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Sample records for autonomous resistance mechanism

  1. TRPM8 mechanism of autonomic nerve response to cold in respiratory airway

    Directory of Open Access Journals (Sweden)

    Wang Cong-Yi

    2008-06-01

    Full Text Available Abstract Breathing cold air without proper temperature exchange can induce strong respiratory autonomic responses including cough, airway constriction and mucosal secretion, and can exacerbate existing asthma conditions and even directly trigger an asthma attack. Vagal afferent fiber is thought to be involved in the cold-induced respiratory responses through autonomic nerve reflex. However, molecular mechanisms by which vagal afferent fibers are excited by cold remain unknown. Using retrograde labeling, immunostaining, calcium imaging, and electrophysiological recordings, here we show that a subpopulation of airway vagal afferent nerves express TRPM8 receptors and that activation of TRPM8 receptors by cold excites these airway autonomic nerves. Thus activation of TRPM8 receptors may provoke autonomic nerve reflex to increase airway resistance. This putative autonomic response may be associated with cold-induced exacerbation of asthma and other pulmonary disorders, making TRPM8 receptors a possible target for prevention of cold-associated respiratory disorders.

  2. Arterial Stiffness and Autonomic Modulation After Free-Weight Resistance Exercises in Resistance Trained Individuals.

    Science.gov (United States)

    Kingsley, J Derek; Mayo, Xián; Tai, Yu Lun; Fennell, Curtis

    2016-12-01

    Kingsley, JD, Mayo, X, Tai, YL, and Fennell, C. Arterial stiffness and autonomic modulation after free-weight resistance exercises in resistance trained individuals. J Strength Cond Res 30(12): 3373-3380, 2016-We investigated the effects of an acute bout of free-weight, whole-body resistance exercise consisting of the squat, bench press, and deadlift on arterial stiffness and cardiac autonomic modulation in 16 (aged 23 ± 3 years; mean ± SD) resistance-trained individuals. Arterial stiffness, autonomic modulation, and baroreflex sensitivity (BRS) were assessed at rest and after 3 sets of 10 repetitions at 75% 1-repetition maximum on each exercise with 2 minutes of rest between sets and exercises. Arterial stiffness was analyzed using carotid-femoral pulse wave velocity (cf-PWV). Linear heart rate variability (log transformed [ln] absolute and normalized units [nu] of low-frequency [LF] and high-frequency [HF] power) and nonlinear heart rate complexity (Sample Entropy [SampEn], Lempel-Ziv Entropy [LZEn]) were measured to determine autonomic modulation. BRS was measured by the sequence method. A 2 × 2 repeated measures analysis of variance (ANOVA) was used to analyze time (rest, recovery) across condition (acute resistance exercise, control). There were significant increases in cf-PWV (p = 0.05), heart rate (p = 0.0001), normalized LF (LFnu; p = 0.001), and the LF/HF ratio (p = 0.0001). Interactions were also noted for ln HF (p = 0.006), HFnu (p = 0.0001), SampEn (p = 0.001), LZEn (p = 0.005), and BRS (p = 0.0001) such that they significantly decreased during recovery from the resistance exercise compared with rest and the control. There was no effect on ln total power, or ln LF. These data suggest that a bout of resistance exercise using free-weights increases arterial stiffness and reduces vagal activity and BRS in comparison with a control session. Vagal tone may not be fully recovered up to 30 minutes after a resistance exercise bout.

  3. Impaired autonomic regulation of resistance arteries in mice with low vascular endothelial growth factor or upon vascular endothelial growth factor trap delivery

    DEFF Research Database (Denmark)

    Storkebaum, Erik; Ruiz de Almodovar, Carmen; Meens, Merlijn

    2010-01-01

    BACKGROUND: Control of peripheral resistance arteries by autonomic nerves is essential for the regulation of blood flow. The signals responsible for the maintenance of vascular neuroeffector mechanisms in the adult, however, remain largely unknown. METHODS AND RESULTS: Here, we report that VEGF( ...

  4. Self-Assessment Exercises in Continuum Mechanics with Autonomous Learning

    Science.gov (United States)

    Marcé-Nogué, Jordi; Gil, LLuís; Pérez, Marco A.; Sánchez, Montserrat

    2013-01-01

    The main objective of this work is to generate a set of exercises to improve the autonomous learning in "Continuum Mechanics" through a virtual platform. Students will have to resolve four exercises autonomously related to the subject developed in class and they will post the solutions on the virtual platform within a deadline. Students…

  5. Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

    Directory of Open Access Journals (Sweden)

    Camilla Figueiredo Grans

    2014-07-01

    Full Text Available Background: Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. Objective: To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Methods: Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week. At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. Results: The maximum load test increased in groups trained control (+32% and trained infarcted (+46% in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%, myocardial performance index (-39% and systolic blood pressure (+6% improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%, as well as in the low frequency band of systolic blood pressure (-46% in rats from group trained infarcted in relation to group sedentary infarcted. Conclusion: Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats.

  6. Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

    International Nuclear Information System (INIS)

    Grans, Camilla Figueiredo; Feriani, Daniele Jardim; Abssamra, Marcos Elias Vergilino; Rocha, Leandro Yanase; Carrozzi, Nicolle Martins; Mostarda, Cristiano; Figueroa, Diego Mendrot; Angelis, Kátia De; Irigoyen, Maria Cláudia; Rodrigues, Bruno

    2014-01-01

    Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats

  7. Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

    Energy Technology Data Exchange (ETDEWEB)

    Grans, Camilla Figueiredo; Feriani, Daniele Jardim; Abssamra, Marcos Elias Vergilino; Rocha, Leandro Yanase; Carrozzi, Nicolle Martins [Laboratório do Movimento Humano, Universidade São Judas Tadeu (USJT), São Paulo, SP (Brazil); Mostarda, Cristiano [Departamento de Educação Física, Universidade Federal do Maranhão (UFMA), São Luís, MA (Brazil); Figueroa, Diego Mendrot [Laboratório de Hipertensão Experimental, Instituto do Coração (InCor), Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP (Brazil); Angelis, Kátia De [Laboratório de Fisiologia Translacional, Universidade Nove de Julho (Uninove), São Paulo, SP (Brazil); Irigoyen, Maria Cláudia [Laboratório de Hipertensão Experimental, Instituto do Coração (InCor), Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP (Brazil); Rodrigues, Bruno, E-mail: bruno.rodrigues@incor.usp.br [Laboratório do Movimento Humano, Universidade São Judas Tadeu (USJT), São Paulo, SP (Brazil)

    2014-07-15

    Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats.

  8. Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

    Science.gov (United States)

    Grans, Camilla Figueiredo; Feriani, Daniele Jardim; Abssamra, Marcos Elias Vergilino; Rocha, Leandro Yanase; Carrozzi, Nicolle Martins; Mostarda, Cristiano; Figueroa, Diego Mendrot; Angelis, Kátia De; Irigoyen, Maria Cláudia; Rodrigues, Bruno

    2014-01-01

    Background Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. Objective To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Methods Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. Results The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Conclusion Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats. PMID:25014059

  9. Relationships between thermic effect of food, insulin resistance and autonomic nervous activity

    OpenAIRE

    Watanabe, Tomonori; Nomura, Masahiro; Nakayasu, Kimiko; Kawano, Tomohito; Ito, Susumu; Nakaya, Yutaka

    2006-01-01

    Background: The thermic effect of food (TEF) is higher in lean than in obese human subjects. Objective: Relationships between TEF and insulin resistance during meals, from the point of view of autonomic nervous activity, were evaluated. Methods : Autonomic nervous activity was evaluated in 20 young adults using the spectral analysis of heart rate variability from one hour before to two hours after a meal. Heart rate data were analyzed based on low frequency components (LF power, 0.04 - 0.15Hz...

  10. Relationships between thermic effect of food, insulin resistance and autonomic nervous activity.

    Science.gov (United States)

    Watanabe, Tomonori; Nomura, Masahiro; Nakayasu, Kimiko; Kawano, Tomohito; Ito, Susumu; Nakaya, Yutaka

    2006-02-01

    The thermic effect of food (TEF) is higher in lean than in obese human subjects. Relationships between TEF and insulin resistance during meals, from the point of view of autonomic nervous activity, were evaluated. Autonomic nervous activity was evaluated in 20 young adults using the spectral analysis of heart rate variability from one hour before to two hours after a meal. Heart rate data were analyzed based on low frequency components (LF power, 0.04-0.15 Hz), high frequency components (HF power, 0.15-0.40 Hz), and LF/HF ratios. Energy expenditure and the TEF were measured 30 min after a meal. Homeostasis model of insulin resistance index (HOMA-IR) was also measured. The LF/HF ratio was significantly increased 30 min after a meal (pinsulin sensitivity induces a poor response of sympathetic nervous activity in the postprandial phase and a reduction in postprandial energy expenditure.

  11. Cardiac autonomic regulation in response to a mixed meal is impaired in obese children and adolescents: the role played by insulin resistance.

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    Cozzolino, Domenico; Esposito, Katherine; Palmiero, Giuseppe; De Bellis, Annamaria; Furlan, Raffaello; Perrotta, Silverio; Perrone, Laura; Torella, Daniele; Miraglia del Giudice, Emanuele

    2014-09-01

    Obesity in children/adolescents has been associated with subtle cardiac abnormalities, including myocardial dysfunction and cardiac autonomic dysregulation at rest, both likely responsible for a higher mortality in adulthood. Food intake induces remarkable adjustments of cardiovascular autonomic activity in healthy subjects. The objective of the study was to evaluate in obese children/adolescents meal-induced cardiac autonomic response and the role played by insulin resistance. Sixty-eight obese and 30 matched normal-weight children/adolescents underwent blood sampling and cardiovascular autonomic analysis while recumbent and 20 minutes after a mixed meal ingestion. Spectrum analysis of the R-R interval and systolic blood pressure (SBP) variability provided the indices of sympathetic [low frequency (LFRR)] and vagal [high frequency (HFRR)] modulation of the sinoatrial node and the low frequency component of SBP. The homeostasis model assessment of insulin resistance served to separate insulin resistant (n = 35) from non insulin resistant (n = 33) obese children/adolescents. At baseline, C-reactive protein, the LFRR to HFRR ratio, SBP, and low frequency oscillatory component of SBP variability in obese children/adolescents were significantly (P meal-induced increase in the LFRR to HFRR ratio was significantly less than in controls and exaggeratedly scanty (or opposite) among insulin resistant subjects. The homeostasis model assessment of insulin resistance index strongly and inversely correlated (r = -0.871; P meal-induced changes in the LFRR to HFRR ratio among obese subjects. Autonomic modulation of the heart was impaired after eating in obese children/adolescents. This abnormality was exaggerated among insulin resistant subjects and strongly correlated with the degree of insulin resistance.

  12. A Neural Path Integration Mechanism for Adaptive Vector Navigation in Autonomous Agents

    DEFF Research Database (Denmark)

    Goldschmidt, Dennis; Dasgupta, Sakyasingha; Wörgötter, Florentin

    2015-01-01

    Animals show remarkable capabilities in navigating their habitat in a fully autonomous and energy-efficient way. In many species, these capabilities rely on a process called path integration, which enables them to estimate their current location and to find their way back home after long-distance...... of autonomous agent navigation, but it also reproduces various aspects of animal navigation. Finally, we discuss how the proposed path integration mechanism may be used as a scaffold for spatial learning in terms of vector navigation.......Animals show remarkable capabilities in navigating their habitat in a fully autonomous and energy-efficient way. In many species, these capabilities rely on a process called path integration, which enables them to estimate their current location and to find their way back home after long...

  13. Cardiorespiratory and autonomic interactions during snoring related resistive breathing.

    Science.gov (United States)

    Mateika, J H; Mitru, G

    2001-03-15

    We hypothesized that blood pressure (BP) is less during snoring as compared to periods of non-snoring in non-apneic individuals. Furthermore, we hypothesized that this reduction may be accompanied by a simultaneous decrease in sympathetic (SNSA) and parasympathetic (PNSA) nervous system activity and an increase in heart rate (HR). N/A. N/A. N/A. The variables mentioned above in addition to breathing frequency were measured in 9 subjects during NREM sleep. In addition, the lowest systolic (SBP) and diastolic blood pressure (DBP) during inspiration and the highest SBP and DBP during expiration was determined breath-by-breath from segments selected from each NREM cycle. Heart rate variability was used as a marker of autonomic nervous system activity. Our results showed that BP during snoring decreased compared to non-snoring and the breath-by-breath BP analysis suggested that this difference may have been mediated by changes in intrathoracic pressure. In conjunction with the decrease in BP, SNSA decreased and HR increased however PNSA remained constant. Thus, a decrease in PNSA was likely not the primary mechanism responsible for the HR response. We conclude that BP responses and SNSA during snoring are similar to that reported previously in non-snoring individuals. However, the causal mechanisms maybe different and manifested in other measures such as HR. Thus, nocturnal cardiovascular and autonomic function maybe uniquely different in non-apneic snoring individuals.

  14. Autonomous biomorphic robots as platforms for sensors

    Energy Technology Data Exchange (ETDEWEB)

    Tilden, M.; Hasslacher, B.; Mainieri, R.; Moses, J.

    1996-10-01

    The idea of building autonomous robots that can carry out complex and nonrepetitive tasks is an old one, so far unrealized in any meaningful hardware. Tilden has shown recently that there are simple, processor-free solutions to building autonomous mobile machines that continuously adapt to unknown and hostile environments, are designed primarily to survive, and are extremely resistant to damage. These devices use smart mechanics and simple (low component count) electronic neuron control structures having the functionality of biological organisms from simple invertebrates to sophisticated members of the insect and crab family. These devices are paradigms for the development of autonomous machines that can carry out directed goals. The machine then becomes a robust survivalist platform that can carry sensors or instruments. These autonomous roving machines, now in an early stage of development (several proof-of-concept prototype walkers have been built), can be developed so that they are inexpensive, robust, and versatile carriers for a variety of instrument packages. Applications are immediate and many, in areas as diverse as prosthetics, medicine, space, construction, nanoscience, defense, remote sensing, environmental cleanup, and biotechnology.

  15. Autonomous biomorphic robots as platforms for sensors

    International Nuclear Information System (INIS)

    Tilden, M.; Hasslacher, B.; Mainieri, R.; Moses, J.

    1996-01-01

    The idea of building autonomous robots that can carry out complex and nonrepetitive tasks is an old one, so far unrealized in any meaningful hardware. Tilden has shown recently that there are simple, processor-free solutions to building autonomous mobile machines that continuously adapt to unknown and hostile environments, are designed primarily to survive, and are extremely resistant to damage. These devices use smart mechanics and simple (low component count) electronic neuron control structures having the functionality of biological organisms from simple invertebrates to sophisticated members of the insect and crab family. These devices are paradigms for the development of autonomous machines that can carry out directed goals. The machine then becomes a robust survivalist platform that can carry sensors or instruments. These autonomous roving machines, now in an early stage of development (several proof-of-concept prototype walkers have been built), can be developed so that they are inexpensive, robust, and versatile carriers for a variety of instrument packages. Applications are immediate and many, in areas as diverse as prosthetics, medicine, space, construction, nanoscience, defense, remote sensing, environmental cleanup, and biotechnology

  16. Intracellular Calcium Dynamics and Autonomic Stimulation in Atrial Fibrillation: Mechanisms and Implications

    Directory of Open Access Journals (Sweden)

    Chung-Chuan Chou, MD

    2008-01-01

    Full Text Available While atrial fibrillation is characterized by the co-existence of multiple activation waves within the atria, rapid activations in the pulmonary veins play an important role for the initiation and maintenance of atrial fibrillation. In addition to reentry, non-reentrant mechanisms resulting from abnormal intracellular calcium handling and intracellular calcium overload can also be responsible for these rapid activations in the pulmonary veins. Meanwhile, alterations of autonomic tone, involving both the sympathetic and parasympathetic nervous system, have been implicated in initiating paroxysmal atrial fibrillation. But the effectiveness of autonomic modulation as an adjunctive therapeutic strategy to catheter ablation of atrial fibrillation has been inconsistent. The interactions between the autonomic nervous system and atrial fibrillation are more complex than currently understood and further mechanistic and clinical studies are warranted.

  17. High-Intensity Progressive Resistance Training Increases Strength With No Change in Cardiovascular Function and Autonomic Neural Regulation in Older Adults.

    Science.gov (United States)

    Kanegusuku, Hélcio; Queiroz, Andréia C; Silva, Valdo J; de Mello, Marco T; Ugrinowitsch, Carlos; Forjaz, Cláudia L

    2015-07-01

    The effects of high-intensity progressive resistance training (HIPRT) on cardiovascular function and autonomic neural regulation in older adults are unclear. To investigate this issue, 25 older adults were randomly divided into two groups: control (CON, N = 13, 63 ± 4 years; no training) and HIPRT (N = 12, 64 ± 4 years; 2 sessions/week, 7 exercises, 2–4 sets, 10–4 RM). Before and after four months, maximal strength, quadriceps cross-sectional area (QCSA), clinic and ambulatory blood pressures (BP), systemic hemodynamics, and cardiovascular autonomic modulation were measured. Maximal strength and QCSA increased in the HIPRT group and did not change in the CON group. Clinic and ambulatory BP, cardiac output, systemic vascular resistance, stroke volume, heart rate, and cardiac sympathovagal balance did not change in the HIPRT group or the CON group. In conclusion, HIPRT was effective at increasing muscle mass and strength without promoting changes in cardiovascular function or autonomic neural regulation.

  18. Both cell-autonomous mechanisms and hormones contribute to sexual development in vertebrates and insects.

    Science.gov (United States)

    Bear, Ashley; Monteiro, Antónia

    2013-08-01

    The differentiation of male and female characteristics in vertebrates and insects has long been thought to proceed via different mechanisms. Traditionally, vertebrate sexual development was thought to occur in two phases: a primary and a secondary phase, the primary phase involving the differentiation of the gonads, and the secondary phase involving the differentiation of other sexual traits via the influence of sex hormones secreted by the gonads. In contrast, insect sexual development was thought to depend exclusively on cell-autonomous expression of sex-specific genes. Recently, however, new evidence indicates that both vertebrates and insects rely on sex hormones as well as cell-autonomous mechanisms to develop sexual traits. Collectively, these new data challenge the traditional vertebrate definitions of primary and secondary sexual development, call for a redefinition of these terms, and indicate the need for research aimed at explaining the relative dependence on cell-autonomous versus hormonally guided sexual development in animals. © 2013 The Authors. BioEssays published by WILEY Periodicals, Inc.

  19. TPM and autonomous maintenance: case study in a metal mechanic company

    Directory of Open Access Journals (Sweden)

    Norberto Carvalho Biehl

    2015-12-01

    Full Text Available The purpose of this article was to describe a case of autonomous maintenance implementation in a pilot area of a metal mechanical industry company. The TPM – Total Productive Maintenance is a managerial technology that can help companies to reduce failures and breakages of machines. One of the most important issues of TPM is autonomous maintenance. The method of research was the case study. A program of twelve points was structured and adopted as stand-alone maintenance deployment guide. The program began in a pilot area, including three machining centers. The main results of the pilot program were: increasing by more than 700% the Mean Time between Failure, reducing by more than 40% in the Mean Time to Repair, as well as the consequent increase of more than five percentage points on the availability of the three machines and almost 60% reduction in the cost of maintenance materials. The main conclusion was that the TPM, and in particular the autonomous maintenance, can increase the efficiency of maintenance as strategic factor, which enhances the competitiveness of manufacturing in industrial companies.

  20. Cell-autonomous mechanisms of chronological aging in the yeast Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Anthony Arlia-Ciommo

    2014-05-01

    Full Text Available A body of evidence supports the view that the signaling pathways governing cellular aging – as well as mechanisms of their modulation by longevity-extending genetic, dietary and pharmacological interventions - are conserved across species. The scope of this review is to critically analyze recent advances in our understanding of cell-autonomous mechanisms of chronological aging in the budding yeast Saccharomyces cerevisiae. Based on our analysis, we propose a concept of a biomolecular network underlying the chronology of cellular aging in yeast. The concept posits that such network progresses through a series of lifespan checkpoints. At each of these checkpoints, the intracellular concentrations of some key intermediates and products of certain metabolic pathways - as well as the rates of coordinated flow of such metabolites within an intricate network of intercompartmental communications - are monitored by some checkpoint-specific ′′master regulator′′ proteins. The concept envisions that a synergistic action of these master regulator proteins at certain early-life and late-life checkpoints modulates the rates and efficiencies of progression of such processes as cell metabolism, growth, proliferation, stress resistance, macromolecular homeostasis, survival and death. The concept predicts that, by modulating these vital cellular processes throughout lifespan (i.e., prior to an arrest of cell growth and division, and following such arrest, the checkpoint-specific master regulator proteins orchestrate the development and maintenance of a pro- or anti-aging cellular pattern and, thus, define longevity of chronologically aging yeast.

  1. Cell-autonomous mechanisms of chronological aging in the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Arlia-Ciommo, Anthony; Leonov, Anna; Piano, Amanda; Svistkova, Veronika; Titorenko, Vladimir I

    2014-05-27

    A body of evidence supports the view that the signaling pathways governing cellular aging - as well as mechanisms of their modulation by longevity-extending genetic, dietary and pharmacological interventions - are conserved across species. The scope of this review is to critically analyze recent advances in our understanding of cell-autonomous mechanisms of chronological aging in the budding yeast Saccharomyces cerevisiae . Based on our analysis, we propose a concept of a biomolecular network underlying the chronology of cellular aging in yeast. The concept posits that such network progresses through a series of lifespan checkpoints. At each of these checkpoints, the intracellular concentrations of some key intermediates and products of certain metabolic pathways - as well as the rates of coordinated flow of such metabolites within an intricate network of intercompartmental communications - are monitored by some checkpoint-specific "master regulator" proteins. The concept envisions that a synergistic action of these master regulator proteins at certain early-life and late-life checkpoints modulates the rates and efficiencies of progression of such processes as cell metabolism, growth, proliferation, stress resistance, macromolecular homeostasis, survival and death. The concept predicts that, by modulating these vital cellular processes throughout lifespan (i.e., prior to an arrest of cell growth and division, and following such arrest), the checkpoint-specific master regulator proteins orchestrate the development and maintenance of a pro- or anti-aging cellular pattern and, thus, define longevity of chronologically aging yeast.

  2. Mechanical deployment system on aries an autonomous mobile robot

    International Nuclear Information System (INIS)

    Rocheleau, D.N.

    1995-01-01

    ARIES (Autonomous Robotic Inspection Experimental System) is under development for the Department of Energy (DOE) to survey and inspect drums containing low-level radioactive waste stored in warehouses at DOE facilities. This paper focuses on the mechanical deployment system-referred to as the camera positioning system (CPS)-used in the project. The CPS is used for positioning four identical but separate camera packages consisting of vision cameras and other required sensors such as bar-code readers and light stripe projectors. The CPS is attached to the top of a mobile robot and consists of two mechanisms. The first is a lift mechanism composed of 5 interlocking rail-elements which starts from a retracted position and extends upward to simultaneously position 3 separate camera packages to inspect the top three drums of a column of four drums. The second is a parallelogram special case Grashof four-bar mechanism which is used for positioning a camera package on drums on the floor. Both mechanisms are the subject of this paper, where the lift mechanism is discussed in detail

  3. An autonomous recovery mechanism against optical distribution network failures in EPON

    Science.gov (United States)

    Liem, Andrew Tanny; Hwang, I.-Shyan; Nikoukar, AliAkbar

    2014-10-01

    Ethernet Passive Optical Network (EPON) is chosen for servicing diverse applications with higher bandwidth and Quality-of-Service (QoS), starting from Fiber-To-The-Home (FTTH), FTTB (business/building) and FTTO (office). Typically, a single OLT can provide services to both residential and business customers on the same Optical Line Terminal (OLT) port; thus, any failures in the system will cause a great loss for both network operators and customers. Network operators are looking for low-cost and high service availability mechanisms that focus on the failures that occur within the drop fiber section because the majority of faults are in this particular section. Therefore, in this paper, we propose an autonomous recovery mechanism that provides protection and recovery against Drop Distribution Fiber (DDF) link faults or transceiver failure at the ONU(s) in EPON systems. In the proposed mechanism, the ONU can automatically detect any signal anomalies in the physical layer or transceiver failure, switching the working line to the protection line and sending the critical event alarm to OLT via its neighbor. Each ONU has a protection line, which is connected to the nearest neighbor ONU, and therefore, when failure occurs, the ONU can still transmit and receive data via the neighbor ONU. Lastly, the Fault Dynamic Bandwidth Allocation for recovery mechanism is presented. Simulation results show that our proposed autonomous recovery mechanism is able to maintain the overall QoS performance in terms of mean packet delay, system throughput, packet loss and EF jitter.

  4. Insecticide resistance and resistance mechanisms in bed bugs, Cimex spp. (Hemiptera: Cimicidae).

    Science.gov (United States)

    Dang, Kai; Doggett, Stephen L; Veera Singham, G; Lee, Chow-Yang

    2017-06-29

    The worldwide resurgence of bed bugs [both Cimex lectularius L. and Cimex hemipterus (F.)] over the past two decades is believed in large part to be due to the development of insecticide resistance. The transcriptomic and genomic studies since 2010, as well as morphological, biochemical and behavioral studies, have helped insecticide resistance research on bed bugs. Multiple resistance mechanisms, including penetration resistance through thickening or remodelling of the cuticle, metabolic resistance by increased activities of detoxification enzymes (e.g. cytochrome P450 monooxygenases and esterases), and knockdown resistance by kdr mutations, have been experimentally identified as conferring insecticide resistance in bed bugs. Other candidate resistance mechanisms, including behavioral resistance, some types of physiological resistance (e.g. increasing activities of esterases by point mutations, glutathione S-transferase, target site insensitivity including altered AChEs, GABA receptor insensitivity and altered nAChRs), symbiont-mediated resistance and other potential, yet undiscovered mechanisms may exist. This article reviews recent studies of resistance mechanisms and the genes governing insecticide resistance, potential candidate resistance mechanisms, and methods of monitoring insecticide resistance in bed bugs. This article provides an insight into the knowledge essential for the development of both insecticide resistance management (IRM) and integrated pest management (IPM) strategies for successful bed bug management.

  5. Mechanisms of Candida biofilm drug resistance

    Science.gov (United States)

    Taff, Heather T; Mitchell, Kaitlin F; Edward, Jessica A; Andes, David R

    2013-01-01

    Candida commonly adheres to implanted medical devices, growing as a resilient biofilm capable of withstanding extraordinarily high antifungal concentrations. As currently available antifungals have minimal activity against biofilms, new drugs to treat these recalcitrant infections are urgently needed. Recent investigations have begun to shed light on the mechanisms behind the profound resistance associated with the biofilm mode of growth. This resistance appears to be multifactorial, involving both mechanisms similar to conventional, planktonic antifungal resistance, such as increased efflux pump activity, as well as mechanisms specific to the biofilm lifestyle. A unique biofilm property is the production of an extracellular matrix. Two components of this material, β-glucan and extracellular DNA, promote biofilm resistance to multiple antifungals. Biofilm formation also engages several stress response pathways that impair the activity of azole drugs. Resistance within a biofilm is often heterogeneous, with the development of a subpopulation of resistant persister cells. In this article we review the molecular mechanisms underlying Candida biofilm antifungal resistance and their relative contributions during various growth phases. PMID:24059922

  6. MECHANICAL DESIGN OF AN AUTONOMOUS MARINE ROBOTIC SYSTEM FOR INTERACTION WITH DIVERS

    Directory of Open Access Journals (Sweden)

    Nikola Stilinović

    2016-09-01

    Full Text Available SCUBA diving, professional or recreational, remains one of the most hazardous activities known by man, mostly due to the fact that the human survival in the underwater environment requires use of technical equipment such as breathing regulators. Loss of breathing gas supply, burst eardrum, decompression sickness and nitrogen narcosis are just a few problems which can occur during an ordinary dive and result in injuries, long-term illnesses or even death. Most common way to reduce the risk of diving is to dive in pairs, thus allowing divers to cooperate with each other and react when uncommon situation occurs. Having the ability to react before an unwanted situation happens would improve diver safety. This paper describes an autonomous marine robotic system that replaces a human dive buddy. Such a robotic system, developed within an FP7 project “CADDY – Cognitive Autonomous Diving Buddy” provides a symbiotic link between robots and human divers in the underwater. The proposed concept consists of a diver, an autonomous underwater vehicle (AUV Buddy and an autonomous surface vehicle (ASV PlaDyPos, acting within a cooperative network linked via an acoustic communication channel. This is a first time that an underwater human-robot system of such a scale has ever been developed. In this paper, focus is put on mechanical characteristics of the robotic vehicles.

