in physics method of computational simulations - a powerful branch of contemporary physics. In this presentation we discuss preliminary results of analysis of fracturing dynamics under external tensional forces using the Discrete Element Method approach. We demonstrate that even under a very simplified tensional conditions, the fragmentation dynamics is a very complex process, including multi-fracturing, spontaneous fracture generation and healing, etc. We also emphasis a role of material heterogeneity on the fragmentation process.

  7. Regulation of Neurovascular Coupling in Autoimmunity to Water and Ion Channels

    PubMed Central

    Jukkola, Peter; Gu, Chen

    2014-01-01

    Much progress has been made in understanding autoimmune channelopathies, but the underlying pathogenic mechanisms are not always clear due to broad expression of some channel proteins. Recent studies show that autoimmune conditions that interfere with neurovascular coupling in the central nervous system (CNS) can lead to neurodegeneration. Cerebral blood flow that meets neuronal activity and metabolic demand is tightly regulated by local neural activity. This process of reciprocal regulation involves coordinated actions of a number of cell types, including neurons, glia, and vascular cells. In particular, astrocytic endfeet cover more than 90% of brain capillaries to assist blood-brain barrier (BBB) function, and wrap around synapses and nodes of Ranvier to communicate with neuronal activity. In this review, we highlight four types of channel proteins that are expressed in astrocytes, regarding their structures, biophysical properties, expression and distribution patterns, and related diseases including autoimmune disorders. Water channel aquaporin 4 (AQP4) and inwardly-rectifying potassium (Kir4.1) channels are concentrated in astrocytic endfeet, whereas some voltage-gated Ca2+ and two-pore-domain K+ channels are expressed throughout the cell body of reactive astrocytes. More channel proteins are found in astrocytes under normal and abnormal conditions. This research field will contribute to a better understanding of pathogenic mechanisms underlying autoimmune disorders. PMID:25462580

  8. The shear response of copper bicrystals with Σ11 symmetric and asymmetric tilt grain boundaries by molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Zhang, Liang; Lu, Cheng; Tieu, Kiet; Zhao, Xing; Pei, Linqing

    2015-04-01

    Grain boundaries (GBs) are important microstructure features and can significantly affect the properties of nanocrystalline materials. Molecular dynamics simulation was carried out in this study to investigate the shear response and deformation mechanisms of symmetric and asymmetric Σ11<1 1 0> tilt GBs in copper bicrystals. Different deformation mechanisms were reported, depending on GB inclination angles and equilibrium GB structures, including GB migration coupled to shear deformation, GB sliding caused by local atomic shuffling, and dislocation nucleation from GB. The simulation showed that migrating Σ11(1 1 3) GB under shear can be regarded as sliding of GB dislocations and their combination along the boundary plane. A non-planar structure with dissociated intrinsic stacking faults was prevalent in Σ11 asymmetric GBs of Cu. This type of structure can significantly increase the ductility of bicrystal models under shear deformation. A grain boundary can be a source of dislocation and migrate itself at different stress levels. The intrinsic free volume involved in the grain boundary area was correlated with dislocation nucleation and GB sliding, while the dislocation nucleation mechanism can be different for a grain boundary due to its different equilibrium structures.Grain boundaries (GBs) are important microstructure features and can significantly affect the properties of nanocrystalline materials. Molecular dynamics simulation was carried out in this study to investigate the shear response and deformation mechanisms of symmetric and asymmetric Σ11<1 1 0> tilt GBs in copper bicrystals. Different deformation mechanisms were reported, depending on GB inclination angles and equilibrium GB structures, including GB migration coupled to shear deformation, GB sliding caused by local atomic shuffling, and dislocation nucleation from GB. The simulation showed that migrating Σ11(1 1 3) GB under shear can be regarded as sliding of GB dislocations and their combination along the boundary plane. A non-planar structure with dissociated intrinsic stacking faults was prevalent in Σ11 asymmetric GBs of Cu. This type of structure can significantly increase the ductility of bicrystal models under shear deformation. A grain boundary can be a source of dislocation and migrate itself at different stress levels. The intrinsic free volume involved in the grain boundary area was correlated with dislocation nucleation and GB sliding, while the dislocation nucleation mechanism can be different for a grain boundary due to its different equilibrium structures. Electronic supplementary information (ESI) available: Movies show the evolution of different grain boundaries under shear deformation: S-0, S-54.74, S-70.53-A, S-70.53-B, S-90. See DOI: 10.1039/c4nr07496c

  9. Osteoarthritis Year in Review 2015: Mechanics

    PubMed Central

    Varady, Nathan H.; Grodzinsky, Alan J.

    2015-01-01

    Motivated by the conceptual framework of multi-scale biomechanics, this narrative review highlights recent major advances with a focus on gait and joint kinematics, then tissue-level mechanics, cell mechanics and mechanotransduction, matrix mechanics, and finally the nanoscale mechanics of matrix macromolecules. A literature review was conducted from January 2014 to April 2015 using PubMed to identify major developments in mechanics related to osteoarthritis (OA). Studies of knee adduction, flexion, rotation, and contact mechanics have extended our understanding of medial compartment loading. In turn, advances in measurement methodologies have shown how injuries to both the meniscus and ligaments, together, can alter joint kinematics. At the tissue scale, novel findings have emerged regarding the mechanics of the meniscus as well as cartilage superficial zone. Moving to the cell level, poroelastic and poroviscoelastic mechanisms underlying chondrocyte deformation have been reported, along with the response to osmotic stress. Further developments have emerged on the role of calcium signaling in chondrocyte mechanobiology, including exciting findings on the function of mechanically activated cation channels newly found to be expressed in chondrocytes. Finally, AFM-based nano-rheology systems have enabled studies of thin murine tissues and brush layers of matrix molecules over a wide range of loading rates including high rates corresponding to impact injury. With OA acknowledged to be a disease of the joint as an organ, understanding mechanical behavior at each length scale helps to elucidate the connections between cell biology, matrix biochemistry and tissue structure/function that may play a role in the pathomechanics of OA. PMID:26707990

  10. Computational mechanics research and support for aerodynamics and hydraulics at TFHRC year 1 quarter 4 progress report.

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

    Lottes, S.A.; Kulak, R.F.; Bojanowski, C.

    2011-12-09

    The computational fluid dynamics (CFD) and computational structural mechanics (CSM) focus areas at Argonne's Transportation Research and Analysis Computing Center (TRACC) initiated a project to support and compliment the experimental programs at the Turner-Fairbank Highway Research Center (TFHRC) with high performance computing based analysis capabilities in August 2010. The project was established with a new interagency agreement between the Department of Energy and the Department of Transportation to provide collaborative research, development, and benchmarking of advanced three-dimensional computational mechanics analysis methods to the aerodynamics and hydraulics laboratories at TFHRC for a period of five years, beginning in October 2010. Themore » analysis methods employ well-benchmarked and supported commercial computational mechanics software. Computational mechanics encompasses the areas of Computational Fluid Dynamics (CFD), Computational Wind Engineering (CWE), Computational Structural Mechanics (CSM), and Computational Multiphysics Mechanics (CMM) applied in Fluid-Structure Interaction (FSI) problems. The major areas of focus of the project are wind and water effects on bridges - superstructure, deck, cables, and substructure (including soil), primarily during storms and flood events - and the risks that these loads pose to structural failure. For flood events at bridges, another major focus of the work is assessment of the risk to bridges caused by scour of stream and riverbed material away from the foundations of a bridge. Other areas of current research include modeling of flow through culverts to assess them for fish passage, modeling of the salt spray transport into bridge girders to address suitability of using weathering steel in bridges, CFD analysis of the operation of the wind tunnel in the TFCHR wind engineering laboratory, vehicle stability under high wind loading, and the use of electromagnetic shock absorbers to improve vehicle stability under high wind conditions. This quarterly report documents technical progress on the project tasks for the period of July through September 2011.« less

  11. Maximization of permanent trapping of CO{sub 2} and co-contaminants in the highest-porosity formations of the Rock Springs Uplift (Southwest Wyoming): experimentation and multi-scale modeling

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

    Piri, Mohammad

    2014-03-31

    Under this project, a multidisciplinary team of researchers at the University of Wyoming combined state-of-the-art experimental studies, numerical pore- and reservoir-scale modeling, and high performance computing to investigate trapping mechanisms relevant to geologic storage of mixed scCO{sub 2} in deep saline aquifers. The research included investigations in three fundamental areas: (i) the experimental determination of two-phase flow relative permeability functions, relative permeability hysteresis, and residual trapping under reservoir conditions for mixed scCO{sub 2}-­brine systems; (ii) improved understanding of permanent trapping mechanisms; (iii) scientifically correct, fine grid numerical simulations of CO{sub 2} storage in deep saline aquifers taking into account themore » underlying rock heterogeneity. The specific activities included: (1) Measurement of reservoir-­conditions drainage and imbibition relative permeabilities, irreducible brine and residual mixed scCO{sub 2} saturations, and relative permeability scanning curves (hysteresis) in rock samples from RSU; (2) Characterization of wettability through measurements of contact angles and interfacial tensions under reservoir conditions; (3) Development of physically-­based dynamic core-­scale pore network model; (4) Development of new, improved high-­performance modules for the UW-­team simulator to provide new capabilities to the existing model to include hysteresis in the relative permeability functions, geomechanical deformation and an equilibrium calculation (Both pore-­ and core-­scale models were rigorously validated against well-­characterized core-­ flooding experiments); and (5) An analysis of long term permanent trapping of mixed scCO{sub 2} through high-­resolution numerical experiments and analytical solutions. The analysis takes into account formation heterogeneity, capillary trapping, and relative permeability hysteresis.« less

  12. Transcriptomic studies reveal a key metabolic pathway contributing to a well-maintained photosynthetic system under drought stress in foxtail millet (Setaria italica L.).

    PubMed

    Shi, Weiping; Cheng, Jingye; Wen, Xiaojie; Wang, Jixiang; Shi, Guanyan; Yao, Jiayan; Hou, Liyuan; Sun, Qian; Xiang, Peng; Yuan, Xiangyang; Dong, Shuqi; Guo, Pingyi; Guo, Jie

    2018-01-01

    Drought stress is one of the most important abiotic factors limiting crop productivity. A better understanding of the effects of drought on millet ( Setaria italica L.) production, a model crop for studying drought tolerance, and the underlying molecular mechanisms responsible for drought stress responses is vital to improvement of agricultural production. In this study, we exposed the drought resistant F 1 hybrid, M79, and its parental lines E1 and H1 to drought stress. Subsequent physiological analysis demonstrated that M79 showed higher photosynthetic energy conversion efficiency and drought tolerance than its parents. A transcriptomic study using leaves collected six days after drought treatment, when the soil water content was about ∼20%, identified 3066, 1895, and 2148 differentially expressed genes (DEGs) in M79, E1 and H1 compared to the respective untreated controls, respectively. Further analysis revealed 17 Gene Ontology (GO) enrichments and 14 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in M79, including photosystem II (PSII) oxygen-evolving complex, peroxidase (POD) activity, plant hormone signal transduction, and chlorophyll biosynthesis. Co-regulation analysis suggested that these DEGs in M79 contributed to the formation of a regulatory network involving multiple biological processes and pathways including photosynthesis, signal transduction, transcriptional regulation, redox regulation, hormonal signaling, and osmotic regulation. RNA-seq analysis also showed that some photosynthesis-related DEGs were highly expressed in M79 compared to its parental lines under drought stress. These results indicate that various molecular pathways, including photosynthesis, respond to drought stress in M79, and provide abundant molecular information for further analysis of the underlying mechanism responding to this stress.

  13. Unraveling the Root Proteome Changes and Its Relationship to Molecular Mechanism Underlying Salt Stress Response in Radish (Raphanus sativus L.)

    PubMed Central

    Sun, Xiaochuan; Wang, Yan; Xu, Liang; Li, Chao; Zhang, Wei; Luo, Xiaobo; Jiang, Haiyan; Liu, Liwang

    2017-01-01

    To understand the molecular mechanism underlying salt stress response in radish, iTRAQ-based proteomic analysis was conducted to investigate the differences in protein species abundance under different salt treatments. In total, 851, 706, and 685 differential abundance protein species (DAPS) were identified between CK vs. Na100, CK vs. Na200, and Na100 vs. Na200, respectively. Functional annotation analysis revealed that salt stress elicited complex proteomic alterations in radish roots involved in carbohydrate and energy metabolism, protein metabolism, signal transduction, transcription regulation, stress and defense and transport. Additionally, the expression levels of nine genes encoding DAPS were further verified using RT-qPCR. The integrative analysis of transcriptomic and proteomic data in conjunction with miRNAs was further performed to strengthen the understanding of radish response to salinity. The genes responsible for signal transduction, ROS scavenging and transport activities as well as several key miRNAs including miR171, miR395, and miR398 played crucial roles in salt stress response in radish. Based on these findings, a schematic genetic regulatory network of salt stress response was proposed. This study provided valuable insights into the molecular mechanism underlying salt stress response in radish roots and would facilitate developing effective strategies toward genetically engineered salt-tolerant radish and other root vegetable crops. PMID:28769938

  14. Model predictions of deformation, embolization and permeability of partially obstructive blood clots under variable shear flow.