  7. Exploring the genetics and non-cell autonomous mechanisms underlying ALS/FTLD.

    Science.gov (United States)

    Chen, Hongbo; Kankel, Mark W; Su, Susan C; Han, Steve W S; Ofengeim, Dimitry

    2018-03-01

    Although amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, was first described in 1874, a flurry of genetic discoveries in the last 10 years has markedly increased our understanding of this disease. These findings have not only enhanced our knowledge of mechanisms leading to ALS, but also have revealed that ALS shares many genetic causes with another neurodegenerative disease, frontotemporal lobar dementia (FTLD). In this review, we survey how recent genetic studies have bridged our mechanistic understanding of these two related diseases and how the genetics behind ALS and FTLD point to complex disorders, implicating non-neuronal cell types in disease pathophysiology. The involvement of non-neuronal cell types is consistent with a non-cell autonomous component in these diseases. This is further supported by studies that identified a critical role of immune-associated genes within ALS/FTLD and other neurodegenerative disorders. The molecular functions of these genes support an emerging concept that various non-autonomous functions are involved in neurodegeneration. Further insights into such a mechanism(s) will ultimately lead to a better understanding of potential routes of therapeutic intervention. Facts ALS and FTLD are severe neurodegenerative disorders on the same disease spectrum. Multiple cellular processes including dysregulation of RNA homeostasis, imbalance of proteostasis, contribute to ALS/FTLD pathogenesis. Aberrant function in non-neuronal cell types, including microglia, contributes to ALS/FTLD. Strong neuroimmune and neuroinflammatory components are associated with ALS/FTLD patients. Open Questions Why can patients with similar mutations have different disease manifestations, i.e., why do C9ORF72 mutations lead to motor neuron loss in some patients while others exhibit loss of neurons in the frontotemporal lobe? Do ALS causal mutations result in microglial dysfunction and contribute to ALS/FTLD pathology? How do microglia

  8. Relationship of autonomic imbalance and circadian disruption with obesity and type 2 diabetes in resistant hypertensive patients

    Directory of Open Access Journals (Sweden)

    Figueiredo Márcio J

    2011-03-01

    Full Text Available Abstract Background Hypertension, diabetes and obesity are not isolated findings, but a series of interacting interactive physiologic derangements. Taking into account genetic background and lifestyle behavior, AI (autonomic imbalance could be a common root for RHTN (resistant hypertension or RHTN plus type 2 diabetes (T2D comorbidity development. Moreover, circadian disruption can lead to metabolic and vasomotor impairments such as obesity, insulin resistance and resistant hypertension. In order to better understand the triggered emergence of obesity and T2D comorbidity in resistant hypertension, we investigated the pattern of autonomic activity in the circadian rhythm in RHTN with and without type 2 diabetes (T2D, and its relationship with serum adiponectin concentration. Methods Twenty five RHTN patients (15 non-T2D and 10 T2D, 15 males, 10 females; age range 34 to 70 years were evaluated using the following parameters: BMI (body mass index, biochemical analysis, serum adiponectinemia, echocardiogram and ambulatory electrocardiograph heart rate variability (HRV in time and frequency domains stratified into three periods: 24 hour, day time and night time. Results Both groups demonstrated similar characteristics despite of the laboratory analysis concerning T2D like fasting glucose, HbA1c levels and hypertriglyceridemia. Both groups also revealed disruption of the circadian rhythm: inverted sympathetic and parasympathetic tones during day (parasympathetic > sympathetic tone and night periods (sympathetic > parasympathetic tone. T2D group had increased BMI and serum triglyceride levels (mean 33.7 ± 4.0 vs 26.6 ± 3.7 kg/m2 - p = 0.00; 254.8 ± 226.4 vs 108.6 ± 48.7 mg/dL - p = 0.04, lower levels of adiponectin (6729.7 ± 3381.5 vs 10911.5 ± 5554.0 ng/mL - p = 0.04 and greater autonomic imbalance evaluated by HRV parameters in time domain compared to non-T2D RHTN patients. Total patients had HRV correlated positively with serum adiponectin (r

  9. Analysis and modeling of resistive switching mechanisms oriented to resistive random-access memory

    International Nuclear Information System (INIS)

    Huang Da; Wu Jun-Jie; Tang Yu-Hua

    2013-01-01

    With the progress of the semiconductor industry, the resistive random-access memory (RAM) has drawn increasing attention. The discovery of the memristor has brought much attention to this study. Research has focused on the resistive switching characteristics of different materials and the analysis of resistive switching mechanisms. We discuss the resistive switching mechanisms of different materials in this paper and analyze the differences of those mechanisms from the view point of circuitry to establish their respective circuit models. Finally, simulations are presented. We give the prospect of using different materials in resistive RAM on account of their resistive switching mechanisms, which are applied to explain their resistive switchings

  10. Diabetic retinopathy is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients

    International Nuclear Information System (INIS)

    Anan, Futoshi; Takayuki, Masaki; Takahashi, Naohiko; Nakagawa, Mikiko; Eshima, Nobuoki; Saikawa, Tetsunori; Yoshimatsu, Hironobu

    2009-01-01

    Diabetic retinopathy (DR) and cardiovascular autonomic dysfunction are associated with high mortality in type 2 diabetic patients. This preliminary study was therefore designed to test the hypothesis that DR is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients without insulin treatment. Seventy persons were diagnosed to have type 2 diabetes in the examination from June 2004 to May 2006. The study group consisted of 29 type 2 diabetic patients with DR (age: 58±6 years, mean±standard deviation (s.d.)) and 41 type 2 diabetic patients with no DR (NDR) (n=41, 58±5 years). Cardiovascular autonomic function was assessed by baroreflex sensitivity (BRS), heart rate variability, plasma norepinephrine concentration and cardiac 123 I-metaiodobenzylguanidine (MIBG) scintigraphic findings. DR patients had lower BRS, early and delayed 123 I-MIBG myocardial uptake values and higher percent washout rate (WR) of 123 I-MIBG than the NDR patients. With respect to metabolic findings, DR patients had higher fasting plasma insulin concentration (P 123 I-MIBG (P 123 I-MIBG are independently associated with DR in Japanese patients with type 2 diabetes mellitus. (author)

  11. The negative-differential-resistance (NDR) mechanism of a hydroelastic microfluidic oscillator

    International Nuclear Information System (INIS)

    Xia, H M; Wu, J W; Wang, Z P

    2017-01-01

    A microfluidic oscillator is of interest because it converts a stable laminar flow to oscillatory flow, especially in view of the fact that turbulence is typically absent in miniaturized fluidic devices. One important design approach is to utilize hydroelastic effect-induced autonomous oscillations to modify the flow, so to reduce the reliance on external controllers. However, as complex fluid-structure interactions are involved, the prediction of its mechanism is rather challenging. Here, we present a simple equivalent circuit model and investigate the negative-differential-resistance (NDR) mechanism of a hydroelastic microfluidic oscillator. We show that a variety of complex flow behaviors including the onset of oscillation, formation of different oscillation patterns, collapse of the channel, etc can be well explained by this model. It provides a generic approach for construction of microfluidic NDR oscillators, following which a new design is also proposed. Relevant findings give more insights into the hydroelastic instability problems in microfluidics, and enrich the study of microfluidic flow control devices based on the electric circuit theory. (paper)

  12. The Role of the Autonomic Nervous System in the Pathophysiology of Obesity

    Directory of Open Access Journals (Sweden)

    Daniela Guarino

    2017-09-01

    Full Text Available Obesity is reaching epidemic proportions globally and represents a major cause of comorbidities, mostly related to cardiovascular disease. The autonomic nervous system (ANS dysfunction has a two-way relationship with obesity. Indeed, alterations of the ANS might be involved in the pathogenesis of obesity, acting on different pathways. On the other hand, the excess weight induces ANS dysfunction, which may be involved in the haemodynamic and metabolic alterations that increase the cardiovascular risk of obese individuals, i.e., hypertension, insulin resistance and dyslipidemia. This article will review current evidence about the role of the ANS in short-term and long-term regulation of energy homeostasis. Furthermore, an increased sympathetic activity has been demonstrated in obese patients, particularly in the muscle vasculature and in the kidneys, possibily contributing to increased cardiovascular risk. Selective leptin resistance, obstructive sleep apnea syndrome, hyperinsulinemia and low ghrelin levels are possible mechanisms underlying sympathetic activation in obesity. Weight loss is able to reverse metabolic and autonomic alterations associated with obesity. Given the crucial role of autonomic dysfunction in the pathophysiology of obesity and its cardiovascular complications, vagal nerve modulation and sympathetic inhibition may serve as therapeutic targets in this condition.

  13. Pharmaceutical Approaches to Target Antibiotic Resistance Mechanisms.

    Science.gov (United States)

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

    2017-10-26

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

  14. Caenorhabditis elegans as a model system for studying non-cell-autonomous mechanisms in protein-misfolding diseases

    Directory of Open Access Journals (Sweden)

    Carmen I. Nussbaum-Krammer

    2014-01-01

    Full Text Available Caenorhabditis elegans has a number of distinct advantages that are useful for understanding the basis for cellular and organismal dysfunction underlying age-associated diseases of protein misfolding. Although protein aggregation, a key feature of human neurodegenerative diseases, has been typically explored in vivo at the single-cell level using cells in culture, there is now increasing evidence that proteotoxicity has a non-cell-autonomous component and is communicated between cells and tissues in a multicellular organism. These discoveries have opened up new avenues for the use of C. elegans as an ideal animal model system to study non-cell-autonomous proteotoxicity, prion-like propagation of aggregation-prone proteins, and the organismal regulation of stress responses and proteostasis. This Review focuses on recent evidence that C. elegans has mechanisms to transmit certain classes of toxic proteins between tissues and a complex stress response that integrates and coordinates signals from single cells and tissues across the organism. These findings emphasize the potential of C. elegans to provide insights into non-cell-autonomous proteotoxic mechanisms underlying age-related protein-misfolding diseases.

  15. Bedaquiline resistance: Its emergence, mechanism and prevention.

    Science.gov (United States)

    Nguyen, Thi Van Anh; Anthony, Richard M; Bañuls, Anne-Laure; Vu, Dinh Hoa; Alffenaar, Jan-Willem C

    2017-11-08

    Bedaquiline, a new anti-tuberculosis drug, has already been used in more than 50 countries. The emergence of bedaquiline resistance is alarming, as it may result in the rapid loss of this new drug. This paper aims to review currently identified mechanisms of resistance, the emergence of bedaquiline resistance, and discuss strategies to delay the resistance acquisition. In vitro and clinical studies as well as reports from the compassionate use have identified the threat of bedaquiline resistance and cross-resistance with clofazimine, emphasizing the crucial need for the systematic surveillance of resistance. Currently known mechanisms of resistance include mutations within the atpE, Rv0678 and pepQ genes. The development of standardized drug susceptibility testing (DST) for bedaquiline is urgently needed.Understanding any target and non-target based mechanisms is essential to minimize the resistance development and treatment failure, help to develop appropriate DST for bedaquiline and genetic based resistance screening. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  16. Study on a mechanical snubber with an adjustment mechanism for resisting force

    International Nuclear Information System (INIS)

    Ohmata, Kenichiro; Miyanaga, Hiroyuki.

    1991-01-01

    The mechanical snubber is an earthquakeproof device for a piping system under particular circumstances such as high temperature and radioactivity. It restrains the piping system by a strong resisting force during an earthquake. This strong force can cause elastic failure of grooves on a brake disk, where steel balls are placed. In this report, an improved mechanical snubber having an adjustment mechanism for resisting force is proposed in order to obtain a mechanical snubber which has almost the same restraint effect and less resisting force in comparison with a conventional mechanical snubber. The resisting force characteristics and the restraint effect of the improved mechanical snubber applied to a simple beam are discussed both numerically and experimentally. The digital simulations are carried out using the Continuous System Simulation Language (CSSL). (author)

  17. THE STUDY OF THE AUTONOMOUS SYNCHRONOUS GENERATOR MODES

    Directory of Open Access Journals (Sweden)

    V. S. Safaryan

    2017-01-01

    Full Text Available The importance of the problem of the static stability of the stationary mode of the power system for its operation is extremely high. The investigation of the static stability of the power system is a subject of a number of works, but the problems of static stability of the stationary points of an autonomous synchronous generator are given little attention. The article considers transient and resonant (stationary modes of the generator under active-inductive and active-capacitive loads. Mathematical model of transients in a natural form and in the coordinate system d, q are plotted. It is discovered that the mathematical model of the transition process of an autonomous synchronous generator is identical to the mathematical model of the transition process of the synchronous machine under three-phase short circuit. Electromagnetic transients of an autonomous synchronous generator are described by a system of linear autonomous differential equations with constant coefficients. However, the equivalent circuit of a generator contains dependent sources. We investigated the stability of stationary motion of an autonomous synchronous generator at a given angular velocity of rotation of the rotor. The condition for the existence and stability of stationary points of an autonomous synchronous generator is derived. The condition for the existence of stationary points of such a generator does not depend on the active load resistance and stator windings, and inductance of the rotor. The determining of stationary points of the generator is reduced to finding roots of a polynomial of the fourth degree. The graphs of electromagnetic torque dependencies on the angular velocity of rotation of the rotor (mechanical characteristics are plotted. The equivalent circuits, corresponding to the equations of the transition process of an autonomous synchronous generator, are featured as well.

  18. Efflux pumps as antimicrobial resistance mechanisms.

    Science.gov (United States)

    Poole, Keith

    2007-01-01

    Antibiotic resistance continues to hamper antimicrobial chemotherapy of infectious disease, and while biocide resistance outside of the laboratory is as yet unrealized, in vitro and in vivo episodes of reduced biocide susceptibility are not uncommon. Efflux mechanisms, both drug-specific and multidrug, are important determinants of intrinsic and/or acquired resistance to these antimicrobials in important human pathogens. Multidrug efflux mechanisms are generally chromosome-encoded, with their expression typically resultant from mutations in regulatory genes, while drug-specific efflux mechanisms are encoded by mobile genetic elements whose acquisition is sufficient for resistance. While it has been suggested that drug-specific efflux systems originated from efflux determinants of self-protection in antibiotic-producing Actinomycetes, chromosomal multidrug efflux determinants, at least in Gram-negative bacteria, are appreciated as having an intended housekeeping function unrelated to drug export and resistance. Thus, it will be important to elucidate the intended natural function of these efflux mechanisms in order, for example, to anticipate environmental conditions or circumstances that might promote their expression and, so, compromise antimicrobial chemotherapy. Given the clinical significance of antimicrobial exporters, it is clear that efflux must be considered in formulating strategies for treatment of drug-resistant infections, both in the development of new agents, for example, less impacted by efflux or in targeting efflux directly with efflux inhibitors.

  19. Mechanisms of Antibiotic Resistance

    Science.gov (United States)

    Munita, Jose M.; Arias, Cesar A.

    2015-01-01

    Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic “attack” is the prime example of bacterial adaptation and the pinnacle of evolution. “Survival of the fittest” is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice providing specific examples in relevant bacterial pathogens. PMID:27227291

  20. Insulin resistance and circadian rhythm of cardiac autonomic modulation

    Directory of Open Access Journals (Sweden)

    Cai Jianwen

    2010-12-01

    Full Text Available Abstract Background Insulin resistance (IR has been associated with cardiovascular diseases (CVD. Heart rate variability (HRV, an index of cardiac autonomic modulation (CAM, is also associated with CVD mortality and CVD morbidity. Currently, there are limited data about the impairment of IR on the circadian pattern of CAM. Therefore, we conducted this investigation to exam the association between IR and the circadian oscillations of CAM in a community-dwelling middle-aged sample. Method Homeostasis models of IR (HOMA-IR, insulin, and glucose were used to assess IR. CAM was measured by HRV analysis from a 24-hour electrocardiogram. Two stage modeling was used in the analysis. In stage one, for each individual we fit a cosine periodic model based on the 48 segments of HRV data. We obtained three individual-level cosine parameters that quantity the circadian pattern: mean (M, measures the overall average of a HRV index; amplitude (Â, measures the amplitude of the oscillation of a HRV index; and acrophase time (θ, measures the timing of the highest oscillation. At the second stage, we used a random-effects-meta-analysis to summarize the effects of IR variables on the three circadian parameters of HRV indices obtained in stage one of the analysis. Results In persons without type diabetes, the multivariate adjusted β (SE of log HOMA-IR and M variable for HRV were -0.251 (0.093, -0.245 (0.078, -0.19 (0.06, -4.89 (1.76, -3.35 (1.31, and 2.14 (0.995, for log HF, log LF, log VLF, SDNN, RMSSD and HR, respectively (all P Conclusion Elevated IR, among non-diabetics significantly impairs the overall mean levels of CAM. However, the  or θ of CAM were not significantly affected by IR, suggesting that the circadian mechanisms of CAM are not impaired. However, among persons with type 2 diabetes, a group clinically has more severe form of IR, the adverse effects of increased IR on all three HRV circadian parameters are much larger.

  1. A hybrid online scheduling mechanism with revision and progressive techniques for autonomous Earth observation satellite

    Science.gov (United States)

    Li, Guoliang; Xing, Lining; Chen, Yingwu

    2017-11-01

    The autonomicity of self-scheduling on Earth observation satellite and the increasing scale of satellite network attract much attention from researchers in the last decades. In reality, the limited onboard computational resource presents challenge for the online scheduling algorithm. This study considered online scheduling problem for a single autonomous Earth observation satellite within satellite network environment. It especially addressed that the urgent tasks arrive stochastically during the scheduling horizon. We described the problem and proposed a hybrid online scheduling mechanism with revision and progressive techniques to solve this problem. The mechanism includes two decision policies, a when-to-schedule policy combining periodic scheduling and critical cumulative number-based event-driven rescheduling, and a how-to-schedule policy combining progressive and revision approaches to accommodate two categories of task: normal tasks and urgent tasks. Thus, we developed two heuristic (re)scheduling algorithms and compared them with other generally used techniques. Computational experiments indicated that the into-scheduling percentage of urgent tasks in the proposed mechanism is much higher than that in periodic scheduling mechanism, and the specific performance is highly dependent on some mechanism-relevant and task-relevant factors. For the online scheduling, the modified weighted shortest imaging time first and dynamic profit system benefit heuristics outperformed the others on total profit and the percentage of successfully scheduled urgent tasks.

  2. Autonomous generator based on Ni-Mn-Ga microactuator as a frequency selective element

    Directory of Open Access Journals (Sweden)

    Barandiaran J.M.

    2013-01-01

    Full Text Available In this work, we suggest the temperature-induced resistivity change at the martensitic transformation in the Ni-Mn-Ga ferromagnetic shape memory alloy as a driving mechanism enabling periodic signal generation. We demonstrated its practical importance by a design of the prototype of a low-frequency autonomous generator. A prominent feature of this new generator is a control of its frequency by the external magnetic field.

  3. DeltaFosB induces osteosclerosis and decreases adipogenesis by two independent cell-autonomous mechanisms

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Sabatakos, George; Chiusaroli, Riccardo

    2004-01-01

    establishes that the skeletal phenotype is cell autonomous to the osteoblast lineage and independent of adipocyte formation. It also strongly suggests that the decreased fat phenotype of NSE-DeltaFosB mice is independent of the changes in the osteoblast lineage. In vitro, overexpression of Delta......Osteoblasts and adipocytes may develop from common bone marrow mesenchymal precursors. Transgenic mice overexpressing DeltaFosB, an AP-1 transcription factor, under the control of the neuron-specific enolase (NSE) promoter show both markedly increased bone formation and decreased adipogenesis...... of DeltaFosB on adipocyte differentiation appears to occur at early stages of stem cell commitment, affecting C/EBPbeta functions. It is concluded that the changes in osteoblast and adipocyte differentiation in DeltaFosB transgenic mice result from independent cell-autonomous mechanisms....

  4. Autonomic cardiac innervation

    Science.gov (United States)

    Hasan, Wohaib

    2013-01-01

    Autonomic cardiac neurons have a common origin in the neural crest but undergo distinct developmental differentiation as they mature toward their adult phenotype. Progenitor cells respond to repulsive cues during migration, followed by differentiation cues from paracrine sources that promote neurochemistry and differentiation. When autonomic axons start to innervate cardiac tissue, neurotrophic factors from vascular tissue are essential for maintenance of neurons before they reach their targets, upon which target-derived trophic factors take over final maturation, synaptic strength and postnatal survival. Although target-derived neurotrophins have a central role to play in development, alternative sources of neurotrophins may also modulate innervation. Both developing and adult sympathetic neurons express proNGF, and adult parasympathetic cardiac ganglion neurons also synthesize and release NGF. The physiological function of these “non-classical” cardiac sources of neurotrophins remains to be determined, especially in relation to autocrine/paracrine sustenance during development.   Cardiac autonomic nerves are closely spatially associated in cardiac plexuses, ganglia and pacemaker regions and so are sensitive to release of neurotransmitter, neuropeptides and trophic factors from adjacent nerves. As such, in many cardiac pathologies, it is an imbalance within the two arms of the autonomic system that is critical for disease progression. Although this crosstalk between sympathetic and parasympathetic nerves has been well established for adult nerves, it is unclear whether a degree of paracrine regulation occurs across the autonomic limbs during development. Aberrant nerve remodeling is a common occurrence in many adult cardiovascular pathologies, and the mechanisms regulating outgrowth or denervation are disparate. However, autonomic neurons display considerable plasticity in this regard with neurotrophins and inflammatory cytokines having a central regulatory

  5. On the development a pneumatic four-legged mechanism autonomous vertical wall climbing robot

    International Nuclear Information System (INIS)

    Mohamad Shukri Zainal Abidin; Shamsudin H.M. Amin . shukri@suria.fke.utm.my

    1999-01-01

    The paper describes the design of a prototype legged mechanism together with suction mechanism, the mechanical design, on-board controller and an initial performance test. The design is implemented in the form of a pneumatically powered multi-legged robot equipped with suction pads at the sole of the feet for wall climbing purpose. The whole mechanism and suction system is controlled by controller which is housed on-board the robot. The gait of the motion depended on the logic control patterns as dictated by the controller. The robot is equipped with sensors both at the front and rear ends that function as an obstacle avoidance facility. Once objects are detected, signals are sent to the controller to start an evasive action that is to move in the opposite direction. The mechanism has been tested and initial results have shown promising potential for an autonomous mobile. (Author)

  6. Autonomous assembly of synthetic oligonucleotides built from an expanded DNA alphabet. Total synthesis of a gene encoding kanamycin resistance

    Directory of Open Access Journals (Sweden)

    Kristen K. Merritt

    2014-10-01

    Full Text Available Background: Many synthetic biologists seek to increase the degree of autonomy in the assembly of long DNA (L-DNA constructs from short synthetic DNA fragments, which are today quite inexpensive because of automated solid-phase synthesis. However, the low information density of DNA built from just four nucleotide “letters”, the presence of strong (G:C and weak (A:T nucleobase pairs, the non-canonical folded structures that compete with Watson–Crick pairing, and other features intrinsic to natural DNA, generally prevent the autonomous assembly of short single-stranded oligonucleotides greater than a dozen or so.Results: We describe a new strategy to autonomously assemble L-DNA constructs from fragments of synthetic single-stranded DNA. This strategy uses an artificially expanded genetic information system (AEGIS that adds nucleotides to the four (G, A, C, and T found in standard DNA by shuffling hydrogen-bonding units on the nucleobases, all while retaining the overall Watson–Crick base-pairing geometry. The added information density allows larger numbers of synthetic fragments to self-assemble without off-target hybridization, hairpin formation, and non-canonical folding interactions. The AEGIS pairs are then converted into standard pairs to produce a fully natural L-DNA product. Here, we report the autonomous assembly of a gene encoding kanamycin resistance using this strategy. Synthetic fragments were built from a six-letter alphabet having two AEGIS components, 5-methyl-2’-deoxyisocytidine and 2’-deoxyisoguanosine (respectively S and B, at their overlapping ends. Gaps in the overlapped assembly were then filled in using DNA polymerases, and the nicks were sealed by ligase. The S:B pairs in the ligated construct were then converted to T:A pairs during PCR amplification. When cloned into a plasmid, the product was shown to make Escherichia coli resistant to kanamycin. A parallel study that attempted to assemble similarly sized genes

  7. Mechanisms of antibiotic resistance in Staphylococcus aureus.

    Science.gov (United States)

    Pantosti, Annalisa; Sanchini, Andrea; Monaco, Monica

    2007-06-01

    Staphylococcus aureus can exemplify better than any other human pathogen the adaptive evolution of bacteria in the antibiotic era, as it has demonstrated a unique ability to quickly respond to each new antibiotic with the development of a resistance mechanism, starting with penicillin and methicillin, until the most recent, linezolid and daptomycin. Resistance mechanisms include enzymatic inactivation of the antibiotic (penicillinase and aminoglycoside-modification enzymes), alteration of the target with decreased affinity for the antibiotic (notable examples being penicillin-binding protein 2a of methicillin-resistant S. aureus and D-Ala-D-Lac of peptidoglycan precursors of vancomycin-resistant strains), trapping of the antibiotic (for vancomycin and possibly daptomycin) and efflux pumps (fluoroquinolones and tetracycline). Complex genetic arrays (staphylococcal chromosomal cassette mec elements or the vanA operon) have been acquired by S. aureus through horizontal gene transfer, while resistance to other antibiotics, including some of the most recent ones (e.g., fluoroquinolones, linezolid and daptomycin) have developed through spontaneous mutations and positive selection. Detection of the resistance mechanisms and their genetic basis is an important support to antibiotic susceptibility surveillance in S. aureus.

  8. Mechanisms of insulin resistance in obesity

    Science.gov (United States)

    Ye, Jianping

    2014-01-01

    Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy. PMID:23471659

  9. Mechanism of quinolone resistance in anaerobic bacteria.

    Science.gov (United States)

    Oh, H; Edlund, C

    2003-06-01

    Several recently developed quinolones have excellent activity against a broad range of aerobic and anaerobic bacteria and are thus potential drugs for the treatment of serious anaerobic and mixed infections. Resistance to quinolones is increasing worldwide, but is still relatively infrequent among anaerobes. Two main mechanisms, alteration of target enzymes (gyrase and topoisomerase IV) caused by chromosomal mutations in encoding genes, or reduced intracellular accumulation due to increased efflux of the drug, are associated with quinolone resistance. These mechanisms have also been found in anaerobic species. High-level resistance to the newer broad-spectrum quinolones often requires stepwise mutations in target genes. The increasing emergence of resistance among anaerobes may be a consequence of previous widespread use of quinolones, which may have enriched first-step mutants in the intestinal tract. Quinolone resistance in the Bacteroides fragilis group strains is strongly correlated with amino acid substitutions at positions 82 and 86 in GyrA (equivalent to positions 83 and 87 of Escherichia coli). Several studies have indicated that B. fragilis group strains possess efflux pump systems that actively expel quinolones, leading to resistance. DNA gyrase seems also to be the primary target for quinolones in Clostridium difficile, since amino acid substitutions in GyrA and GyrB have been detected in resistant strains. To what extent other mechanisms, such as mutational events in other target genes or alterations in outer-membrane proteins, contribute to resistance among anaerobes needs to be further investigated.

  10. Mechanisms of drug resistance in cancer cells

    International Nuclear Information System (INIS)

    Iqbal, M.P.

    2003-01-01

    Development of drug resist chemotherapy. For the past several years, investigators have been striving hard to unravel mechanisms of drug resistance in cancer cells. Using different experimental models of cancer, some of the major mechanisms of drug resistance identified in mammalian cells include: (a) Altered transport of the drug (decreased influx of the drug; increased efflux of the drug (role of P-glycoprotein; role of polyglutamation; role of multiple drug resistance associated protein)), (b) Increase in total amount of target enzyme/protein (gene amplification), (c) alteration in the target enzyme/protein (low affinity enzyme), (d) Elevation of cellular glutathione, (e) Inhibition of drug-induced apoptosis (mutation in p53 tumor suppressor gene; increased expression of bcl-xl gene). (author)

  11. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    Free fatty acids are known to play a key role in promoting loss of insulin sensitivity, thereby causing insulin resistance and type 2 diabetes. However, the underlying mechanism involved is still unclear. In searching for the cause of the mechanism, it has been found that palmitate inhibits insulin receptor (IR) gene expression, ...

  12. Mechanisms of resistance to alkylating agents

    OpenAIRE

    Damia, G.; D‘Incalci, M.

    1998-01-01

    Alkylating agents are the most widely used anticancer drugs whose main target is the DNA, although how exactly the DNA lesions cause cell death is still not clear. The emergence of resistance to this class of drugs as well as to other antitumor agents is one of the major causes of failure of cancer treatment. This paper reviews some of the best characterized mechanisms of resistance to alkylating agents. Pre- and post-target mechanisms are recognized, the former able to limit the formation of...

  13. Nature's Autonomous Oscillators

    Science.gov (United States)

    Mayr, H. G.; Yee, J.-H.; Mayr, M.; Schnetzler, R.

    2012-01-01

    Nonlinearity is required to produce autonomous oscillations without external time dependent source, and an example is the pendulum clock. The escapement mechanism of the clock imparts an impulse for each swing direction, which keeps the pendulum oscillating at the resonance frequency. Among nature's observed autonomous oscillators, examples are the quasi-biennial oscillation and bimonthly oscillation of the Earth atmosphere, and the 22-year solar oscillation. The oscillations have been simulated in numerical models without external time dependent source, and in Section 2 we summarize the results. Specifically, we shall discuss the nonlinearities that are involved in generating the oscillations, and the processes that produce the periodicities. In biology, insects have flight muscles, which function autonomously with wing frequencies that far exceed the animals' neural capacity; Stretch-activation of muscle contraction is the mechanism that produces the high frequency oscillation of insect flight, discussed in Section 3. The same mechanism is also invoked to explain the functioning of the cardiac muscle. In Section 4, we present a tutorial review of the cardio-vascular system, heart anatomy, and muscle cell physiology, leading up to Starling's Law of the Heart, which supports our notion that the human heart is also a nonlinear oscillator. In Section 5, we offer a broad perspective of the tenuous links between the fluid dynamical oscillators and the human heart physiology.

  14. Potential mechanisms of resistance to microtubule inhibitors.

    Science.gov (United States)

    Kavallaris, Maria; Annereau, Jean-Philippe; Barret, Jean-Marc

    2008-06-01

    Antimitotic drugs targeting the microtubules, such as the taxanes and vinca alkaloids, are widely used in the treatment of neoplastic diseases. Development of drug resistance over time, however, limits the efficacy of these agents and poses a clinical challenge to long-term improvement of patient outcomes. Understanding the mechanism(s) of drug resistance becomes paramount to allowing for alternative, if not improved, therapeutic options that might circumvent this challenge. Vinflunine, a novel microtubule inhibitor, has shown superior preclinical antitumor activity, and displays a different pattern of resistance, compared with other agents in the vinca alkaloid class.

  15. Resistant mechanisms and molecular epidemiology of imipenem-resistant Acinetobacter baumannii.

    Science.gov (United States)

    Xiao, Shu-Zhen; Chu, Hai-Qing; Han, Li-Zhong; Zhang, Zhe-Min; Li, Bing; Zhao, Lan; Xu, Liyun

    2016-09-01

    The aim of the study was to investigate the resistant mechanisms and homology of imipenem-resistant Acinetobacter baumannii (A. baumannii). A total of 46 non-duplicate imipenem‑resistant A. baumannii clinical isolates were collected from three tertiary hospitals between July, 2011 and June, 2012. The minimal inhibitory concentrations (MICs) of antimicrobial agents were determined using the agar dilution method. Phenylalanine‑arginine β-naphthylamide was used to detect the presence of the efflux pump-mediated resistant mechanism. Polymerase chain reaction was employed to amplify genes associated with drug resistance, including β‑lactamase genes, efflux pump genes and outer membrane protein gene CarO. A few amplicons were randomly selected and sequenced. Multilocus sequence analysis (MLST) was employed in typing A. baumanni. A. baumannii was resistant to imipenem, simultaneously showing resistance to several other antimicrobials. In addtition, 13 A. baumannii were found to mediate drug resistance through operation of the efflux pump. Of the various drug resistance genes tested, blaOXA‑51 was present in 46 isolates, blaOXA‑23 gene was present in 44 isolates and blaNDM gene was found in only one strain. Other drug resistant‑associated genes, including blaKPC, blaIMP, blaOXA-24, blaOXA‑58, blaSHV, blaGIM and blaVIM were not detected. Mutation of adeS and outer membrane protein gene CarO were found in a few of the imipenem‑resistant isolates. The MLST analysis revealed that all 46 clinical isolates were clustered into 11 genotypes and the most frequent genotype was ST208. In conclusion, β‑lactamase genes, genes involved in efflux pump and mutation of outer membrane protein encoding gene may be important in mediating imipenem resistance in A. baumannii. Of the 11 different genotypes, ST11 was shared by the majority of A. baumannii, which may be due to horizontal transfer of patients from hospitals.

  16. Hard-real-time resource management for autonomous spacecraft

    Science.gov (United States)

    Gat, E.

    2000-01-01

    This paper describes tickets, a computational mechanism for hard-real-time autonomous resource management. Autonomous spacecraftcontrol can be considered abstractly as a computational process whose outputs are spacecraft commands.

  17. Shigella Antimicrobial Drug Resistance Mechanisms, 2004-2014.

    Science.gov (United States)

    Nüesch-Inderbinen, Magdalena; Heini, Nicole; Zurfluh, Katrin; Althaus, Denise; Hächler, Herbert; Stephan, Roger

    2016-06-01

    To determine antimicrobial drug resistance mechanisms of Shigella spp., we analyzed 344 isolates collected in Switzerland during 2004-2014. Overall, 78.5% of isolates were multidrug resistant; 10.5% were ciprofloxacin resistant; and 2% harbored mph(A), a plasmid-mediated gene that confers reduced susceptibility to azithromycin, a last-resort antimicrobial agent for shigellosis.

  18. Mechanisms of buffer therapy resistance.

    Science.gov (United States)

    Bailey, Kate M; Wojtkowiak, Jonathan W; Cornnell, Heather H; Ribeiro, Maria C; Balagurunathan, Yoganand; Hashim, Arig Ibrahim; Gillies, Robert J

    2014-04-01

    Many studies have shown that the acidity of solid tumors contributes to local invasion and metastasis. Oral pH buffers can specifically neutralize the acidic pH of tumors and reduce the incidence of local invasion and metastatic formation in multiple murine models. However, this effect is not universal as we have previously observed that metastasis is not inhibited by buffers in some tumor models, regardless of buffer used. B16-F10 (murine melanoma), LL/2 (murine lung) and HCT116 (human colon) tumors are resistant to treatment with lysine buffer therapy, whereas metastasis is potently inhibited by lysine buffers in MDA-MB-231 (human breast) and PC3M (human prostate) tumors. In the current work, we confirmed that sensitive cells utilized a pH-dependent mechanism for successful metastasis supported by a highly glycolytic phenotype that acidifies the local tumor microenvironment resulting in morphological changes. In contrast, buffer-resistant cell lines exhibited a pH-independent metastatic mechanism involving constitutive secretion of matrix degrading proteases without elevated glycolysis. These results have identified two distinct mechanisms of experimental metastasis, one of which is pH-dependent (buffer therapy sensitive cells) and one which is pH-independent (buffer therapy resistant cells). Further characterization of these models has potential for therapeutic benefit. Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.

  19. Characterisation of glufosinate resistance mechanisms in Eleusine indica.

    Science.gov (United States)

    Jalaludin, Adam; Yu, Qin; Zoellner, Peter; Beffa, Roland; Powles, Stephen B

    2017-06-01

    An Eleusine indica population has evolved resistance to glufosinate, a major post-emergence herbicide of global agriculture. This population was analysed for target-site (glutamine synthetase) and non-target-site (glufosinate uptake, translocation and metabolism) resistance mechanisms. Glutamine synthetase (GS) activity extracted from susceptible (S) and resistant (R*) plants was equally sensitive to glufosinate inhibition, with IC 50 values of 0.85 mm and 0.99 mm, respectively. The extractable GS activity was also similar in S and R* samples. Foliar uptake of [ 14 C]-glufosinate did not differ in S and R* plants, nor did glufosinate net uptake in leaf discs. Translocation of [ 14 C]-glufosinate into untreated shoots and roots was also similar in both populations, with 44% to 47% of the herbicide translocated out from the treated leaf 24 h after treatment. The HPLC and LC-MS analysis of glufosinate metabolism revealed no major metabolites in S or R* leaf tissue. Glufosinate resistance in this resistant population is not due to an insensitive GS, or increased activity, or altered glufosinate uptake and translocation, or enhanced glufosinate metabolism. Thus, target-site resistance is likely excluded and the exact resistance mechanism(s) remain to be determined. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  20. Global Governance Mechanisms to Address Antimicrobial Resistance.