    PubMed

    Xu, Shixin; Xu, Zhiliang; Kim, Oleg V; Litvinov, Rustem I; Weisel, John W; Alber, Mark

    2017-11-01

    Thromboembolism, one of the leading causes of morbidity and mortality worldwide, is characterized by formation of obstructive intravascular clots (thrombi) and their mechanical breakage (embolization). A novel two-dimensional multi-phase computational model is introduced that describes active interactions between the main components of the clot, including platelets and fibrin, to study the impact of various physiologically relevant blood shear flow conditions on deformation and embolization of a partially obstructive clot with variable permeability. Simulations provide new insights into mechanisms underlying clot stability and embolization that cannot be studied experimentally at this time. In particular, model simulations, calibrated using experimental intravital imaging of an established arteriolar clot, show that flow-induced changes in size, shape and internal structure of the clot are largely determined by two shear-dependent mechanisms: reversible attachment of platelets to the exterior of the clot and removal of large clot pieces. Model simulations predict that blood clots with higher permeability are more prone to embolization with enhanced disintegration under increasing shear rate. In contrast, less permeable clots are more resistant to rupture due to shear rate-dependent clot stiffening originating from enhanced platelet adhesion and aggregation. These results can be used in future to predict risk of thromboembolism based on the data about composition, permeability and deformability of a clot under specific local haemodynamic conditions. © 2017 The Author(s).

  15. A novel perspective on neuron study: damaging and promoting effects in different neurons induced by mechanical stress.

    PubMed

    Wang, Yazhou; Wang, Wei; Li, Zong; Hao, Shilei; Wang, Bochu

    2016-10-01

    A growing volume of experimental evidence demonstrates that mechanical stress plays a significant role in growth, proliferation, apoptosis, gene expression, electrophysiological properties and many other aspects of neurons. In this review, first, the mechanical microenvironment and properties of neurons under in vivo conditions are introduced and analyzed. Second, research works in recent decades on the effects of different mechanical forces, especially compression and tension, on various neurons, including dorsal root ganglion neurons, retinal ganglion cells, cerebral cortex neurons, hippocampus neurons, neural stem cells, and other neurons, are summarized. Previous research results demonstrate that mechanical stress can not only injure neurons by damaging their morphology, impacting their electrophysiological characteristics and gene expression, but also promote neuron self-repair. Finally, some future perspectives in neuron research are discussed.

  16. Origin and Proliferation of Multiple-Drug Resistance in Bacterial Pathogens

    PubMed Central

    Chang, Hsiao-Han; Cohen, Ted; Grad, Yonatan H.; Hanage, William P.; O'Brien, Thomas F.

    2015-01-01

    SUMMARY Many studies report the high prevalence of multiply drug-resistant (MDR) strains. Because MDR infections are often significantly harder and more expensive to treat, they represent a growing public health threat. However, for different pathogens, different underlying mechanisms are traditionally used to explain these observations, and it is unclear whether each bacterial taxon has its own mechanism(s) for multidrug resistance or whether there are common mechanisms between distantly related pathogens. In this review, we provide a systematic overview of the causes of the excess of MDR infections and define testable predictions made by each hypothetical mechanism, including experimental, epidemiological, population genomic, and other tests of these hypotheses. Better understanding the cause(s) of the excess of MDR is the first step to rational design of more effective interventions to prevent the origin and/or proliferation of MDR. PMID:25652543

  17. Protein conformational modulation by photons: a mechanism for laser treatment effects.

    PubMed

    Liebert, Ann D; Bicknell, Brian T; Adams, Roger D

    2014-03-01

    Responsiveness to low-level laser treatment (LLTT) at a wavelength of 450-910 nm has established it as an effective treatment of medical, veterinary and dental chronic pain, chronic inflammation conditions (arthritis and macular degeneration), wound repair, and lymphoedema, yet the mechanisms underlying the effectiveness of LLLT remain unclear. However, there is now sufficient evidence from recent research to propose an integrated model of LLLT action. The hypothesis presented in this paper is that external applications of photons (through laser at an appropriate dose) modulates the nervous system through an integrated mechanism. This stimulated mechanism involves protein-to-protein interaction, where two or more proteins bind together to facilitate molecular processes, including modification of proteins by members of SUMO (small ubiquitin-related modifier proteins) and also protein phosphorylation and tyrosination. SUMO has been shown to have a role in multiple nuclear and perinuclear targets, including ion channels, and in the maintenance of telomeres and the post-translational modification of genes. The consequence of laser application in treatment, therefore, can be seen as influencing the transmission of neural information via an integrated and rapid modulation of ion channels, achieved through both direct action on photo-acceptors (such as cytochrome c-oxidase) and through indirect modulation via enzymes, including tyrosine hydroxylase (TH), tyrosine kinases and tyrosine kinase receptors. This exogenous action then facilitates an existing photonic biomodulation mechanism within the body, and initiates ion channel modulation both in the periphery and the central nervous system (CNS). Evidence indicates that the ion channel modulation functions predominately through the potassium channels, including two pore leak channels (K2P), which act as signal integrators from the periphery to the cortex. Photonic action also transforms SUMOylation processes at the cell membrane, nucleus and telomeres via signalling processes from the mitochondria (which is the main target of laser absorption) to these targets. Under the hypothesis, these observed biological effects would play a part in the bystander effect, the abscopal effect, and other systemic effects observed with the application of low level laser (LLLT). The implications of the hypothesis are important in that they point to mechanisms that can account for the effectiveness of laser in the treatment and prevention of inflammatory diseases, chronic pain and neurodegenerative disorders. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Key to Prevention of Bradycardia: Be Relax Postoperatively: A Case Report.

    PubMed

    Chowdhury, Tumul; Schaller, Bernhard

    2016-05-01

    Hypotension and bradycardia are commonly observed after the spinal anesthesia and various mechanisms have been postulated for these hemodynamic changes.A middle-aged otherwise healthy male Caucasian patient developed several episodes of bradycardia postoperatively after the umbilical hernia repair under subarachnoid block (SAB) while trying to lean forward and move his legs. Episodes were aborted when patient was advised to relax in supine position.The common mechanism of bradycardia and hypotension under SAB is postulated as sympathetic blockade, decrease venous return, and parasympathetic over-dominance leading to a decrease in right arterial pressure and pressure in the great veins as they enter the right atrium. But over time, the parasympathetic inhibition is usually withdrawn first, leading to the risk of severe bradycardia that is probably favored by the reverse Trendelenburg position as described in our case.Postoperative severe hemodynamic changes can occur even under stable spinal anesthesia; however, can be prevented by vigilant monitoring and simple maneuver which includes maintenance of relax posture on the bed.

  19. Multiscale Modeling of Primary Cilium Deformations Under Local Forces and Shear Flows

    NASA Astrophysics Data System (ADS)

    Peng, Zhangli; Feng, Zhe; Resnick, Andrew; Young, Yuan-Nan

    2017-11-01

    We study the detailed deformations of a primary cilium under local forces and shear flows by developing a multiscale model based on the state-of-the-art understanding of its molecular structure. Most eukaryotic cells are ciliated with primary cilia. Primary cilia play important roles in chemosensation, thermosensation, and mechanosensation, but the detailed mechanism for mechanosensation is not well understood. We apply the dissipative particle dynamics (DPD) to model an entire well with a primary cilium and consider its different components, including the basal body, microtubule doublets, actin cortex, and lipid bilayer. We calibrate the mechanical properties of individual components and their interactions from experimental measurements and molecular dynamics simulations. We validate the simulations by comparing the deformation profile of the cilium and the rotation of the basal body with optical trapping experiments. After validations, we investigate the deformation of the primary cilium under shear flows. Furthermore, we calculate the membrane tensions and cytoskeleton stresses, and use them to predict the activation of mechanosensitive channels.

  20. Microgravity

    NASA Image and Video Library

    1998-01-25

    Astronaut James Reilly uses a laptop computer monitor the Mechanics of Granular Materials (MGM) experiment during STS-89. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditons that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: NASA/Marshall Space Flight Center (MSFC)

  1. Microgravity

    NASA Image and Video Library

    1996-09-18

    Astronaut Carl Walz installs Mechanics of Granular Materials (MGM) test cell on STS-79. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditons that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: NASA/John Space Center

  2. Stress-corrosion behavior of aluminum-lithium alloys in aqueous salt environments

    NASA Technical Reports Server (NTRS)

    Pizzo, P. P.; Galvin, R. P.; Nelson, H. G.

    1984-01-01

    The stress corrosion susceptibility of two powder metallurgy (P/M) alloys, Al-Li-Cu and Al-Li-Cu-Mg; two mechanically attrited (M/A) alloys, Al-Li-Cu and Al-Li-Mg; and two wrought, ingot alloys, X-2020 and AA7475, are compared. Time-dependent fracture in an aqueous sodium chloride environment under alternate immersion condition was found to vary significantly between alloys. The stress corrosion behavior of the two powder metallurgy processed alloys was studied in detail under conditions of crack initiation, static crack growth, and fatigue crack growth. A variety of stress corrosion tests were performed including smooth surface, time-to-failure tests; potentiostatic tests on smooth surfaces exposed to constant applied strain rates; and fracture mechanics-type tests under static and cyclic loads. Both alloys show surface pitting and subsequent intergranular corrosion. Pitting is more severe in the magnesium-bearing alloy and is associated with stringer particles strung along the extrusion direction as a result of P/M processing.

  3. Putative Brain Networks Underlying Repetitive Negative Thinking and Comorbid Internalizing Problems in Autism

    PubMed Central

    Burrows, Catherine A.; Timpano, Kiara R.; Uddin, Lucina Q.

    2016-01-01

    Many high-functioning individuals with autism spectrum disorder (ASD) also experience depression and anxiety, yet little is known about mechanisms underlying this comorbidity. Repetitive negative thinking (RNT) about self-referential information is a transdiagnostic cognitive vulnerability factor that may account for the relationship between these two classes of symptoms. We propose a model where self-referential processing and cognitive inflexibility interact to increase risk for RNT, leading to internalizing problems in ASD. Examination of interactions within and between two well-characterized large-scale brain networks, the default mode network and the salience network, may provide insights into neurobiological mechanisms underlying RNT in ASD. We summarize previous literature supporting this model, emphasizing moving towards understanding RNT as a factor accounting for the high rates of internalizing problems in ASD. Future research avenues include understanding heterogeneity in clinical presentation, and promise for identifying and treating cognitive flexibility and RNT to reduce comorbid internalizing problems in ASD. PMID:28603665

  4. Installing Mechanics of Granular Materials (MGM) experiment Test Cell

    NASA Technical Reports Server (NTRS)

    1996-01-01

    Astronaut Jay Apt installs Mechanics of Granular Materials (MGM0 test cell on STS-79. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. MGM experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditions that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. (Credit: NASA/John Space Center).

  5. Mechanics of Granular Materials labeled hardware

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Mechanics of Granular Materials (MGM) flight hardware takes two twin double locker assemblies in the Space Shuttle middeck or the Spacehab module. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. MGM experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditions that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. (Credit: NASA/MSFC).

  6. Stress-corrosion behavior of aluminum-lithium alloys in aqueous environments

    NASA Technical Reports Server (NTRS)

    Pizzo, P. P.; Galvin, R. P.; Nelson, H. G.

    1983-01-01

    The stress corrosion susceptibility of two powder metallurgy (P/M) alloys, Al-Li-Cu and Al-Li-Cu-Mg two mechanically attrited (M/A) alloys, Al-Li-Cu and Al-Li-Mg; and two wrought, ingot alloys, X-2020 and AA7475, are compared. Time-dependent fracture in an aqueous sodium chloride environment under alternate immersion condition was found to vary significantly between alloys. The stress corrosion behavior of the two powder metallurgy processed alloys was studied in detail under conditions of crack initiation, static crack growth, and fatigue crack growth. A variety of stress corrosion tests were performed including smooth surface, time-to-failure tests; potentiostatic tests on smooth surfaces exposed to constant applied strain rates; and fracture mechanics-type tests under static and cyclic loads. Both alloys show surface pitting and subsequent intergranular corrosion. Pitting is more severe in the magnesium-bearing alloy and is associated with stringer particles strung along the extrusion direction as a result of P/M processing.

  7. Animal models of fibromyalgia

    PubMed Central

    2013-01-01

    Animal models of disease states are valuable tools for developing new treatments and investigating underlying mechanisms. They should mimic the symptoms and pathology of the disease and importantly be predictive of effective treatments. Fibromyalgia is characterized by chronic widespread pain with associated co-morbid symptoms that include fatigue, depression, anxiety and sleep dysfunction. In this review, we present different animal models that mimic the signs and symptoms of fibromyalgia. These models are induced by a wide variety of methods that include repeated muscle insults, depletion of biogenic amines, and stress. All potential models produce widespread and long-lasting hyperalgesia without overt peripheral tissue damage and thus mimic the clinical presentation of fibromyalgia. We describe the methods for induction of the model, pathophysiological mechanisms for each model, and treatment profiles. PMID:24314231

  8. Neurotrophin signaling endosomes; biogenesis, regulation, and functions

    PubMed Central

    Yamashita, Naoya; Kuruvilla, Rejji

    2016-01-01

    In the nervous system, communication between neurons and their post-synaptic target cells is critical for the formation, refinement and maintenance of functional neuronal connections. Diffusible signals secreted by target tissues, exemplified by the family of neurotrophins, impinge on nerve terminals to influence diverse developmental events including neuronal survival and axonal growth. Key mechanisms of action of target-derived neurotrophins include the cell biological processes of endocytosis and retrograde trafficking of their Trk receptors from growth cones to cell bodies. In this review, we summarize the molecular mechanisms underlying this endosome-mediated signaling, focusing on the instructive role of neurotrophin signaling itself in directing its own trafficking. Recent studies have linked impaired neurotrophin trafficking to neurodevelopmental disorders, highlighting the relevance of neurotrophin endosomes in human health. PMID:27327126

  9. 46 CFR 160.133-13 - Approval inspections and tests for prototype release mechanisms.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... as built, in triplicate. The plans must include the instructions for training and maintenance... for Lifeboats and Rescue Boats § 160.133-13 Approval inspections and tests for prototype release...) Conforms with the plans reviewed under § 160.133-9 of this subpart; (B) Is constructed by the methods and...

  10. A Role for the Right Superior Temporal Sulcus in Categorical Perception of Musical Chords

    ERIC Educational Resources Information Center

    Klein, Mike E.; Zatorre, Robert J.

    2011-01-01

    Categorical perception (CP) is a mechanism whereby non-identical stimuli that have the same underlying meaning become invariantly represented in the brain. Through behavioral identification and discrimination tasks, CP has been demonstrated to occur broadly across the auditory modality, including in perception of speech (e.g. phonemes) and music…

  11. Project Physics Reader 3, The Triumph of Mechanics.

    ERIC Educational Resources Information Center

    Harvard Univ., Cambridge, MA. Harvard Project Physics.

    As a supplement to Project Physics Unit 3, a collection of articles is presented in this reader for student browsing. Four excerpts are given under the following headings: On the kinetic theory of gases, Maxwell's Demon, Introduction to Waves, and Scientific Cranks. Five articles are included in terms of energy, barometers, randomness, fiddle…

  12. Vocational Exploration and Skill Building in Marine and Related Occupations. Final Report, 1979-1980.

    ERIC Educational Resources Information Center

    Schaefer, Larry; And Others

    The first year of a project to train high school aged handicapped and/or disadvantaged youth for employment in marine and related trades was considered successful. Specific areas of training included motor mechanics, electrical, woodworking, refinishing, restoration, fiberglass work, and blueprint reading under the direction of skilled…

  13. Failure mechanism characterization of platinum alloy

    NASA Technical Reports Server (NTRS)

    Rosen, J. M.; Mcfarlen, W. T.

    1986-01-01

    This article describes procedures and results of testing performed on a platinum/10-percent rhodium, thin-wall tubular product. The purpose of the testing was to develop exemplar SEM fractographs to be used to characterize failures under various environmental conditions. Conditions evaluated for the platinum alloys included high temperature, hydrogen environment, braze metal contamination, and cyclic loading.

  14. Internal hydrological mechanism of permeable pavement and interaction with subsurface water - slides

    EPA Science Inventory

    A permeable pavement site located at the Seitz Elementary School on Fort Riley, Kansas was selected for this study. An 80-space parking lot was built behind the school as part of an EPA ORD collaboration with the U.S. Army under the Net Zero program. The parking lot design includ...

  15. Science Achievement Gaps Begin Very Early, Persist, and Are Largely Explained by Modifiable Factors

    ERIC Educational Resources Information Center

    Morgan, Paul L.; Farkas, George; Hillemeier, Marianne M.; Maczuga, Steve

    2016-01-01

    We examined the age of onset, over-time dynamics, and mechanisms underlying science achievement gaps in U.S. elementary and middle schools. To do so, we estimated multilevel growth models that included as predictors children's own general knowledge, reading and mathematics achievement, behavioral self-regulation, sociodemographics, other child-…

  16. Research on aviation fuel instability

    NASA Technical Reports Server (NTRS)

    Baker, C. E.; Bittker, D. A.; Cohen, S. M.; Seng, G. T.

    1983-01-01

    The underlying causes of fuel thermal degradation are discussed. Topics covered include: nature of fuel instability and its temperature dependence, methods of measuring the instability, chemical mechanisms involved in deposit formation, and instrumental methods for characterizing fuel deposits. Finally, some preliminary thoughts on design approaches for minimizing the effects of lowered thermal stability are briefly discussed.

  17. Hematology/immunology (M110 series). [human hemodynamic response to weightlessness simulation

    NASA Technical Reports Server (NTRS)

    1973-01-01

    The hematology/immunology experiments in the Skylab mission study various aspects of the red blood cell, including its metabolism and life span, and blood volume changes under zero gravity conditions to determine the precise mechanism of the transient changes which have been seen on the relatively brief missions of the past.

  18. Lunar soil properties and soil mechanics

    NASA Technical Reports Server (NTRS)

    Mitchell, J. K.; Houston, W. N.; Hovland, H. J.

    1972-01-01

    The study to identify and define recognizable fabrics in lunar soil in order to determine the history of the lunar regolith in different locations is reported. The fabric of simulated lunar soil, and lunar soil samples are discussed along with the behavior of simulated lunar soil under dynamic and static loading. The planned research is also included.

  19. UNIX-based operating systems robustness evaluation

    NASA Technical Reports Server (NTRS)

    Chang, Yu-Ming

    1996-01-01

    Robust operating systems are required for reliable computing. Techniques for robustness evaluation of operating systems not only enhance the understanding of the reliability of computer systems, but also provide valuable feed- back to system designers. This thesis presents results from robustness evaluation experiments on five UNIX-based operating systems, which include Digital Equipment's OSF/l, Hewlett Packard's HP-UX, Sun Microsystems' Solaris and SunOS, and Silicon Graphics' IRIX. Three sets of experiments were performed. The methodology for evaluation tested (1) the exception handling mechanism, (2) system resource management, and (3) system capacity under high workload stress. An exception generator was used to evaluate the exception handling mechanism of the operating systems. Results included exit status of the exception generator and the system state. Resource management techniques used by individual operating systems were tested using programs designed to usurp system resources such as physical memory and process slots. Finally, the workload stress testing evaluated the effect of the workload on system performance by running a synthetic workload and recording the response time of local and remote user requests. Moderate to severe performance degradations were observed on the systems under stress.

  20. Constitutive models for the Etchegoin Sands, Belridge Diatomite, and overburden formations at the Lost Hills oil field, California

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

    FOSSUM,ARLO F.; FREDRICH,JOANNE T.

    2000-04-01

    This report documents the development of constitutive material models for the overburden formations, reservoir formations, and underlying strata at the Lost Hills oil field located about 45 miles northwest of Bakersfield in Kern County, California. Triaxial rock mechanics tests were performed on specimens prepared from cores recovered from the Lost Hills field, and included measurements of axial and radial stresses and strains under different load paths. The tested intervals comprise diatomaceous sands of the Etchegoin Formation and several diatomite types of the Belridge Diatomite Member of the Monterey Formation, including cycles both above and below the diagenetic phase boundary betweenmore » opal-A and opal-CT. The laboratory data are used to drive constitutive parameters for the Extended Sandler-Rubin (ESR) cap model that is implemented in Sandia's structural mechanics finite element code JAS3D. Available data in the literature are also used to derive ESR shear failure parameters for overburden formations. The material models are being used in large-scale three-dimensional geomechanical simulations of the reservoir behavior during primary and secondary recovery.« less

  1. Towards a richer evolutionary game theory

    PubMed Central

    McNamara, John M.

    2013-01-01

    Most examples of the application of evolutionary game theory to problems in biology involve highly simplified models. I contend that it is time to move on and include much more richness in models. In particular, more thought needs to be given to the importance of (i) between-individual variation; (ii) the interaction between individuals, and hence the process by which decisions are reached; (iii) the ecological and life-history context of the situation; (iv) the traits that are under selection, and (v) the underlying psychological mechanisms that lead to behaviour. I give examples where including variation between individuals fundamentally changes predicted outcomes of a game. Variation also selects for real-time responses, again resulting in changed outcomes. Variation can select for other traits, such as choosiness and social sensitivity. More generally, many problems involve coevolution of more than one trait. I identify situations where a reductionist approach, in which a game is isolated from is ecological setting, can be misleading. I also highlight the need to consider flexibility of behaviour, mental states and other issues concerned with the evolution of mechanism. PMID:23966616

  2. Effects of rail dynamics and friction characteristics on curve squeal

    NASA Astrophysics Data System (ADS)

    Ding, B.; Squicciarini, G.; Thompson, D. J.

    2016-09-01

    Curve squeal in railway vehicles is an instability mechanism that arises in tight curves under certain running and environmental conditions. In developing a model the most important elements are the characterisation of friction coupled with an accurate representation of the structural dynamics of the wheel. However, the role played by the dynamics of the rail is not fully understood and it is unclear whether this should be included in a model or whether it can be safely neglected. This paper makes use of previously developed time domain and frequency domain curve squeal models to assess whether the presence of the rail and the falling characteristics of the friction force can modify the instability mechanisms and the final response. For this purpose, the time-domain model has been updated to include the rail dynamics in terms of its state space representation in various directions. Frequency domain and time domain analyses results show that falling friction is not the only reason for squeal and rail dynamics can play an important role, especially under constant friction conditions.

  3. Therapeutic Effects of Breviscapine in Cardiovascular Diseases: A Review.

    PubMed

    Gao, Jialiang; Chen, Guang; He, Haoqiang; Liu, Chao; Xiong, Xingjiang; Li, Jun; Wang, Jie

    2017-01-01

    Breviscapine is a crude extract of several flavonoids of Erigeron breviscapus (Vant.) Hand.-Mazz. , containing more than 85% of scutellarin, which has been traditionally used in China as an activating blood circulation medicine to improve cerebral blood supply. Accumulating evidence from various in vivo and in vitro studies has shown that breviscapine exerts a broad range of cardiovascular pharmacological effects, including vasodilation, protection against ischaemia/reperfusion (I/R), anti-inflammation, anticoagulation, antithrombosis, endothelial protection, myocardial protection, reduction of smooth muscle cell migration and proliferation, anticardiac remodeling, antiarrhythmia, blood lipid reduction, and improvement of erectile dysfunction. In addition, several clinical studies have reported that breviscapine could be used in conjunction with Western medicine for cardiovascular diseases (CVDs) including coronary heart disease, myocardial infarction, hypertension, atrial fibrillation, hyperlipidaemia, viral myocarditis, chronic heart failure, and pulmonary heart disease. However, the protective effects of breviscapine on CVDs based on experimental studies along with its underlying mechanisms have not been reviewed systematically. This paper reviewed the underlying pharmacological mechanisms in the cardioprotective effects of breviscapine and elucidated its clinical applications.