    Science.gov (United States)

    Padiyara, Ponnu; Inoue, Hajime; Sprenger, Marc

    2018-01-01

    Since their discovery, antibiotics, and more broadly, antimicrobials, have been a cornerstone of modern medicine. But the overuse and misuse of these drugs have led to rising rates of antimicrobial resistance, which occurs when bacteria adapt in ways that render antibiotics ineffective. A world without effective antibiotics can have drastic impacts on population health, global development, and the global economy. As a global common good, antibiotic effectiveness is vulnerable to the tragedy of the commons, where a shared limited resource is overused by a community when each individual exploits the finite resource for their own benefit. A borderless threat like antimicrobial resistance requires global governance mechanisms to mitigate its emergence and spread, and it is the responsibility of all countries and relevant multilateral organizations. These mechanisms can be in the form of legally binding global governance mechanisms such as treaties and regulatory standards or nonbinding mechanisms such as political declarations, resolutions, or guidelines. In this article, we argue that while both are effective methods, the strong, swift, and coordinated action needed to address rising rates of antimicrobial resistance will be better served through legally binding governance mechanisms.

  1. [Resistance risk, cross-resistance and biochemical resistance mechanism of Laodelphax striatellus to buprofezin].

    Science.gov (United States)

    Mao, Xu-lian; Liu, Jin; Li, Xu-ke; Chi, Jia-jia; Liu, Yong-jie

    2016-01-01

    In order to investigate the resistance development law and biochemical resistance mechanism of Laodelphax striatellus to buprofezin, spraying rice seedlings was used to continuously screen resistant strains of L. striatellus and dipping rice seedlings was applied to determine the toxicity and cross-resistance of L. striatellus to insecticides. After 32-generation screening with buprofezin, L. striatellus developed 168.49 folds resistance and its reality heritability (h2) was 0.11. If the killing rate was 80%-90%, L. striatellus was expected to develop 10-fold resistance to buprofezin only after 5 to 6 generations breeding. Because the actual reality heritability of field populations was usually lower than that of the resistant strains, the production of field populations increasing with 10-fold resistance would need much longer time. The results of cross-resistance showed that resistant strain had high level cross-resistance with thiamethoxam and imidacloprid, low level cross-resistance with acetamiprid, and no cross-resistance with pymetrozine and chlorpyrifos. The activity of detoxification enzymes of different strains and the syergism of synergist were measured. The results showed that cytochrome P450 monooxygenase played a major role in the resistance of L. striatellus to buprofezin, the esterase played a minor role and the GSH-S-transferase had no effect. Therefore, L. striatellus would have high risk to develop resistance to buprofezin when used in the field and might be delayed by using pymetrozine and chlorpyrifos.

  2. Mechanisms of Resistance to Neurotoxins

    National Research Council Canada - National Science Library

    Schubert, David

    2002-01-01

    .... During all of these events, some groups of nerve cells are spared relative to others. It is therefore likely that biochemical mechanisms exist which lead to increased resistance to oxidative stress and other forms of cytotoxicity...

  3. Mechanisms and circumvention of cellular resistance to cisplatin.

    NARCIS (Netherlands)

    Hospers, Geesiena Alberdina Petronella

    1989-01-01

    Cisplatin (CDDP) is an active cytostatic agent. A limitation to its effectiveness initially or appearing during cystatic treatment is the occurrence of resistance. This thesis describes mechanisms wich are responsible for acquired cellular CDDP resistance. To investigate cellular CDDP resistance, a

  4. Lagrangian-Hamiltonian unified formalism for autonomous higher order dynamical systems

    International Nuclear Information System (INIS)

    Prieto-Martinez, Pedro Daniel; Roman-Roy, Narciso

    2011-01-01

    The Lagrangian-Hamiltonian unified formalism of Skinner and Rusk was originally stated for autonomous dynamical systems in classical mechanics. It has been generalized for non-autonomous first-order mechanical systems, as well as for first-order and higher order field theories. However, a complete generalization to higher order mechanical systems is yet to be described. In this work, after reviewing the natural geometrical setting and the Lagrangian and Hamiltonian formalisms for higher order autonomous mechanical systems, we develop a complete generalization of the Lagrangian-Hamiltonian unified formalism for these kinds of systems, and we use it to analyze some physical models from this new point of view. (paper)

  5. Antimicrobial resistance mechanisms among Campylobacter.

    Science.gov (United States)

    Wieczorek, Kinga; Osek, Jacek

    2013-01-01

    Campylobacter jejuni and Campylobacter coli are recognized as the most common causative agents of bacterial gastroenteritis in the world. Humans most often become infected by ingesting contaminated food, especially undercooked chicken, but also other sources of bacteria have been described. Campylobacteriosis is normally a self-limiting disease. Antimicrobial treatment is needed only in patients with more severe disease and in those who are immunologically compromised. The most common antimicrobial agents used in the treatment of Campylobacter infections are macrolides, such as erythromycin, and fluoroquinolones, such as ciprofloxacin. Tetracyclines have been suggested as an alternative choice in the treatment of clinical campylobacteriosis but in practice are not often used. However, during the past few decades an increasing number of resistant Campylobacter isolates have developed resistance to fluoroquinolones and other antimicrobials such as macrolides, aminoglycosides, and beta-lactams. Trends in antimicrobial resistance have shown a clear correlation between use of antibiotics in the veterinary medicine and animal production and resistant isolates of Campylobacter in humans. In this review, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter are discussed.

  6. Action and resistance mechanisms of antibiotics: A guide for clinicians

    Directory of Open Access Journals (Sweden)

    Garima Kapoor

    2017-01-01

    Full Text Available Infections account for a major cause of death throughout the developing world. This is mainly due to the emergence of newer infectious agents and more specifically due to the appearance of antimicrobial resistance. With time, the bacteria have become smarter and along with it, massive imprudent usage of antibiotics in clinical practice has resulted in resistance of bacteria to antimicrobial agents. The antimicrobial resistance is recognized as a major problem in the treatment of microbial infections. The biochemical resistance mechanisms used by bacteria include the following: antibiotic inactivation, target modification, altered permeability, and “bypass” of metabolic pathway. Determination of bacterial resistance to antibiotics of all classes (phenotypes and mutations that are responsible for bacterial resistance to antibiotics (genetic analysis are helpful. Better understanding of the mechanisms of antibiotic resistance will help clinicians regarding usage of antibiotics in different situations. This review discusses the mechanism of action and resistance development in commonly used antimicrobials.

  7. Concretes with high mechanical resistance

    International Nuclear Information System (INIS)

    Mauny, Pierre.

    1973-01-01

    Description is given of a method for manufacturing concretes with high mechanical resistance in compression, obtained by mixing gravels highly resistant to compression, sand and cement in an aqueous medium. Use is made of sands of porous ceramics, such as terra-cotta, of a grain size from 0,1 to 5mm, the pore diameter of which is from 0.5 to 15 microns, chosen so as to be slighty bigger than the crystals of the cement used. This can be applied to the pre-stressed structures used in the nuclear field [fr

  8. Pathophysiological mechanisms of insulin resistance

    NARCIS (Netherlands)

    Brands, M.

    2013-01-01

    In this thesis we studied pathophysiological mechanisms of insulin resistance in different conditions in humans, i.e. in obesity, during lipid infusions, after hypercaloric feeding, and glucocorticoid treatment. We focused on 3 important hypotheses that are suggested to be implicated in the

  9. Analysis and modeling of resistive switching mechanism oriented to fault tolerance of resistive memory based on memristor

    International Nuclear Information System (INIS)

    Huang Da; Wu Jun-Jie; Tang Yu-Hua

    2014-01-01

    With the progress of the semiconductor industry, resistive memories, especially the memristor, have drawn increasing attention. The resistive memory based on memrsitor has not been commercialized mainly because of data error. Currently, there are more studies focused on fault tolerance of resistive memory. This paper studies the resistive switching mechanism which may have time-varying characteristics. Resistive switching mechanism is analyzed and its respective circuit model is established based on the memristor Spice model

  10. Bedaquiline resistance: Its emergence, mechanism and prevention.

    NARCIS (Netherlands)

    Nguyen, Thi Van Anh; Anthony, Richard M; Bañuls, Anne-Laure; Vu, Dinh Hoa; Alffenaar, Jan-Willem C

    2017-01-01

    Bedaquiline, a new anti-tuberculosis drug, has already been used in more than 50 countries. The emergence of bedaquiline resistance is alarming, as it may result in the rapid loss of this new drug. This paper aims to review currently identified mechanisms of resistance, the emergence of bedaquiline

  11. Volume Resistivity and Mechanical Behavior of Epoxy Nanocomposite Materials

    Directory of Open Access Journals (Sweden)

    M. F. Abdelkarim

    2015-04-01

    Full Text Available Electrical and mechanical properties of polymer composite materials are investigated through the determination of resistivity and hardness for composites samples. Epoxy composite samples have been prepared with different concentrations of certain inorganic fillers such as; Titanium dioxide (TiO2 and Silica (SiO2, of various size (micro, nano and hybrid to study the electrical and mechanical behavior. The volume resistivity reaches 3.23×1014 ohm.cm for the micro silica composite. Surface of composite material has been mechanically examined by hardness test. The results show that the resistivity of microcomposites and nanocmposites are increased with the decrease of filler concentration. But the resistivity of hybrid composites is increased with the increase of filler concentration. Maximum hardness value was obtained from hybrid silica composite with 0.1% filler concentration.

  12. Molecular Mechanisms of Chromium in Alleviating Insulin Resistance

    Science.gov (United States)

    Hua, Yinan; Clark, Suzanne; Ren, Jun; Sreejayan, Nair

    2011-01-01

    Type 2 diabetes is often associated with obesity, dyslipidemia, and cardiovascular anomalies and is a major health problem approaching global epidemic proportions. Insulin resistance, a prediabetic condition, precedes the onset of frank type 2 diabetes and offers potential avenues for early intervention to treat the disease. Although lifestyle modifications and exercise can reduce the incidence of diabetes, compliance has proved to be difficult, warranting pharmacological interventions. However, most of the currently available drugs that improve insulin sensitivity have adverse effects. Therefore, attractive strategies to alleviate insulin resistance include dietary supplements. One such supplement is chromium, which has been shown reduce insulin resistance in some, but not all, studies. Furthermore, the molecular mechanisms of chromium in alleviating insulin resistance remain elusive. This review examines emerging reports on the effect of chromium, as well as molecular and cellular mechanisms by which chromium may provide beneficial effects in alleviating insulin resistance. PMID:22423897

  13. Mechanisms of Evolution in High-Consequence Drug Resistance Plasmids

    Directory of Open Access Journals (Sweden)

    Susu He

    2016-12-01

    Full Text Available The dissemination of resistance among bacteria has been facilitated by the fact that resistance genes are usually located on a diverse and evolving set of transmissible plasmids. However, the mechanisms generating diversity and enabling adaptation within highly successful resistance plasmids have remained obscure, despite their profound clinical significance. To understand these mechanisms, we have performed a detailed analysis of the mobilome (the entire mobile genetic element content of a set of previously sequenced carbapenemase-producing Enterobacteriaceae (CPE from the National Institutes of Health Clinical Center. This analysis revealed that plasmid reorganizations occurring in the natural context of colonization of human hosts were overwhelmingly driven by genetic rearrangements carried out by replicative transposons working in concert with the process of homologous recombination. A more complete understanding of the molecular mechanisms and evolutionary forces driving rearrangements in resistance plasmids may lead to fundamentally new strategies to address the problem of antibiotic resistance.

  14. Mechanism of Resistance to Glyphosate in Lolium perenne from Argentina

    Directory of Open Access Journals (Sweden)

    Marcos Yanniccari

    2017-10-01

    Full Text Available In Argentina, glyphosate resistance was reported in a Lolium perenne population after 12 years of successful herbicide use. The aim of the current paper was to put in evidence for the mechanism of glyphosate resistance of this weed. Susceptible leaves treated with different doses of glyphosate and incubated in vitro showed an accumulation of shikimic acid of around three to five times the basal level, while no changes were detected in leaves of glyphosate-resistant plants. The resistance mechanism prevents shikimate accumulation in leaves, even under such tissue-isolation conditions. The activity of the glyphosate target enzyme (EPSPS: 5-enolpyruvylshikimate-3-phosphate synthase was quantified at different herbicide concentrations. EPSPS from resistant plants showed no difference in glyphosate-sensitivity compared to EPSPS from susceptible plants, and, accordingly, no amino acid substitution causing mutations associated with resistance were found. While the glyphosate target enzymes were equally sensitive, the basal EPSPS activity in glyphosate resistant plants was approximately 3-fold higher than the EPSPS activity in susceptible plants. This increased EPSPS activity in glyphosate resistant plants was associated with a 15-fold higher expression of EPSPS compared with susceptible plants. Therefore, the over-expression of EPSPS appears to be the main mechanism responsible for resistance to glyphosate. This mechanism has a constitutive character and has important effects on plant fitness, as recently reported.

  15. Mechanisms of Evolution in High-Consequence Drug Resistance Plasmids.

    Science.gov (United States)

    He, Susu; Chandler, Michael; Varani, Alessandro M; Hickman, Alison B; Dekker, John P; Dyda, Fred

    2016-12-06

    The dissemination of resistance among bacteria has been facilitated by the fact that resistance genes are usually located on a diverse and evolving set of transmissible plasmids. However, the mechanisms generating diversity and enabling adaptation within highly successful resistance plasmids have remained obscure, despite their profound clinical significance. To understand these mechanisms, we have performed a detailed analysis of the mobilome (the entire mobile genetic element content) of a set of previously sequenced carbapenemase-producing Enterobacteriaceae (CPE) from the National Institutes of Health Clinical Center. This analysis revealed that plasmid reorganizations occurring in the natural context of colonization of human hosts were overwhelmingly driven by genetic rearrangements carried out by replicative transposons working in concert with the process of homologous recombination. A more complete understanding of the molecular mechanisms and evolutionary forces driving rearrangements in resistance plasmids may lead to fundamentally new strategies to address the problem of antibiotic resistance. The spread of antibiotic resistance among Gram-negative bacteria is a serious public health threat, as it can critically limit the types of drugs that can be used to treat infected patients. In particular, carbapenem-resistant members of the Enterobacteriaceae family are responsible for a significant and growing burden of morbidity and mortality. Here, we report on the mechanisms underlying the evolution of several plasmids carried by previously sequenced clinical Enterobacteriaceae isolates from the National Institutes of Health Clinical Center (NIH CC). Our ability to track genetic rearrangements that occurred within resistance plasmids was dependent on accurate annotation of the mobile genetic elements within the plasmids, which was greatly aided by access to long-read DNA sequencing data and knowledge of their mechanisms. Mobile genetic elements such as

  16. Low Prevalence of Carbapenem-Resistant Bacteria in River Water: Resistance Is Mostly Related to Intrinsic Mechanisms.

    Science.gov (United States)

    Tacão, Marta; Correia, António; Henriques, Isabel S

    2015-10-01

    Carbapenems are last-resort antibiotics to handle serious infections caused by multiresistant bacteria. The incidence of resistance to these antibiotics has been increasing and new resistance mechanisms have emerged. The dissemination of carbapenem resistance in the environment has been overlooked. The main goal of this research was to assess the prevalence and diversity of carbapenem-resistant bacteria in riverine ecosystems. The presence of frequently reported carbapenemase-encoding genes was inspected. The proportion of imipenem-resistant bacteria was on average 2.24 CFU/ml. Imipenem-resistant strains (n=110) were identified as Pseudomonas spp., Stenotrophomonas maltophilia, Aeromonas spp., Chromobacterium haemolyticum, Shewanella xiamenensis, and members of Enterobacteriaceae. Carbapenem-resistant bacteria were highly resistant to other beta-lactams such as quinolones, aminoglycosides, chloramphenicol, tetracyclines, and sulfamethoxazole/trimethoprim. Carbapenem resistance was mostly associated with intrinsically resistant bacteria. As intrinsic resistance mechanisms, we have identified the blaCphA gene in 77.3% of Aeromonas spp., blaL1 in all S. maltophilia, and blaOXA-48-like in all S. xiamenensis. As acquired resistance mechanisms, we have detected the blaVIM-2 gene in six Pseudomonas spp. (5.45%). Integrons with gene cassettes encoding resistance to aminoglycosides (aacA and aacC genes), trimethoprim (dfrB1b), and carbapenems (blaVIM-2) were found in Pseudomonas spp. Results suggest that carbapenem resistance dissemination in riverine ecosystems is still at an early stage. Nevertheless, monitoring these aquatic compartments for the presence of resistance genes and its host organisms is essential to outline strategies to minimize resistance dissemination.

  17. Mechanisms of ouabain resistance

    International Nuclear Information System (INIS)

    Schulz, J.T. III.

    1987-01-01

    Experiments were designed to investigate the mechanism of ouabain resistance in two distinct types of transfected cells derived from ouabain-sensitive CV-1 cell parents. The first type of transfectant is the recipient of a gene encoding the alpha subunit of the rodent renal Na,K-ATPase (R-alphal gene); the second type of transfectant is the recipient of the mouse ouabain resistance gene. Measurements of 86 Rb + uptake and Na,K=ATPase activity in R-alphal gene transfectant cells and CV-1 parent cells indicate that the ouabain-resistant phenotype of the transfectants is due to expression of a relatively ouabain-insensitive Na,K=ATPase. CV-1 parent cells express one component of ouabain sensitive 86 Rb + uptake and one component of ouabain-sensitive Na, K-ATPase activity. R-alpha 1 gene transfectants express the parental forms of ouabain-sensitive 86 Rb + uptake and Na,K-ATPase activity, but in addition express new,relatively ouabain-insensitive forms of 86 Rb + uptake activity and Na,K-ATPase activity

  18. Pathophysiological mechanisms of death resistance in colorectal carcinoma.

    Science.gov (United States)

    Huang, Ching-Ying; Yu, Linda Chia-Hui

    2015-11-07

    Colon cancers develop adaptive mechanisms to survive under extreme conditions and display hallmarks of unlimited proliferation and resistance to cell death. The deregulation of cell death is a key factor that contributes to chemoresistance in tumors. In a physiological context, balance between cell proliferation and death, and protection against cell damage are fundamental processes for maintaining gut epithelial homeostasis. The mechanisms underlying anti-death cytoprotection and tumor resistance often bear common pathways, and although distinguishing them would be a challenge, it would also provide an opportunity to develop advanced anti-cancer therapeutics. This review will outline cell death pathways (i.e., apoptosis, necrosis, and necroptosis), and discuss cytoprotective strategies in normal intestinal epithelium and death resistance mechanisms of colon tumor. In colorectal cancers, the intracellular mechanisms of death resistance include the direct alteration of apoptotic and necroptotic machinery and the upstream events modulating death effectors such as tumor suppressor gene inactivation and pro-survival signaling pathways. The autocrine, paracrine and exogenous factors within a tumor microenvironment can also instigate resistance against apoptotic and necroptotic cell death in colon cancers through changes in receptor signaling or transporter uptake. The roles of cyclooxygenase-2/prostaglandin E2, growth factors, glucose, and bacterial lipopolysaccharides in colorectal cancer will be highlighted. Targeting anti-death pathways in the colon cancer tissue might be a promising approach outside of anti-proliferation and anti-angiogenesis strategies for developing novel drugs to treat refractory tumors.

  19. Molecular mechanisms of methicillin resistance in Staphylococcus aureus.

    Science.gov (United States)

    Domínguez, M A; Liñares, J; Martín, R

    1997-09-01

    Methicillin-resistant Staphylococcus aureus (MRSA) strains are among the most common nosocomial pathogens. The most significant mechanism of resistance to methicillin in this-species is the acquisition of a genetic determinant (mecA gene). However, resistance seems to have a more complex molecular basis, since additional chromosomal material is involved in such resistance. Besides, overproduction of penicillinase and/or alterations in the PBPs can contribute to the formation of resistance phenotypes. Genetic and environmental factors leading to MRSA are reviewed.

  20. Cross-resistance of bisultap resistant strain of Nilaparvata lugens and its biochemical mechanism.

    Science.gov (United States)

    Ling, Shanfeng; Zhang, Runjie

    2011-02-01

    The resistant (R) strain of the planthopper Nilaparvata lugens (Stål) selected for bisultap resistance displayed 7.7-fold resistance to bisultap and also had cross-resistance to nereistoxin (monosultap, thiocyclam, and cartap), chlorpyrifos, dimethoate, and malathion but no cross-resistance to buprofezin, imidacloprid, and fipronil. To find out the biochemical mechanism of resistance to bisultap, biochemical assay was done. The results showed that cytochrome P450 monooxygenases (P450) activity in R strain was 2.71-fold that in susceptible strain (S strain), in which the changed activity for general esterase (EST) was 1.91 and for glutathione S-transferases only 1.32. Piperonyl butoxide (PBO) could significantly inhibit P450 activity (percentage of inhibition [PI]: 37.31%) in the R strain, with ESTs PI = 16.04% by triphenyl phosphate (TPP). The results also demonstrated that diethyl maleate had no synergism with bisultap. However, PBO displayed significant synergism in three different strains, and the synergism increased with resistance (S strain 1.42, Lab strain, 2.24 and R strain, 3.23). TPP also showed synergism for three strains, especially in R strain (synergistic ratio = 2.47). An in vitro biochemical study and in vivo synergistic study indicated that P450 might be play important role in the biochemical mechanism of bisultap resistance and that esterase might be the important factor of bisultap resistance. Acetylcholinesterase (AChE) insensitivity play important role in bisultap resistance. We suggest that buprofezin, imidacloprid, and fipronil could be used in resistance management programs for N. lugens via alternation and rotation with bisultap.

  1. Mechanisms of antimicrobial resistance among hospital-associated pathogens.

    Science.gov (United States)

    Khan, Ayesha; Miller, William R; Arias, Cesar A

    2018-04-01

    The introduction of antibiotics revolutionized medicine in the 20th-century permitting the treatment of once incurable infections. Widespread use of antibiotics, however, has led to the development of resistant organisms, particularly in the healthcare setting. Today, the clinician is often faced with pathogens carrying a cadre of resistance determinants that severely limit therapeutic options. The genetic plasticity of microbes allows them to adapt to stressors via genetic mutations, acquisition or sharing of genetic material and modulation of genetic expression leading to resistance to virtually any antimicrobial used in clinical practice. Areas covered: This is a comprehensive review that outlines major mechanisms of resistance in the most common hospital-associated pathogens including bacteria and fungi. Expert commentary: Understanding the genetic and biochemical mechanisms of such antimicrobial adaptation is crucial to tackling the rapid spread of resistance, can expose unconventional therapeutic targets to combat multidrug resistant pathogens and lead to more accurate prediction of antimicrobial susceptibility using rapid molecular diagnostics. Clinicians making treatment decisions based on the molecular basis of resistance may design therapeutic strategies that include de-escalation of broad spectrum antimicrobial usage, more focused therapies or combination therapies. These strategies are likely to improve patient outcomes and decrease the risk of resistance in hospital settings.

  2. Autonomous Operations System: Development and Application

    Science.gov (United States)

    Toro Medina, Jaime A.; Wilkins, Kim N.; Walker, Mark; Stahl, Gerald M.

    2016-01-01

    Autonomous control systems provides the ability of self-governance beyond the conventional control system. As the complexity of mechanical and electrical systems increases, there develops a natural drive for developing robust control systems to manage complicated operations. By closing the bridge between conventional automated systems to knowledge based self-awareness systems, nominal control of operations can evolve into relying on safe critical mitigation processes to support any off-nominal behavior. Current research and development efforts lead by the Autonomous Propellant Loading (APL) group at NASA Kennedy Space Center aims to improve cryogenic propellant transfer operations by developing an automated control and health monitoring system. As an integrated systems, the center aims to produce an Autonomous Operations System (AOS) capable of integrating health management operations with automated control to produce a fully autonomous system.

  3. Evolving spiking networks with variable resistive memories.

    Science.gov (United States)

    Howard, Gerard; Bull, Larry; de Lacy Costello, Ben; Gale, Ella; Adamatzky, Andrew

    2014-01-01

    Neuromorphic computing is a brainlike information processing paradigm that requires adaptive learning mechanisms. A spiking neuro-evolutionary system is used for this purpose; plastic resistive memories are implemented as synapses in spiking neural networks. The evolutionary design process exploits parameter self-adaptation and allows the topology and synaptic weights to be evolved for each network in an autonomous manner. Variable resistive memories are the focus of this research; each synapse has its own conductance profile which modifies the plastic behaviour of the device and may be altered during evolution. These variable resistive networks are evaluated on a noisy robotic dynamic-reward scenario against two static resistive memories and a system containing standard connections only. The results indicate that the extra behavioural degrees of freedom available to the networks incorporating variable resistive memories enable them to outperform the comparative synapse types.

  4. Mechanisms of bacterial resistance to antimicrobial agents.

    NARCIS (Netherlands)

    van Duijkeren, Engeline; Schink, Anne-Kathrin; Roberts, Marilyn C; Wang, Yang; Schwarz, Stefan

    During the past decades resistance to virtually all antimicrobial agents has been observed in bacteria of animal origin. This chapter describes in detail the mechanisms so far encountered for the various classes of antimicrobial agents. The main mechanisms include enzymatic inactivation by either

  5. Mechanisms of resistance to decitabine in the myelodysplastic syndrome.

    Directory of Open Access Journals (Sweden)

    Taichun Qin

    Full Text Available The DNA methylation inhibitor 5-aza-2'-deoxycytidine (DAC is approved for the treatment of myelodysplastic syndromes (MDS, but resistance to DAC develops during treatment and mechanisms of resistance remain unknown. Therefore, we investigated mechanisms of primary and secondary resistance to DAC in MDS.We performed Quantitative Real-Time PCR to examine expression of genes related to DAC metabolism prior to therapy in 32 responders and non-responders with MDS as well as 14 patients who achieved a complete remission and subsequently relapsed while on therapy (secondary resistance. We then performed quantitative methylation analyses by bisulfite pyrosequencing of 10 genes as well as Methylated CpG Island Amplification Microarray (MCAM analysis of global methylation in secondary resistance.Most genes showed no differences by response, but the CDA/DCK ratio was 3 fold higher in non-responders than responders (P<.05, suggesting that this could be a mechanism of primary resistance. There were no significant differences at relapse in DAC metabolism genes, and no DCK mutations were detected. Global methylation measured by the LINE1 assay was lower at relapse than at diagnosis (P<.05. On average, the methylation of 10 genes was lower at relapse (16.1% compared to diagnosis (18.1% (P<.05. MCAM analysis showed decreased methylation of an average of 4.5% (range 0.6%-9.7% of the genes at relapse. By contrast, new cytogenetic changes were found in 20% of patients.Pharmacological mechanisms are involved in primary resistance to DAC, whereas hypomethylation does not prevent a relapse for patients with DAC treatment.

  6. Autonomous Voltage Oscillations in a Direct Methanol Fuel Cell

    International Nuclear Information System (INIS)

    Nogueira, Jéssica A.; Peña Arias, Ivonne K.; Hanke-Rauschenbach, Richard; Vidakovic-Koch, Tanja; Varela, Hamilton; Sundmacher, Kai

    2016-01-01

    Proton exchange membrane fuel cells fed with H_2/CO mixtures at the anode have a considerably lower performance than fuel cells fed with pure hydrogen. However, when operated in an autonomous oscillatory regime, the overall voltage loss decreases due to a self-cleaning mechanism. Another molecule, also widely used as feed in the fuel cell and susceptible to kinetic instabilities, is methanol. To the best of our knowledge, there are no reports on autonomous voltage oscillations in the direct methanol fuel cell (DMFC). The purpose of this work was to explore if such instabilities also occur in the DMFC system. Initially, half-cell experiments with a gas diffusion electrode were performed. Then, a DMFC was operated under current control and studied by means of electrochemical impedance spectroscopy. The half-cell measurements revealed that the induction period for oscillations depends on the mass transfer conditions, where on stagnant electrode the induction time was shorter than in the case of forced convection. The DMFC showed also autonomous voltage oscillations above a certain threshold current. The results obtained by electrochemical impedance spectroscopy give evidence of a negative differential resistance in the fuel cell, hitherto not described in the literature, which can be related to the appearance of oscillations during galvanostatic methanol electro-oxidation. These results open the possibility to evaluate the performance of low-temperature fuel cells fed with carbon-containing fuels under oscillatory operating conditions.

  7. Physiological mechanism of resistance to anthracnose of different ...

    African Journals Online (AJOL)

    However, enzyme activity of resistant cultivars improved markedly after pathogen inoculation, while those of susceptible cultivars did not change. This study broadens the understanding of the mechanisms of disease resistance in Camellia. Keywords: Anthracnose, Camellia oleifera, phenylalanine ammonia lyase, ...

  8. Resistance Mechanisms of Anopheles stephensi (Diptera: Culicidae to Temephos

    Directory of Open Access Journals (Sweden)

    Aboozar Soltani

    2015-10-01

    Full Text Available Background: Anopheles stephensi is a sub-tropical species and has been considered as one of the most important vector of human malaria throughout the Middle East and South Asian region including the malarious areas of southern Iran. Current reports confirmed An. stephensi resistance to temephos in Oman and India. However, there is no comprehensive research on mechanisms of temephos resistance in An. stephensi in the literature. This study was designed in order to clarify the enzymatic and molecular mechanisms of temephos resistance in this species.Methods: Profile activities of α- and ß-esterases, mixed function oxidase (MFO, glutathione-S-transferase (GST, insensitive acetylcholinesterase, and para-nitrophenyl acetate (PNPA-esterase enzymes were tested for An. stephensi strain with resistance ratio of 15.82 to temephos in comparison with susceptible strain.Results: Results showed that the mean activity of α-EST, GST and AChE enzymes were classified as altered indicating metabolic mechanisms have considerable role in resistance of An. stephensi to temephos. Molecular study using PCR-RFLP method to trace the G119S mutation in ACE-1 gene showed lack of the mutation responsible for organophosphate insecticide resistance in the temephos-selected strain of An. stephensi.Conclusion: This study showed that the altered enzymes but not targets site insensitivity of ACE-1 are responsible for temephos resistance in An. stephensi in south of Iran.

  9. Mechanisms of Resistance to Neurotoxins (Addendum)

    National Research Council Canada - National Science Library

    Schubert, David

    2003-01-01

    .... During all of these events, some groups of nerve cells are spared relative to others. It is therefore likely that biochemical mechanisms exist which lead to increased resistance to oxidative stress and other forms of cytotoxicity...

  10. Conduction Mechanism of Valence Change Resistive Switching Memory: A Survey

    Directory of Open Access Journals (Sweden)

    Ee Wah Lim

    2015-09-01

    Full Text Available Resistive switching effect in transition metal oxide (TMO based material is often associated with the valence change mechanism (VCM. Typical modeling of valence change resistive switching memory consists of three closely related phenomena, i.e., conductive filament (CF geometry evolution, conduction mechanism and temperature dynamic evolution. It is widely agreed that the electrochemical reduction-oxidation (redox process and oxygen vacancies migration plays an essential role in the CF forming and rupture process. However, the conduction mechanism of resistive switching memory varies considerably depending on the material used in the dielectric layer and selection of electrodes. Among the popular observations are the Poole-Frenkel emission, Schottky emission, space-charge-limited conduction (SCLC, trap-assisted tunneling (TAT and hopping conduction. In this article, we will conduct a survey on several published valence change resistive switching memories with a particular interest in the I-V characteristic and the corresponding conduction mechanism.

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

    Science.gov (United States)

    Upcroft, Peter; Upcroft, Jacqueline A.

    2001-01-01

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

  12. Cross-resistance and biochemical mechanisms of resistance to indoxacarb in the diamondback moth, Plutella xylostella.

    Science.gov (United States)

    Zhang, Shuzhen; Zhang, Xiaolei; Shen, Jun; Li, Dongyang; Wan, Hu; You, Hong; Li, Jianhong

    2017-08-01

    Indoxacarb belongs to a class of insecticides known as oxadiazines and is the first commercialized pyrazoline-type voltage-dependent sodium channel blocker. A moderate level of resistance to indoxacarb has evolved in field populations of Plutella xylostella from Central China. In the present study, cross-resistance, resistance stability and metabolic mechanisms of indoxacarb resistance were investigated in this moth species. A P. xylostella strain with a high level of resistance to indoxacarb was obtained through continuous selection in the laboratory. The strain showed cross-resistance to metaflumizone, beta-cypermethrin and chlorfenapyr, but no resistance to cyantraniliprole, chlorantraniliprole, abamectin, chlorfluazuron, spinosad and diafenthiuron compared with the susceptible strain. Synergism tests revealed that piperonyl butoxide (PBO) (synergistic ratio, SR=7.8) and diethyl maleate (DEF) (SR=3.5) had considerable synergistic effects on indoxacarb toxicity in the resistant strain (F 58 ). Enzyme activity data showed there was an approximate 5.8-fold different in glutathione S-transferase (GST) and a 6.8-fold different in cytochrome P450 monooxygenase between the resistant strain (F 58 ) and susceptible strain, suggesting that the increased activity of these two enzymes is likely the main detoxification mechanism responsible for the species' resistance to indoxacarb. These results will be helpful for insecticide resistance management strategies to delay the development of indoxacarb resistance in fields. Copyright © 2017. Published by Elsevier Inc.