  4. Therapeutic Effects of Breviscapine in Cardiovascular Diseases: A Review

    PubMed Central

    Gao, Jialiang; Chen, Guang; He, Haoqiang; Liu, Chao; Xiong, Xingjiang; Li, Jun; Wang, Jie

    2017-01-01

    Breviscapine is a crude extract of several flavonoids of Erigeron breviscapus (Vant.) Hand.-Mazz., containing more than 85% of scutellarin, which has been traditionally used in China as an activating blood circulation medicine to improve cerebral blood supply. Accumulating evidence from various in vivo and in vitro studies has shown that breviscapine exerts a broad range of cardiovascular pharmacological effects, including vasodilation, protection against ischaemia/reperfusion (I/R), anti-inflammation, anticoagulation, antithrombosis, endothelial protection, myocardial protection, reduction of smooth muscle cell migration and proliferation, anticardiac remodeling, antiarrhythmia, blood lipid reduction, and improvement of erectile dysfunction. In addition, several clinical studies have reported that breviscapine could be used in conjunction with Western medicine for cardiovascular diseases (CVDs) including coronary heart disease, myocardial infarction, hypertension, atrial fibrillation, hyperlipidaemia, viral myocarditis, chronic heart failure, and pulmonary heart disease. However, the protective effects of breviscapine on CVDs based on experimental studies along with its underlying mechanisms have not been reviewed systematically. This paper reviewed the underlying pharmacological mechanisms in the cardioprotective effects of breviscapine and elucidated its clinical applications. PMID:28588491

  5. Yoga clinical research review.

    PubMed

    Field, Tiffany

    2011-02-01

    In this paper recent research is reviewed on the effects of yoga poses on psychological conditions including anxiety and depression, on pain syndromes, cardiovascular, autoimmune and immune conditions and on pregnancy. Further, the physiological effects of yoga including decreased heartrate and blood pressure and the physical effects including weight loss and increased muscle strength are reviewed. Finally, potential underlying mechanisms are proposed including the stimulation of pressure receptors leading to enhanced vagal activity and reduced cortisol. The reduction in cortisol, in turn, may contribute to positive effects such as enhanced immune function and a lower prematurity rate. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Low-Intensity Ultrasound-Induced Anti-inflammatory Effects Are Mediated by Several New Mechanisms Including Gene Induction, Immunosuppressor Cell Promotion, and Enhancement of Exosome Biogenesis and Docking

    PubMed Central

    Yang, Qian; Nanayakkara, Gayani K.; Drummer, Charles; Sun, Yu; Johnson, Candice; Cueto, Ramon; Fu, Hangfei; Shao, Ying; Wang, Luqiao; Yang, William Y.; Tang, Peng; Liu, Li-Wen; Ge, Shuping; Zhou, Xiao-Dong; Khan, Mohsin; Wang, Hong; Yang, Xiaofeng

    2017-01-01

    Background: Low-intensity ultrasound (LIUS) was shown to be beneficial in mitigating inflammation and facilitating tissue repair in various pathologies. Determination of the molecular mechanisms underlying the anti-inflammatory effects of LIUS allows to optimize this technique as a therapy for the treatment of malignancies and aseptic inflammatory disorders. Methods: We conducted cutting-edge database mining approaches to determine the anti-inflammatory mechanisms exerted by LIUS. Results: Our data revealed following interesting findings: (1) LIUS anti-inflammatory effects are mediated by upregulating anti-inflammatory gene expression; (2) LIUS induces the upregulation of the markers and master regulators of immunosuppressor cells including MDSCs (myeloid-derived suppressor cells), MSCs (mesenchymal stem cells), B1-B cells and Treg (regulatory T cells); (3) LIUS not only can be used as a therapeutic approach to deliver drugs packed in various structures such as nanobeads, nanospheres, polymer microspheres, and lipidosomes, but also can make use of natural membrane vesicles as small as exosomes derived from immunosuppressor cells as a novel mechanism to fulfill its anti-inflammatory effects; (4) LIUS upregulates the expression of extracellular vesicle/exosome biogenesis mediators and docking mediators; (5) Exosome-carried anti-inflammatory cytokines and anti-inflammatory microRNAs inhibit inflammation of target cells via multiple shared and specific pathways, suggesting exosome-mediated anti-inflammatory effect of LIUS feasible; and (6) LIUS-mediated physical effects on tissues may activate specific cellular sensors that activate downstream transcription factors and signaling pathways. Conclusions: Our results have provided novel insights into the mechanisms underlying anti-inflammatory effects of LIUS, and have provided guidance for the development of future novel therapeutic LIUS for cancers, inflammatory disorders, tissue regeneration and tissue repair. PMID:29109687

  7. Migraine and circle of Willis anomalies.

    PubMed

    Cucchiara, Brett; Detre, John

    2008-01-01

    Several mechanisms are currently thought to contribute to migraine pathogenesis, including interictal neuronal hyperexcitability, cortical spreading depression underlying the symptom of aura, and trigeminal nerve activation at a peripheral and central level. However, these mechanistic concepts incompletely explain migraine susceptibility in individual patients and do not fully account for the well documented association between migraine and ischemic cerebrovascular disease, including increased risk of both clinical stroke and subclinical brain lesions in migraine patients. The circle of Willis is a major source of collateral blood flow supply in the human brain, and developmental morphologic variants of the circle of Willis are extremely frequent. Altered cerebral blood flow (CBF) has been demonstrated in regions supplied by variant circle of Willis vessels. Our central hypothesis is that circle of Willis anomalies correlate with alterations in cerebral hemodynamics and contribute to migraine susceptibility and ischemic complications of migraine. Dysregulation of CBF may allow relative ischemia to develop in the setting of increased metabolic demand related to neuronal hyperexcitability, may trigger cortical spreading depression, and may predispose individuals with migraine to ischemic lesions and stroke. Identification of structural alterations in the cerebral vasculature in migraine patients would have several important pathophysiological and clinical implications. First, it would provide a developmental mechanism for migraine susceptibility that may lead to further insights into genetic predisposition to migraine. Second, it would expand understanding of potential mechanisms underlying migraine aura and linking migraine with both clinical and subclinical cerebral infarction. Third, it could help to identify the subpopulation of patients at risk of progressive cerebral ischemia so as to target preventative therapies appropriately. Fourth, it would suggest a role for further diagnostic evaluation to determine migraine mechanism in individual patients, analogous to the current paradigm in ischemic stroke in which determination of stroke mechanism is critical to therapeutic decision-making.

  8. Molecular deformation mechanisms of the wood cell wall material.

    PubMed

    Jin, Kai; Qin, Zhao; Buehler, Markus J

    2015-02-01

    Wood is a biological material with outstanding mechanical properties resulting from its hierarchical structure across different scales. Although earlier work has shown that the cellular structure of wood is a key factor that renders it excellent mechanical properties at light weight, the mechanical properties of the wood cell wall material itself still needs to be understood comprehensively. The wood cell wall material features a fiber reinforced composite structure, where cellulose fibrils act as stiff fibers, and hemicellulose and lignin molecules act as soft matrix. The angle between the fiber direction and the loading direction has been found to be the key factor controlling the mechanical properties. However, how the interactions between theses constitutive molecules contribute to the overall properties is still unclear, although the shearing between fibers has been proposed as a primary deformation mechanism. Here we report a molecular model of the wood cell wall material with atomistic resolution, used to assess the mechanical behavior under shear loading in order to understand the deformation mechanisms at the molecular level. The model includes an explicit description of cellulose crystals, hemicellulose, as well as lignin molecules arranged in a layered nanocomposite. The results obtained using this model show that the wood cell wall material under shear loading deforms in an elastic and then plastic manner. The plastic regime can be divided into two parts according to the different deformation mechanisms: yielding of the matrix and sliding of matrix along the cellulose surface. Our molecular dynamics study provides insights of the mechanical behavior of wood cell wall material at the molecular level, and paves a way for the multi-scale understanding of the mechanical properties of wood. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Features of structure-phase transformations and segregation processes under irradiation of austenitic and ferritic-martensitic steels

    NASA Astrophysics Data System (ADS)

    Neklyudov, I. M.; Voyevodin, V. N.

    1994-09-01

    The difference between crystal lattices of austenitic and ferritic steels leads to distinctive features in mechanisms of physical-mechanical change. This paper presents the results of investigations of dislocation structure and phase evolution, and segregation phenomena in austenitic and ferritic-martensitic steels and alloys during irradiation with heavy ions in the ESUVI and UTI accelerators and by neutrons in fast reactors BOR-60 and BN-600. The influence of different factors (including different alloying elements) on processes of structure-phase transformation was studied.

  10. Lateral patellar dislocation: mechanism of disease, radiographic presentation, and management.

    PubMed

    Abramov, Michael; Stock, Harlan

    2013-04-01

    Lateral patellar dislocation is a common injury occurring in young active adults. The mechanism is that of twisting injury to the knee on a planted foot with valgus stress. Several predisposing factors, including femoral trochlear dysplasia, patella alta, and lateralization of the tibial tuberosity, contribute to patellar instability and lateral patellar dislocation. Magnetic resonance (MR) imaging of the knee is the modality of choice to evaluate underlying bone contusion patterns, associated soft-tissue injuries, and additional complex ligamentous and osteochondral injuries, many of which are not apparent on conventional radiographs.

  11. Locking mechanism for orthopedic braces

    NASA Technical Reports Server (NTRS)

    I-Lechao, J.; Epps, C. H., Jr. (Inventor)

    1976-01-01

    A locking mechanism for orthopedic braces is described which automatically prevents or permits the relative pivotable movement between a lower brace member and an upper brace member. The upper and lower brace members are provided with drilled bores within which a slidable pin is disposed, and depending upon the inclination of the brace members with respect to a vertical plane, the slidable pin will be interposed between both brace members. The secondary or auxiliary latching device includes a spring biased, manually operable lever bar arrangement which is manually unlatched and automatically latched under the influence of the spring.

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

    Hansen, Frank; Popp, Till; Wieczorek, Klaus

    The purposes of this paper are to review the vast amount of knowledge concerning crushed salt reconsolidation and its attendant hydraulic properties (i.e., its capability for fluid or gas transport) and to provide a sufficient basis to understand reconsolidation and healing rates under repository conditions. Topics covered include: deformation mechanisms and hydro-mechanical interactions during reconsolidation; the experimental data base pertaining to crushed salt reconsolidation; transport properties of consolidating granulated salt and provides quantitative substantiation of its evolution to characteristics emulating undisturbed rock salt; and extension of microscopic and laboratory observations and data to the applicable field scale.

  13. Isolation of Mouse Primary Gastric Epithelial Cells to Investigate the Mechanisms of Helicobacter pylori Associated Disease.

    PubMed

    Tran, Le Son; Ferrero, Richard L

    2018-01-01

    The gastrointestinal epithelium provides the first line of defense against invading pathogens, among which Helicobacter pylori is linked to numerous gastric pathologies, including chronic gastritis and cancer. Primary gastric epithelial cells represent a useful model for the investigation of the underlying molecular and cellular mechanisms involved in these H. pylori associated diseases. In this chapter, we describe a method for the isolation of primary gastric epithelial cells from mice and detection of epithelial cell adhesion molecule (EpCAM) expression in the isolated cells.

  14. Towards aging mechanisms of cross-linked polyethylene (XLPE) cable insulation materials in nuclear power plants

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

    Liu, Shuaishuai; Fifield, Leonard S.; Bowler, Nicola

    Cross-linked polyethylene (XLPE) cable insulation material undergoes simultaneous, accelerated thermal and gamma-radiation aging to simulate the long-term aging environment within nuclear power plants (NPPs). A variety of materials characterization tests, including scanning electron microscopy, thermo-gravimetric analysis, differential scanning calorimetry, oxidation induction time, gel-fraction and dielectric properties measurement, are conducted on pristine and differently aged XLPE samples. A preliminary model of one possible aging mechanism of XLPE cable insulation material under gamma radiation at elevated temperature of 115 °C is suggested.

  15. Effects of Number Scaling on Entangled States in Quantum Mechanics

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

    Benioff, Paul

    A summary of number structure scaling is followed by a description of the effects of number scaling in nonrelativistic quantum mechanics. The description extends earlier work to include the effects on the states of two or more interacting particles. Emphasis is placed on the effects on entangled states. The resulting scaling field is generalized to describe the effects on these states. It is also seen that one can use fiber bundles with fibers associated with single locations of the underlying space to describe the effects of scaling on arbitrary numbers of particles.

  16. Temperature-Dependent Effects on the Mechanical Behavior and Deformation Substructure of Haynes 188 Under Low-Cycle Fatigue

    NASA Technical Reports Server (NTRS)

    1996-01-01

    The mechanical behavior of a cobalt-nickel-chromium-tungsten superalloy, Haynes 188, is being critically examined at the NASA Lewis Research Center. This dynamic, strain-aging (DSA) alloy is used for combustor liners in many military and commercial aircraft turbine engines and for the liquid oxygen posts in the main injectors of the space shuttle main engine. Its attractive features include a good combination of high monotonic yield and tensile strength, and excellent fabricability, weldability, and resistance to high-temperature oxidation for prolonged exposures.

  17. Substorm theories: United they stand, divided they fall

    NASA Technical Reports Server (NTRS)

    Erickson, Gary M.

    1995-01-01

    Consensus on the timing and mapping of substorm features has permitted a synthesis of substorm models. Within the synthesis model the mechanism for onset of substorm expansion is still unknown. Possible mechanisms are: growth of an ion tearing mode, current disruption by a cross-field current instability, and magnetosphere-ionosphere coupling. While the synthesis model is consistent with overall substorm morphology, including near-Earth onset, none of the onset theories, taken individually, appear to account for substorm expansion onset. A grand synthesis with unification of the underlying onset theories appears necessary.

  18. Historical carbonyl sulfide observations support long-term growth in atmospheric CO2 seasonal amplitude

    NASA Astrophysics Data System (ADS)

    Campbell, J. E.; Hilton, T. W.; Laine, M.; Wang, Y.; Berry, J. A.; Hannigan, J. W.

    2017-12-01

    The seasonal amplitude in atmospheric CO2 has grown over the last 50 years, pointing to a fundamental shift in the regional carbon cycle. Theoretical drivers from the amplitude growth include changes in terrestrial photosynthesis and heterotrophic respiration. However, large-scale, measurement-based evidence for these mechanisms is unclear. Here we analyze historical measurements of carbonyl sulfide which also show long-term growth in seasonal amplitude. We use this new trend to interpret the underlying mechanisms of CO2 amplitude growth and to validate global ecosystem models.

  19. Mechanism of force mode dip-pen nanolithography

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

    Yang, Haijun, E-mail: yanghaijun@sinap.ac.cn, E-mail: swguo@sjtu.edu.cn, E-mail: wanghuabin@cigit.ac.cn; Interfacial Water Division and Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, CAS, Shanghai 201800; Xie, Hui

    In this work, the underlying mechanism of the force mode dip-pen nanolithography (FMDPN) is investigated in depth by analyzing force curves, tapping mode deflection signals, and “Z-scan” voltage variations during the FMDPN. The operation parameters including the relative “trigger threshold” and “surface delay” parameters are vital to control the loading force and dwell time for ink deposition during FMDPN. A model is also developed to simulate the interactions between the atomic force microscope tip and soft substrate during FMDPN, and verified by its good performance in fitting our experimental data.

  20. Preparation of multilayer graphene sheets and their applications for particle accelerators

    NASA Astrophysics Data System (ADS)

    Tatami, Atsushi; Tachibana, Masamitsu; Yagi, Takashi; Murakami, Mutsuaki

    2018-05-01

    Multilayer graphene sheets were prepared by heat treatment of polyimide films at temperatures of up to 3000 °C. The sheets consist of highly oriented graphite layers with excellent mechanical robustness and flexibility. Key features of these sheets include their high thermal conductivity in the in-plane direction, good mechanical properties, and high carbon purity. The results suggest that the multilayer graphene sheets have great potential for charge stripping foils that persist even under the highest ion beam intensities irradiation and can be used for accelerator applications.

  1. Quantum mechanics/coarse-grained molecular mechanics (QM/CG-MM)

    NASA Astrophysics Data System (ADS)

    Sinitskiy, Anton V.; Voth, Gregory A.

    2018-01-01

    Numerous molecular systems, including solutions, proteins, and composite materials, can be modeled using mixed-resolution representations, of which the quantum mechanics/molecular mechanics (QM/MM) approach has become the most widely used. However, the QM/MM approach often faces a number of challenges, including the high cost of repetitive QM computations, the slow sampling even for the MM part in those cases where a system under investigation has a complex dynamics, and a difficulty in providing a simple, qualitative interpretation of numerical results in terms of the influence of the molecular environment upon the active QM region. In this paper, we address these issues by combining QM/MM modeling with the methodology of "bottom-up" coarse-graining (CG) to provide the theoretical basis for a systematic quantum-mechanical/coarse-grained molecular mechanics (QM/CG-MM) mixed resolution approach. A derivation of the method is presented based on a combination of statistical mechanics and quantum mechanics, leading to an equation for the effective Hamiltonian of the QM part, a central concept in the QM/CG-MM theory. A detailed analysis of different contributions to the effective Hamiltonian from electrostatic, induction, dispersion, and exchange interactions between the QM part and the surroundings is provided, serving as a foundation for a potential hierarchy of QM/CG-MM methods varying in their accuracy and computational cost. A relationship of the QM/CG-MM methodology to other mixed resolution approaches is also discussed.

  2. Quantum mechanics/coarse-grained molecular mechanics (QM/CG-MM).

    PubMed

    Sinitskiy, Anton V; Voth, Gregory A

    2018-01-07

    Numerous molecular systems, including solutions, proteins, and composite materials, can be modeled using mixed-resolution representations, of which the quantum mechanics/molecular mechanics (QM/MM) approach has become the most widely used. However, the QM/MM approach often faces a number of challenges, including the high cost of repetitive QM computations, the slow sampling even for the MM part in those cases where a system under investigation has a complex dynamics, and a difficulty in providing a simple, qualitative interpretation of numerical results in terms of the influence of the molecular environment upon the active QM region. In this paper, we address these issues by combining QM/MM modeling with the methodology of "bottom-up" coarse-graining (CG) to provide the theoretical basis for a systematic quantum-mechanical/coarse-grained molecular mechanics (QM/CG-MM) mixed resolution approach. A derivation of the method is presented based on a combination of statistical mechanics and quantum mechanics, leading to an equation for the effective Hamiltonian of the QM part, a central concept in the QM/CG-MM theory. A detailed analysis of different contributions to the effective Hamiltonian from electrostatic, induction, dispersion, and exchange interactions between the QM part and the surroundings is provided, serving as a foundation for a potential hierarchy of QM/CG-MM methods varying in their accuracy and computational cost. A relationship of the QM/CG-MM methodology to other mixed resolution approaches is also discussed.

  3. Bioinspired fabrication and characterization of a synthetic fish skin for the protection of soft materials.

    PubMed

    Funk, Natasha; Vera, Marc; Szewciw, Lawrence J; Barthelat, Francois; Stoykovich, Mark P; Vernerey, Franck J

    2015-03-18

    The scaled skin of fish is a high-performance natural armor that represents a source of inspiration for novel engineering designs. In this paper, we present a biomimetic fish skin material, fabricated with a design and components that are simple, that achieves many of the advantageous attributes of natural materials, including the unique combination of flexibility and mechanical robustness. The bioinspired fish skin material is designed to replicate the structural, mechanical, and functional aspects of a natural teleost fish skin comprised of leptoid-like scales, similar to that of the striped red mullet Mullus surmuletus. The man-made fish skin material consists of a low-modulus elastic mesh or "dermis" layer that holds rigid, plastic scales. The mechanics of the synthetic material is characterized under in-plane, bending, and indentation modes of deformation and is successfully described by theoretical deformation models that have been developed. This combined experimental and modeling approach elucidates the critical mechanisms by which the composite material achieves its unique properties and provides design rules that allow for the engineering of scaled skins. Such artificial scaled skins that are flexible, lightweight, transparent, and robust under mechanical deformation may thus have potential as thin protective coatings for soft materials.

  4. Fibrous tissues growth and remodeling: Evolutionary micro-mechanical theory

    NASA Astrophysics Data System (ADS)

    Lanir, Yoram

    2017-10-01

    Living fibrous tissues are composite materials having the unique ability to adapt their size, shape, structure and mechanical properties in response to external loading. This adaptation, termed growth and remodeling (G&R), occurs throughout life and is achieved via cell-induced turnover of tissue constituents where some are degraded and new ones are produced. Realistic mathematical modeling of G&R provides insight into the basic processes, allows for hypotheses testing, and constitutes an essential tool for establishing clinical thresholds of pathological remodeling and for the production of tissue substitutes aimed to achieve target structure and properties. In this study, a general 3D micro-mechanical multi-scale theory of G&R in fibrous tissue was developed which connects between the evolution of the tissue structure and properties, and the underlying mechano-biological turnover events of its constituents. This structural approach circumvents a fundamental obstacle in modeling growth mechanics since the growth motion is not bijective. The model was realized for a flat tissue under two biaxial external loadings using data-based parameter values. The predictions show close similarity to characteristics of remodeled adult tissue including its structure, anisotropic and non-linear mechanical properties, and the onset of in situ pre-strain and pre-stress. The results suggest that these important features of living fibrous tissues evolve as they grow.

  5. Transverse crack initiation under combined thermal and mechanical loading of Fibre Metal Laminates and Glass Fibre Reinforced Polymers

    NASA Astrophysics Data System (ADS)

    van de Camp, W.; Dhallé, M. M. J.; Warnet, L.; Wessel, W. A. J.; Vos, G. S.; Akkerman, R.; ter Brake, H. J. M.

    2017-02-01

    The paper describes a temperature-dependent extension of the classical laminate theory (CLT) that may be used to predict the mechanical behaviour of Fibre Metal Laminates (FML) at cryogenic conditions, including crack initiation. FML are considered as a possible alternative class of structural materials for the transport and storage of liquified gasses such as LNG. Combining different constituents in a laminate opens up the possibility to enhance its functionality, e.g. offering lower specific weight and increased damage tolerance. To explore this possibility, a test programme is underway at the University of Twente to study transverse crack initiation in different material combinations under combined thermal and mechanical loading. Specifically, the samples are tested in a three-point bending experiment at temperatures ranging from 77 to 293 K. These tests will serve as a validation of the model presented in this paper which, by incorporating temperature-dependent mechanical properties and differential thermal expansion, will allow to select optimal material combinations and laminate layouts. By combining the temperature-dependent mechanical properties and the differential thermal contraction explicitly, the model allows for a more accurate estimate of the resulting thermal stresses which can then be compared to the strength of the constituent materials.

  6. Low‑level mechanical vibration enhances osteoblastogenesis via a canonical Wnt signaling‑associated mechanism.

    PubMed

    Gao, Heqi; Zhai, Mingming; Wang, Pan; Zhang, Xuhui; Cai, Jing; Chen, Xiaofei; Shen, Guanghao; Luo, Erping; Jing, Da

    2017-07-01

    Osteoporosis is a skeletal metabolic disease characterized by reduced bone mass and a high susceptibility to fractures, in which osteoblasts and osteoclasts are highly involved in the abnormal bone remodeling processes. Recently, low‑magnitude, high‑frequency whole‑body vibration has been demonstrated to significantly reduce osteopenia experimentally and clinically. However, the underlying mechanism regarding how osteoblastic activity is altered when bone tissues adapt to mechanical vibration remains elusive. The current study systematically investigated the effect and potential molecular signaling mechanisms in mediating the effects of mechanical vibration (0.5 gn, 45 Hz) on primary osteoblasts in vitro. The results of the present study demonstrated that low‑level mechanical stimulation promoted osteoblastic proliferation and extracellular matrix mineralization. In addition, it was also revealed that mechanical vibration induced improved cytoskeleton arrangement in primary osteoblasts. Furthermore, mechanical vibration resulted in significantly increased gene expression of alkaline phosphatase, bone morphogenetic protein 2 and osteoprotegerin, and suppressed sclerostin gene expression, as determined by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analyses. Mechanical vibration was observed to upregulate gene and protein expression levels of osteogenesis‑associated biomarkers, including osteocalcin and Runt‑related transcription factor 2. In addition, RT‑qPCR and western blotting analysis demonstrated that mechanical vibration promoted gene and protein expression of canonical Wnt signaling genes, including Wnt3a, low‑density lipoprotein receptor‑related protein 6 and β‑catenin. In conclusion, the present study demonstrated that mechanical vibration stimulates osteoblastic activities and may function through a potential canonical Wnt signaling‑associated mechanism. These findings provided novel information that improves the understanding of the molecular mechanisms involved in osteoblastic activities in response to mechanical vibration, which may facilitate the scientific application of mechanical vibration for the treatment of osteoporosis in the clinic.

  7. A mechanical argument for the differential performance of coronary artery grafts.

    PubMed

    Prim, David A; Zhou, Boran; Hartstone-Rose, Adam; Uline, Mark J; Shazly, Tarek; Eberth, John F

    2016-02-01

    Coronary artery bypass grafting (CABG) acutely disturbs the homeostatic state of the transplanted vessel making retention of graft patency dependent on chronic remodeling processes. The time course and extent to which remodeling restores vessel homeostasis will depend, in part, on the nature and magnitude of the mechanical disturbances induced upon transplantation. In this investigation, biaxial mechanical testing and histology were performed on the porcine left anterior descending artery (LAD) and analogs of common autografts, including the internal thoracic artery (ITA), radial artery (RA), great saphenous vein (GSV) and lateral saphenous vein (LSV). Experimental data were used to quantify the parameters of a structure-based constitutive model enabling prediction of the acute vessel mechanical response pre-transplantation and under coronary loading conditions. A novel metric Ξ was developed to quantify mechanical differences between each graft vessel in situ and the LAD in situ, while a second metric Ω compares the graft vessels in situ to their state under coronary loading. The relative values of these metrics among candidate autograft sources are consistent with vessel-specific variations in CABG clinical success rates with the ITA as the superior and GSV the inferior graft choices based on mechanical performance. This approach can be used to evaluate other candidate tissues for grafting or to aid in the development of synthetic and tissue engineered alternatives. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. [Disease-syndrome combination in integrated traditional Chinese and Western medicine in andrology: Confusions and countermeasures in studies].