  13. Mechanisms of Intrinsic Tumor Resistance to Immunotherapy

    Directory of Open Access Journals (Sweden)

    John Rieth

    2018-05-01

    Full Text Available An increased understanding of the interactions between the immune system and tumors has opened the door to immunotherapy for cancer patients. Despite some success with checkpoint inhibitors including ipilimumab, pembrolizumab, and nivolumab, most cancer patients remain unresponsive to such immunotherapy, likely due to intrinsic tumor resistance. The mechanisms most likely involve reducing the quantity and/or quality of antitumor lymphocytes, which ultimately are driven by any number of developments: tumor mutations and adaptations, reduced neoantigen generation or expression, indoleamine 2,3-dioxygenase (IDO overexpression, loss of phosphatase and tensin homologue (PTEN expression, and overexpression of the Wnt–β-catenin pathway. Current work in immunotherapy continues to identify various tumor resistance mechanisms; future work is needed to develop adjuvant treatments that target those mechanisms, in order to improve the efficacy of immunotherapy and to expand its scope.

  14. Genetic Mechanisms of Antibiotic Resistance and the Role of Antibiotic Adjuvants.

    Science.gov (United States)

    Pontes, Daniela Santos; de Araujo, Rodrigo Santos Aquino; Dantas, Natalina; Scotti, Luciana; Scotti, Marcus Tullius; de Moura, Ricardo Olimpio; Mendonca-Junior, Francisco Jaime Bezerra

    2018-01-01

    The ever increasing number of multidrug-resistant microorganism pathogens has become a great and global public health threat. Antibiotic mechanisms of action and the opposing mechanisms of resistance are intimately associated, but comprehension of the biochemical and molecular functions of such drugs is not a simple exercise. Both the environment, and genetic settings contribute to alterations in phenotypic resistance (natural bacterial evolution), and make it difficult to control the emergence and impacts of antibiotic resistance. Under such circumstances, comprehension of how bacteria develop and/or acquire antibiotic resistance genes (ARG) has a critical role in developing propositions to fight against these superbugs, and to search for new drugs. In this review, we present and discuss both general information and examples of common genetic and molecular mechanisms related to antibiotic resistance, as well as how the expression and interactions of ARGs are important to drug resistance. At the same time, we focus on the recent achievements in the search for antibiotic adjuvants, which help combat antibiotic resistance through deactivation of bacterial mechanisms of action such as β-lactamases. Recent advances involving the use of anti-resistance drugs such as: efflux pump inhibitors; anti-virulence drugs; drugs against quorum sensing; and against type II/III secretion systems are revealed. Such antibiotic adjuvants (as explored herein) collaborate against the problems of antibiotic resistance, and may restore or prolong the therapeutic activity of known antibiotics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Charge dividing mechanism on resistive electrode in position-sensitive detectors

    International Nuclear Information System (INIS)

    Radeka, V.; Rehak, P.

    1978-10-01

    A complete charge-division mechanism, including both the diffusion and the electromagnetic wave propagation on resistive electrodes, is presented. The charge injected into such a transmission line divides between the two ends according to the ratio of resistancies and independently of the value of the line resistance, of the propagation mechanism and of the distribution of inductance and capacitance along the line. The shortest charge division time is achieved for Rl = 2π (L/C) 1 / 2 , where R, L, C are resistance, inductance and capacitance per unit length and l is the length of the line

  16. Molecular mechanisms of cisplatin resistance in cervical cancer

    Directory of Open Access Journals (Sweden)

    Zhu H

    2016-06-01

    Full Text Available Haiyan Zhu, Hui Luo, Wenwen Zhang, Zhaojun Shen, Xiaoli Hu, Xueqiong Zhu Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China Abstract: Patients with advanced or recurrent cervical cancer have poor prognosis, and their 1-year survival is only 10%–20%. Chemotherapy is considered as the standard treatment for patients with advanced or recurrent cervical cancer, and cisplatin appears to treat the disease effectively. However, resistance to cisplatin may develop, thus substantially compromising the efficacy of cisplatin to treat advanced or recurrent cervical cancer. In this article, we systematically review the recent literature and summarize the recent advances in our understanding of the molecular mechanisms underlying cisplatin resistance in cervical cancer. Keywords: cisplatin, epithelial–mesenchymal transition, microRNA, molecular mechanism, resistance

  17. Some resistance mechanisms to ultraviolet radiation

    International Nuclear Information System (INIS)

    Alcantara D, D.

    2002-12-01

    The cyclical exposure of bacterial cells to the ultraviolet light (UV) it has as consequence an increment in the resistance to the lethal effects of this type of radiation, increment that happens as a result of a selection process of favorable genetic mutations induced by the same UV light. With object to study the reproducibility of the genetic changes and the associate mechanisms to the resistance to UV in the bacteria Escherichia coli, was irradiated cyclically with UV light five different derived cultures of a single clone, being obtained five stumps with different resistance grades. The genetic mapping Hfr revealed that so much the mutation events like of selection that took place during the adaptation to the UV irradiation, happened of random manner, that is to say, each one of the resistant stumps it is the result of the unspecified selection of mutations arisen at random in different genes related with the repair and duplication of the DNA. (Author)

  18. Autonomous Power Management in LVDC Microgrids based on a Superimposed Frequency Droop

    DEFF Research Database (Denmark)

    Peyghami, Saeed; Mokhtari, Hossein; Blaabjerg, Frede

    2018-01-01

    In this paper a novel droop approach for autonomous power management in low voltage dc microgrids based on a master-slave concept is presented. Conventional voltage-based droop approaches suffer from poor power sharing due to line resistance effects on a virtual resistance, which is solved a by i...

  19. Multiple mechanisms increase levels of resistance in Rapistrum rugosum to ALS herbicides

    Directory of Open Access Journals (Sweden)

    Zhara M Hatami

    2016-02-01

    Full Text Available Rapistrum rugosum (turnip weed is a common weed of wheat fields in Iran, which is most often controlled by tribenuron-methyl (TM, a sulfonylurea (SU belonging to the acetolactate synthase (ALS inhibiting herbicides group. Several cases of unexplained control failure of R. rugosum by TM have been seen, especially in Golestan province-Iran. Hence, there is lack of research in evaluation of the level of resistance of the R. rugosum populations to TM, using whole plant dose–response and enzyme assays, then investigating some potential resistance mechanisms Results revealed that the resistance factor (RF for resistant (R populations was 2.5 to 6.6 fold higher than susceptible (S plant. Neither foliar retention, nor 14C-TM absorption and translocation were the mechanisms responsible for resistance in turnip weed. Metabolism of TM was the second resistant mechanism in two populations (Ag-R5 and G-1, in which three metabolites were found. The concentration of TM for 50% inhibition of ALS enzyme activity in vitro showed a high level of resistance to the herbicide (resistance factors were from 28 to 38 and cross-resistance to sulfonyl-aminocarbonyl-triazolinone (SCT, pyrimidinyl-thiobenzoate (PTB and triazolopyrimidine (TP, with no cross-resistance to imidazolinone (IMI. Substitution Pro 197 to Ser 197 provided resistance to four of five ALS-inhibiting herbicides including SU, TP, PTB and SCT with no resistance to IMI. These results documented the first case of R. rugosum resistant population worldwide and demonstrated that both RST and NRST mechanisms are involved to the resistance level to TM.

  20. Identification of Mechanical parameters for Resistance Welding Machines

    DEFF Research Database (Denmark)

    Wu, Pei; Zhang, Wenqi; Bay, Niels

    2003-01-01

    Mechanical dynamic responses of resistance welding machine have a significant influence on weld quality and electrode service life, it must be considered when the real welding production is carried out or the welding process is simulated. The mathematical models for characterizing the mechanical...

  1. Macrolide resistance mechanisms in Enterobacteriaceae: Focus on azithromycin.

    Science.gov (United States)

    Gomes, Cláudia; Martínez-Puchol, Sandra; Palma, Noemí; Horna, Gertrudis; Ruiz-Roldán, Lidia; Pons, Maria J; Ruiz, Joaquim

    2017-02-01

    From its introduction in 1952 onwards, the clinical use of macrolides has been steadily increasing, both in human and veterinary medicine. Although initially designed to the treatment of Gram-positive microorganisms, this antimicrobial family has also been used to treat specific Gram-negative bacteria. Some of them, as azithromycin, are considered in the armamentarium against Enterobacteriaceae infections. However, the facility that this bacterial genus has to gain or develop mechanisms of antibiotic resistance may compromise the future usefulness of these antibiotics to fight against Enterobacteriaceae infections. The present review is focused on the mechanisms of macrolide resistance, currently described in Enterobacteriaceae.

  2. An Evolutionarily Conserved Mechanism for Intrinsic and Transferable Polymyxin Resistance.

    Science.gov (United States)

    Xu, Yongchang; Wei, Wenhui; Lei, Sheng; Lin, Jingxia; Srinivas, Swaminath; Feng, Youjun

    2018-04-10

    Polymyxins, a family of cationic antimicrobial cyclic peptides, act as a last line of defense against severe infections by Gram-negative pathogens with carbapenem resistance. In addition to the intrinsic resistance to polymyxin E (colistin) conferred by Neisseria eptA , the plasmid-borne mobilized colistin resistance gene mcr-1 has been disseminated globally since the first discovery in Southern China, in late 2015. However, the molecular mechanisms for both intrinsic and transferable resistance to colistin remain largely unknown. Here, we aim to address this gap in the knowledge of these proteins. Structural and functional analyses of EptA and MCR-1 and -2 have defined a conserved 12-residue cavity that is required for the entry of the lipid substrate, phosphatidylethanolamine (PE). The in vitro and in vivo data together have allowed us to visualize the similarities in catalytic activity shared by EptA and MCR-1 and -2. The expression of either EptA or MCR-1 or -2 is shown to remodel the surface of enteric bacteria (e.g., Escherichia coli , Salmonella enterica , Klebsiella pneumoniae , etc.), rendering them resistant to colistin. The parallels in the PE substrate-binding cavities among EptA, MCR-1, and MCR-2 provide a comprehensive understanding of both intrinsic and transferable colistin resistance. Domain swapping between EptA and MCR-1 and -2 reveals that the two domains (transmembrane [TM] region and p hospho e thanol a mine [PEA] transferase) are not functionally exchangeable. Taken together, the results represent a common mechanism for intrinsic and transferable PEA resistance to polymyxin, a last-resort antibiotic against multidrug-resistant pathogens. IMPORTANCE EptA and MCR-1 and -2 remodel the outer membrane, rendering bacteria resistant to colistin, a final resort against carbapenem-resistant pathogens. Structural and functional analyses of EptA and MCR-1 and -2 reveal parallel PE lipid substrate-recognizing cavities, which explains intrinsic and

  3. [Mutations of resistance of HIV-1 in previously untreated patients at penitentiary centers of the Autonomous Community of Valencia, Spain. REPRICOVA study].

    Science.gov (United States)

    García-Guerrero, Julio; Herrero, Agustín; Vera, Enrique; Almenara, José M; Araújo, Rosa; Saurí, Vicente V; Castellano, Juan C; Fernández-Clemente, Luis; Bedia, Miguel; Llorente, María I; González-Morán, Francisco

    2002-03-02

    Our purpose was to determine the prevalence of mutations of resistance to nucleoside inhibitors of reverse transcriptase (NIRT) and protease inhibitors (PI) in the HIV-1 genotype of naïve infected subjects in the prisons of the Autonomous Community of Valencia, Spain. Multicentric, descriptive, cross-sectional study of prevalence including a systematic stratified and randomised sampling by centres. Demographic, clinical, virological and immunological data were collected. The HIV gene of protease and transcriptase was studied in peripheral blood plasma samples by means of double PCR amplification and subsequent automatic sequence. Reference: wild strain HXB2. Plasma was obtained from 133 individuals (119 men and 14 women). 117 samples were selected and the rest did not have enough copies for transcription. With regard to NIRT, 7 samples (5.2% of total) showed some mutation of resistance: M41L, D67N, L210W and K219Q, all them secondary to and associated with resistance to zidovudine, abacavir as well as group B multinucleoside-resistance. With regard to PI, only one sample showed a primary mutation, M46I, which was associated with resistance to indinavir. Moreover, a further 41 samples were found to express some secondary mutation. In our series, there was a low number of primary mutations of resistance. These results allow us to exclude the systematic use of resistance tests before an initiation antiretroviral therapy.

  4. Mechanism of quinolone action and resistance.

    Science.gov (United States)

    Aldred, Katie J; Kerns, Robert J; Osheroff, Neil

    2014-03-18

    Quinolones are one of the most commonly prescribed classes of antibacterials in the world and are used to treat a variety of bacterial infections in humans. Because of the wide use (and overuse) of these drugs, the number of quinolone-resistant bacterial strains has been growing steadily since the 1990s. As is the case with other antibacterial agents, the rise in quinolone resistance threatens the clinical utility of this important drug class. Quinolones act by converting their targets, gyrase and topoisomerase IV, into toxic enzymes that fragment the bacterial chromosome. This review describes the development of the quinolones as antibacterials, the structure and function of gyrase and topoisomerase IV, and the mechanistic basis for quinolone action against their enzyme targets. It will then discuss the following three mechanisms that decrease the sensitivity of bacterial cells to quinolones. Target-mediated resistance is the most common and clinically significant form of resistance. It is caused by specific mutations in gyrase and topoisomerase IV that weaken interactions between quinolones and these enzymes. Plasmid-mediated resistance results from extrachromosomal elements that encode proteins that disrupt quinolone-enzyme interactions, alter drug metabolism, or increase quinolone efflux. Chromosome-mediated resistance results from the underexpression of porins or the overexpression of cellular efflux pumps, both of which decrease cellular concentrations of quinolones. Finally, this review will discuss recent advancements in our understanding of how quinolones interact with gyrase and topoisomerase IV and how mutations in these enzymes cause resistance. These last findings suggest approaches to designing new drugs that display improved activity against resistant strains.

  5. Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy

    Directory of Open Access Journals (Sweden)

    Heung Yong Jin

    2015-12-01

    Full Text Available Diabetic neuropathy is one of the major complications of diabetes, and it increases morbidity and mortality in patients with both type 1 diabetes mellitus (T1DM and type 2 diabetes mellitus (T2DM. Because the autonomic nervous system, for example, parasympathetic axons, has a diffuse and wide distribution, we do not know the morphological changes that occur in autonomic neural control and their exact mechanisms in diabetic patients with diabetic autonomic neuropathy (DAN. Although the prevalence of sympathetic and parasympathetic neuropathy is similar in T1DM versus T2DM patients, sympathetic nerve function correlates with parasympathetic neuropathy only in T1DM patients. The explanation for these discrepancies might be that parasympathetic nerve function was more severely affected among T2DM patients. As parasympathetic nerve damage seems to be more advanced than sympathetic nerve damage, it might be that parasympathetic neuropathy precedes sympathetic neuropathy in T2DM, which was Ewing's concept. This could be explained by the intrinsic morphologic difference. Therefore, the morphological changes in the sympathetic and parasympathetic nerves of involved organs in T1DM and T2DM patients who have DAN should be evaluated. In this review, evaluation methods for morphological changes in the epidermal nerves of skin, and the intrinsic nerves of the stomach will be discussed.

  6. Resistance Status and Resistance Mechanisms in a Strain of Aedes aegypti (Diptera: Culicidae) From Puerto Rico.

    Science.gov (United States)

    Estep, Alden S; Sanscrainte, Neil D; Waits, Christy M; Louton, Jessica E; Becnel, James J

    2017-11-07

    Puerto Rico (PR) has a long history of vector-borne disease and insecticide-resistant Aedes aegypti (L.). Defining contributing mechanisms behind phenotypic resistance is critical for effective vector control intervention. However, previous studies from PR have each focused on only one mechanism of pyrethroid resistance. This study examines the contribution of P450-mediated enzymatic detoxification and sodium channel target site changes to the overall resistance phenotype of Ae. aegypti collected from San Juan, PR, in 2012. Screening of a panel of toxicants found broad resistance relative to the lab susceptible Orlando (ORL1952) strain. We identified significant resistance to representative Type I, Type II, and nonester pyrethroids, a sodium channel blocker, and a sodium channel blocking inhibitor, all of which interact with the sodium channel. Testing of fipronil, a chloride channel agonist, also showed low but significant levels of resistance. In contrast, the PR and ORL1952 strains were equally susceptible to chlorfenapyr, which has been suggested as an alternative public health insecticide. Molecular characterization of the strain indicated that two common sodium channel mutations were fixed in the population. Topical bioassay with piperonyl butoxide (PBO) indicated cytochrome P450-mediated detoxification accounts for approximately half of the resistance profile. Transcript expression screening of cytochrome P450s and glutathione-S-transferases identified the presence of overexpressed transcripts. This study of Puerto Rican Ae. aegypti with significant contributions from both genetic changes and enzymatic detoxification highlights the necessity of monitoring for resistance but also defining the multiple resistance mechanisms to inform effective mosquito control. Published by Oxford University Press on behalf of Entomological Society of America 2017. This work is written by US Government employees and is in the public domain in the US.

  7. Biologically-Inspired Concepts for Autonomic Self-Protection in Multiagent Systems

    Science.gov (United States)

    Sterritt, Roy; Hinchey, Mike

    2006-01-01

    Biologically-inspired autonomous and autonomic systems (AAS) are essentially concerned with creating self-directed and self-managing systems based on metaphors &om nature and the human body, such as the autonomic nervous system. Agent technologies have been identified as a key enabler for engineering autonomy and autonomicity in systems, both in terms of retrofitting into legacy systems and in designing new systems. Handing over responsibility to systems themselves raises concerns for humans with regard to safety and security. This paper reports on the continued investigation into a strand of research on how to engineer self-protection mechanisms into systems to assist in encouraging confidence regarding security when utilizing autonomy and autonomicity. This includes utilizing the apoptosis and quiescence metaphors to potentially provide a self-destruct or self-sleep signal between autonomic agents when needed, and an ALice signal to facilitate self-identification and self-certification between anonymous autonomous agents and systems.

  8. Systolic and Diastolic Left Ventricular Mechanics during and after Resistance Exercise.

    Science.gov (United States)

    Stöhr, Eric J; Stembridge, Mike; Shave, Rob; Samuel, T Jake; Stone, Keeron; Esformes, Joseph I

    2017-10-01

    To improve the current understanding of the impact of resistance exercise on the heart, by examining the acute responses of left ventricular (LV) strain, twist, and untwisting rate ("LV mechanics"). LV echocardiographic images were recorded in systole and diastole before, during and immediately after (7-12 s) double-leg press exercise at two intensities (30% and 60% of maximum strength, one-repetition maximum). Speckle tracking analysis generated LV strain, twist, and untwisting rate data. Additionally, beat-by-beat blood pressure was recorded and systemic vascular resistance (SVR) and LV wall stress were calculated. Responses in both exercise trials were statistically similar (P > 0.05). During effort, stroke volume decreased, whereas SVR and LV wall stress increased (P mechanics (P 0.05). Immediately after exercise, systolic LV mechanics returned to baseline levels (P mechanics, but increases diastolic mechanics after exercise, suggesting that resistance exercise has a differential impact on systolic and diastolic heart muscle function. The findings may explain why acute resistance exercise has been associated with reduced stroke volume but chronic exercise training may result in increased LV volumes.

  9. Mechanisms of resistance to quinolones and epidemiological significance of Salmonella spp.

    OpenAIRE

    Velhner, Maja

    2016-01-01

    Bacteria develop resistance to antimicrobial agents by a number of different mechanisms. The resistance to (fluoro)quinolones in Salmonella is of particular importance especially if therapy in humans is required. For decades there has been a significant interest in studying the biology of Salmonella because these bacteria are among the leading causes of foodborne illnesses around the globe. To this date, two main mechanisms of quinolone resistance have been established: alteration in the targ...

  10. Blood pressure regulation in diabetic autonomic neuropathy

    DEFF Research Database (Denmark)

    Hilsted, J

    1985-01-01

    Defective blood pressure responses to standing, exercise and epinephrine infusions have been demonstrated in diabetic patients with autonomic neuropathy. The circulatory mechanisms underlying blood pressure responses to exercise and standing up in these patients are well characterized: In both...... which may contribute to exercise hypotension in these patients. During hypoglycemia, blood pressure regulation seems intact in patients with autonomic neuropathy. This is probably due to release of substantial amounts of catecholamines during these experiments. During epinephrine infusions a substantial...... blood pressure fall ensues in patients with autonomic neuropathy, probably due to excessive muscular vasodilation. It is unresolved why blood pressure regulation is intact during hypoglycemia and severely impaired--at similar catecholamine concentrations--during epinephrine infusions....

  11. Insecticide Resistance and Metabolic Mechanisms Involved in Larval and Adult Stages of Aedes aegypti Insecticide-Resistant Reference Strains from Cuba.

    Science.gov (United States)

    Bisset, Juan Andrés; Rodríguez, María Magdalena; French, Leydis; Severson, David W; Gutiérrez, Gladys; Hurtado, Daymi; Fuentes, Ilario

    2014-12-01

    Studies were conducted to compare levels of insecticide resistance and to determine the metabolic resistance mechanisms in larval and adult stages of Aedes aegypti from Cuba. Three insecticide-resistant reference strains of Ae. aegypti from Cuba were examined. These strains were derived from a Santiago de Cuba strain isolated in 1997; it was previously subjected to a strong selection for resistance to temephos (SAN-F6), deltamethrin (SAN-F12), and propoxur (SAN-F13) and routinely maintained in the laboratory under selection pressure up to the present time, when the study was carried out. In addition, an insecticide-susceptible strain was used for comparison. The insecticide resistance in larvae and adults was determined using standard World Health Organization methodologies. Insecticide resistance mechanisms were determined by biochemical assays. The esterases (α EST and β EST) and mixed function oxidase (MFO) activities were significantly higher in adults than in the larvae of the three resistant strains studied. The association of resistance level with the biochemical mechanism for each insecticide was established for each stage. The observed differences between larval and adult stages of Ae. aegypti in their levels of insecticide resistance and the biochemical mechanisms involved should be included as part of monitoring and surveillance activities in Ae. aegypti vector control programs.

  12. Diversity and evolution of drug resistance mechanisms in Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Al-Saeedi M

    2017-10-01

    Full Text Available Mashael Al-Saeedi, Sahal Al-Hajoj Department of Infection and Immunity, Mycobacteriology Research Section, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia Abstract: Despite the efficacy of antibiotics to protect humankind against many deadly pathogens, such as Mycobacterium tuberculosis, nothing can prevent the emergence of drug-resistant strains. Several mechanisms facilitate drug resistance in M. tuberculosis including compensatory evolution, epistasis, clonal interference, cell wall integrity, efflux pumps, and target mimicry. In this study, we present recent findings relevant to these mechanisms, which can enable the discovery of new drug targets and subsequent development of novel drugs for treatment of drug-resistant M. tuberculosis. Keywords: Mycobacterium tuberculosis, antibiotic resistance, compensatory evolution, epistasis, efflux pumps, fitness cost

  13. A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel

    Directory of Open Access Journals (Sweden)

    Andrew P. Wojtovich

    2013-03-01

    Full Text Available Opening of BK-type Ca2+ activated K+ channels protects the heart against ischemia-reperfusion (IR injury. However, the location of BK channels responsible for cardioprotection is debated. Herein we confirmed that openers of the SLO1 BK channel, NS1619 and NS11021, were protective in a mouse perfused heart model of IR injury. As anticipated, deletion of the Slo1 gene blocked this protection. However, in an isolated cardiomyocyte model of IR injury, protection by NS1619 and NS11021 was insensitive to Slo1 deletion. These data suggest that protection in intact hearts occurs by a non-cardiomyocyte autonomous, SLO1-dependent, mechanism. In this regard, an in-situ assay of intrinsic cardiac neuronal function (tachycardic response to nicotine revealed that NS1619 preserved cardiac neurons following IR injury. Furthermore, blockade of synaptic transmission by hexamethonium suppressed cardioprotection by NS1619 in intact hearts. These results suggest that opening SLO1 protects the heart during IR injury, via a mechanism that involves intrinsic cardiac neurons. Cardiac neuronal ion channels may be useful therapeutic targets for eliciting cardioprotection.

  14. Alkali-Resistant Mechanism of a Hollandite DeNOx Catalyst.

    Science.gov (United States)

    Hu, Pingping; Huang, Zhiwei; Gu, Xiao; Xu, Fei; Gao, Jiayi; Wang, Yue; Chen, Yaxin; Tang, Xingfu

    2015-06-02

    A thorough understanding of the deactivation mechanism by alkalis is of great importance for rationally designing improved alkali-resistant deNOx catalysts, but a traditional ion-exchange mechanism cannot often accurately describe the nature of the deactivation, thus hampering the development of superior catalysts. Here, we establish a new exchange-coordination mechanism on the basis of the exhaustive study on the strong alkali resistance of a hollandite manganese oxide (HMO) catalyst. A combination of isothermal adsorption measurements of ammonia with X-ray absorption near-edge structure spectra and X-ray photoelectron spectra reveals that alkali metal ions first react with protons from Brønsted acid sites of HMO via the ion exchange. Synchrotron X-ray diffraction patterns and extended X-ray absorption fine structure spectra coupled with theoretical calculations demonstrate that the exchanged alkali metal ions are subsequently stabilized at size-suitable cavities in the HMO pores via a coordination model with an energy savings. This exchange-coordination mechanism not only gives a wholly convincing explanation for the intrinsic nature of the deactivation of the reported catalysts by alkalis but also provides a strategy for rationally designing improved alkali-resistant deNOx catalysts in general.

  15. Mechanisms linking brain insulin resistance to Alzheimer's disease

    Science.gov (United States)

    Matioli, Maria Niures P.S.; Nitrini, Ricardo

    2015-01-01

    Several studies have indicated that Diabetes Mellitus (DM) can increase the risk of developing Alzheimer's disease (AD). This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF) resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, accumulation of AGEs, ROS and RNS with increased production of neuro-inflammation and activation of pro-apoptosis cascade. Impairment in insulin receptor function and increased expression and activation of insulin-degrading enzyme (IDE) have also been described. These processes compromise neuronal and glial function, with a reduction in neurotransmitter homeostasis. Insulin/IGF resistance causes the accumulation of AβPP-Aβ oligomeric fibrils or insoluble larger aggregated fibrils in the form of plaques that are neurotoxic. Additionally, there is production and accumulation of hyper-phosphorylated insoluble fibrillar tau which can exacerbate cytoskeletal collapse and synaptic disconnection. PMID:29213950

  16. Mechanisms linking brain insulin resistance to Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Maria Niures P.S. Matioli

    Full Text Available Several studies have indicated that Diabetes Mellitus (DM can increase the risk of developing Alzheimer's disease (AD. This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, accumulation of AGEs, ROS and RNS with increased production of neuro-inflammation and activation of pro-apoptosis cascade. Impairment in insulin receptor function and increased expression and activation of insulin-degrading enzyme (IDE have also been described. These processes compromise neuronal and glial function, with a reduction in neurotransmitter homeostasis. Insulin/IGF resistance causes the accumulation of AβPP-Aβ oligomeric fibrils or insoluble larger aggregated fibrils in the form of plaques that are neurotoxic. Additionally, there is production and accumulation of hyper-phosphorylated insoluble fibrillar tau which can exacerbate cytoskeletal collapse and synaptic disconnection.

  17. Autonomic Regulation of Splanchnic Circulation

    Directory of Open Access Journals (Sweden)

    Kathleen A Fraser

    1991-01-01

    Full Text Available The role of the autonomic nervous system in circulatory regulation of the splanchnic organs (stomach, small intestine, colon, liver, pancreas and spleen is reviewed. In general, the sympathetic nervous system is primarily involved in vasoconstriction, while the parasympathetic contributes to vasodilation. Vasoconstriction in the splanchnic circulation appears to be mediated by alpha-2 receptors and vasodilation by activation of primary afferent nerves with subsequent release of vasodilatory peptides, or by stimulation of beta-adrenergic receptors. As well, an important function of the autonomic nervous system is to provide a mechanism by which splanchnic vascular reserve can be mobilized during stress to maintain overall cardiovascular homeostasis.

  18. Genetic resistance in experimental autoimmune encephalomyelitis. I. Analysis of the mechanism of LeR resistance using radiation chimeras

    International Nuclear Information System (INIS)

    Pelfrey, C.M.; Waxman, F.J.; Whitacre, C.C.

    1989-01-01

    Experimental autoimmune encephalomyelitis (EAE) is a cell-mediated autoimmune disease of the central nervous system that has been extensively studied in the rat. The Lewis rat is highly susceptible to the induction of EAE, while the Lewis resistant (LeR) rat is known to be resistant. In this paper, we demonstrate that the LeR rat, which was derived from the Lewis strain by inbreeding of fully resistant animals, is histocompatible with the Lewis strain. Radiation chimeras, a tool for distinguishing between immunologic and nonimmunologic resistance mechanisms, were utilized to analyze the cellular mechanisms involved in genetic resistance to EAE. By transplanting bone marrow cells from LeR rats into irradiated Lewis recipients, Lewis rats were rendered resistant to EAE induction. Likewise, transplanting Lewis bone marrow cells into irradiated LeR recipients rendered LeR rats susceptible. Mixed lymphoid cell chimeras using bone marrow, spleen, and thymus cells in Lewis recipient rats revealed individual lymphoid cell types and cell interactions that significantly affected the incidence and severity of EAE. Our results suggest that LeR resistance is mediated by hematopoietic/immune cells, and that cells located in the spleen appear to play a critical role in the resistance/susceptibility to EAE induction. Depletion of splenic adherent cells did not change the patterns of EAE resistance. In vivo cell mixing studies suggested the presence of a suppressor cell population in the LeR spleen preparations which exerted an inhibitory effect on Lewis autoimmune responses. Thus, the mechanism of LeR resistance appears to be different from that in other EAE-resistant animals

  19. Metabolic and cardiovascular responses to epinephrine in diabetic autonomic neuropathy

    DEFF Research Database (Denmark)

    Hilsted, J; Richter, E; Madsbad, S

    1987-01-01

    with autonomic neuropathy (P less than 0.01) but was unchanged in the other groups. Since cardiac output increased to a similar extent in the three groups, the decrease in blood pressure was due to a significantly larger decrease (P less than 0.01) in total peripheral vascular resistance in the patients......Norepinephrine-induced vasoconstriction, which is mediated by alpha-adrenergic receptors, is accentuated in patients with autonomic neuropathy. In contrast, responses mediated by beta-adrenergic receptors, including vasodilatation and metabolic changes, have not been evaluated in these patients....... To study these responses, we administered epinephrine in a graded intravenous infusion (0.5 to 5 micrograms per minute) to seven diabetic patients without neuropathy, seven diabetic patients with autonomic neuropathy, and seven normal subjects. Mean arterial pressure decreased significantly in the patients...

  20. New extracellular resistance mechanism for cisplatin.

    Science.gov (United States)

    Centerwall, Corey R; Kerwood, Deborah J; Goodisman, Jerry; Toms, Bonnie B; Dabrowiak, James C

    2008-01-01

    The HSQC NMR spectrum of 15N-cisplatin in cell growth media shows resonances corresponding to the monocarbonato complex, cis-[Pt(NH3)2(CO3)Cl](-), 4, and the dicarbonato complex, cis-[Pt(NH3)2(CO3)2](-2), 5, in addition to cisplatin itself, cis-[Pt(NH3)2Cl2], 1. The presence of Jurkat cells reduces the amount of detectable carbonato species by (2.8+/-0.7) fmol per cell and has little effect on species 1. Jurkat cells made resistant to cisplatin reduce the amount of detectable carbonato species by (7.9+/-5.6) fmol per cell and also reduce the amount of 1 by (3.4+/-0.9) fmol per cell. The amount of detectable carbonato species is also reduced by addition of the drug to medium that has previously been in contact with normal Jurkat cells (cells removed); the reduction is greater when drug is added to medium previously in contact with resistant Jurkat cells (cells removed). This shows that the platinum species are modified by a cell-produced substance that is released to the medium. Since the modified species have been shown not to enter or bind to cells, and since resistant cells modify more than non-resistant cells, the modification constitutes a new extracellular mechanism for cisplatin resistance which merits further attention.

  1. Insecticides resistance in the Culex quinquefasciatus populations from northern Thailand and possible resistance mechanisms.