    PubMed

    Zhang, Min-Jian

    2017-07-01

    Researches on the mechanisms underlying the therapeutic effects of the disease-syndrome combination approach in integrated traditional Chinese and Western medicine are becoming a hot spot in andrology, but many recent studies of this kind have failed to explain the connotation of integrated traditional Chinese and Western medicine in andrology. Related existing problems include repeated researches into the same indexes of action mechanisms of different therapeutic principles of traditional Chinese medicine (TCM), Chinese herbal compound and special prescriptions, studies focusing on individual diseases but ignoring symptoms, immature syndrome models for studies of mechanisms, and too much attention to uncertain or immature target mechanisms. The stress should be placed on the action mechanisms of Chinese herbal compound and special prescriptions on male diseases and, what is more important, on the clarification of the essential principles of differentiation and treatment of TCM syndromes. In the recent years, proteomics, genomics, transcriptomics and metabolomics have shed some light upon researches into the mechanisms underlying the therapeutic effects of the disease-syndrome combination approach in integrated traditional Chinese and Western medicine in andrology. An insight into the TCM syndrome, a macroscopic inductive analysis, and a comprehension of such microcosmic aspects as the gene, protein, metabolism and metagenome may contribute to some breakthroughs and new ideas in the studies of disease-syndrome combination in integrated traditional Chinese and Western medicine in andrology.

  9. The contribution of collagen fibers to the mechanical compressive properties of the temporomandibular joint disc.

    PubMed

    Fazaeli, S; Ghazanfari, S; Everts, V; Smit, T H; Koolstra, J H

    2016-07-01

    The Temporomandibular Joint (TMJ) disc is a fibrocartilaginous structure located between the mandibular condyle and the temporal bone, facilitating smooth movements of the jaw. The load-bearing properties of its anisotropic collagenous network have been well characterized under tensile loading conditions. However, recently it has also been speculated that the collagen fibers may contribute dominantly in reinforcing the disc under compression. Therefore, in this study, the structural-functional role of collagen fibers in mechanical compressive properties of TMJ disc was investigated. Intact porcine TMJ discs were enzymatically digested with collagenase to disrupt the collagenous network of the cartilage. The digested and non-digested articular discs were analyzed mechanically, biochemically and histologically in five various regions. These tests included: (1) cyclic compression tests, (2) biochemical quantification of collagen and glycosaminoglycan (GAG) content and (3) visualization of collagen fibers' alignment by polarized light microscopy (PLM). The instantaneous compressive moduli of the articular discs were reduced by as much as 50-90% depending on the region after the collagenase treatment. The energy dissipation properties of the digested discs showed a similar tendency. Biochemical analysis of the digested samples demonstrated an average of 14% and 35% loss in collagen and GAG, respectively. Despite the low reduction of collagen content the PLM images showed considerable perturbation of the collagenous network of the TMJ disc. The results indicated that even mild disruption of collagen fibers can lead to substantial mechanical softening of TMJ disc undermining its reinforcement and mechanical stability under compression. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  10. Experimental Investigation of Fibre Reinforced Composite Materials Under Impact Load

    NASA Astrophysics Data System (ADS)

    Koppula, Sravani; Kaviti, Ajay kumar; Namala, Kiran kumar

    2018-03-01

    Composite materials are extensively used in various engineering applications. They have very high flexibility design which allows prescribe tailoring of material properties by lamination of composite fibres with reinforcement of resin to it. Complex failure condition prevail in the composite materials under the action of impact loads, major modes of failure in composite may include matrix cracking, fibre matrix, fibre breakage, de-bonding or de- lamination between composite plies. This paper describes the mechanical properties of glass fibre reinforced composite material under impact loading conditions through experimental setup. Experimental tests are performed according to ASTM standards using impact testing machines like Charpy test, computerized universal testing machine.

  11. Friction Stir Weld Failure Mechanisms in Aluminum-Armor Structures Under Ballistic Impact Loading Conditions

    DTIC Science & Technology

    2013-01-01

    REPORT Friction Stir Weld Failure Mechanisms in Aluminum -Armor Structures Under Ballistic Impact Loading Conditions 14. ABSTRACT 16. SECURITY...Stir Weld Failure Mechanisms in Aluminum -Armor Structures Under Ballistic Impact Loading Conditions M. Grujicic, B. Pandurangan, A. Arakere, C-F. Yen...K.O. Pedersen, Fracture Mechanisms of Aluminum Alloy AA7075-T651 Under Various Loading Conditions , Int. J. Impact Eng., 2010, 37, p 537–551 24. T

  12. Cell Surface Mechanochemistry and the Determinants of Bleb Formation, Healing, and Travel Velocity

    PubMed Central

    Manakova, Kathryn; Yan, Huaming; Lowengrub, John; Allard, Jun

    2016-01-01

    Blebs are pressure-driven cell protrusions implicated in cellular functions such as cell division, apoptosis, and cell motility, including motility of protease-inhibited cancer cells. Because of their mechanical nature, blebs inform us about general cell-surface mechanics, including membrane dynamics, pressure propagation throughout the cytoplasm, and the architecture and dynamics of the actin cortex. Mathematical models including detailed fluid dynamics have previously been used to understand bleb expansion. Here, we develop mathematical models in two and three dimensions on longer timescales that recapitulate the full bleb life cycle, including both expansion and healing by cortex reformation, in terms of experimentally accessible biophysical parameters such as myosin contractility, osmotic pressure, and turnover of actin and ezrin. The model provides conditions under which blebbing occurs, and naturally gives rise to traveling blebs. The model predicts conditions under which blebs travel or remain stationary, as well as the bleb traveling velocity, a quantity that has remained elusive in previous models. As previous studies have used blebs as reporters of membrane tension and pressure dynamics within the cell, we have used our system to investigate various pressure equilibration models and dynamic, nonuniform membrane tension to account for the shape of a traveling bleb. We also find that traveling blebs tend to expand in all directions unless otherwise constrained. One possible constraint could be provided by spatial heterogeneity in, for example, adhesion density. PMID:27074688

  13. [Pontomedullary lacerations and concomitant injuries: a review of possible underlying mechanisms].

    PubMed

    Živković, Vladimir; Nikolić, Slobodan

    2013-01-01

    Anatomically, brainstem is constituted of medulla oblongata, pons and mesencephalon. Traumatic lesions of brainstem most commonly occur on pontomedullary junction. There are several possible mechanisms of pontomedullary lacerations. The first mechanism includes impact to the chin, with or without a skull base fracture, and most often leads to this fatal injury, due to impact force transmission through the jawbone and temporomandibular joint. The second mechanism includes lateral and posterior head impacts with subsequent hinge fractures, where occurrence of pontomedullary lacerations in these cases may depend on the energy of impact, as well as on the exact position of the fracture line, but less so on the head's movement. The third mechanism includes frontoposterior hyperextension of the head, due to frontal impact, concomitant with fractures or dislocations of upper spine. In the fourth mechanism, there is an absence of direct impact to the head, due to the indirect force of action after feet or buttocks-first impact. Most of these cases are accompanied by ring fractures as well. In situations such as these, the impact force is transmitted up the spinal column and upper vertebrae, and telescopically intruded into the skull, causing brainstem laceration. The jawbone and other facial bones can act as shock absorbers, and their fracture could diminish the energy transfer towards the skull and protect the brain and brainstem from injury. In all the cases with pontomedullary laceration posterior neck dissection should be performed during the autopsy, since upper spine injuries are often associated with this type of injury.

  14. Overlap between functional GI disorders and other functional syndromes: what are the underlying mechanisms?

    PubMed Central

    KIM, S. E.; CHANG, L.

    2013-01-01

    Background Irritable bowel syndrome and other gastrointestinal (GI) and non-GI disorders such as functional dyspepsia, fibromyalgia, temporomandibular joint disorder, interstitial cystitis/painful bladder syndrome, and chronic fatigue syndrome are known as functional pain syndromes. They commonly coexist within the same individual. The pathophysiologic mechanisms of these disorders are not well understood, but it has been hypothesized that they share a common pathogenesis. Purpose The objective of this review is to discuss the proposed pathophysiologic mechanisms, which have been similarly studied in these conditions. These mechanisms include enhanced pain perception, altered regional brain activation, infectious etiologies, dysregulations in immune and neuroendocrine function, and genetic susceptibility. Studies suggest that these functional disorders are multifactorial, but factors which increase the vulnerability of developing these conditions are shared. PMID:22863120

  15. Quantum mechanical modeling the emission pattern and polarization of nanoscale light emitting diodes.

    PubMed

    Wang, Rulin; Zhang, Yu; Bi, Fuzhen; Frauenheim, Thomas; Chen, GuanHua; Yam, ChiYung

    2016-07-21

    Understanding of the electroluminescence (EL) mechanism in optoelectronic devices is imperative for further optimization of their efficiency and effectiveness. Here, a quantum mechanical approach is formulated for modeling the EL processes in nanoscale light emitting diodes (LED). Based on non-equilibrium Green's function quantum transport equations, interactions with the electromagnetic vacuum environment are included to describe electrically driven light emission in the devices. The presented framework is illustrated by numerical simulations of a silicon nanowire LED device. EL spectra of the nanowire device under different bias voltages are obtained and, more importantly, the radiation pattern and polarization of optical emission can be determined using the current approach. This work is an important step forward towards atomistic quantum mechanical modeling of the electrically induced optical response in nanoscale systems.

  16. Neural Cross-Frequency Coupling: Connecting Architectures, Mechanisms, and Functions.

    PubMed

    Hyafil, Alexandre; Giraud, Anne-Lise; Fontolan, Lorenzo; Gutkin, Boris

    2015-11-01

    Neural oscillations are ubiquitously observed in the mammalian brain, but it has proven difficult to tie oscillatory patterns to specific cognitive operations. Notably, the coupling between neural oscillations at different timescales has recently received much attention, both from experimentalists and theoreticians. We review the mechanisms underlying various forms of this cross-frequency coupling. We show that different types of neural oscillators and cross-frequency interactions yield distinct signatures in neural dynamics. Finally, we associate these mechanisms with several putative functions of cross-frequency coupling, including neural representations of multiple environmental items, communication over distant areas, internal clocking of neural processes, and modulation of neural processing based on temporal predictions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Characterization of Thermal and Mechanical Impact on Aluminum Honeycomb Structures

    NASA Technical Reports Server (NTRS)

    Robinson, Christen M.

    2013-01-01

    This study supports NASA Kennedy Space Center's research in the area of intelligent thermal management systems and multifunctional thermal systems. This project addresses the evaluation of the mechanical and thermal properties of metallic cellular solid (MCS) materials; those that are lightweight; high strength, tunable, multifunctional and affordable. A portion of the work includes understanding the mechanical properties of honeycomb structured cellular solids upon impact testing under ambient, water-immersed, liquid nitrogen-cooled, and liquid nitrogen-immersed conditions. Additionally, this study will address characterization techniques of the aluminum honeycomb's ability to resist multiple high-rate loadings or impacts in varying environmental conditions, using various techniques for the quantitative and qualitative determination for commercial applicability.

  18. Roux-en-Y gastric bypass: effects on feeding behavior and underlying mechanisms

    PubMed Central

    Manning, Sean; Pucci, Andrea; Batterham, Rachel L.

    2015-01-01

    Bariatric surgery is the most effective treatment for severe obesity, producing marked sustained weight loss with associated reduced morbidity and mortality. Roux-en-Y gastric bypass surgery (RYGBP), the most commonly performed procedure, was initially viewed as a hybrid restrictive-malabsorptive procedure. However, over the last decade, it has become apparent that alternative physiologic mechanisms underlie its beneficial effects. RYGBP-induced altered feeding behavior, including reduced appetite and changes in taste/food preferences, is now recognized as a key driver of the sustained postoperative weight loss. The brain ultimately determines feeding behavior, and here we review the mechanisms by which RYGBP may affect central appetite-regulating pathways. PMID:25729850

  19. An Update on Inflamm-Aging: Mechanisms, Prevention, and Treatment

    PubMed Central

    Wu, Junzhen

    2016-01-01

    Inflamm-aging is a challenging and promising new branch of aging-related research fields that includes areas such as immunosenescence. Increasing evidence indicates that inflamm-aging is intensively associated with many aging diseases, such as Alzheimer's disease, atherosclerosis, heart disease, type II diabetes, and cancer. Mounting studies have focused on the role of inflamm-aging in disease progression and many advances have been made in the last decade. However, the underlying mechanisms by which inflamm-aging affects pathological changes and disease development are still unclear. Here, we review studies of inflamm-aging that explore the concept, pathological features, mechanisms, intervention, and the therapeutic strategies of inflamm-aging in disease progression. PMID:27493973

  20. A Mechanical Model of Brownian Motion for One Massive Particle Including Slow Light Particles

    NASA Astrophysics Data System (ADS)

    Liang, Song

    2018-01-01

    We provide a connection between Brownian motion and a classical mechanical system. Precisely, we consider a system of one massive particle interacting with an ideal gas, evolved according to non-random mechanical principles, via interaction potentials, without any assumption requiring that the initial velocities of the environmental particles should be restricted to be "fast enough". We prove the convergence of the (position, velocity)-process of the massive particle under a certain scaling limit, such that the mass of the environmental particles converges to 0 while the density and the velocities of them go to infinity, and give the precise expression of the limiting process, a diffusion process.

  1. Principle, design and validation of a power-generated magnetorheological energy absorber with velocity self-sensing capability

    NASA Astrophysics Data System (ADS)

    Bai, Xian-Xu; Zhong, Wei-Min; Zou, Qi; Zhu, An-Ding; Sun, Jun

    2018-07-01

    Based on the structural design concept of ‘functional integration’, this paper proposes the principle of a power-generated magnetorheological energy absorber with velocity self-sensing capability (PGMREA), which realizes the integration of controllable damping mechanism and mechanical energy-electrical energy conversion mechanism in structure profile and multiple functions in function profile, including controllable damping, power generation and velocity self-sensing. The controllable damping mechanism consists of an annular gap and a ball screw. The annular gap fulfilled with MR fluid that operates in pure shear mode under controllable electromagnetic field. The rotational damping torque generated from the controllable damping mechanism is translated to a linear damping force via the ball screw. The mechanical energy-electrical energy conversion mechanism is realized by the ball screw and a generator composed of a permanent magnet rotor and a generator stator. The ball screw based mechanical energy-electrical energy conversion mechanism converts the mechanical energy of excitations to electrical energy for storage or directly to power the controllable damping mechanism of the PGMREA. The velocity self-sensing capability of the PGMREA is achieved via signal processing using the mechanical energy-electrical energy conversion information. Based on the principle of the proposed PGMREA, the mathematical model of the PGMREA is established, including the damping force, generated power and self-sensing velocity. The electromagnetic circuit of the PGMREA is simulated and verified via a finite element analysis software ANSYS. The developed PGMREA prototype is experimentally tested on a servo-hydraulic testing system. The model-based predicted results and the experimental results are compared and analyzed.

  2. Polarity mechanisms such as contact inhibition of locomotion regulate persistent rotational motion of mammalian cells on micropatterns

    PubMed Central

    Camley, Brian A.; Zhang, Yunsong; Zhao, Yanxiang; Li, Bo; Ben-Jacob, Eshel; Levine, Herbert; Rappel, Wouter-Jan

    2014-01-01

    Pairs of endothelial cells on adhesive micropatterns rotate persistently, but pairs of fibroblasts do not; coherent rotation is present in normal mammary acini and kidney cells but absent in cancerous cells. Why? To answer this question, we develop a computational model of pairs of mammalian cells on adhesive micropatterns using a phase field method and study the conditions under which persistent rotational motion (PRM) emerges. Our model couples the shape of the cell, the cell’s internal chemical polarity, and interactions between cells such as volume exclusion and adhesion. We show that PRM can emerge from this minimal model and that the cell-cell interface may be influenced by the nucleus. We study the effect of various cell polarity mechanisms on rotational motion, including contact inhibition of locomotion, neighbor alignment, and velocity alignment, where cells align their polarity to their velocity. These polarity mechanisms strongly regulate PRM: Small differences in polarity mechanisms can create significant differences in collective rotation. We argue that the existence or absence of rotation under confinement may lead to insight into the cell’s methods for coordinating collective cell motility. PMID:25258412

  3. An accurate and efficient method for piezoelectric coated functional devices based on the two-dimensional Green’s function for a normal line force and line charge

    NASA Astrophysics Data System (ADS)

    Hou, Peng-Fei; Zhang, Yang

    2017-09-01

    Because most piezoelectric functional devices, including sensors, actuators and energy harvesters, are in the form of a piezoelectric coated structure, it is valuable to present an accurate and efficient method for obtaining the electro-mechanical coupling fields of this coated structure under mechanical and electrical loads. With this aim, the two-dimensional Green’s function for a normal line force and line charge on the surface of coated structure, which is a combination of an orthotropic piezoelectric coating and orthotropic elastic substrate, is presented in the form of elementary functions based on the general solution method. The corresponding electro-mechanical coupling fields of this coated structure under arbitrary mechanical and electrical loads can then be obtained by the superposition principle and Gauss integration. Numerical results show that the presented method has high computational precision, efficiency and stability. It can be used to design the best coating thickness in functional devices, improve the sensitivity of sensors, and improve the efficiency of actuators and energy harvesters. This method could be an efficient tool for engineers in engineering applications.

  4. Statistical Characterization of the Mechanical Parameters of Intact Rock Under Triaxial Compression: An Experimental Proof of the Jinping Marble

    NASA Astrophysics Data System (ADS)

    Jiang, Quan; Zhong, Shan; Cui, Jie; Feng, Xia-Ting; Song, Leibo

    2016-12-01

    We investigated the statistical characteristics and probability distribution of the mechanical parameters of natural rock using triaxial compression tests. Twenty cores of Jinping marble were tested under each different levels of confining stress (i.e., 5, 10, 20, 30, and 40 MPa). From these full stress-strain data, we summarized the numerical characteristics and determined the probability distribution form of several important mechanical parameters, including deformational parameters, characteristic strength, characteristic strains, and failure angle. The statistical proofs relating to the mechanical parameters of rock presented new information about the marble's probabilistic distribution characteristics. The normal and log-normal distributions were appropriate for describing random strengths of rock; the coefficients of variation of the peak strengths had no relationship to the confining stress; the only acceptable random distribution for both Young's elastic modulus and Poisson's ratio was the log-normal function; and the cohesive strength had a different probability distribution pattern than the frictional angle. The triaxial tests and statistical analysis also provided experimental evidence for deciding the minimum reliable number of experimental sample and for picking appropriate parameter distributions to use in reliability calculations for rock engineering.

  5. Interactome Mapping Guided by Tissue-Specific Phosphorylation in Age-Related Macular Degeneration

    PubMed Central

    Sripathi, Srinivas R.; He, Weilue; Prigge, Cameron L.; Sylvester, O’Donnell; Um, Ji-Yeon; Powell, Folami L.; Neksumi, Musa; Bernstein, Paul S.; Choo, Dong-Won; Bartoli, Manuela; Gutsaeva, Diana R.; Jahng, Wan Jin

    2017-01-01

    The current study aims to determine the molecular mechanisms of age-related macular degeneration (AMD) using the phosphorylation network. Specifically, we examined novel biomarkers for oxidative stress by protein interaction mapping using in vitro and in vivo models that mimic the complex and progressive characteristics of AMD. We hypothesized that the early apoptotic reactions could be initiated by protein phosphorylation in region-dependent (peripheral retina vs. macular) and tissue-dependent (retinal pigment epithelium vs. retina) manner under chronic oxidative stress. The analysis of protein interactome and oxidative biomarkers showed the presence of tissue- and region-specific post-translational mechanisms that contribute to AMD progression and suggested new therapeutic targets that include ubiquitin, erythropoietin, vitronectin, MMP2, crystalline, nitric oxide, and prohibitin. Phosphorylation of specific target proteins in RPE cells is a central regulatory mechanism as a survival tool under chronic oxidative imbalance. The current interactome map demonstrates a positive correlation between oxidative stress-mediated phosphorylation and AMD progression and provides a basis for understanding oxidative stress-induced cytoskeletal changes and the mechanism of aggregate formation induced by protein phosphorylation. This information could provide an effective therapeutic approach to treat age-related neurodegeneration. PMID:28580316

  6. Interactome Mapping Guided by Tissue-Specific Phosphorylation in Age-Related Macular Degeneration.

    PubMed

    Sripathi, Srinivas R; He, Weilue; Prigge, Cameron L; Sylvester, O'Donnell; Um, Ji-Yeon; Powell, Folami L; Neksumi, Musa; Bernstein, Paul S; Choo, Dong-Won; Bartoli, Manuela; Gutsaeva, Diana R; Jahng, Wan Jin

    2017-02-01

    The current study aims to determine the molecular mechanisms of age-related macular degeneration (AMD) using the phosphorylation network. Specifically, we examined novel biomarkers for oxidative stress by protein interaction mapping using in vitro and in vivo models that mimic the complex and progressive characteristics of AMD. We hypothesized that the early apoptotic reactions could be initiated by protein phosphorylation in region-dependent (peripheral retina vs. macular) and tissue-dependent (retinal pigment epithelium vs. retina) manner under chronic oxidative stress. The analysis of protein interactome and oxidative biomarkers showed the presence of tissue- and region-specific post-translational mechanisms that contribute to AMD progression and suggested new therapeutic targets that include ubiquitin, erythropoietin, vitronectin, MMP2, crystalline, nitric oxide, and prohibitin. Phosphorylation of specific target proteins in RPE cells is a central regulatory mechanism as a survival tool under chronic oxidative imbalance. The current interactome map demonstrates a positive correlation between oxidative stress-mediated phosphorylation and AMD progression and provides a basis for understanding oxidative stress-induced cytoskeletal changes and the mechanism of aggregate formation induced by protein phosphorylation. This information could provide an effective therapeutic approach to treat age-related neurodegeneration.

  7. Mechanisms Linking Colorectal Cancer to the Consumption of (Processed) Red Meat: A Review.

    PubMed

    Demeyer, Daniel; Mertens, Birgit; De Smet, Stefaan; Ulens, Michèle

    2016-12-09

    Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world. The vast majority of CRC cases have been linked to environmental causes rather than to heritable genetic changes. Over the last decades, epidemiological evidence linking the consumption of red and, more convincingly, of processed red meat to CRC has accumulated. In parallel, hypotheses on carcinogenic mechanisms underlying an association between CRC and the intake of red and processed red meat have been proposed and investigated in biological studies. The hypotheses that have received most attention until now include (1) the presence of polycyclic aromatic hydrocarbons and heterocyclic aromatic amines, two groups of compounds recognized as carcinogenic, (2) the enhancing effect of (nitrosyl)heme on the formation of carcinogenic N-nitroso compounds and lipid peroxidation. However, none of these hypotheses completely explains the link between red and processed red meat intake and the CRC risk. Consequently, scientists have proposed additional mechanisms or refined their hypotheses. This review first briefly summarizes the development of CRC followed by an in-depth overview and critical discussion of the different potential carcinogenic mechanisms underlying the increased CRC risk associated with the consumption of red and processed red meat.

  8. The Potential of iPSCs for the Treatment of Premature Aging Disorders

    PubMed Central

    Compagnucci, Claudia; Bertini, Enrico

    2017-01-01

    Premature aging disorders including Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome, are a group of rare monogenic diseases leading to reduced lifespan of the patients. Importantly, these disorders mimic several features of physiological aging. Despite the interest on the study of these diseases, the underlying biological mechanisms remain unknown and no treatment is available. Recent studies on HGPS (due to mutations of the LMNA gene encoding for the nucleoskeletal proteins lamin A/C) have reported disruptions in cellular and molecular mechanisms modulating genomic stability and stem cell populations, thus giving the nuclear lamina a relevant function in nuclear organization, epigenetic regulation and in the maintenance of the stem cell pool. In this context, modeling premature aging with induced pluripotent stem cells (iPSCs) offers the possibility to study these disorders during self-renewal and differentiation into relevant cell types. iPSCs generated by cellular reprogramming from adult somatic cells allows researchers to understand pathophysiological mechanisms and enables the performance of drug screenings. Moreover, the recent development of precision genome editing offers the possibility to study the complex mechanisms underlying senescence and the possibility to correct disease phenotypes, paving the way for future therapeutic interventions. PMID:29112121

  9. A Brief History of Research on Mitotic Mechanisms.

    PubMed

    McIntosh, J Richard; Hays, Thomas

    2016-12-21

    This chapter describes in summary form some of the most important research on chromosome segregation, from the discovery and naming of mitosis in the nineteenth century until around 1990. It gives both historical and scientific background for the nine chapters that follow, each of which provides an up-to-date review of a specific aspect of mitotic mechanism. Here, we trace the fruits of each new technology that allowed a deeper understanding of mitosis and its underlying mechanisms. We describe how light microscopy, including phase, polarization, and fluorescence optics, provided descriptive information about mitotic events and also enabled important experimentation on mitotic functions, such as the dynamics of spindle fibers and the forces generated for chromosome movement. We describe studies by electron microscopy, including quantitative work with serial section reconstructions. We review early results from spindle biochemistry and genetics, coupled to molecular biology, as these methods allowed scholars to identify key molecular components of mitotic mechanisms. We also review hypotheses about mitotic mechanisms whose testing led to a deeper understanding of this fundamental biological event. Our goal is to provide modern scientists with an appreciation of the work that has laid the foundations for their current work and interests.