    Science.gov (United States)

    Yanola, Jintana; Chamnanya, Saowanee; Lumjuan, Nongkran; Somboon, Pradya

    2015-09-01

    The mosquito vector Culex quinquefasciatus is known to be resistant to insecticides worldwide, including Thailand. This study was the first investigation of the insecticide resistance mechanisms, involving metabolic detoxification and target site insensitivity in C. quinquefasciatus from Thailand. Adult females reared from field-caught larvae from six provinces of northern Thailand were determined for resistant status by exposing to 0.05% deltamethrin, 0.75% permethrin and 5% malathion papers using the standard WHO susceptibility test. The overall mortality rates were 45.8%, 11.4% and 80.2%, respectively. A fragment of voltage-gated sodium channel gene was amplified and sequenced to identify the knock down resistance (kdr) mutation. The ace-1 gene mutation was determined by using PCR-RFLP. The L1014F kdr mutation was observed in all populations, but the homozygous mutant F/F1014 genotype was found only in two of the six provinces where the kdr mutation was significantly correlated with deltamethrin resistance. However, none of mosquitoes had the G119S mutation in the ace-1 gene. A laboratory deltamethrin resistant strain, Cq_CM_R, has been established showing a highly resistant level after selection for a few generations. The mutant F1014 allele frequency was significantly increased after one generation of selection. A synergist assay was performed to assess the metabolic detoxifying enzymes. Addition of bis(4-nitrophenyl)-phosphate (BNPP) and diethyl maleate (DEM), inhibitors of esterases and glutathione S-transferases (GST), respectively, into the larval bioassay of the Cq_CM strain with deltamethrin showed no significant reduction. By contrast, addition of piperonyl butoxide (PBO), an inhibitor of cytochrome P450 monooxygenases, showed a 9-fold reduction of resistance. Resistance to pyrethroids in C. quinquefasciatus is widely distributed in northern Thailand. This study reports for the first time for the detection of the L1014F kdr mutation in wild populations

  2. Autonomic and metabolic effects of OSA in childhood obesity.

    Science.gov (United States)

    Oliveira, F M; Tran, W H; Lesser, D; Bhatia, R; Ortega, R; Mittelman, S D; Keens, T G; Davidson Ward, S L; Khoo, M C

    2010-01-01

    This study investigates the effects of exposure to intermittent hypoxia on cardiovascular autonomic control and metabolic function in obese children with obstructive sleep apnea (OSA). Each subject underwent: (1) a polysomnography; (2) morning fasting blood samples and a subsequent FSIVGTT; (3) noninvasive measurement of respiration, arterial blood pressure, and heart rate during supine and standing postures. Assessment of adiposity was performed using a DEXA scan. From these measurements, we deduced the pertinent sleep parameters, Bergman minimal model parameters and the parameters characterizing a minimal model of cardiovascular variability. Results suggest that intermittent hypoxia in OSA contributes independently to insulin resistance and autonomic dysfunction in overweight children.

  3. Mechanisms of Acquired Resistance to Trastuzumab Emtansine in Breast Cancer Cells.

    Science.gov (United States)

    Li, Guangmin; Guo, Jun; Shen, Ben-Quan; Bumbaca Yadav, Daniela; Sliwkowski, Mark X; Crocker, Lisa M; Lacap, Jennifer A; Lewis Phillips, Gail D

    2018-04-25

    The receptor tyrosine kinase HER2 is overexpressed in approximately 20% of breast cancer, and its amplification is associated with reduced survival. Trastuzumab emtansine (Kadcyla®, T-DM1), an antibody-drug conjugate that is comprised of trastuzumab covalently linked to the anti-mitotic agent DM1 through a stable linker, was designed to selectively deliver DM1 to HER2-overexpressing tumor cells. T-DM1 is approved for the treatment of patients with HER2-positive metastatic breast cancer following progression on trastuzumab and a taxane. Despite the improvement in clinical outcome, many patients who initially respond to T-DM1 treatment eventually develop progressive disease. The mechanisms that contribute to T-DM1 resistance are not fully understood. To this end, we developed T-DM1-resistant in vitro models to examine the mechanisms of acquired T-DM1 resistance. We demonstrate that decreased HER2 and up-regulation of MDR1 contribute to T-DM1 resistance in KPL-4 T-DM1 resistant cells. In contrast, both loss of SLC46A3 and PTEN deficiency play a role in conferring resistance in BT-474M1 T-DM1 resistant cells. Our data suggest that these two cell lines acquire resistance through distinct mechanisms. Furthermore, we show that the KPL-4 T-DM1 resistance can be overcome by treatment with an inhibitor of MDR1, whereas a PI3K inhibitor can rescue PTEN loss-induced resistance in T-DM1-resistant BT-474M1 cells. Our results provide a rationale for developing therapeutic strategies to enhance T-DM1 clinical efficacy by combining T-DM1 and other inhibitors that target signaling transduction or resistance pathways. Copyright ©2018, American Association for Cancer Research.

  4. Mechanism of insulin resistance in normal pregnancy.

    Science.gov (United States)

    Hodson, K; Man, C Dalla; Smith, F E; Thelwall, P E; Cobelli, C; Robson, S C; Taylor, R

    2013-08-01

    Normal pregnancy is associated with insulin resistance although the mechanism is not understood. Increased intramyocellular lipid is closely associated with the insulin resistance of type 2 diabetes and obesity, and the aim of this study was to determine whether this was so for the physiological insulin resistance of pregnancy. Eleven primiparous healthy pregnant women (age: 27-39 years, body mass index 24.0±3.1 kg/m2) and no personal or family history of diabetes underwent magnetic resonance studies to quantify intramyocellular lipid, plasma lipid fractions, and insulin sensitivity. The meal-related insulin sensitivity index was considerably lower in pregnancy (45.6±9.9 vs. 193.0±26.1; 10(-4) dl/kg/min per pmol/l, p=0.0002). Fasting plasma triglyceride levels were elevated 3-fold during pregnancy (2.3±0.2 vs. 0.8±0.1 mmol/l, pinsulin resistance is distinct from that underlying type 2 diabetes. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Autonomic nervous system response patterns specificity to basic emotions.

    Science.gov (United States)

    Collet, C; Vernet-Maury, E; Delhomme, G; Dittmar, A

    1997-01-12

    The aim of this study was to test the assumption that the autonomic nervous system responses to emotional stimuli are specific. A series of six slides was randomly presented to the subjects while six autonomic nervous system (ANS) parameters were recorded: skin conductance, skin potential, skin resistance, skin blood flow, skin temperature and instantaneous respiratory frequency. Each slide induced a basic emotion: happiness, surprise, anger, fear, sadness and disgust. Results have been first considered with reference to electrodermal responses (EDR) and secondly through thermo-vascular and respiratory variations. Classical as well as original indices were used to quantify autonomic responses. The six basic emotions were distinguished by Friedman variance analysis. Thus, ANS values corresponding to each emotion were compared two-by-two. EDR distinguished 13 emotion-pairs out of 15. 10 emotion-pairs were separated by skin resistance as well as skin conductance ohmic perturbation duration indices whereas conductance amplitude was only capable of distinguishing 7 emotion-pairs. Skin potential responses distinguished surprise and fear from sadness, and fear from disgust, according to their elementary pattern analysis in form and sign. Two-by-two comparisons of skin temperature, skin blood flow (estimated by the new non-oscillary duration index) and instantaneous respiratory frequency, enabled the distinction of 14 emotion-pairs out of 15. 9 emotion-pairs were distinguished by the non-oscillatory duration index values. Skin temperature was demonstrated to be different i.e. positive versus negative in response to anger and fear. The instantaneous respiratory frequency perturbation duration index was the only one capable of separating sadness from disgust. From the six ANS parameters study, different autonomic patterns were identified, each characterizing one of the six basic emotion used as inducing signals. No index alone, nor group of parameters (EDR and thermovascular

  6. Mobile Autonomous Reconfigurable System

    Directory of Open Access Journals (Sweden)

    Pavliuk N.A.

    2018-04-01

    Full Text Available The object of this study is a multifunctional modular robot able to assemble independently in a given configuration and responsively change it in the process of operation depending on the current task. In this work we aim at developing and examining unified modules for a modular robot, which can both perform autonomous movement and form a complex structure by connecting to other modules. The existing solutions in the field of modular robotics were reviewed and classified by power supply, the ways of interconnection, the ways of movement and the possibility of independent movement of separate modules. Basing on the analysis of the shortcomings of existing analogues, we have developed a module of mobile autonomous reconfigurable system, including a base unit, a set of magneto-mechanical connectors and two motor wheels. The basic kinematic scheme of the modular robot, the features of a single module, as well as the modular structure formed by an array of similar modules were described. Two schemes for placing sets of magneto-mechanical connectors in the basic module have been proposed. We described the principle of operation of a magneto-mechanical connector based on redirection of the magnetic flux of a permanent magnet. This solution simplifies the system for controlling a mechanism of connection with other modules, increases energy efficiency and a battery life of the module. Since the energy is required only at the moment of switching the operating modes of the connector, there is no need to power constantly the connector mechanism to maintain the coupling mode.

  7. Mechanisms of antifungal drug resistance in Candida dubliniensis.

    LENUS (Irish Health Repository)

    Coleman, David C

    2010-06-01

    Candida dubliniensis was first described in 1995 and is the most closely related species to the predominant human fungal pathogen Candida albicans. C. dubliniensis is significantly less prevalent and less pathogenic than C. albicans and is primarily associated with infections in HIV-infected individuals and other immunocompromised cohorts. The population structure of C. dubliniensis consists of three well-defined major clades and is significantly less diverse than C. albicans. The majority of C. dubliniensis isolates are susceptible to antifungal drugs commonly used to treat Candida infections. To date only two major patterns of antifungal drug resistance have been identified and the molecular mechanisms of these are very similar to the resistance mechanisms that have been described previously in C. albicans. However, significant differences are evident in the predominant antifungal drug mechanisms employed by C. dubliniensis, differences that reflect its more clonal nature, its lower prevalence and characteristics of its genome, the complete sequence of which has only recently been determined.

  8. Insulin Resistance and Cancer Risk: An Overview of the Pathogenetic Mechanisms

    Directory of Open Access Journals (Sweden)

    Biagio Arcidiacono

    2012-01-01

    Full Text Available Insulin resistance is common in individuals with obesity or type 2 diabetes (T2D, in which circulating insulin levels are frequently increased. Recent epidemiological and clinical evidence points to a link between insulin resistance and cancer. The mechanisms for this association are unknown, but hyperinsulinaemia (a hallmark of insulin resistance and the increase in bioavailable insulin-like growth factor I (IGF-I appear to have a role in tumor initiation and progression in insulin-resistant patients. Insulin and IGF-I inhibit the hepatic synthesis of sex-hormone binding globulin (SHBG, whereas both hormones stimulate the ovarian synthesis of sex steroids, whose effects, in breast epithelium and endometrium, can promote cellular proliferation and inhibit apoptosis. Furthermore, an increased risk of cancer among insulin-resistant patients can be due to overproduction of reactive oxygen species (ROS that can damage DNA contributing to mutagenesis and carcinogenesis. On the other hand, it is possible that the abundance of inflammatory cells in adipose tissue of obese and diabetic patients may promote systemic inflammation which can result in a protumorigenic environment. Here, we summarize recent progress on insulin resistance and cancer, focusing on various implicated mechanisms that have been described recently, and discuss how these mechanisms may contribute to cancer initiation and progression.

  9. Clostridium difficile Infections: A Global Overview of Drug Sensitivity and Resistance Mechanisms

    Directory of Open Access Journals (Sweden)

    Saeed S. Banawas

    2018-01-01

    Full Text Available Clostridium difficile (C. difficile is the most prevalent causative pathogen of healthcare-associated diarrhea. Notably, over the past 10 years, the number of Clostridium difficile outbreaks has increased with the rate of morbidity and mortality. The occurrence and spread of C. difficile strains that are resistant to multiple antimicrobial drugs complicate prevention as well as potential treatment options. Most C. difficile isolates are still susceptible to metronidazole and vancomycin. Incidences of C. difficile resistance to other antimicrobial drugs have also been reported. Most of the antibiotics correlated with C. difficile infection (CDI, such as ampicillin, amoxicillin, cephalosporins, clindamycin, and fluoroquinolones, continue to be associated with the highest risk for CDI. Still, the detailed mechanism of resistance to metronidazole or vancomycin is not clear. Alternation in the target sites of the antibiotics is the main mechanism of erythromycin, fluoroquinolone, and rifamycin resistance in C. difficile. In this review, different antimicrobial agents are discussed and C. difficile resistance patterns and their mechanism of survival are summarized.

  10. Autonomic headache with autonomic seizures: a case report.

    Science.gov (United States)

    Ozge, Aynur; Kaleagasi, Hakan; Yalçin Tasmertek, Fazilet

    2006-10-01

    The aim of the report is to present a case of an autonomic headache associated with autonomic seizures. A 19-year-old male who had had complex partial seizures for 15 years was admitted with autonomic complaints and left hemicranial headache, independent from seizures, that he had had for 2 years and were provoked by watching television. Brain magnetic resonance imaging showed right hippocampal sclerosis and electroencephalography revealed epileptic activity in right hemispheric areas. Treatment with valproic acid decreased the complaints. The headache did not fulfil the criteria for the diagnosis of trigeminal autonomic cephalalgias, and was different from epileptic headache, which was defined as a pressing type pain felt over the forehead for several minutes to a few hours. Although epileptic headache responds to anti-epileptics and the complaints of the present case decreased with antiepileptics, it has been suggested that the headache could be a non-trigeminal autonomic headache instead of an epileptic headache.

  11. The Autonomic Nervous System Regulates the Heart Rate through cAMP-PKA Dependent and Independent Coupled-Clock Pacemaker Cell Mechanisms.

    Science.gov (United States)

    Behar, Joachim; Ganesan, Ambhighainath; Zhang, Jin; Yaniv, Yael

    2016-01-01

    Sinoatrial nodal cells (SANCs) generate spontaneous action potentials (APs) that control the cardiac rate. The brain modulates SANC automaticity, via the autonomic nervous system, by stimulating membrane receptors that activate (adrenergic) or inactivate (cholinergic) adenylyl cyclase (AC). However, these opposing afferents are not simply additive. We showed that activation of adrenergic signaling increases AC-cAMP/PKA signaling, which mediates the increase in the SANC AP firing rate (i.e., positive chronotropic modulation). However, there is a limited understanding of the underlying internal pacemaker mechanisms involved in the crosstalk between cholinergic receptors and the decrease in the SANC AP firing rate (i.e., negative chronotropic modulation). We hypothesize that changes in AC-cAMP/PKA activity are crucial for mediating either decrease or increase in the AP firing rate and that the change in rate is due to both internal and membrane mechanisms. In cultured adult rabbit pacemaker cells infected with an adenovirus expressing the FRET sensor AKAR3, PKA activity and AP firing rate were tightly linked in response to either adrenergic receptor stimulation (by isoproterenol, ISO) or cholinergic stimulation (by carbachol, CCh). To identify the main molecular targets that mediate between PKA signaling and pacemaker function, we developed a mechanistic computational model. The model includes a description of autonomic-nervous receptors, post- translation signaling cascades, membrane molecules, and internal pacemaker mechanisms. Yielding results similar to those of the experiments, the model simulations faithfully reproduce the changes in AP firing rate in response to CCh or ISO or a combination of both (i.e., accentuated antagonism). Eliminating AC-cAMP-PKA signaling abolished the core effect of autonomic receptor stimulation on the AP firing rate. Specifically, disabling the phospholamban modulation of the SERCA activity resulted in a significantly reduced effect

  12. Cisplatin Resistant Spheroids Model Clinically Relevant Survival Mechanisms in Ovarian Tumors.

    Directory of Open Access Journals (Sweden)

    Winyoo Chowanadisai

    Full Text Available The majority of ovarian tumors eventually recur in a drug resistant form. Using cisplatin sensitive and resistant cell lines assembled into 3D spheroids we profiled gene expression and identified candidate mechanisms and biological pathways associated with cisplatin resistance. OVCAR-8 human ovarian carcinoma cells were exposed to sub-lethal concentrations of cisplatin to create a matched cisplatin-resistant cell line, OVCAR-8R. Genome-wide gene expression profiling of sensitive and resistant ovarian cancer spheroids identified 3,331 significantly differentially expressed probesets coding for 3,139 distinct protein-coding genes (Fc >2, FDR < 0.05 (S2 Table. Despite significant expression changes in some transporters including MDR1, cisplatin resistance was not associated with differences in intracellular cisplatin concentration. Cisplatin resistant cells were significantly enriched for a mesenchymal gene expression signature. OVCAR-8R resistance derived gene sets were significantly more biased to patients with shorter survival. From the most differentially expressed genes, we derived a 17-gene expression signature that identifies ovarian cancer patients with shorter overall survival in three independent datasets. We propose that the use of cisplatin resistant cell lines in 3D spheroid models is a viable approach to gain insight into resistance mechanisms relevant to ovarian tumors in patients. Our data support the emerging concept that ovarian cancers can acquire drug resistance through an epithelial-to-mesenchymal transition.

  13. The influence of resistance exercise with emphasis on specific contractions (concentric vs. eccentric on muscle strength and post-exercise autonomic modulation: a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Mariana O. Gois

    2014-01-01

    Full Text Available Background: Compared to eccentric contractions, concentric contractions result in higher cardiovascular stress. However, we do not know how these two types of contractions influence cardiac autonomic modulation during the post-exercise recovery period. Objective: to compare the effect of resistance training that is performed with concentric vs. eccentric emphasis on muscle strength and on post-exercise recovery which was assessed by examining heart rate variability (HRV, for the knee extensor muscle group in young healthy adults. Methods: For this study, 105 men between 18 and 30 years of age were randomized into 4 groups: concentric control (CONCC, eccentric control (ECCC, concentric training (CONCT and eccentric training (ECCT. The CONCC and ECCC groups underwent one session of resistance exercise (RE using the knee extensor muscle group (3 sets of 1 repetition at 100% of the maximal repetition [1MR] and the CONCT and ECCT groups performed 10 training sessions. The HRV was analyzed at baseline and across four recovery periods (T1, T2, T3 and T4. Results: The ECCT group exhibited increased muscle strength at the end of the study. Regarding cardiac autonomic modulation, the CONCC and ECCC groups exhibited increases in overall variability (SDNN and SD2 at T1 compared to baseline, and the ECCT group demonstrated increases in variables reflecting vagal modulation and the recovery process (RMSSD, SD1 and HF [ms2] at T1, T2 and T4 compared to baseline. Conclusions: Resistance training with emphasis on eccentric contractions promoted strength gain and an increase in cardiac vagal modulation during recovery compared to baseline.

  14. Cross-resistance, inheritance and biochemical mechanisms of imidacloprid resistance in B-biotype Bemisia tabaci.

    Science.gov (United States)

    Wang, Zhenyu; Yao, Mingde; Wu, Yidong

    2009-11-01

    The B-type Bemisia tabaci (Gennadius) has become established in many regions in China, and neonicotinoids are extensively used to control this pest. Imidacloprid resistance in a laboratory-selected strain of B-type B. tabaci was characterised in order to provide the basis for recommending resistance management tactics. The NJ-Imi strain of B-type B. tabaci was selected from the NJ strain with imidacloprid for 30 generations. The NJ-Imi strain exhibited 490-fold resistance to imidacloprid, high levels of cross-resistance to three other neonicotinoids, low levels of cross-resistance to monosultap, cartap and spinosad, but no cross-resistance to abamectin and cypermethrin. Imidacloprid resistance in the NJ-Imi strain was autosomal and semi-dominant. It is shown that enhanced detoxification mediated by cytochrome-P450-dependent monooxygenases contributes to imidacloprid resistance to some extent in the NJ-Imi strain. Results from synergist bioassays and cross-resistance patterns indicated that target-site insensitivity may be involved in imidacloprid resistance in the NJ-Imi strain of B. tabaci. Although oxidative detoxification mediated by P450 monooxygenases is involved in imidacloprid resistance in the NJ-Imi strain of B-type B. tabaci, target-site modification as an additional resistance mechanism cannot be ruled out. Considering the high risk of cross-resistance, neonicotinoids should be regarded as a single group when implementing an insecticide rotation scheme in B. tabaci control. (c) 2009 Society of Chemical Industry.

  15. May a unitary autonomic index help assess autonomic cardiac regulation in elite athletes? Preliminary observations on the national Italian Olympic committee team.

    Science.gov (United States)

    Sala, Roberto; Malacarne, Mara; Tosi, Fabio; Benzi, Manuela; Solaro, Nadia; Tamorri, Stefano; Spataro, Antonio; Pagani, Massimo; Lucini, Daniela

    2017-12-01

    Long term endurance training, as occurring in elite athletes, is associated to cardiac neural remodeling in favor of cardioprotective vagal mechanisms, resulting in resting bradycardia and augmented contribution of cardiac parasympathetic nerve activity. Autonomic assessment can be performed by way of heart rate variability. This technique however provides multiple indices, and there is not yet complete agreement on their specific significance. Purpose of the study was to assess whether a rank transformation and radar plot could provide a unitary autonomic index, capable to show a correlation between intensity of individual work and quality of autonomic regulation. We studied 711 (23.6±6.2 years) elite athletes that took part in the selection procedure for the 2016 Rio Olympic Games for the National Italian Olympic Committee (CONI). Indices from Heart Rate Variability HRV obtained at rest, during standing up and during recovery from an exercise test were used to compute a percent ranked unitary autonomic index for sport (ANSIs), taken as proxy of quality of autonomic regulation. Within the observed wide range of energy expenditure, the unitary autonomic index ANSIs appears significantly correlated to individual and discipline specific training workloads (r=0.25, P<0.001 and r=0.78, P<0.001, respectively), correcting for possible age and gender bias. ANSIs also positively correlates to lipid profile. Estimated intensity of physical activity correlates with quality of cardiac autonomic regulation, as expressed by a novel unitary index of cardiac autonomic regulation. ANSIs could provide a novel and convenient approach to individual autonomic evaluation in athletes.

  16. New insights into Vinca alkaloids resistance mechanism and circumvention in lung cancer.

    Science.gov (United States)

    Zhang, Ying; Yang, Shao-Hui; Guo, Xiu-Li

    2017-12-01

    Nowadays, lung cancer, as a health problem in worldwide, has high mortality both in men and women. Despite advances in diagnosis and surgical techniques of lung cancer in recent decades, chemotherapy is still a fundamentally and extensively useful strategy. Vinca alkaloids are a class of important and widely used drugs in the treatment of lung cancer, targeting on the Vinca binding site at the exterior of microtubule plus ends. Either intrinsic or acquired resistance to chemotherapy of Vinca alkaloids has been a major obstacle to the treatment of lung cancer, which arose great interests in studies of understanding and overcoming resistance. In this review, we focused on the application and resistance mechanisms of the Vinca alkaloids such as vinblastine, vincristine, vinorelbine and vinflunine in lung cancer. We reviewed characteristic resistance mechanisms in lung cancer including over-expression of ATP-binding cassette (ABC) transporters P-glycoprotein and structural, functional or expression alterations of β-tubulin (βII, βIII, βIV) which may devote to the development of acquired resistance to the Vinca alkaloids; multidrug-resistance proteins (MRP1, MRP2, MRP3) and RLIP76 protein have also been identified that probably play a significant role in intrinsic resistance. Lung resistance-related protein (LRP) is contributed to lung cancer therapy resistance, but is not deal with the Vinca alkaloids resistance in lung cancer. Understanding the principle of the Vinca alkaloids in clinical application and mechanisms of drug resistance will support individualized lung cancer therapy and improve future therapies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. Heat-resistant mechanism of transgenic rape by 45Ca isotope tracer

    International Nuclear Information System (INIS)

    Xu Falun; Yang Yuanyou; Liu Ning; Liao Jiali; Yang Jijun; Tang Jun; Liu Zhibin; Yang Yi

    2012-01-01

    The Ca 2+ uptake differences of the rape with heat-resistant gene and the general rape were investigated by 45 Ca isotope tracer. The results showed that the rape with heat-resistant gene can strengthen the regulation of calcium absorption. The calcium regulation ability of the heat-resistant genes may be able to play in the rape aspect of the mechanism of resistance. (authors)

  18. Epidemiological and Genomic Landscape of Azole Resistance Mechanisms in Aspergillus Fungi

    Science.gov (United States)

    Hagiwara, Daisuke; Watanabe, Akira; Kamei, Katsuhiko; Goldman, Gustavo H.

    2016-01-01

    Invasive aspergillosis is a life-threatening mycosis caused by the pathogenic fungus Aspergillus. The predominant causal species is Aspergillus fumigatus, and azole drugs are the treatment of choice. Azole drugs approved for clinical use include itraconazole, voriconazole, posaconazole, and the recently added isavuconazole. However, epidemiological research has indicated that the prevalence of azole-resistant A. fumigatus isolates has increased significantly over the last decade. What is worse is that azole-resistant strains are likely to have emerged not only in response to long-term drug treatment but also because of exposure to azole fungicides in the environment. Resistance mechanisms include amino acid substitutions in the target Cyp51A protein, tandem repeat sequence insertions at the cyp51A promoter, and overexpression of the ABC transporter Cdr1B. Environmental azole-resistant strains harboring the association of a tandem repeat sequence and punctual mutation of the Cyp51A gene (TR34/L98H and TR46/Y121F/T289A) have become widely disseminated across the world within a short time period. The epidemiological data also suggests that the number of Aspergillus spp. other than A. fumigatus isolated has risen. Some non-fumigatus species intrinsically show low susceptibility to azole drugs, imposing the need for accurate identification, and drug susceptibility testing in most clinical cases. Currently, our knowledge of azole resistance mechanisms in non-fumigatus Aspergillus species such as A. flavus, A. niger, A. tubingensis, A. terreus, A. fischeri, A. lentulus, A. udagawae, and A. calidoustus is limited. In this review, we present recent advances in our understanding of azole resistance mechanisms particularly in A. fumigatus. We then provide an overview of the genome sequences of non-fumigatus species, focusing on the proteins related to azole resistance mechanisms. PMID:27708619

  19. Multidrug-Resistant Candida: Epidemiology, Molecular Mechanisms, and Treatment.

    Science.gov (United States)

    Arendrup, Maiken Cavling; Patterson, Thomas F

    2017-08-15

    Invasive Candida infections remain an important cause of morbidity and mortality, especially in hospitalized and immunocompromised or critically ill patients. A limited number of antifungal agents from only a few drug classes are available to treat patients with these serious infections. Resistance can be either intrinsic or acquired. Resistance mechanisms are not exchanged between Candida; thus, acquired resistance either emerges in response to an antifungal selection pressure in the individual patient or, more rarely, occur due to horizontal transmission of resistant strains between patients. Although multidrug resistance is uncommon, increasing reports of multidrug resistance to the azoles, echinocandins, and polyenes have occurred in several Candida species, most notably Candida glabrata and more recently Candida auris. Drivers are overall antifungal use, subtherapeutic drug levels at sites of infection/colonization, drug sequestration in the biofilm matrix, and, in the setting of outbreaks, suboptimal infection control. Moreover, recent research suggests that DNA mismatch repair gene mutations may facilitate acquisition of resistance mutations in C. glabrata specifically. Diagnosis of antifungal-resistant Candida infections is critical to the successful management of patients with these infections. Reduction of unnecessary use of antifungals via antifungal stewardship is critical to limit multidrug resistance emergence. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  20. Nucleus geometry and mechanical properties of resistance spot ...

    Indian Academy of Sciences (India)

    Keywords. Automotive steels; resistance spot welding; mechanical properties; nucleus geometry. 1. .... High va- lues of hardness can be explained with martensitic forma- ... interface of DP450–DP600 steels may have stainless steel properties.

  1. Autonomous path planning solution for industrial robot manipulator using backpropagation algorithm

    Directory of Open Access Journals (Sweden)

    PeiJiang Yuan

    2015-12-01

    Full Text Available Here, we propose an autonomous path planning solution using backpropagation algorithm. The mechanism of movement used by humans in controlling their arms is analyzed and then applied to control a robot manipulator. Autonomous path planning solution is a numerical method. The model of industrial robot manipulator used in this article is a KUKA KR 210 R2700 EXTRA robot. In order to show the performance of the autonomous path planning solution, an experiment validation of path tracking is provided. Experiment validation consists of implementation of the autonomous path planning solution and the control of physical robot. The process of converging to target solution is provided. The mean absolute error of position for tool center point is also analyzed. Comparison between autonomous path planning solution and the numerical methods based on Newton–Raphson algorithm is provided to demonstrate the efficiency and accuracy of the autonomous path planning solution.

  2. Characterisation of Dynamic Mechanical Properties of Resistance Welding Machines

    DEFF Research Database (Denmark)

    Wu, Pei; Zhang, Wenqi; Bay, Niels

    2005-01-01

    characterizing the dynamic mechanical characteristics of resistance welding machines is suggested, and a test set-up is designed determining the basic, independent machine parameters required in the model. The model is verified by performing a series of mechanical tests as well as real projection welds.......The dynamic mechanical properties of a resistance welding machine have significant influence on weld quality, which must be considered when simulating the welding process numerically. However, due to the complexity of the machine structure and the mutual coupling of components of the machine system......, it is very difficult to measure or calculate the basic, independent machine parameters required in a mathematical model of the machine dynamics, and no test method has so far been presented in literature, which can be applied directly in an industrial environment. In this paper, a mathematical model...

  3. [Molecular characterization of resistance mechanisms: methicillin resistance Staphylococcus aureus, extended spectrum β-lactamases and carbapenemases].

    Science.gov (United States)

    Oteo, Jesús; Belén Aracil, María

    2015-07-01

    Multi-drug resistance in bacterial pathogens increases morbidity and mortality in infected patients and it is a threat to public health concern by their high capacity to spread. For both reasons, the rapid detection of multi-drug resistant bacteria is critical. Standard microbiological procedures require 48-72 h to provide the antimicrobial susceptibility results, thus there is emerging interest in the development of rapid detection techniques. In recent years, the use of selective and differential culture-based methods has widely spread. However, the capacity for detecting antibiotic resistance genes and their low turnaround times has made molecular methods a reference for diagnosis of multidrug resistance. This review focusses on the molecular methods for detecting some mechanisms of antibiotic resistance with a high clinical and epidemiological impact: a) Enzymatic resistance to broad spectrum β-lactam antibiotics in Enterobacteriaceae, mainly extended spectrum β-lactamases (ESBL) and carbapenemases; and b) methicillin resistance in Staphylococcus aureus. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  4. Quantitative proteomic studies in resistance mechanisms of Eimeria tenella against polyether ionophores.

    Science.gov (United States)

    Thabet, Ahmed; Honscha, Walther; Daugschies, Arwid; Bangoura, Berit

    2017-05-01

    Polyether ionophores are widely used to treat and control coccidiosis in chickens. Widespread use of anticoccidials resulted in worldwide resistance. Mechanisms of resistance development and expansion are complex and poorly understood. Relative proteomic quantification using LC-MS/MS was used to compare sensitive reference strains (Ref-1, Ref-2) with putatively resistant and moderately sensitive field strains (FS-R, FS-mS) of Eimeria tenella after isotopic labelling with tandem mass tags (TMT). Ninety-seven proteins were identified, and 25 of them were regulated. Actin was significantly upregulated in resistant strains in comparison with their sensitive counterparts. On the other hand, microneme protein (MIC4) was downregulated in resistant strains. Optimization of labelling E. tenella sporozoites by TMT might identify further proteins that play a role in the obvious complex mechanism leading to resistance against Monensin.

  5. Widespread Pyrethroid and DDT Resistance in the Major Malaria Vector Anopheles funestus in East Africa Is Driven by Metabolic Resistance Mechanisms

    Science.gov (United States)

    Mulamba, Charles; Riveron, Jacob M.; Ibrahim, Sulaiman S.; Irving, Helen; Barnes, Kayla G.; Mukwaya, Louis G.; Birungi, Josephine; Wondji, Charles S.