  10. A Brief History of Research on Mitotic Mechanisms

    PubMed Central

    McIntosh, J. Richard; Hays, Thomas

    2016-01-01

    This chapter describes in summary form some of the most important research on chromosome segregation, from the discovery and naming of mitosis in the nineteenth century until around 1990. It gives both historical and scientific background for the nine chapters that follow, each of which provides an up-to-date review of a specific aspect of mitotic mechanism. Here, we trace the fruits of each new technology that allowed a deeper understanding of mitosis and its underlying mechanisms. We describe how light microscopy, including phase, polarization, and fluorescence optics, provided descriptive information about mitotic events and also enabled important experimentation on mitotic functions, such as the dynamics of spindle fibers and the forces generated for chromosome movement. We describe studies by electron microscopy, including quantitative work with serial section reconstructions. We review early results from spindle biochemistry and genetics, coupled to molecular biology, as these methods allowed scholars to identify key molecular components of mitotic mechanisms. We also review hypotheses about mitotic mechanisms whose testing led to a deeper understanding of this fundamental biological event. Our goal is to provide modern scientists with an appreciation of the work that has laid the foundations for their current work and interests. PMID:28009830

  11. Mechanisms of metabolic memory and renal hypoxia as a therapeutic target in diabetic kidney disease.

    PubMed

    Hirakawa, Yosuke; Tanaka, Tetsuhiro; Nangaku, Masaomi

    2017-05-01

    Diabetic kidney disease (DKD) is a worldwide public health problem. The definition of DKD is under discussion. Although the term DKD was originally defined as 'kidney disease specific to diabetes,' DKD frequently means chronic kidney disease with diabetes mellitus and includes not only classical diabetic nephropathy, but also kidney dysfunction as a result of nephrosclerosis and other causes. Metabolic memory plays a crucial role in the progression of various complications of diabetes, including DKD. The mechanisms of metabolic memory in DKD are supposed to include advanced glycation end-products, deoxyribonucleic acid methylation, histone modifications and non-coding ribonucleic acid including micro ribonucleic acid. Regardless of the presence of diabetes mellitus, the final common pathway in chronic kidney disease is chronic kidney hypoxia, which influences epigenetic processes, including deoxyribonucleic acid methylation, histone modification, and conformational changes in micro ribonucleic acid and chromatin. Therefore, hypoxia and oxidative stress are appropriate targets of therapies against DKD. Prolyl hydroxylase domain inhibitor enhances the defensive mechanisms against hypoxia. Bardoxolone methyl protects against oxidative stress, and can even reverse impaired renal function; a phase 2 trial with considerable attention to heart complications is currently ongoing in Japan. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  12. The impact of non-isothermal soil moisture transport on evaporation fluxes in a maize cropland

    NASA Astrophysics Data System (ADS)

    Shao, Wei; Coenders-Gerrits, Miriam; Judge, Jasmeet; Zeng, Yijian; Su, Ye

    2018-06-01

    The process of evaporation interacts with the soil, which has various comprehensive mechanisms. Multiphase flow models solve air, vapour, water, and heat transport equations to simulate non-isothermal soil moisture transport of both liquid water and vapor flow, but are only applied in non-vegetated soils. For (sparsely) vegetated soils often energy balance models are used, however these lack the detailed information on non-isothermal soil moisture transport. In this study we coupled a multiphase flow model with a two-layer energy balance model to study the impact of non-isothermal soil moisture transport on evaporation fluxes (i.e., interception, transpiration, and soil evaporation) for vegetated soils. The proposed model was implemented at an experimental agricultural site in Florida, US, covering an entire maize-growing season (67 days). As the crops grew, transpiration and interception became gradually dominated, while the fraction of soil evaporation dropped from 100% to less than 20%. The mechanisms of soil evaporation vary depending on the soil moisture content. After precipitation the soil moisture content increased, exfiltration of the liquid water flow could transport sufficient water to sustain evaporation from soil, and the soil vapor transport was not significant. However, after a sufficient dry-down period, the soil moisture content significantly reduced, and the soil vapour flow significantly contributed to the upward moisture transport in topmost soil. A sensitivity analysis found that the simulations of moisture content and temperature at the soil surface varied substantially when including the advective (i.e., advection and mechanical dispersion) vapour transport in simulation, including the mechanism of advective vapour transport decreased soil evaporation rate under wet condition, while vice versa under dry condition. The results showed that the formulation of advective soil vapor transport in a soil-vegetation-atmosphere transfer continuum can affect the simulated evaporation fluxes, especially under dry condition.

  13. Test method research on weakening interface strength of steel - concrete under cyclic loading

    NASA Astrophysics Data System (ADS)

    Liu, Ming-wei; Zhang, Fang-hua; Su, Guang-quan

    2018-02-01

    The mechanical properties of steel - concrete interface under cyclic loading are the key factors affecting the rule of horizontal load transfer, the calculation of bearing capacity and cumulative horizontal deformation. Cyclic shear test is an effective method to study the strength reduction of steel - concrete interface. A test system composed of large repeated direct shear test instrument, hydraulic servo system, data acquisition system, test control software system and so on is independently designed, and a set of test method, including the specimen preparation, the instrument preparation, the loading method and so on, is put forward. By listing a set of test results, the validity of the test method is verified. The test system and the test method based on it provide a reference for the experimental study on mechanical properties of steel - concrete interface.

  14. Postural Control Impairments in Individuals With Autism Spectrum Disorder: A Critical Review of Current Literature

    PubMed Central

    Memari, Amir Hossein; Ghanouni, Parisa; Shayestehfar, Monir; Ghaheri, Banafsheh

    2014-01-01

    Context: Motor impairments in individuals with autism spectrum disorder (ASD) have been frequently reported. In this review, we narrow our focus on postural control impairments to summarize current literature for patterns, underlying mechanisms, and determinants of posture in this population. Evidence Acquisition: A literature search was conducted through Medline, ISI web of Knowledge, Scopus and Google Scholar to include studies between 1992 and February 2013. Results: Individuals with ASD have problems in maintaining postural control in infancy that well persists into later years. However, the patterns and underlying mechanisms are still unclear. Conclusions: Examining postural control as an endophenotype or early diagnostic marker of autism is a conceptual premise which should be considered in future investigations. At the end of the review, methodological recommendations on the assessment of postural control have also been provided. PMID:25520765

  15. Cardiovascular Benefits of Dark Chocolate?

    PubMed

    Higginbotham, Erin; Taub, Pam R

    2015-12-01

    The use of cacao for health benefits dates back at least 3000 years. Our understanding of cacao has evolved with modern science. It is now felt based on extensive research the main health benefits of cacao stem from epicatechin, a flavanol found in cacao. The process of manufacturing dark chocolate retains epicatechin, whereas milk chocolate does not contain significant amounts of epicatechin. Thus, most of the current research studies are focused on dark chocolate. Both epidemiological and clinical studies suggest a beneficial effect of dark chocolate on blood pressure, lipids, and inflammation. Proposed mechanisms underlying these benefits include enhanced nitric oxide bioavailability and improved mitochondrial structure/function. Ultimately, further studies of this promising compound are needed to elucidate its potential for prevention and treatment of cardiovascular and metabolic diseases as well as other diseases that have underlying mechanisms of mitochondrial dysfunction and nitric oxide deficiency.

  16. Opportunities and Challenges for the Emerging Field of Positive Emotion Regulation: A Commentary on the Special Edition on Positive Emotions and Cognitions in Clinical Psychology.

    PubMed

    Dunn, Barnaby D

    2017-01-01

    The importance of developing a better understanding of positive emotion regulation in both healthy and clinical populations is now recognised. This special edition brings together leading figures in the positive emotion regulation field and has contributions characterizing positive phenomena, differentiating them from negative phenomena, and evaluating underlying psychological mechanisms that drive these phenomena. This commentary reviews these articles to highlight challenges and opportunities for this emerging field, including the need to better characterize positive phenomena, to be more explicit about how the links between negative and positive phenomena are conceptualised, to evaluate more robustly underlying mechanisms, to standardize measurement of positive constructs, and to ensure that these scientific findings lead to meaningful changes in real-world policy and practice.

  17. Hedgehog Signaling Regulates the Survival of Gastric Cancer Cells by Regulating the Expression of Bcl-2

    PubMed Central

    Han, Myoung-Eun; Lee, Young-Suk; Baek, Sun-Yong; Kim, Bong-Seon; Kim, Jae-Bong; Oh, Sae-Ock

    2009-01-01

    Gastric cancer is the second most common cause of cancer deaths worldwide. The underlying molecular mechanisms of its carcinogenesis are relatively poorly characterized. Hedgehog (Hh) signaling, which is critical for development of various organs including the gastrointestinal tract, has been associated with gastric cancer. The present study was undertaken to reveal the underlying mechanism by which Hh signaling controls gastric cancer cell proliferation. Treatment of gastric cancer cells with cyclopamine, a specific inhibitor of Hh signaling pathway, reduced proliferation and induced apoptosis of gastric cancer cells. Cyclopamine treatment induced cytochrome c release from mitochondria and cleavage of caspase 9. Moreover, Bcl-2 expression was significantly reduced by cyclopamine treatment. These results suggest that Hh signaling regulates the survival of gastric cancer cells by regulating the expression of Bcl-2. PMID:19742123

  18. Prevalence and proposed mechanisms of chronic low back pain in baseball: part i

    PubMed Central

    Wasser, Joseph G.; Zaremski, Jason L.; Herman, Daniel C.; Vincent, Heather K.

    2017-01-01

    The prevalence of low back pain (LBP) among active baseball players ranges between 3 and 15%. The execution of baseball-specific manoeuvres, such as pitching or batting, may be related to the onset of LBP. These baseball motions are complex and require appropriate activation of the core musculature to produce a well-timed motion with forces minimized at the extremities. The spine, core and back musculature are involved with acceleration and deceleration of rotational motions. This narrative review synopsizes the available evidence of the prevalence of and mechanical factors underlying LBP in the baseball population. Possible mechanical mechanisms linking baseball play to LBP include aberrant motion, improper timing, high lumbar stress due to mechanical loading and lumbopelvic strength deficits. Potential clinical implications relating to these possible mechanical mechanisms will also be highlighted. The state of the evidence suggests that there are deficits in understanding the role of baseball motion and playing history in the development of spine conditions. PMID:28128007

  19. Prevalence and proposed mechanisms of chronic low back pain in baseball: part i.

    PubMed

    Wasser, Joseph G; Zaremski, Jason L; Herman, Daniel C; Vincent, Heather K

    2017-01-01

    The prevalence of low back pain (LBP) among active baseball players ranges between 3 and 15%. The execution of baseball-specific manoeuvres, such as pitching or batting, may be related to the onset of LBP. These baseball motions are complex and require appropriate activation of the core musculature to produce a well-timed motion with forces minimized at the extremities. The spine, core and back musculature are involved with acceleration and deceleration of rotational motions. This narrative review synopsizes the available evidence of the prevalence of and mechanical factors underlying LBP in the baseball population. Possible mechanical mechanisms linking baseball play to LBP include aberrant motion, improper timing, high lumbar stress due to mechanical loading and lumbopelvic strength deficits. Potential clinical implications relating to these possible mechanical mechanisms will also be highlighted. The state of the evidence suggests that there are deficits in understanding the role of baseball motion and playing history in the development of spine conditions.

  20. Thermal-mechanical fatigue behavior of nickel-base superalloys

    NASA Technical Reports Server (NTRS)

    Pelloux, R. M.; Marchand, N.

    1986-01-01

    The main achievements of a 36-month research program are presented. The main objective was to gain more insight into the problem of crack growth under thermal mechanical fatigue (TMF) conditions. This program was conducted at M.I.T. for the period of September 1982 to September 1985. The program was arranged into five technical tasks. Under Task I, the literature of TMF data was reviewed. The goal was to identify the crack propagation conditions in aircraft engines (hot section) and to assess the validity of conventional fracture mechanics parameters to address TMF crack growth. The second task defined the test facilities, test specimen and the testing conditions needed to establish the effectiveness of data correlation parameters identified in Task I. Three materials (Inconel X-750, Hastelloy-X, and B-1900) were chosen for the program. Task II was accomplished in collaboration with Pratt & Whitney Aircraft engineers. Under Task III, a computerized testing system to measure the TMF behavior (LCF and CG behaviors) of various alloys systems was built. The software used to run isothermal and TMF tests was also developed. Built around a conventional servohydraulic machine, the system is capable of push-pull tests under stress or strain and temperature controlled conditions in the temperature range of 25C to 1050C. A crack propagation test program was defined and conducted under Task IV. The test variables included strain range, strain rate (frequency) and temperature. Task V correlated and generalized the Task IV data for isothermal and variable temperature conditions so that several crack propagation parameters could be compared and evaluated. The structural damage (mode of cracking and dislocation substructure) under TMF cycling was identified and contrasted with the isothermal damage to achieve a sound fundamental mechanistic understanding of TMF.

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