    2014-01-01

    Background Establishing the extent, geographical distribution and mechanisms of insecticide resistance in malaria vectors is a prerequisite for resistance management. Here, we report a widespread distribution of insecticide resistance in the major malaria vector An. funestus across Uganda and western Kenya under the control of metabolic resistance mechanisms. Methodology/Principal Findings Female An. funestus collected throughout Uganda and western Kenya exhibited a Plasmodium infection rate between 4.2 to 10.4%. Widespread resistance against both type I (permethrin) and II (deltamethrin) pyrethroids and DDT was observed across Uganda and western Kenya. All populations remain highly susceptible to carbamate, organophosphate and dieldrin insecticides. Knockdown resistance plays no role in the pyrethroid and DDT resistance as no kdr mutation associated with resistance was detected despite the presence of a F1021C replacement. Additionally, no signature of selection was observed on the sodium channel gene. Synergist assays and qRT-PCR indicated that metabolic resistance plays a major role notably through elevated expression of cytochrome P450s. DDT resistance mechanisms differ from West Africa as the L119F-GSTe2 mutation only explains a small proportion of the genetic variance to DDT resistance. Conclusion The extensive distribution of pyrethroid and DDT resistance in East African An. funestus populations represents a challenge to the control of this vector. However, the observed carbamate and organophosphate susceptibility offers alternative solutions for resistance management. PMID:25333491

  6. Are Autonomous and Controlled Motivations School-Subjects-Specific?

    Science.gov (United States)

    Chanal, Julien; Guay, Frédéric

    2015-01-01

    This research sought to test whether autonomous and controlled motivations are specific to school subjects or more general to the school context. In two cross-sectional studies, 252 elementary school children (43.7% male; mean age = 10.7 years, SD = 1.3 years) and 334 junior high school children (49.7% male, mean age = 14.07 years, SD = 1.01 years) were administered a questionnaire assessing their motivation for various school subjects. Results based on structural equation modeling using the correlated trait-correlated method minus one model (CTCM-1) showed that autonomous and controlled motivations assessed at the school subject level are not equally school-subject-specific. We found larger specificity effects for autonomous (intrinsic and identified) than for controlled (introjected and external) motivation. In both studies, results of factor loadings and the correlations with self-concept and achievement demonstrated that more evidence of specificity was obtained for autonomous regulations than for controlled ones. These findings suggest a new understanding of the hierarchical and multidimensional academic structure of autonomous and controlled motivations and of the mechanisms involved in the development of types of regulations for school subjects. PMID:26247788

  7. Fracture processes and mechanisms of crack growth resistance in human enamel

    Science.gov (United States)

    Bajaj, Devendra; Park, Saejin; Quinn, George D.; Arola, Dwayne

    2010-07-01

    Human enamel has a complex micro-structure that varies with distance from the tooth’s outer surface. But contributions from the microstructure to the fracture toughness and the mechanisms of crack growth resistance have not been explored in detail. In this investigation the apparent fracture toughness of human enamel and the mechanisms of crack growth resistance were evaluated using the indentation fracture approach and an incremental crack growth technique. Indentation cracks were introduced on polished surfaces of enamel at selected distances from the occlusal surface. In addition, an incremental crack growth approach using compact tension specimens was used to quantify the crack growth resistance as a Junction of distance from the occlusal surface. There were significant differences in the apparent toughness estimated using the two approaches, which was attributed to the active crack length and corresponding scale of the toughening mechanisms.

  8. Infection control implications of heterogeneous resistance mechanisms in carbapenem-resistant Enterobacteriaceae (CRE).

    Science.gov (United States)

    Goodman, K E; Simner, P J; Tamma, P D; Milstone, A M

    2016-01-01

    The Centers for Disease Control and Prevention (CDC) defines carbapenem-resistant Enterobacteriaceae (CRE) based upon a phenotypic demonstration of carbapenem resistance. However, considerable heterogeneity exists within this definitional umbrella. CRE may mechanistically differ by whether they do or do not produce carbapenemases. Moreover, patients can acquire CRE through multiple pathways: endogenously through antibiotic selective pressure on intestinal microbiota, exogenously through horizontal transmission or through a combination of these factors. Some evidence suggests that non-carbapenemase-producing CRE may be more frequently acquired by antibiotic exposure and carbapenemase-producing CRE via horizontal transmission, but definitive data are lacking. This review examines types of CRE resistance mechanisms, antibiotic exposure and horizontal transmission pathways of CRE acquisition, and the implications of these heterogeneities to the development of evidence-based CRE healthcare epidemiology policies. In our Expert Commentary & Five-Year View, we outline specific nosocomial CRE knowledge gaps and potential methodological approaches for their resolution.

  9. Testing and Modeling of Mechanical Characteristics of Resistance Welding Machines

    DEFF Research Database (Denmark)

    Wu, Pei; Zhang, Wenqi; Bay, Niels

    2003-01-01

    for both upper and lower electrode systems. This has laid a foundation for modeling the welding process and selecting the welding parameters considering the machine factors. The method is straightforward and easy to be applied in industry since the whole procedure is based on tests with no requirements......The dynamic mechanical response of resistance welding machine is very important to the weld quality in resistance welding especially in projection welding when collapse or deformation of work piece occurs. It is mainly governed by the mechanical parameters of machine. In this paper, a mathematical...... model for characterizing the dynamic mechanical responses of machine and a special test set-up called breaking test set-up are developed. Based on the model and the test results, the mechanical parameters of machine are determined, including the equivalent mass, damping coefficient, and stiffness...

  10. Different Erythromycin Resistance Mechanisms in Group C and Group G Streptococci

    OpenAIRE

    Kataja, Janne; Seppälä, Helena; Skurnik, Mikael; Sarkkinen, Hannu; Huovinen, Pentti

    1998-01-01

    Different mechanisms of erythromycin resistance predominate in group C and G streptococcus (GCS and GGS, respectively) isolates collected from 1992 to 1995 in Finland. Of the 21 erythromycin-resistant GCS and 32 erythromycin-resistant GGS isolates, 95% had the mefA or mefE drug efflux gene and 94% had the ermTR methylase gene, respectively.

  11. Human autonomic rhythms: vagal cardiac mechanisms in tetraplegic subjects

    Science.gov (United States)

    Koh, J.; Brown, T. E.; Beightol, L. A.; Ha, C. Y.; Eckberg, D. L.

    1994-01-01

    1. We studied eight young men (age range: 20-37 years) with chronic, clinically complete high cervical spinal cord injuries and ten age-matched healthy men to determine how interruption of connections between the central nervous system and spinal sympathetic motoneurones affects autonomic cardiovascular control. 2. Baseline diastolic pressures and R-R intervals (heart periods) were similar in the two groups. Slopes of R-R interval responses to brief neck pressure changes were significantly lower in tetraplegic than in healthy subjects, but slopes of R-R interval responses to steady-state arterial pressure reductions and increases were comparable. Plasma noradrenaline levels did not change significantly during steady-state arterial pressure reductions in tetraplegic patients, but rose sharply in healthy subjects. The range of arterial pressure and R-R interval responses to vasoactive drugs (nitroprusside and phenylephrine) was significantly greater in tetraplegic than healthy subjects. 3. Resting R-R interval spectral power at respiratory and low frequencies was similar in the two groups. During infusions of vasoactive drugs, low-frequency R-R interval spectral power was directly proportional to arterial pressure in tetraplegic patients, but was unrelated to arterial pressure in healthy subjects. Vagolytic doses of atropine nearly abolished both low- and respiratory-frequency R-R interval spectral power in both groups. 4. Our conclusions are as follows. First, since tetraplegic patients have significant levels of low-frequency arterial pressure and R-R interval spectral power, human Mayer arterial pressure waves may result from mechanisms that do not involve stimulation of spinal sympathetic motoneurones by brainstem neurones. Second, since in tetraplegic patients, low-frequency R-R interval spectral power is proportional to arterial pressure, it is likely to be mediated by a baroreflex mechanism. Third, since low-frequency R-R interval rhythms were nearly abolished

  12. Biomarkers and mechanisms of natural disease resistance in dairy cows

    NARCIS (Netherlands)

    Altena, van S.E.C.

    2016-01-01

    The aim of this thesis was to define and test biomarkers for disease resistance in dairy cows and to determine the underlying mechanism in natural disease resistance. The health status of the cows is an important issue in dairy farming. Due to the mandatory reduction in the use of antibiotics,

  13. Mechanism of high-temperature resistant water-base mud

    Energy Technology Data Exchange (ETDEWEB)

    Luo, P

    1981-01-01

    Based on experiments, the causes and laws governing the changes in the performance of water-base mud under high temperature are analyzed, and the requisites and mechanism of treating agents resisting high temperature are discussed. Ways and means are sought for inhibiting, delaying and making use of the effect of high temperature on the performance of mud, while new ideas and systematic views have been expressed on the preparation of treating agents and set-up of a high temperature resistant water-base mud system. High temperature dispersion and high temperature surface inactivation of clay in the mud, as well as their effect and method of utilization are reviewed. Subjects also touched upon include degradation and cross-linking of the high-temperature resistant treating agents, their use and effect. Based on the above, the preparation of a water-base and system capable of resisting 180 to 250/sup 0/C is recommended.

  14. Characterization of resistance mechanisms and genetic relatedness of carbapenem-resistant Acinetobacter baumannii isolated from blood, Italy.

    Science.gov (United States)

    Migliavacca, Roberta; Espinal, Paula; Principe, Luigi; Drago, Monica; Fugazza, Giulia; Roca, Ignasi; Nucleo, Elisabetta; Bracco, Silvia; Vila, Jordi; Pagani, Laura; Luzzaro, Francesco

    2013-02-01

    The aim of this study was to characterize the resistance mechanisms and genetic relatedness of 21 carbapenem-resistant Acinetobacter baumannii blood isolates collected in Italy during a 1-year multicenter prospective surveillance study. Genes coding for carbapenemase production were identified by polymerase chain reaction (PCR) and sequencing. Pulsed-field gel electrophoresis (PFGE), multiplex PCRs for group identification, and multilocus sequence typing (MLST) were used to determine genetic relationships. Carbapenem resistance was consistently related to the production of oxacillinases, mostly the plasmid-mediated OXA-58 enzyme. Strains producing the OXA-23 enzyme (chromosomally mediated) were also detected. Seven PFGE clones were identified, some of which being related to international (ICL- I and ICL-II) or national clonal lineages. Multiplex PCRs identified 4 different groups (group 2 being dominant), further distinguishable in 6 sequence types by MLST. The heterogeneity of profiles highlights the diffusion of international and national clonal lineages in Italy. Continuous surveillance is needed for monitoring the spread of these worrisome strains equipped with multiple drug resistance mechanisms. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Autonomic Neuropathy

    Science.gov (United States)

    ... risk of autonomic neuropathy. Other diseases. Amyloidosis, porphyria, hypothyroidism and cancer (usually due to side effects from treatment) may also increase the risk of autonomic neuropathy. ...

  16. Antimicrobial Resistance of Hypervirulent Klebsiella pneumoniae: Epidemiology, Hypervirulence-Associated Determinants, and Resistance Mechanisms

    Directory of Open Access Journals (Sweden)

    Chang-Ro Lee

    2017-11-01

    Full Text Available Klebsiella pneumoniae is one of the most clinically relevant species in immunocompromised individuals responsible for community-acquired and nosocomial infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Since the mid-1980s, hypervirulent K. pneumoniae, generally associated with the hypermucoviscosity phenotype, has emerged as a clinically significant pathogen responsible for serious disseminated infections, such as pyogenic liver abscesses, osteomyelitis, and endophthalmitis, in a generally younger and healthier population. Hypervirulent K. pneumoniae infections were primarily found in East Asia and now are increasingly being reported worldwide. Although most hypervirulent K. pneumoniae isolates are antibiotic-susceptible, some isolates with combined virulence and resistance, such as the carbapenem-resistant hypervirulent K. pneumoniae isolates, are increasingly being detected. The combination of multidrug resistance and enhanced virulence has the potential to cause the next clinical crisis. To better understand the basic biology of hypervirulent K. pneumoniae, this review will provide a summarization and discussion focused on epidemiology, hypervirulence-associated factors, and antibiotic resistance mechanisms of such hypervirulent strains. Epidemiological analysis of recent clinical isolates in China warns the global dissemination of hypervirulent K. pneumoniae strains with extensive antibiotic resistance in the near future. Therefore, an immediate response to recognize the global dissemination of this hypervirulent strain with resistance determinants is an urgent priority.

  17. Mechanisms of action of systemic antibiotics used in periodontal treatment and mechanisms of bacterial resistance to these drugs

    Directory of Open Access Journals (Sweden)

    Geisla Mary Silva Soares

    2012-06-01

    Full Text Available Antibiotics are important adjuncts in the treatment of infectious diseases, including periodontitis. The most severe criticisms to the indiscriminate use of these drugs are their side effects and, especially, the development of bacterial resistance. The knowledge of the biological mechanisms involved with the antibiotic usage would help the medical and dental communities to overcome these two problems. Therefore, the aim of this manuscript was to review the mechanisms of action of the antibiotics most commonly used in the periodontal treatment (i.e. penicillin, tetracycline, macrolide and metronidazole and the main mechanisms of bacterial resistance to these drugs. Antimicrobial resistance can be classified into three groups: intrinsic, mutational and acquired. Penicillin, tetracycline and erythromycin are broad-spectrum drugs, effective against gram-positive and gram-negative microorganisms. Bacterial resistance to penicillin may occur due to diminished permeability of the bacterial cell to the antibiotic; alteration of the penicillin-binding proteins, or production of β-lactamases. However, a very small proportion of the subgingival microbiota is resistant to penicillins. Bacteria become resistant to tetracyclines or macrolides by limiting their access to the cell, by altering the ribosome in order to prevent effective binding of the drug, or by producing tetracycline/macrolide-inactivating enzymes. Periodontal pathogens may become resistant to these drugs. Finally, metronidazole can be considered a prodrug in the sense that it requires metabolic activation by strict anaerobe microorganisms. Acquired resistance to this drug has rarely been reported. Due to these low rates of resistance and to its high activity against the gram-negative anaerobic bacterial species, metronidazole is a promising drug for treating periodontal infections.

  18. Molecular Level Investigation of Staphylococci’s Resistance Mechanisms to Antibiotics

    Directory of Open Access Journals (Sweden)

    Lavinia Lorena PRUTEANU

    2017-09-01

    Full Text Available Polymerase chain reaction (PCR techniques development allows elaboration of many assays for identification of bacteria’s resistance mechanisms to antibiotics. Following this idea, the results of molecular level investigation of bacteria’s resistance mechanisms to antibiotics may give many opportunities to find more rapid methods for identifying the genes which are responsible for antibiotic resistance induction. The aim of this study was to investigate antibiotic resistance genes in Staphylococcus bacteria on molecular level. As classes of antibiotics it was used macrolides-lincosamides-streptogramin B (MLSB and beta-lactams. In the proposed study the bacterial strains are represented by 50 isolates of Staphylococcus. The bacterial strains were analyzed using polymerase chain reaction to identify the nuc, tuf, tst, sea, pathogenic activity genes. After this, the bacteria were tested for ermA, ermB, ermC genes and for mecA, femA which are involved in resistance to macrolides, lincosamides, streptogramin B and to beta-lactams, respectively. The presence or the absence of these genes confirms that tested strains are resistant to specific antibiotic or not. Bacteria pathogenic activity was emphasized by genes as follows: sea (enterotoxin which was found at all isolates, tst (toxic shock toxin gene was not detected in any of isolates and tuf gene (elongation factor was obtained with one pair of primers. Resistance to beta-lactams was evidenced by the presence of mecA in all isolates and femA in some strains. Each of ermC, ermA and ermB, macrolides-lincosamides-streptogramin B resistance genes, were detected.

  19. An Evolutionarily Conserved Mechanism for Intrinsic and Transferable Polymyxin Resistance

    Directory of Open Access Journals (Sweden)

    Yongchang Xu

    2018-04-01

    Full Text Available Polymyxins, a family of cationic antimicrobial cyclic peptides, act as a last line of defense against severe infections by Gram-negative pathogens with carbapenem resistance. In addition to the intrinsic resistance to polymyxin E (colistin conferred by Neisseria eptA, the plasmid-borne mobilized colistin resistance gene mcr-1 has been disseminated globally since the first discovery in Southern China, in late 2015. However, the molecular mechanisms for both intrinsic and transferable resistance to colistin remain largely unknown. Here, we aim to address this gap in the knowledge of these proteins. Structural and functional analyses of EptA and MCR-1 and -2 have defined a conserved 12-residue cavity that is required for the entry of the lipid substrate, phosphatidylethanolamine (PE. The in vitro and in vivo data together have allowed us to visualize the similarities in catalytic activity shared by EptA and MCR-1 and -2. The expression of either EptA or MCR-1 or -2 is shown to remodel the surface of enteric bacteria (e.g., Escherichia coli, Salmonella enterica, Klebsiella pneumoniae, etc., rendering them resistant to colistin. The parallels in the PE substrate-binding cavities among EptA, MCR-1, and MCR-2 provide a comprehensive understanding of both intrinsic and transferable colistin resistance. Domain swapping between EptA and MCR-1 and -2 reveals that the two domains (transmembrane [TM] region and phosphoethanolamine [PEA] transferase are not functionally exchangeable. Taken together, the results represent a common mechanism for intrinsic and transferable PEA resistance to polymyxin, a last-resort antibiotic against multidrug-resistant pathogens.

  20. Pool of resistance mechanisms to glyphosate in Digitaria insularis.

    Science.gov (United States)

    de Carvalho, Leonardo Bianco; Alves, Pedro Luis da Costa Aguiar; González-Torralva, Fidel; Cruz-Hipolito, Hugo Enrique; Rojano-Delgado, Antonia María; De Prado, Rafael; Gil-Humanes, Javier; Barro, Francisco; de Castro, María Dolores Luque

    2012-01-18

    Digitaria insularis biotypes resistant to glyphosate have been detected in Brazil. Studies were carried out in controlled conditions to determine the role of absorption, translocation, metabolism, and gene mutation as mechanisms of glyphosate resistance in D. insularis. The susceptible biotype absorbed at least 12% more (14)C-glyphosate up to 48 h after treatment (HAT) than resistant biotypes. High differential (14)C-glyphosate translocation was observed at 12 HAT, so that >70% of the absorbed herbicide remained in the treated leaf in resistant biotypes, whereas 42% remained in the susceptible biotype at 96 HAT. Glyphosate was degraded to aminomethylphosphonic acid (AMPA), glyoxylate, and sarcosine by >90% in resistant biotypes, whereas a small amount of herbicide (up to 11%) was degraded by the susceptible biotype up to 168 HAT. Two amino acid changes were found at positions 182 and 310 in EPSPS, consisting of a proline to threonine and a tyrosine to cysteine substitution, respectively, in resistant biotypes. Therefore, absorption, translocation, metabolism, and gene mutation play an important role in the D. insularis glyphosate resistance.

  1. Bulgecin A as a β-lactam enhancer for carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii clinical isolates containing various resistance mechanisms.

    Science.gov (United States)

    Skalweit, Marion J; Li, Mei

    2016-01-01

    Genetic screening of Pseudomonas aeruginosa (PSDA) and Acinetobacter baumannii (ACB) reveals genes that confer increased susceptibility to β-lactams when disrupted, suggesting novel drug targets. One such target is lytic transglycosylase. Bulgecin A (BlgA) is a natural product of Pseudomonas mesoacidophila and a lytic transglycosolase inhibitor that works synergistically with β-lactams targeting PBP3 for Enterobacteriaceae. BlgA also weakly inhibits di-Zn 2+ metallo-β-lactamases like L1 of Stenotrophomonas maltophilia . We hypothesized that because of its unique mechanism of action, BlgA could restore susceptibility to carbapenems in carbapenem-resistant PSDA (CR-PSDA) and carbapenem-resistant ACB, as well as ACB resistant to sulbactam. A BlgA-containing extract was prepared using a previously published protocol. CR-PSDA clinical isolates demonstrating a variety of carbapenem resistance mechanisms (VIM-2 carbapenemases, efflux mechanisms, and AmpC producer expression) were characterized with agar dilution minimum inhibitory concentration (MIC) testing and polymerase chain reaction. Growth curves using these strains were prepared using meropenem, BlgA extract, and meropenem plus BlgA extract. A concentrated Blg A extract combined with low concentrations of meropenem, was able to inhibit the growth of clinical strains of CR-PSDA for strains that had meropenem MICs ≥8 mg/L by agar dilution, and a clinical strain of an OXA-24 producing ACB that had a meropenem MIC >32 mg/L and intermediate ampicillin/sulbactam susceptibility. Similar experiments were conducted on a TEM-1 producing ACB strain resistant to sulbactam. BlgA with ampicillin/sulbactam inhibited the growth of this organism. As in Enterobacteriaceae, BlgA appears to restore the efficacy of meropenem in suppressing the growth of CR-PSDA and carbapenem-resistant ACB strains with a variety of common carbapenem resistance mechanisms. BlgA extract also inhibits VIM-2 β-lactamase in vitro. BlgA may prove to be

  2. Molecular mechanisms of cisplatin resistance in cervical cancer.

    Science.gov (United States)

    Zhu, Haiyan; Luo, Hui; Zhang, Wenwen; Shen, Zhaojun; Hu, Xiaoli; Zhu, Xueqiong

    2016-01-01

    Patients with advanced or recurrent cervical cancer have poor prognosis, and their 1-year survival is only 10%-20%. Chemotherapy is considered as the standard treatment for patients with advanced or recurrent cervical cancer, and cisplatin appears to treat the disease effectively. However, resistance to cisplatin may develop, thus substantially compromising the efficacy of cisplatin to treat advanced or recurrent cervical cancer. In this article, we systematically review the recent literature and summarize the recent advances in our understanding of the molecular mechanisms underlying cisplatin resistance in cervical cancer.

  3. Distinguishing Antimicrobial Models with Different Resistance Mechanisms via Population Pharmacodynamic Modeling.

    Directory of Open Access Journals (Sweden)

    Matthieu Jacobs

    2016-03-01

    Full Text Available Semi-mechanistic pharmacokinetic-pharmacodynamic (PK-PD modeling is increasingly used for antimicrobial drug development and optimization of dosage regimens, but systematic simulation-estimation studies to distinguish between competing PD models are lacking. This study compared the ability of static and dynamic in vitro infection models to distinguish between models with different resistance mechanisms and support accurate and precise parameter estimation. Monte Carlo simulations (MCS were performed for models with one susceptible bacterial population without (M1 or with a resting stage (M2, a one population model with adaptive resistance (M5, models with pre-existing susceptible and resistant populations without (M3 or with (M4 inter-conversion, and a model with two pre-existing populations with adaptive resistance (M6. For each model, 200 datasets of the total bacterial population were simulated over 24h using static antibiotic concentrations (256-fold concentration range or over 48h under dynamic conditions (dosing every 12h; elimination half-life: 1h. Twelve-hundred random datasets (each containing 20 curves for static or four curves for dynamic conditions were generated by bootstrapping. Each dataset was estimated by all six models via population PD modeling to compare bias and precision. For M1 and M3, most parameter estimates were unbiased (<10% and had good imprecision (<30%. However, parameters for adaptive resistance and inter-conversion for M2, M4, M5 and M6 had poor bias and large imprecision under static and dynamic conditions. For datasets that only contained viable counts of the total population, common statistical criteria and diagnostic plots did not support sound identification of the true resistance mechanism. Therefore, it seems advisable to quantify resistant bacteria and characterize their MICs and resistance mechanisms to support extended simulations and translate from in vitro experiments to animal infection models and

  4. A review of mechanisms of circumvention and modulation of chemotherapeutic drug resistance.

    Science.gov (United States)

    O'Connor, R

    2009-05-01

    Drug resistance is a serious limitation to the effective treatment of a number of common malignancies. Thirty years of laboratory and clinical research have greatly defined the molecular alterations underlying many drug resistance processes in cancer. Based on this knowledge, strategies to overcome the impact of resistance and increase the efficacy of cancer treatment have been translated from laboratory models to clinical trials. This article reviews laboratory and, in particular, clinical attempts at drug resistance circumvention from early forays in the inhibition of cellular efflux pump-mediated drug resistance through to more selective circumvention agent strategies and into inhibition of the other important mechanisms which can allow cancer cells to survive therapy, such as apoptosis resistance. Despite some promising results to date, resistance inhibition strategies have largely failed due to poor understanding of the pharmacology, dynamics and complexity of the resistance phenotype. With the realisation that new molecularly-targeted agents can also be rendered ineffectual by the actions of resistance mechanisms, a major focus is once again emerging on identifying new strategies/pharmaceuticals which can augment the activity of the arsenal of more conventional cytotoxics and newer targeted anti-cancer drugs. Future tactical directions where old and new resistance strategies may merge to overcome this challenge are discussed.

  5. Genetic autonomic disorders.

    Science.gov (United States)

    Axelrod, Felicia B

    2013-03-01

    Genetic disorders affecting the autonomic nervous system can result in abnormal development of the nervous system or they can be caused by neurotransmitter imbalance, an ion-channel disturbance or by storage of deleterious material. The symptoms indicating autonomic dysfunction, however, will depend upon whether the genetic lesion has disrupted peripheral or central autonomic centers or both. Because the autonomic nervous system is pervasive and affects every organ system in the body, autonomic dysfunction will result in impaired homeostasis and symptoms will vary. The possibility of genetic confirmation by molecular testing for specific diagnosis is increasing but treatments tend to remain only supportive and directed toward particular symptoms. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Investigating the effects of ABC transporter-based acquired drug resistance mechanisms at the cellular and tissue scale.

    Science.gov (United States)

    Liu, Cong; Krishnan, J; Xu, Xiao Yun

    2013-03-01

    In this paper we systematically investigate the effects of acquired drug resistance at the cellular and tissue scale, with a specific focus on ATP-binding cassette (ABC) transporter-based mechanisms and contrast this with other representative intracellular resistance mechanisms. This is done by developing in silico models wherein the drug resistance mechanism is overlaid on a coarse-grained description of apoptosis; these cellular models are coupled with interstitial drug transport, allowing for a transparent examination of the effect of acquired drug resistances at the tissue level. While ABC transporter-mediated resistance mechanisms counteract drug effect at the cellular level, its tissue-level effect is more complicated, revealing unexpected trends in tissue response as drug stimuli are systematically varied. Qualitatively different behaviour is observed in other drug resistance mechanisms. Overall the paper (i) provides insight into the tissue level functioning of a particular resistance mechanism, (ii) shows that this is very different from other resistance mechanisms of an apparently similar type, and (iii) demonstrates a concrete instance of how the functioning of a negative feedback based cellular adaptive mechanism can have unexpected higher scale effects.

  7. Mechanisms Underlying the Antidepressant Response and Treatment Resistance

    Directory of Open Access Journals (Sweden)

    Marjorie Rose Levinstein

    2014-06-01

    Full Text Available Depression is a complex and heterogeneous disorder affecting millions of Americans. There are several different medications and other treatments that are available and effective for many patients with depression. However, a substantial percentage of patients fail to achieve remission with these currently available interventions, and relapse rates are high. Therefore, it is necessary to determine both the mechanisms underlying the antidepressant response and the differences between responders and non-responders to treatment. Delineation of these mechanisms largely relies on experiments that utilize animal models. Therefore, this review provides an overview of the various mouse models that are currently used to assess the antidepressant response, such as chronic mild stress, social defeat, and chronic corticosterone. We discuss how these mouse models can be used to advance our understanding of the differences between responders and non-responders to antidepressant treatment. We also provide an overview of experimental treatment modalities that are used for treatment-resistant depression, such as deep brain stimulation and ketamine administration. We will then review the various genetic polymorphisms and transgenic mice that display resistance to antidepressant treatment. Finally, we synthesize the published data to describe a potential neural circuit underlying the antidepressant response and treatment resistance.

  8. Patients With Fibromyalgia Have Significant Autonomic Symptoms But Modest Autonomic Dysfunction.

    Science.gov (United States)

    Vincent, Ann; Whipple, Mary O; Low, Phillip A; Joyner, Michael; Hoskin, Tanya L

    2016-05-01

    Research suggests that disordered autonomic function may be one contributor to deconditioning reported in fibromyalgia; however, no study to date has assessed these variables simultaneously with comprehensive measures. To characterize physical fitness and autonomic function with the use of clinically validated measures and subjective questionnaires between patients with fibromyalgia and healthy controls. Cross-sectional, observational, controlled study. Community sample of patients with fibromyalgia and healthy controls. Thirty patients with fibromyalgia and 30 pain and fatigue-free controls. Participants completed a battery of self-report questionnaires and physiological measures, including clinically validated measures of physical fitness and autonomic function. Six-Minute Walk Test total distance, maximal oxygen consumption as assessed by cardiopulmonary exercise testing, total steps using activity monitor, Composite Autonomic Scoring Scale as assessed by Autonomic Reflex Screen, total metabolic equivalents per week using the International Physical Activity Questionnaire, and self-reported autonomic symptoms via the 31-item Composite Autonomic Symptom Score questionnaire. Autonomic function, as assessed by self-report, was significantly different between patients and controls (P physical activity was not significantly different between patients and controls (P = .99), but levels of moderate and vigorous physical activity as measured by actigraphy were significantly lower in patients (P = .012 and P = .047, respectively). Exercise capacity (6-Minute Walk) was poorer in patients (P = .0006), but there was no significant difference in maximal volume of oxygen consumption (P = .07). Patients with fibromyalgia report more severe symptoms across all domains, including physical activity and autonomic symptoms, compared with controls, but the objective assessments only showed modest differences. Our results suggest that patients with widespread subjective impairment of

  9. Functional Imaging of Autonomic Regulation: Methods and Key Findings

    Directory of Open Access Journals (Sweden)

    Paul M Macey

    2016-01-01

    Full Text Available Central nervous system processing of autonomic function involves a network of regions throughout the brain which can be visualized and measured with neuroimaging techniques, notably functional magnetic resonance imaging (fMRI. The development of fMRI procedures has both confirmed and extended earlier findings from animal models, and human stroke and lesion studies. Assessments with fMRI can elucidate interactions between different central sites in regulating normal autonomic patterning, and demonstrate how disturbed systems can interact to produce aberrant regulation during autonomic challenges. Understanding autonomic dysfunction in various illnesses reveals mechanisms that potentially lead to interventions in the impairments. The objectives here are to: 1 describe the fMRI neuroimaging methodology for assessment of autonomic neural control, 2 outline the widespread, lateralized distribution of function in autonomic sites in the normal brain which includes structures from the neocortex through the medulla and cerebellum, 3 illustrate the importance of the time course of neural changes when coordinating responses, and how those patterns are impacted in conditions of sleep-disordered breathing, and 4 highlight opportunities for future research studies with emerging methodologies. Methodological considerations specific to autonomic testing include timing of challenges relative to the underlying fMRI signal, spatial resolution sufficient to identify autonomic brainstem nuclei, blood pressure and blood oxygenation influences on the fMRI signal, and the sustained timing, often measured in minutes of challenge periods and recovery. Key findings include the lateralized nature of autonomic organization, which is reminiscent of asymmetric motor, sensory and language pathways. Testing brain function during autonomic challenges demonstrate closely-integrated timing of responses in connected brain areas during autonomic challenges, and the involvement with

  10. Molecular mechanisms of resistance to Rituximab and pharmacologic strategies for its circumvention.

    Science.gov (United States)

    Stolz, Claudia; Schuler, Martin

    2009-06-01

    The introduction of Rituximab has greatly improved therapeutic options for patients with B-cell non-Hodgkin lymphoma (B-NHL). However, a substantial fraction of patients with aggressive B-NHL fails first-line therapy, and most patients with relapsing indolent B-NHL eventually acquire Rituximab resistance. Molecular understanding of the underlying mechanisms facilitates the development of pharmacologic strategies to overcome resistance. Rituximab exerts its activity on CD20-expressing B-cells by indirect and direct effector mechanisms. Indirect mechanisms are complement-dependent cytotoxicity (CDC), and antibody-dependent cell-mediated cytotoxicity (ADCC). Direct activities, such as growth inhibition, induction of apoptosis and chemosensitisation, have been reported, but are less defined. Moreover, the relative contribution of CDC, ADCC and direct mechanisms to the activity of Rituximab in vivo is unclear. Down-regulation of CD20 and expression of complement inhibitors have been described as escape mechanisms in B-NHL. Recent reports suggest that deregulated phosphoinositide-3-kinase (PI3K)/Akt, mitogen-activated kinases (MAPK) and nuclear-factor kappaB (NF-kappaB), as well as up-regulation of anti-apoptotic proteins may determine the efficacy of Rituximab to kill B-NHL cells in vitro and in vivo. The latter signalling pathways are attractive targets for pharmacologic modulation of resistance to Rituximab. With the advent of new inhibitors and antibodies, rationally designed clinical trials addressing Rituximab resistance are feasible.

  11. Mechanisms of Resistance to Endocrine Therapy in Breast Cancer: Focus on Signaling Pathways, miRNAs and Genetically Based Resistance

    Science.gov (United States)

    García-Becerra, Rocío; Santos, Nancy; Díaz, Lorenza; Camacho, Javier

    2013-01-01

    Breast cancer is the most frequent malignancy diagnosed in women. Approximately 70% of breast tumors express the estrogen receptor (ER). Tamoxifen and aromatase inhibitors (AIs) are the most common and effective therapies for patients with ERα-positive breast cancer. Alone or combined with chemotherapy, tamoxifen significantly reduces disease progression and is associated with more favorable impact on survival in patients. Unfortunately, endocrine resistance occurs, either de novo or acquired during the course of the treatment. The mechanisms that contribute to hormonal resistance include loss or modification in the ERα expression, regulation of signal transduction pathways, altered expression of specific microRNAs, balance of co-regulatory proteins, and genetic polymorphisms involved in tamoxifen metabolic activity. Because of the clinical consequences of endocrine resistance, new treatment strategies are arising to make the cells sensitive to tamoxifen. Here, we will review the current knowledge on mechanisms of endocrine resistance in breast cancer cells. In addition, we will discuss novel therapeutic strategies to overcome such resistance. Undoubtedly, circumventing endocrine resistance should help to improve therapy for the benefit of breast cancer patients. PMID:23344024

  12. Treatment Resistance Mechanisms of Malignant Glioma Tumor Stem Cells

    International Nuclear Information System (INIS)

    Schmalz, Philip G.R.; Shen, Michael J.; Park, John K.

    2011-01-01

    Malignant gliomas are highly lethal because of their resistance to conventional treatments. Recent evidence suggests that a minor subpopulation of cells with stem cell properties reside within these tumors. These tumor stem cells are more resistant to radiation and chemotherapies than their counterpart differentiated tumor cells and may underlie the persistence and recurrence of tumors following treatment. The various mechanisms by which tumor stem cells avoid or repair the damaging effects of cancer therapies are discussed

  13. Chemotherapeutics-resistance "arms" race: An update on mechanisms involved in resistance limiting EGFR inhibitors in lung cancer.

    Science.gov (United States)

    Singh, Pankaj Kumar; Silakari, Om

    2017-10-01

    Clinical reports suggest that EGFR-mutated lung cancer usually respond significantly towards small molecule tyrosine kinase inhibitors. Same studies also report the eventual development of acquired resistance within a median time interval of 9 to 14months. One of the major mechanisms involved in this acquired resistance was found to be a secondary point mutation at gate-keeper residue, EGFR T790M. However, there are other recent studies which disclose the role of few other novel key players such as, ZEB1, TOPK etc., in the development of tolerance towards the EGFR TKI's, along with other commonly known mechanisms, such as amplification of signalling pathways such as, c-MET, Erbb2, AXL, additional acquired secondary mutations (PIK3CA, BRAF), or phenotypic transformation (small cell or epithelial to mesenchymal transitions). Interestingly, a recent study showed development of resistance via another point mutation, C797S, in case of tumors which were previously resistant and were administered agents capable of overcoming T790M gatekeeper mutation based resistance. Thus, raising serious concern over the direction of drug development involving tyrosine kinases such as EGFR. Current approaches focussing on development of third generation inhibitors, dual inhibitors or inhibitors of HSP90 have shown significant activity but do not answer the long term question of resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. HYDRO-ABRASIVE RESISTANCE AND MECHANICAL PROPERTIES OF CONCRETE WITH ADDED FLY ASH

    OpenAIRE

    Ristić, Nenad; Grdić, Zoran; Topličić-Ćurčić, Gordana

    2015-01-01

    The durability of hydraulic engineering structures mostly depends on the resistance of their concrete surfaces to mechanical abrasion. In this paper, we study the hydro-abrasive resistance and mechanical properties of concrete in which cement is partially replaced with fly ash in various proportions. To evaluate these concretes, we measured their compressive strength, flexural strength, static modulus of elasticity, ultrasound velocity through concrete, and sclerometer rebound. The hydro-abra...

  15. Genomic sequencing of a strain of Acinetobacter baumannii and potential mechanisms to antibiotics resistance.

    Science.gov (United States)

    Zhao, Lei; Li, Hongru; Zhu, Ziwen; Wakefield, Mark R; Fang, Yujiang; Ye, Ying

    2017-06-01

    Acinetobacter baumannii has been becoming a great challenge to clinicians due to their resistance to almost all available antibiotics. In this study, we sequenced the genome from a multiple antibiotics resistant Acinetobacter baumannii stain which was named A. baumannii-1isolated from China by SMRT sequencing technology to explore its potential mechanisms to antibiotic resistance. We found that several mechanisms might contribute to the antibiotic resistance of Acinetobacter baumannii. Specifically, we found that SNP in genes associated with nucleotide excision repair and ABC transporter might contribute to its resistance to multiple antibiotics; we also found that specific genes associated with bacterial DNA integration and recombination, DNA-mediated transposition and response to antibiotics might contribute to its resistance to multiple antibiotics; Furthermore, specific genes associated with penicillin and cephalosporin biosynthetic pathway and specific genes associated with CHDL and MBL β-lactamase genes might contribute to its resistance to multiple antibiotics. Thus, the detailed mechanisms by which Acinetobacter baumannii show extensive resistance to multiple antibiotics are very complicated. Such a study might be helpful to develop new strategies to control Acinetobacter baumannii infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Investigating of four main carbapenem-resistance mechanisms in high-level carbapenem resistant Pseudomonas aeruginosa isolated from burn patients

    Directory of Open Access Journals (Sweden)

    Soodabeh Rostami

    2018-02-01

    Conclusion: Emerging antimicrobial resistance in burn wound bacterial pathogens is a serious therapeutic challenge for clinicians. In the present study, most of the isolates were MDR. This finding indicated an alarming spread of resistant isolates and suggested that infection control strategies should be considered. Resistance to carbapenems is influenced by several factors, not all of which were evaluated in our study; however, the results showed that production of MBLs and overexpression of the mexB gene were the most frequent mechanisms in carbapenem-resistant isolates.

  17. The use of high-throughput sequencing to investigate an outbreak of glycopeptide-resistant Enterococcus faecium with a novel quinupristin-dalfopristin resistance mechanism.

    Science.gov (United States)

    Shaw, Timothy D; Fairley, D J; Schneiders, T; Pathiraja, M; Hill, R L R; Werner, G; Elborn, J S; McMullan, R

    2018-02-24

    High-throughput sequencing (HTS) has successfully identified novel resistance genes in enterococci and determined clonal relatedness in outbreak analysis. We report the use of HTS to investigate two concurrent outbreaks of glycopeptide-resistant Enterococcus faecium (GRE) with an uncharacterised resistance mechanism to quinupristin-dalfopristin (QD). Seven QD-resistant and five QD-susceptible GRE isolates from a two-centre outbreak were studied. HTS was performed to identify genes or predicted proteins that were associated with the QD-resistant phenotype. MLST and SNP typing on HTS data was used to determine clonal relatedness. Comparative genomic analysis confirmed this GRE outbreak involved two distinct clones (ST80 and ST192). HTS confirmed the absence of known QD resistance genes, suggesting a novel mechanism was conferring resistance. Genomic analysis identified two significant genetic determinants with explanatory power for the high level of QD resistance in the ST80 QD-resistant clone: an additional 56aa leader sequence at the N-terminus of the lsaE gene and a transposon containing seven genes encoding proteins with possible drug or drug-target modification activities. However, HTS was unable to conclusively determine the QD resistance mechanism and did not reveal any genetic basis for QD resistance in the ST192 clone. This study highlights the usefulness of HTS in deciphering the degree of relatedness in two concurrent GRE outbreaks. Although HTS was able to reveal some genetic candidates for uncharacterised QD resistance, this study demonstrates the limitations of HTS as a tool for identifying putative determinants of resistance to QD.

  18. Semi-Autonomous Systems Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — VisionThe Semi-Autonomous Systems Lab focuses on developing a comprehensive framework for semi-autonomous coordination of networked robotic systems. Semi-autonomous...

  19. The Use of Autonomous Systems in Emergency Medical Services: Bridging Human Intelligence and Technology

    Science.gov (United States)

    2015-12-01

    Google’s Autonomous Car Applies Lessons Learned from Driverless Races by Alan Brown, the literature provides the reader with a basic understanding of...Brown, “Google’s Autonomous Car Applies Lessons Learned from Driverless Races,” Mechanical Engineering 133, no. 2 (February 2011): 31. 11 Robert...sensormonitoring.files.wordpress. com/2014/03/iot.png. B. AUTONOMOUS VEHICLE TECHNOLOGY The “Google Car,” “automatic car,” “ driverless vehicle

  20. Novel drug-resistance mechanisms of pemetrexed-treated non-small cell lung cancer.

    Science.gov (United States)

    Tanino, Ryosuke; Tsubata, Yukari; Harashima, Nanae; Harada, Mamoru; Isobe, Takeshi

    2018-03-30

    Pemetrexed (PEM) improves the overall survival of patients with advanced non-small cell lung cancer (NSCLC) when administered as maintenance therapy. However, PEM resistance often appears during the therapy. Although thymidylate synthase is known to be responsible for PEM resistance, no other mechanisms have been investigated in detail. In this study, we explored new drug resistance mechanisms of PEM-treated NSCLC using two combinations of parental and PEM-resistant NSCLC cell lines from PC-9 and A549. PEM increased the apoptosis cells in parental PC-9 and the senescent cells in parental A549. However, such changes were not observed in the respective PEM-resistant cell lines. Quantitative RT-PCR analysis revealed that, besides an increased gene expression of thymidylate synthase in PEM-resistant PC-9 cells, the solute carrier family 19 member1 ( SLC19A1) gene expression was markedly decreased in PEM-resistant A549 cells. The siRNA-mediated knockdown of SLC19A1 endowed the parental cell lines with PEM resistance. Conversely, PEM-resistant PC-9 cells carrying an epidermal growth factor receptor (EGFR) mutation acquired resistance to a tyrosine kinase inhibitor erlotinib. Although erlotinib can inhibit the phosphorylation of EGFR and Erk, it is unable to suppress the phosphorylation of Akt in PEM-resistant PC-9 cells. Additionally, PEM-resistant PC-9 cells were less sensitive to the PI3K inhibitor LY294002 than parental PC-9 cells. These results indicate that SLC19A1 negatively regulates PEM resistance in NSCLC, and that EGFR-tyrosine-kinase-inhibitor resistance was acquired with PEM resistance through Akt activation in NSCLC harboring EGFR mutations.

  1. Molecular mechanisms associated with nosocomial carbapenem-resistant Acinetobacter baumannii in Mexico.

    Science.gov (United States)

    Alcántar-Curiel, María Dolores; García-Torres, Luis Francisco; González-Chávez, María Inés; Morfín-Otero, Rayo; Gayosso-Vázquez, Catalina; Jarillo-Quijada, Ma Dolores; Fernández-Vázquez, José Luis; Giono-Cerezo, Silvia; Rodríguez-Noriega, Eduardo; Santos-Preciado, José Ignacio

    2014-10-01

    Acinetobacter baumannii is an emerging pathogen worldwide that is most commonly associated with nosocomial infections and multi-drug resistance. In the present study we determined the mechanisms of carbapenem resistance and clonal diversity of A. baumannii nosocomial isolates in Hospital Civil de Guadalajara, Mexico. A total of 303 clinical isolates of A. baumannii identified during a period expanding from 2004-2011 were analyzed for carbapenem resistance using several microbiological and molecular methods. Clonal relatedness of these isolates was determined using pulsed-field gel electrophoresis. Of the 303 isolates, 84% were resistant to meropenem, 71.3% to imipenem and 78.3% the resistant isolates were positive for metallo-β-lactamases as determined by the phenotypic assay. In addition, 49.6% of carbapenem-intermediate or -resistant isolates carried the blaOXA-72 gene and 1.2% carried the blaVIM-1 gene. Efflux pump phenotype was responsible for reduced susceptibility to meropenem in 14.5% and to imipenem in 31.6% of the resistant isolates, respectively in the presence of the efflux pump inhibitor, carbonyl cyanide 3-chlorophenylhydrazone. Strains representing different carbapenem-resistant patterns exhibited reduced expression of 22, 29, 33, and 43 kDa OMPs. Among the bacterial collection studied, 48 different clones were identified, two of which were predominant and persistently transmitted. Carbapenemase production in combination with efflux pump expression, reduction in OMPs expression and the cross-transmission of clones appear to be major contributors to the high frequency of carbapenem-resistance observed in A. baumannii. To our knowledge, this is the first study to define the molecular mechanisms associated with carbapenem-resistance in A. baumannii in Mexico. Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.

  2. Mechanisms of methicillin resistance in Staphylococcus aureus and methods for laboratory detection.

    Science.gov (United States)

    Jorgensen, J H

    1991-01-01

    Three distinctly different mechanisms of methicillin resistance have been described in Staphylococcus aureus. The best-documented and probably most important mechanism is production of a unique, low affinity penicillin-binding protein, PBP 2a. Strains possessing PBP 2a are resistant to methicillin, oxacillin, and probably all other currently available beta-lactam antibiotics. Two additional mechanisms of reduced susceptibility to methicillin have been described. Borderline resistance (BORSA) to the semi-synthetic penicillins has been attributed to the hyperproduction of normal staphylococcal beta-lactamase. A third mechanism has recently been advanced that describes an intermediate level of resistance to methicillin due to production of modified, normal PBPs with reduced affinity for beta-lactams (MODSA). Little is known regarding the prevalence or clinical significance of the BORSA and MODSA strains. The most reliable in vitro susceptibility test methods for detecting MRSA (strains possessing PBP 2a) include the microdilution minimum inhibitory concentration (MIC) test (with 2% NaCl supplemented broth), the oxacillin agar screen plate test (incorporating 6 micrograms/ml oxacillin in 4% NaCl supplemented agar), and the National Committee for Clinical Laboratory Standards (NCCLS) disk diffusion test with oxacillin. All three methods use direct inoculum preparation and incubation of tests at 35 degrees C for a full 24 hours.

  3. Environmental resistance and mechanical performance of basalt and glass fibers

    International Nuclear Information System (INIS)

    Wei Bin; Cao Hailin; Song Shenhua

    2010-01-01

    The treated basalt and glass fibers with sodium hydroxide and hydrochloric acid solutions for different times were analyzed, respectively. This paper summarized the mass loss ratio and the strength maintenance ratios of the fibers after treatment. The fibers' surface corrosion morphologies were characterized using scanning electron microscopy and their compositions were detected using energy dispersive X-ray spectroscopy. The acid resistance was much better than the alkali resistance for the basalt fibers. Nevertheless, for the glass fibers the situation is different: the acid resistance was almost the same as the alkali resistance. Among the two types of aqueous environments evaluated, the alkali solution is the most aggressive to the fibers' surface. The possible corrosion mechanisms are revealed.

  4. On heart rate variability and autonomic activity in homeostasis and in systemic inflammation.

    Science.gov (United States)

    Scheff, Jeremy D; Griffel, Benjamin; Corbett, Siobhan A; Calvano, Steve E; Androulakis, Ioannis P

    2014-06-01

    Analysis of heart rate variability (HRV) is a promising diagnostic technique due to the noninvasive nature of the measurements involved and established correlations with disease severity, particularly in inflammation-linked disorders. However, the complexities underlying the interpretation of HRV complicate understanding the mechanisms that cause variability. Despite this, such interpretations are often found in literature. In this paper we explored mathematical modeling of the relationship between the autonomic nervous system and the heart, incorporating basic mechanisms such as perturbing mean values of oscillating autonomic activities and saturating signal transduction pathways to explore their impacts on HRV. We focused our analysis on human endotoxemia, a well-established, controlled experimental model of systemic inflammation that provokes changes in HRV representative of acute stress. By contrasting modeling results with published experimental data and analyses, we found that even a simple model linking the autonomic nervous system and the heart confound the interpretation of HRV changes in human endotoxemia. Multiple plausible alternative hypotheses, encoded in a model-based framework, equally reconciled experimental results. In total, our work illustrates how conventional assumptions about the relationships between autonomic activity and frequency-domain HRV metrics break down, even in a simple model. This underscores the need for further experimental work towards unraveling the underlying mechanisms of autonomic dysfunction and HRV changes in systemic inflammation. Understanding the extent of information encoded in HRV signals is critical in appropriately analyzing prior and future studies. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. High-frequency autonomic modulation: a new model for analysis of autonomic cardiac control.

    Science.gov (United States)

    Champéroux, Pascal; Fesler, Pierre; Judé, Sebastien; Richard, Serge; Le Guennec, Jean-Yves; Thireau, Jérôme

    2018-05-03

    Increase in high-frequency beat-to-beat heart rate oscillations by torsadogenic hERG blockers appears to be associated with signs of parasympathetic and sympathetic co-activation which cannot be assessed directly using classic methods of heart rate variability analysis. The present work aimed to find a translational model that would allow this particular state of the autonomic control of heart rate to be assessed. High-frequency heart rate and heart period oscillations were analysed within discrete 10 s intervals in a cohort of 200 healthy human subjects. Results were compared to data collected in non-human primates and beagle dogs during pharmacological challenges and torsadogenic hERG blockers exposure, in 127 genotyped LQT1 patients on/off β-blocker treatment and in subgroups of smoking and non-smoking subjects. Three states of autonomic modulation, S1 (parasympathetic predominance) to S3 (reciprocal parasympathetic withdrawal/sympathetic activation), were differentiated to build a new model of heart rate variability referred to as high-frequency autonomic modulation. The S2 state corresponded to a specific state during which both parasympathetic and sympathetic systems were coexisting or co-activated. S2 oscillations were proportionally increased by torsadogenic hERG-blocking drugs, whereas smoking caused an increase in S3 oscillations. The combined analysis of the magnitude of high-frequency heart rate and high-frequency heart period oscillations allows a refined assessment of heart rate autonomic modulation applicable to long-term ECG recordings and offers new approaches to assessment of the risk of sudden death both in terms of underlying mechanisms and sensitivity. © 2018 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

  6. Modulation of autonomic activity in neurological conditions: Epilepsy and Tourette syndrome

    Directory of Open Access Journals (Sweden)

    Yoko eNagai

    2015-09-01

    Full Text Available This manuscript considers the central but neglected role of the autonomic nervous system in the expression and control of seizures in Epilepsy and tics in Tourette Syndrome (TS. In epilepsy, consideration of autonomic involvement is typically confined to differential diagnoses (e.g. syncope, or in relation to Sudden Unexpected Death in Epilepsy (SUDEP. Investigation is more limited in Tourette Syndrome. The role of the autonomic nervous system in the generation and prevention of epileptic seizures is largely overlooked. Emotional stimuli such as anxiety and stress are potent causes of seizures and tic activity in TS, respectively. This manuscript will describe a possible neural mechanism by which afferent autonomic projections linked to cognition and behaviour influence central nervous system thalamo-cortical regulation, which appears to be an important means for controlling both seizure and tic activity. It also summarizes the link between the integrity of the default mode network and autonomic regulation in patients with epilepsy as well as the link between impaired motor control and autonomic regulation in patients with TS. Two neurological conditions; epilepsy and TS were chosen, as seizures and tics represent parameters that can be easily measured to investigate influences of autonomic functions. The EDA biofeedback approach is anticipated

  7. Molecular Mechanisms of Insulin Resistance in Chronic Kidney Disease

    Science.gov (United States)

    Thomas, Sandhya S.; Zhang, Liping; Mitch, William E.

    2015-01-01

    Insulin resistance refers to reduced sensitivity of organs to insulin-initiated biologic processes that result in metabolic defects. Insulin resistance is common in patients with end-stage renal disease but also occurs in patients with chronic kidney disease (CKD), even when the serum creatinine is minimally increased. Following insulin binding to its receptor, auto-phosphorylation of the insulin receptor is followed by kinase reactions that phosphorylate insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3-kinase (PI3K) and Akt. In fact, low levels of Akt phosphorylation (p-Akt) identifies the presence of the insulin resistance that leads to metabolic defects in insulin-initiated metabolism of glucose, lipids and muscle proteins. Besides CKD, other complex conditions (e.g., inflammation, oxidative stress, metabolic acidosis, aging and excess angiotensin II) reduce p-Akt resulting in insulin resistance. Insulin resistance in each of these conditions is due to activation of different, E3 ubiquitin ligases which specifically conjugate ubiquitin to IRS-1 marking it for degradation in the ubiquitin-proteasome system (UPS). Consequently, IRS-1 degradation suppresses insulin-induced intracellular signaling, causing insulin resistance. Understanding mechanisms of insulin resistance could lead to therapeutic strategies that improve the metabolism of patients with CKD. PMID:26444029

  8. Dissemination and Mechanism for the MCR-1 Colistin Resistance.

    Directory of Open Access Journals (Sweden)

    Rongsui Gao

    2016-11-01

    Full Text Available Polymyxins are the last line of defense against lethal infections caused by multidrug resistant Gram-negative pathogens. Very recently, the use of polymyxins has been greatly challenged by the emergence of the plasmid-borne mobile colistin resistance gene (mcr-1. However, the mechanistic aspects of the MCR-1 colistin resistance are still poorly understood. Here we report the comparative genomics of two new mcr-1-harbouring plasmids isolated from the human gut microbiota, highlighting the diversity in plasmid transfer of the mcr-1 gene. Further genetic dissection delineated that both the trans-membrane region and a substrate-binding motif are required for the MCR-1-mediated colistin resistance. The soluble form of the membrane protein MCR-1 was successfully prepared and verified. Phylogenetic analyses revealed that MCR-1 is highly homologous to its counterpart PEA lipid A transferase in Paenibacili, a known producer of polymyxins. The fact that the plasmid-borne MCR-1 is placed in a subclade neighboring the chromosome-encoded colistin-resistant Neisseria LptA (EptA potentially implies parallel evolutionary paths for the two genes. In conclusion, our finding provids a first glimpse of mechanism for the MCR-1-mediated colistin resistance.

  9. Survey on the phage resistance mechanisms displayed by a dairy Lactobacillus helveticus strain.

    Science.gov (United States)

    Zago, Miriam; Orrù, Luigi; Rossetti, Lia; Lamontanara, Antonella; Fornasari, Maria Emanuela; Bonvini, Barbara; Meucci, Aurora; Carminati, Domenico; Cattivelli, Luigi; Giraffa, Giorgio

    2017-09-01

    In this study the presence and functionality of phage defence mechanisms in Lactobacillus helveticus ATCC 10386, a strain of dairy origin which is sensitive to ΦLh56, were investigated. After exposure of ATCC 10386 to ΦLh56, the whole-genome sequences of ATCC 10386 and of a phage-resistant derivative (LhM3) were compared. LhM3 showed deletions in the S-layer protein and a higher expression of the genes involved in the restriction/modification (R/M) system. Genetic data were substantiated by measurements of bacteriophage adsorption rates, efficiency of plaquing, cell wall protein size and by gene expression analysis. In LhM3 two phage resistance mechanisms, the inhibition of phage adsorption and the upregulation of Type I R/M genes, take place and explain its resistance to ΦLh56. Although present in both ATCC 10386 and LhM3 genomes, the CRISPR machinery did not seem to play a role in the phage resistance of LhM3. Overall, the natural selection of phage resistant strains resulted successful in detecting variants carrying multiple phage defence mechanisms in L. helveticus. The concurrent presence of multiple phage-resistance systems should provide starter strains with increased fitness and robustness in dairy ecosystems. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Mechanism of cisplatin resistance in human urothelial carcinoma cells.

    Science.gov (United States)

    Yu, Hui-Min; Wang, Tsing-Cheng

    2012-05-01

    An isogenic pair of cisplatin-susceptible (NTUB1) and -resistant (NTUB1/P) human urothelial carcinoma cell lines was used to elucidate the mechanism of cisplatin resistance. The significantly lower intracellular platinum (IP) concentration, which resulted from the decreased cisplatin uptake, was found in NTUB1/P cells. The enhancement of IP concentration did not increase the susceptibility of NTUB1/P cells to cisplatin treatment. The reduction of IP concentration as well was unable to enhance the cisplatin-resistance in susceptible NTUB1 cells. This indicated that reduction of IP concentration was not the account for the development of cisplatin resistance here. Instead, the over expression of anti-apoptotic Bcl-2, anti-oxidative heme oxygenase-1 (HO-1) and cell cycle regulator p16INK4 seemed to be more important for the gaining of cisplatin in these human urothelial carcinoma cell. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Antimicrobial resistance (AMR) nanomachines-mechanisms for fluoroquinolone and glycopeptide recognition, efflux and/or deactivation.

    Science.gov (United States)

    Phillips-Jones, Mary K; Harding, Stephen E

    2018-04-01

    In this review, we discuss mechanisms of resistance identified in bacterial agents Staphylococcus aureus and the enterococci towards two priority classes of antibiotics-the fluoroquinolones and the glycopeptides. Members of both classes interact with a number of components in the cells of these bacteria, so the cellular targets are also considered. Fluoroquinolone resistance mechanisms include efflux pumps (MepA, NorA, NorB, NorC, MdeA, LmrS or SdrM in S. aureus and EfmA or EfrAB in the enterococci) for removal of fluoroquinolone from the intracellular environment of bacterial cells and/or protection of the gyrase and topoisomerase IV target sites in Enterococcus faecalis by Qnr-like proteins. Expression of efflux systems is regulated by GntR-like (S. aureus NorG), MarR-like (MgrA, MepR) regulators or a two-component signal transduction system (TCS) (S. aureus ArlSR). Resistance to the glycopeptide antibiotic teicoplanin occurs via efflux regulated by the TcaR regulator in S. aureus. Resistance to vancomycin occurs through modification of the D-Ala-D-Ala target in the cell wall peptidoglycan and removal of high affinity precursors, or by target protection via cell wall thickening. Of the six Van resistance types (VanA-E, VanG), the VanA resistance type is considered in this review, including its regulation by the VanSR TCS. We describe the recent application of biophysical approaches such as the hydrodynamic technique of analytical ultracentrifugation and circular dichroism spectroscopy to identify the possible molecular effector of the VanS receptor that activates expression of the Van resistance genes; both approaches demonstrated that vancomycin interacts with VanS, suggesting that vancomycin itself (or vancomycin with an accessory factor) may be an effector of vancomycin resistance. With 16 and 19 proteins or protein complexes involved in fluoroquinolone and glycopeptide resistances, respectively, and the complexities of bacterial sensing mechanisms that

  12. Acute and chronic effects of aerobic exercise on blood pressure in resistant hypertension: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Nascimento, L S; Santos, A C; Lucena, Jms; Silva, Lgo; Almeida, Aem; Brasileiro-Santos, M S

    2017-06-02

    Resistant hypertension is a specific condition that affects approximately 10% of subjects with hypertension, and is characterized by persistently high blood pressure levels even using therapy of three or more antihypertensive agents or with blood pressure control using therapy with four or more antihypertensive agents. Changes in lifestyle, such as physical exercise, are indicated for controlling blood pressure. However, investigating studies about this therapy in individuals with resistant hypertension are few. This is a randomized controlled clinical trial. Forty-eight patients with resistant hypertension will be submitted to perform four short-term interventions: aerobic exercise sessions (mild-, moderate- and high-intensity) and control session, in random order and on separate days. After the short-term sessions, the patients will be randomly allocated into four groups for 8 weeks of follow-up: mild-, moderate- and high-intensity aerobic exercise, and a control group. The primary outcome is the occurrence of blood pressure reduction (office and ambulatory analysis, and acute and chronic effects). Secondary outcomes are autonomic and hemodynamic mechanisms: cardiac and vasomotor autonomic modulation, spontaneous baroreflex sensitivity, forearm blood flow and vascular resistance. The importance of exercise for hypertension has been known for decades, but little is known about the effects on patients with resistant hypertension. This study will help to understand whether different aerobic exercise intensities can induce different responses, as well as by what mechanisms adjustments in blood pressure levels may occur. ClinicalTrials.gov, ID: NCT02670681 . Registered on 28 January 2016 (first version); Brazilian Registry Platform Clinical Trials: protocol RBR-5q24zh . Registered on 24 June 2015.

  13. Buprofezin susceptibility survey, resistance selection and preliminary determination of the resistance mechanism in Nilaparvata lugens (Homoptera: Delphacidae).

    Science.gov (United States)

    Wang, Yanhua; Gao, Congfen; Xu, Zhiping; Zhu, Yu Cheng; Zhang, Jiushuang; Li, Wenhong; Dai, Dejiang; Lin, Youwei; Zhou, Weijun; Shen, Jinliang

    2008-10-01

    Buprofezin has been used for many years to control Nilaparvata lugens (Stål). Assessment of susceptibility change in the insect is essential for maintaining control efficiency and resistance management. Eleven-year surveys showed that most field populations were susceptible before 2004. However, substantially higher levels of resistance (up to 28-fold) were found in most of the rice fields in China after 2004. A field population was collected and periodically selected for buprofezin resistance in the laboratory. After 65 generations (56 were selected), the colony successfully obtained 3599-fold resistance to buprofezin. Synergism tests showed that O,O-diethyl-O-phenyl phosphorothioate (SV1), piperonyl butoxide (PBO) and diethyl maleate (DEM) increased buprofezin toxicity in the resistant strain by only 1.5-1.6 fold, suggesting that esterases, P450-monooxygenases and glutathione S-transferases had no substantial effect on buprofezin resistance development. The results from this study indicate that N. lugens has the potential to develop high resistance to buprofezin. A resistance management program with rotation of buprofezin and other pesticides may efficiently delay or slow down resistance development in the insect. Further investigation is also necessary to understand the resistance mechanisms in N. lugens.

  14. Ciprofloxacin-resistant Escherichia coli in Central Greece: mechanisms of resistance and molecular identification

    Directory of Open Access Journals (Sweden)

    Mavroidi Angeliki

    2012-12-01

    Full Text Available Abstract Background Fluoroquinolone resistant E. coli isolates, that are also resistant to other classes of antibiotics, is a significant challenge to antibiotic treatment and infection control policies. In Central Greece a significant increase of ciprofloxacin-resistant Escherichia coli has occurred during 2011, indicating the need for further analysis. Methods A total of 106 ciprofloxacin-resistant out of 505 E. coli isolates consecutively collected during an eight months period in a tertiary Greek hospital of Central Greece were studied. Antimicrobial susceptibility patterns and mechanisms of resistance to quinolones were assessed, whereas selected isolates were further characterized by multilocus sequence typing and β-lactamase content. Results Sequence analysis of the quinolone-resistance determining region of the gyrA and parC genes has revealed that 63% of the ciprofloxacin-resistant E. coli harbored a distinct amino acid substitution pattern (GyrA:S83L + D87N; ParC:S80I + E84V, while 34% and 3% carried the patterns GyrA:S83L + D87N; ParC:S80I and GyrA:S83L + D87N; ParC:S80I + E84G respectively. The aac (6’-1b-cr plasmid-mediated quinolone resistance determinant was also detected; none of the isolates was found to carry the qnrA, qnrB and qnrS. Genotyping of a subset of 35 selected ciprofloxacin-resistant E. coli by multilocus sequence typing has revealed the presence of nine sequence types; ST131 and ST410 were the most prevalent and were exclusively correlated with hospital and health care associated infections, while strains belonging to STs 393, 361 and 162 were associated with community acquired infections. The GyrA:S83L + D87N; ParC:S80I + E84V substitution pattern was found exclusively among ST131 ciprofloxacin-resistant E. coli. Extended-spectrum β-lactamase-positive ST131 ciprofloxacin-resistant isolates produced CTX-M-type enzymes; eight the CTX-M-15 and one the CTX-M-3 variant. CTX-M-1 like and KPC-2 enzymes were detected

  15. Pilot In Command: A Feasibility Assessment of Autonomous Flight Management Operations

    Science.gov (United States)

    Wing, David J.; Ballin, Mark G.; Krishnamurthy, Karthik

    2004-01-01

    Several years of NASA research have produced the air traffic management operational concept of Autonomous Flight Management with high potential for operational feasibility, significant system and user benefits, and safety. Among the chief potential benefits are demand-adaptive or scalable capacity, user flexibility and autonomy that may finally enable truly successful business strategies, and compatibility with current-day operations such that the implementation rate can be driven from within the user community. A concept summary of Autonomous Flight Management is provided, including a description of how these operations would integrate in shared airspace with existing ground-controlled flight operations. The mechanisms enabling the primary benefits are discussed, and key findings of a feasibility assessment of airborne autonomous operations are summarized. Concept characteristics that impact safety are presented, and the potential for initially implementing Autonomous Flight Management is discussed.

  16. Toward autonomous operation and maintenance of nuclear power plants

    International Nuclear Information System (INIS)

    Kitamura, M.

    1994-01-01

    Issues toward realization of autonomous operation as well as maintenance of nuclear power plants are reviewed in this paper. First, the necessity and significance of the technical program aiming at the establishment of autonomous nuclear plant are discussed through reviewing the history and current status computerized operation of complex artifacts. Then, key technologies currently studied to meet the need within the framework of artificial intelligence (AI) and advanced robotics are described. Among such AI-technologies are distributed multi-agent system, operator thinking model, and advanced man-machine interface design. Advances in robot technology attained include active sensing technique and multi-unit autonomous maintenance robot systems. Techniques for simulation of human action have been pursued as basic issues for understanding mechanisms behind human behavior. In addition to the individual developments, methodological topics relevant to the autonomy of nuclear facilities are briefly addressed. The concepts called methodology diversity and dynamic functionality restoration (realization) are introduced and discussed as the underlining principles to be considered in the development of the autonomous nuclear power plants. (author)

  17. Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options

    Science.gov (United States)

    Lee, Chang-Ro; Lee, Jung Hun; Park, Moonhee; Park, Kwang Seung; Bae, Il Kwon; Kim, Young Bae; Cha, Chang-Jun; Jeong, Byeong Chul; Lee, Sang Hee

    2017-01-01

    Acinetobacter baumannii is undoubtedly one of the most successful pathogens responsible for hospital-acquired nosocomial infections in the modern healthcare system. Due to the prevalence of infections and outbreaks caused by multi-drug resistant A. baumannii, few antibiotics are effective for treating infections caused by this pathogen. To overcome this problem, knowledge of the pathogenesis and antibiotic resistance mechanisms of A. baumannii is important. In this review, we summarize current studies on the virulence factors that contribute to A. baumannii pathogenesis, including porins, capsular polysaccharides, lipopolysaccharides, phospholipases, outer membrane vesicles, metal acquisition systems, and protein secretion systems. Mechanisms of antibiotic resistance of this organism, including acquirement of β-lactamases, up-regulation of multidrug efflux pumps, modification of aminoglycosides, permeability defects, and alteration of target sites, are also discussed. Lastly, novel prospective treatment options for infections caused by multi-drug resistant A. baumannii are summarized. PMID:28348979

  18. A cfr-positive clinical staphylococcal isolate from India with multiple mechanisms of linezolid-resistance

    Directory of Open Access Journals (Sweden)

    Vineeth Rajan

    2014-01-01

    Full Text Available Background & objectives: Linezolid, a member of the oxazolidinone class of antibiotics, has been an effective therapeutic option to treat severe infections caused by multidrug resistant Gram positive bacteria. Emergence of linezolid resistant clinical strains is a serious issue in the healthcare settings worldwide. We report here the molecular characterization of a linezolid resistant clinical isolate of Staphylococcus haemolyticus from India. Methods: The species of the clinical isolate was identified by 16S rRNA gene sequencing. The minimum inhibitory concentrations (MICs of linezolid, clindamycin, chloramphenicol and oxacillin were determined by E-test method. To elucidate the mechanism of linezolid-resistance, presence of cfr gene (chloramphenicol florfenicol resistance and mutations in 23S rRNA and ribosomal proteins (L3, L4 and L22 were investigated. Staphylococcal Cassette Chromosome mec (SCCmec typing was performed by multiplex PCR. Results: The study documented a rare clinical S. haemolyticus strain with three independent mechanisms of linezolid-resistance. The strain carried cfr gene, the only known transmissible mechanism of linezolid-resistance. The strain also possessed resistance-conferring mutations such as G 2576 T in domain V of 23S rRNA gene and Met 156 Thr in L3 ribosomal protein. The other ribosomal proteins (L4 and L22 did not exhibit mutations accountable for linezolid-resistance. Restriction digestion by NheI revealed that all the alleles of 23S rRNA gene were mutated. The isolate showed elevated MIC values (>256 ΅g ml -[1] of linezolid, clindamycin, chloramphenicol and oxacillin. Methicillin resistance was conferred by type I SCCmec element. The strain also harboured lsa(B gene which encodes an ABC transporter that can efflux clindamycin. Interpretation & conclusions: The present study reports the first clinical strain from India with transmissible and multiple mechanisms of linezolid-resistance. Judicious use of

  19. Mechanisms of azole resistance in a clinical isolate of Candida tropicalis.

    Science.gov (United States)

    Vandeputte, Patrick; Larcher, Gérald; Bergès, Thierry; Renier, Gilles; Chabasse, Dominique; Bouchara, Jean-Philippe

    2005-11-01

    Azole resistance has been insufficiently investigated in the yeast Candida tropicalis. Here we determined the molecular mechanisms responsible for azole resistance in a clinical isolate of this pathogenic yeast. Antifungal susceptibility testing performed by a disk diffusion method showed resistance or markedly decreased susceptibility to azoles, which was confirmed by determination of MICs. Considering the relationship between azole susceptibility and the respiration reported for other yeast species, the respiratory activity of this isolate was investigated. Flow cytometry using rhodamine 123 and oxygraphy demonstrated an increased respiratory activity, which was not linked to an overexpression or increased number of copies of the mitochondrial genome. Among previously described resistance mechanisms, an increased activity of efflux pumps was investigated by flow cytometry using rhodamine 6G. However, the efflux of rhodamine 6G was lower in the resistant isolate than in susceptible ones. Likewise, real-time reverse transcription-PCR quantification of the expression of C. tropicalis MDR1 (CtMDR1), which encodes an efflux protein belonging to the major facilitator superfamily, did not show overexpression of this gene. In contrast, the resistant isolate overexpressed the CtERG11 gene coding for lanosterol 14alpha-demethylase. This was in agreement with the larger amount of ergosterol found in this isolate. Moreover, sequencing of CtERG11 showed a point mutation leading to a tyrosine substitution in the protein sequence, which might lead to decreased binding affinity for azoles. In conclusion, overexpression of CtERG11 associated with a missense mutation in this gene seemed to be responsible for the acquired azole resistance of this clinical isolate.

  20. Mechanisms of quinolone resistance in Salmonella spp. / Mecanismos de resistência às quinolonas em Salmonella spp.

    Directory of Open Access Journals (Sweden)

    Tereza Cristina Rocha Moreira de Oliveira

    2010-07-01

    Full Text Available Salmonellosis is a common and widespread zoonotic disease of humans and a frequent cause of foodborne disease. Treatment of severe and systemic salmonellosis is usually done with fluoroquinolones. In this review resistance mechanisms of Salmonella to quinolones are discussed. Single point mutations in the quinolone resistant determining region (QRDR of the gyrA gene may be sufficient to generate high levels of resistance to non-fluorated quinolones and also may decrease the fluoroquinolones susceptibility. Other resistance mechanisms that should be considered are mutations in parC gene, the possibility of acquiring resistance through plasmidial transference and hyper-expression of efflux pumps. Fluoroquinolones resistance is still relatively uncommon in Salmonella compared to other species belonging to the Enterobacteriaceae family. However, the more careful use of fluoroquinolones in veterinary and human medicine is essential to decrease the selective pressure which can avoid the emergence and spread of resistant clones and consequently maintain the clinical efficacy of this group of antibiotics.A salmonelose é uma zoonose de importância mundial e uma das mais freqüentes doenças de origem alimentar. As fluoroquinolonas são a principal opção para o tratamento de salmoneloses graves ou sistêmicas. Esta revisão de literatura teve como objetivo apresentar os principais mecanismos envolvidos na resistência de Salmonella spp a estes antimicrobianos. Mutações de ponto na Região Determinante de Resistência à Quinolona (QRDR do gene gyrA podem gerar altos níveis de resistência a quinolonas não-fluoradas, além de reduzir a suscetibilidade as fluoroquinolonas. Outros mecanismos de resistência que também precisam ser considerados são as mutações no gene parC, a possibilidade do envolvimento de plasmídios de resistência e o sistema de efluxo ativo. A resistência às fluoroquinolonas ainda é incomum em Salmonella spp., quando

  1. The operational mechanism of ferroelectric-driven organic resistive switches

    NARCIS (Netherlands)

    Kemerink, M.; Asadi, K.; Blom, P.W.M.; Leeuw, D.M. de

    2012-01-01

    The availability of a reliable memory element is crucial for the fabrication of 'plastic' logic circuits. We use numerical simulations to show that the switching mechanism of ferroelectric-driven organic resistive switches is the stray field of the polarized ferroelectric phase. The stray field

  2. The operational mechanism of ferroelectric-driven organic resistive switches

    NARCIS (Netherlands)

    Kemerink, M.; Asadi, K. (Kamal); Blom, P.W.M.; Leeuw, de D.M.

    2012-01-01

    The availability of a reliable memory element is crucial for the fabrication of ‘plastic’ logic circuits. We use numerical simulations to show that the switching mechanism of ferroelectric-driven organic resistive switches is the stray field of the polarized ferroelectric phase. The stray field

  3. The operational mechanism of ferroelectric-driven organic resistive switches

    NARCIS (Netherlands)

    Kemerink, Martijn; Asadi, Kamal; Blom, Paul W. M.; de Leeuw, Dago M.

    The availability of a reliable memory element is crucial for the fabrication of 'plastic' logic circuits. We use numerical simulations to show that the switching mechanism of ferroelectric-driven organic resistive switches is the stray field of the polarized ferroelectric phase. The stray field

  4. miR126-5p down-regulation facilitates axon degeneration and NMJ disruption via a non-cell-autonomous mechanism in ALS.

    Science.gov (United States)

    Maimon, Roy; Ionescu, Ariel; Bonnie, Avichai; Sweetat, Sahar; Wald-Altman, Shane; Inbar, Shani; Gradus, Tal; Trotti, Davide; Weil, Miguel; Behar, Oded; Perlson, Eran

    2018-05-17

    Axon degeneration and disruption of neuromuscular junctions (NMJs) are key events in Amyotrophic Lateral Sclerosis (ALS) pathology. Although the disease's etiology is not fully understood, it is thought to involve a non-cell-autonomous mechanism and alterations in RNA metabolism. Here, we identified reduced levels of miR-126-5p in pre-symptomatic ALS male mice models, and an increase in its targets: axon destabilizing type-3 Semaphorins and their co-receptor Neuropilins. Utilizing compartmentalized in vitro co-cultures, we demonstrated that myocytes expressing diverse ALS-causing mutations promote axon degeneration and NMJ dysfunction, which were inhibited by applying Neuropilin1 (NRP1) blocking antibody. Finally, overexpressing miR126-5p is sufficient to transiently rescue axon degeneration and NMJ disruption both in vitro and in vivo Thus, we demonstrate a novel mechanism underlying ALS pathology, in which alterations in miR126-5p facilitate a non-cell-autonomous mechanism of motor neuron degeneration in ALS. SIGNIFICANCE STATEMENT In spite of some progress, currently no effective treatment is available for ALS. We suggest a novel regulatory role for miR126-5p in ALS and demonstrate for the first time a mechanism by which alterations in miR126-5p contribute to axon degeneration and NMJ disruption observed in ALS. We show that miR126-5p is altered in ALS models and that it can modulate Sema3 and NRP protein expression. Furthermore, NRP1 elevations in motor neurons and muscle secretion of Sema3A contribute to axon degeneration and NMJ disruption in ALS. Finally, overexpressing miR126-5p is sufficient to transiently rescue NMJ disruption and axon degeneration both in vitro and in vivo. Copyright © 2018 Maimon et al.

  5. Contact resistance at ceramic interfaces and its dependence on mechanical load

    DEFF Research Database (Denmark)

    Koch, Søren; Hendriksen, P.V.

    2004-01-01

    Low contact resistance between individual components is important for solid oxide fuel cell stacks if high performance is to be achieved. Several mechanisms may result in high contact resistance, e.g., current constriction due to low area of contact and formation of resistive phases between...... the components. In this study, the importance of current constriction due to limited area of contact at an interface is investigated by comparing the characteristics of contacts between LSM pellets with different surface finish. The load behaviour of the contact resistance has been investigated and a power law...... of the contact resistance was calculated using a simple model describing the variation of the contact area with load based on the measured surface roughness. Good agreement between the calculations and the experimentally observed resistances was found. (C) 2004 Elsevier B.V. All rights reserved....

  6. A Multifunctional Coating for Autonomous Corrosion Control

    Science.gov (United States)

    Calle, Luz M.; Li, Wenyan; Buhrow, Jerry W.; Jolley, Scott t.

    2011-01-01

    Nearly all metals and their alloys are subject to corrosion that causes them to lose their structural integrity or other critical functionality. Protective coatings are the most commonly used method of corrosion control. However, progressively stricter environmental regulations have resulted in the ban of many commercially available corrosion protective coatings due to the harmful effects of their solvents or corrosion inhibitors. This work concerns the development of a multifunctional smart coating for the autonomous control of corrosion. This coating is being developed to have the inherent ability to detect the chemical changes associated with the onset of corrosion and respond autonomously to indicate it and control it. The multi-functionality of the coating is based on microencapsulation technology specifically designed for corrosion control applications. This design has, in addition to all the advantages of existing microcapsulation designs, the corrosion controlled release function that triggers the delivery of corrosion indicators and inhibitors on demand, only when and where needed. Microencapsulation of self-healing agents for autonomous repair of mechanical damage to the coating is also being pursued. Corrosion indicators, corrosion inhibitors, as well as self-healing agents, have been encapsulated and dispersed into several paint systems to test the corrosion detection, inhibition, and self-healing properties of the coating. Key words: Corrosion, coating, autonomous corrosion control, corrosion indication, corrosion inhibition, self-healing coating, smart coating, multifunctional coating, microencapsulation.

  7. Recurrent myocardial infarction: Mechanisms of free-floating adaptation and autonomic derangement in networked cardiac neural control.

    Science.gov (United States)

    Kember, Guy; Ardell, Jeffrey L; Shivkumar, Kalyanam; Armour, J Andrew

    2017-01-01

    The cardiac nervous system continuously controls cardiac function whether or not pathology is present. While myocardial infarction typically has a major and catastrophic impact, population studies have shown that longer-term risk for recurrent myocardial infarction and the related potential for sudden cardiac death depends mainly upon standard atherosclerotic variables and autonomic nervous system maladaptations. Investigative neurocardiology has demonstrated that autonomic control of cardiac function includes local circuit neurons for networked control within the peripheral nervous system. The structural and adaptive characteristics of such networked interactions define the dynamics and a new normal for cardiac control that results in the aftermath of recurrent myocardial infarction and/or unstable angina that may or may not precipitate autonomic derangement. These features are explored here via a mathematical model of cardiac regulation. A main observation is that the control environment during pathology is an extrapolation to a setting outside prior experience. Although global bounds guarantee stability, the resulting closed-loop dynamics exhibited while the network adapts during pathology are aptly described as 'free-floating' in order to emphasize their dependence upon details of the network structure. The totality of the results provide a mechanistic reasoning that validates the clinical practice of reducing sympathetic efferent neuronal tone while aggressively targeting autonomic derangement in the treatment of ischemic heart disease.

  8. Emergence and mechanism of carbapenem-resistant Escherichia coli in Henan, China, 2014

    Directory of Open Access Journals (Sweden)

    Wen-juan Liang

    2018-05-01

    Full Text Available The emergence and dissemination of carbapenem-resistant Escherichia coli (E. coli strains is a main risk for global public health, but little is known of carbapenemase producing E. coli in Henan, China. The study was undertaken to investigate the prevalence and mechanism of carbapenem-resistant E. coli strains in a hospital in Xinxiang, Henan, China, 2014. A total of 5 carbapenemase-producing E. coli strains were screened from 1014 isolates. We found that they were all resistant to meropenem and imipenem. Amikacin showed the best sensitivity, with gentamicin coming up next. The positive rate of blaNDM was 80% (4/5. The sequencing results showed that two isolates belonged to blaNDM-1 whereas other 2 isolates carried the blaNDM-5. Other carbapenemase genes including blaIMP, blaVIM, blaKPC and blaOXA-48 were not detected. The blaCTX-M-15, blaTEM-1, sul2, aad, and aac(6”–Ib–cr were also detected. MLST analysis showed that NDM-producing E. coli were sporadic. Conjugation test indicated blaNDM could be transferred. In conclusion, the blaNDM was the principal resistance mechanism of carbapenem-resistant E. coli in the hospital, Henan, China. Keywords: blaNDM, Carbapenem-resistant, Escherichia coli

  9. Mechanical And Microstructural Evaluation Of A Wear Resistant Steel

    International Nuclear Information System (INIS)

    Santos, F.L.F. dos; Vieira, A.G.; Correa, E.C.S.; Pinheiro, I.P.

    2010-01-01

    In the present work, the analysis of the mechanical properties and the microstructural features of a high strength low alloy steel, containing chromium, molybdenum and boron, subjected to different heat treatments, was conducted. After austenitizing at 910 deg C for 10 minutes, three operations were carried out: oil quenching, oil quenching followed by tempering at 200 deg C for 120 minutes and austempering at 400 deg C for 5 minutes followed by water cooling. The analysis was performed through tensile and hardness tests, optical microscopy and X-ray diffraction. The bainitic structure led to high strength and toughness, both essential mechanical properties for wear resistant steels. The occurrence of allotriomorphic ferrite and retained austenite in the samples also increased the wear resistance. This phenomenon is related to the fact that both structures are able to be deformed and, in the case of the retained austenite, the transformation induced plasticity TRIP effect may take place as the material is used. (author)

  10. Autonomous development and learning in artificial intelligence and robotics: Scaling up deep learning to human-like learning.

    Science.gov (United States)

    Oudeyer, Pierre-Yves

    2017-01-01

    Autonomous lifelong development and learning are fundamental capabilities of humans, differentiating them from current deep learning systems. However, other branches of artificial intelligence have designed crucial ingredients towards autonomous learning: curiosity and intrinsic motivation, social learning and natural interaction with peers, and embodiment. These mechanisms guide exploration and autonomous choice of goals, and integrating them with deep learning opens stimulating perspectives.

  11. mTOR Signaling Confers Resistance to Targeted Cancer Drugs.

    Science.gov (United States)

    Guri, Yakir; Hall, Michael N

    2016-11-01

    Cancer is a complex disease and a leading cause of death worldwide. Extensive research over decades has led to the development of therapies that target cancer-specific signaling pathways. However, the clinical benefits of such drugs are at best transient due to tumors displaying intrinsic or adaptive resistance. The underlying compensatory pathways that allow cancer cells to circumvent a drug blockade are poorly understood. We review here recent studies suggesting that mammalian TOR (mTOR) signaling is a major compensatory pathway conferring resistance to many cancer drugs. mTOR-mediated resistance can be cell-autonomous or non-cell-autonomous. These findings suggest that mTOR signaling should be monitored routinely in tumors and that an mTOR inhibitor should be considered as a co-therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Elucidating the mechanisms of resistance to tyrosine kinase inhibitors in lung cancer patients

    Directory of Open Access Journals (Sweden)

    Asim Joshi

    2017-10-01

    Results: The whole exome data was analyzed using an in-house developed pipeline. Of all the known resistance mutations, we identified EGFR T790M mutation in five out of fifteen patients. Other than T790M we expect to identify novel resistance causing mutations from the analysis of ten patients with unknown resistance mechanisms. Functional validation of these resistance specific alterations would be performed in vitro using drug sensitive lung cancer cell lines.

  13. Elucidation of Mechanisms of Ceftazidime Resistance among Clinical Isolates of Pseudomonas aeruginosa by Using Genomic Data.

    Science.gov (United States)

    Kos, Veronica N; McLaughlin, Robert E; Gardner, Humphrey A

    2016-06-01

    Ceftazidime is one of the few cephalosporins with activity against Pseudomonas aeruginosa Using whole-genome comparative analysis, we set out to determine the prevalent mechanism(s) of resistance to ceftazidime (CAZ) using a set of 181 clinical isolates. These isolates represented various multilocus sequence types that consisted of both ceftazidime-susceptible and -resistant populations. A presumptive resistance mechanism against ceftazidime was identified in 88% of the nonsusceptible isolates using this approach. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  14. Autonomic Dysfunction in Muscular Dystrophy: A Theoretical Framework for Muscle Reflex Involvement

    Directory of Open Access Journals (Sweden)

    Scott Alan Smith

    2014-02-01

    Full Text Available Muscular dystrophies are a heterogeneous group of genetically inherited disorders whose most prominent clinical feature is progressive degeneration of skeletal muscle. In several forms of the disease, the function of cardiac muscle is likewise affected. The primary defect in this group of diseases is caused by mutations in myocyte proteins important to cellular structure and/or performance. That being stated, a growing body of evidence suggests that the development of autonomic dysfunction may secondarily contribute to the generation of skeletal and cardio-myopathy in muscular dystrophy. Indeed, abnormalities in the regulation of both sympathetic and parasympathetic nerve activity have been reported in a number of muscular dystrophy variants. However, the mechanisms mediating this autonomic dysfunction remain relatively unknown. An autonomic reflex originating in skeletal muscle, the exercise pressor reflex, is known to contribute significantly to the control of sympathetic and parasympathetic activity when stimulated. Given the skeletal myopathy that develops with muscular dystrophy, it is logical to suggest that the function of this reflex might also be abnormal with the pathogenesis of disease. As such, it may contribute to or exacerbate the autonomic dysfunction that manifests. This possibility along with a basic description of exercise pressor reflex function in health and disease are reviewed. A better understanding of the mechanisms that possibly underlie autonomic dysfunction in muscular dystrophy may not only facilitate further research but could also lead to the identification of new therapeutic targets for the treatment of muscular dystrophy.

  15. Testing for autonomic neuropathy

    DEFF Research Database (Denmark)

    Hilsted, J

    1984-01-01

    Autonomic neuropathy is a common complication in long-term diabetes, about 30% of the patients showing measurable signs of autonomic dysfunction after 10 years duration of disease. The diagnosis is often difficult to establish because clinical symptoms generally occur late in the course of the di......Autonomic neuropathy is a common complication in long-term diabetes, about 30% of the patients showing measurable signs of autonomic dysfunction after 10 years duration of disease. The diagnosis is often difficult to establish because clinical symptoms generally occur late in the course...

  16. Mechanisms of acquired resistance to EGFR-tyrosine kinase inhibitor in Korean patients with lung cancer

    International Nuclear Information System (INIS)

    Ji, Wonjun; Lee, Dae Ho; Lee, Jae Cheol; Choi, Chang-Min; Rho, Jin Kyung; Jang, Se Jin; Park, Young Soo; Chun, Sung-Min; Kim, Woo Sung; Lee, Jung-Shin; Kim, Sang-We

    2013-01-01

    Despite an initial good response to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), resistance to treatment eventually develops. Although several resistance mechanisms have been discovered, little data exist regarding Asian patient populations. Among patients at a tertiary referral hospital in Korea who initially responded well to gefitinib and later acquired resistance to treatment, we selected those with enough tissues obtained before EGFR-TKI treatment and after the onset of resistance to examine mutations by mass spectrometric genotyping technology (Asan-Panel), MET amplification by fluorescence in situ hybridization (FISH), and analysis of AXL status, epithelial-to-mesenchymal transition (EMT) and neuroendocrine markers by immunohistochemistry. Twenty-six patients were enrolled, all of whom were diagnosed with adenocarcinoma with EGFR mutations (19del: 16, L858R: 10) except one (squamous cell carcinoma with 19del). Secondary T790M mutation was detected in 11 subjects (42.3%) and four of these patients had other co-existing resistance mechanisms; increased AXL expression was observed in 5/26 patients (19.2%), MET gene amplification was noted in 3/26 (11.5%), and one patient acquired a mutation in the phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) gene. None of the patients exhibited EMT; however, increased CD56 expression suggesting neuroendocrine differentiation was observed in two patients. Interestingly, conversion from L858R-mutant to wild-type EGFR occurred in one patient. Seven patients (26.9%) did not exhibit any known resistance mechanisms. Patients with a T790M mutation showed a more favorable prognosis. The mechanisms and frequency of acquired EGFR-TKI resistance in Koreans are comparable to those observed in Western populations; however, more data regarding the mechanisms that drive EGFR-TKI resistance are necessary

  17. Autonomous stimulus triggered self-healing in smart structural composites

    International Nuclear Information System (INIS)

    Norris, C J; White, J A P; McCombe, G; Chatterjee, P; Bond, I P; Trask, R S

    2012-01-01

    Inspired by the ability of biological systems to sense and autonomously heal damage, this research has successfully demonstrated the first autonomous, stimulus triggered, self-healing system in a structural composite material. Both the sensing and healing mechanisms are reliant on microvascular channels incorporated within a laminated composite material. For the triggering mechanism, a single air filled vessel was pressurized, sealed and monitored. Upon drop weight impact (10 J), delamination and microcrack connectivity between the pressurized vessel and those open to ambient led to a pressure loss which, with the use of a suitable sensor, triggered a pump to deliver a healing agent to the damage zone. Using this autonomous healing approach, near full recovery of post-impact compression strength was achieved (94% on average). A simplified alternative system with healing agent continuously flowing through the vessels, akin to blood flow, was found to offer 100% recovery of the material’s virgin strength. Optical microscopy and ultrasonic C-scanning provided further evidence of large-scale infusion of matrix damage with the healing agent. The successful implementation of this bioinspired technology could substantially enhance the integrity and reliability of aerospace structures, whilst offering benefits through improved performance/weight ratios and extended lifetimes. (paper)

  18. Mechanisms of resistance to HER family targeting antibodies

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-04-15

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

  19. Dissecting the Mechanisms of Drug Resistance in BRCA1/2-Mutant Breast Cancers

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0600 TITLE: Dissecting the Mechanisms of Drug Resistance in BRCA1/2-Mutant Breast Cancers PRINCIPAL INVESTIGATOR: Dr...2017 4. TITLE AND SUBTITLE Dissecting the Mechanisms of Drug Resistance in BRCA1/2- Mutant Breast Cancers 5a. CONTRACT NUMBER W81XWH-16-1-0600 5b...therapeutic modality for targeting homologous recombination (HR) deficient tumors such as BRCA1 and BRCA2-mutated triple negative breast cancers

  20. Resistive switching properties and physical mechanism of europium oxide thin films

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Wei; Zou, Changwei [School of Physical Science and Technology, Lingnan Normal University, Zhanjiang (China); Bao, Dinghua [State Key Laboratory of Optoelectronic Materials and Technologies, School of Materials Science and Engineering, Sun Yat-Sen University, Guangzhou (China)

    2017-09-15

    A forming-free resistive switching effect was obtained in Pt/Eu{sub 2}O{sub 3}/Pt devices in which the Eu{sub 2}O{sub 3} thin films were fabricated by a chemical solution deposition method. The devices show unipolar resistive switching with excellent switching parameters, such as high resistance ratio (10{sup 7}), stable resistance values (read at 0.2 V), low reset voltage, good endurance, and long retention time (up to 10{sup 4} s). On the basis of the analysis of the current-voltage (I-V) curves and the resistance-temperature dependence, it can be concluded that the dominant conducting mechanisms were ohmic behavior and Schottky emission at low resistance state and high resistance state, respectively. The resistive switching behavior could be explained by the formation and rupture of conductive filament, which is related to the abundant oxygen vacancies generated in the deposition process. This work demonstrates the great potential opportunities of Eu{sub 2}O{sub 3} thin film in resistive switching memory applications, which might possess distinguished properties. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  1. Exercise improves cardiac autonomic function in obesity and diabetes.

    Science.gov (United States)

    Voulgari, Christina; Pagoni, Stamatina; Vinik, Aaron; Poirier, Paul

    2013-05-01

    Physical activity is a key element in the prevention and management of obesity and diabetes. Regular physical activity efficiently supports diet-induced weight loss, improves glycemic control, and can prevent or delay type 2 diabetes diagnosis. Furthermore, physical activity positively affects lipid profile, blood pressure, reduces the rate of cardiovascular events and associated mortality, and restores the quality of life in type 2 diabetes. However, recent studies have documented that a high percentage of the cardiovascular benefits of exercise cannot be attributed solely to enhanced cardiovascular risk factor modulation. Obesity in concert with diabetes is characterized by sympathetic overactivity and the progressive loss of cardiac parasympathetic influx. These are manifested via different pathogenetic mechanisms, including hyperinsulinemia, visceral obesity, subclinical inflammation and increased thrombosis. Cardiac autonomic neuropathy is an underestimated risk factor for the increased cardiovascular morbidity and mortality associated with obesity and diabetes. The same is true for the role of physical exercise in the restoration of the heart cardioprotective autonomic modulation in these individuals. This review addresses the interplay of cardiac autonomic function in obesity and diabetes, and focuses on the importance of exercise in improving cardiac autonomic dysfunction. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Strengthening mechanisms and mechanical properties of high interstitial stainless steel for drill collar and its corrosion resistance

    Science.gov (United States)

    Lee, Eunkyung

    Two types (CN66, CN71) of high interstitial stainless steels (HISSs) were investigated for down-hole application in sour gas well environments. Experiments were designed to identify factors that have a significant effect on mechanical properties. The three factors examined in the study were carbon + nitrogen content (0.66 or 0.71 mass %), cooling rate in quenching (air or water), and heat treatment time (2 or 4 hours). The results showed that the cooling rate, C+N content, and the two-factor interaction of these variables have a significant effect on the mechanical properties of HISSs. Based on the statistical analysis results on mechanical properties, extensive analyses were undertaken to understand the strengthening mechanisms of HISSs. Microstructure analysis revealed that a pearlite phase with a high carbide and/or nitride content is dissolved in the matrix by heat treatment at 1,200 ºC which is considered the dissolution to increase the concentration of interstitial elements in steels. The distribution of elements in HISSs was investigated by quantitative mapping using EPMA, which showed that the high carbon concentration (carbide/cementite) area was decreased by increases in both the cooling rate and C+N content. The ferrite volume fraction of each specimen is increased by an increase in cooling rate, because there is insufficient time to form austenite from retained ferrite. The lattice expansion of HISS was investigated by the calculation of lattice parameters under various conditions, and these investigations confirm the solid solution strengthening effect on HISSs. CN66 with heat treatment at fast cooling has the highest wear resistance; a finding that was consistent with hardening mechanisms that occur due to an increased ferrite volume fraction. In addition, precipitates on the surface and the chemical bonding of chromium were investigated. As the amount of CrN bonding increased, the wear resistance also increased. This study also assessed the

  3. Molecular epidemiology and drug resistant mechanism in carbapenem-resistant Klebsiella pneumoniae isolated from pediatric patients in Shanghai, China.

    Science.gov (United States)

    Zhang, Xingyu; Chen, Di; Xu, Guifeng; Huang, Weichun; Wang, Xing

    2018-01-01

    Infection by carbapenem-resistant Klebsiella pneumoniae (CR-KP) is a public health challenge worldwide, in particular among children, which was associated with high morbidity and mortality rates. There was limited data in pediatric populations, thus this study aimed to investigate molecular epidemiology and drug resistant mechanism of CR-KP strains from pediatric patients in Shanghai, China. A total of 41 clinical CR-KP isolates from sputum, urine, blood or drainage fluid were collected between July 2014 and May 2015 in Shanghai Children's Medical Center. Multilocus sequence typing (MLST), antibiotic susceptibility testing, PCR amplification and sequencing of the drug resistance associated genes were applied to all these isolates. MLST analysis revealed 16 distinct STs identified within the 41 isolates, among which the most frequently represented were ST11(19.5%),ST25(14.6%),ST76(14.6%),ST37(9.8%).One new ST was first identified. All CR-KP isolates showed MDR phenotypes and were resistance to ceftazidime, imipenem, piperacillin / tazobactam, ceftriaxone, ampicillin /sulbactam, aztreonam. They were confirmed as carbapenemase producer, NDM-1 (56.1%, 23/41), IMP (26.8%, 11/41), KPC-2 (22.0%, 9/41) were detected. Of note, two isolates carried simultaneously both NDM-1 and IMP-4. All CR-KP strains contained at least one of extended spectrum β-lactamase genes tested(TEM, SHV, OXA-1, CTX-M group) and six isolates carried both ESBL and AmpC genes(DHA-1). Among the penicllinase and β-lactamase genes, the most frequently one is SHV(92.7%,38/41), followed by TEM-1(68.3%,28/41), CTX-M-14(43.9%,18/41), CTX-M-15(43.9%,14/41), OXA-1(14.6%,6/41). In the present study, NDM-1-producing isolates was the predominant CR-KP strains in children, follow by IMP and KPC-producing strains. NDM-1and IMP-4 were more frequent than KPC-2 and showed a multiclonal background. Those suggested carbapenem-resistant in children is diverse, and certain resistance mechanisms differ from prevalent

  4. Modulation of autonomic activity in neurological conditions: Epilepsy and Tourette Syndrome.

    Science.gov (United States)

    Nagai, Yoko

    2015-01-01

    This manuscript considers the central but neglected role of the autonomic nervous system in the expression and control of seizures in epilepsy (small) and tics in Tourette Syndrome (TS). In epilepsy, consideration of autonomic involvement is typically confined to differential diagnoses (e.g., syncope), or in relation to Sudden Unexpected Death in Epilepsy (SUDEP). Investigation is more limited in Tourette Syndrome. The role of the autonomic nervous system in the generation and prevention of epileptic seizures is largely overlooked. Emotional stimuli such as anxiety and stress are potent causes of seizures and tic activity in epilepsy and TS, respectively. This manuscript will describe a possible neural mechanism by which afferent autonomic projections linked to cognition and behavior influence central thalamo-cortical regulation, which appears to be an important means for controlling both seizure and tic activity. It also summarizes the link between the integrity of the default mode network and autonomic regulation in patients with epilepsy as well as the link between impaired motor control and autonomic regulation in patients with TS. Two neurological conditions; epilepsy and TS were chosen, as seizures and tics represent parameters that can be easily measured to investigate influences of autonomic functions. The EDA biofeedback approach is anticipated to gain a strong position within the next generation of treatment for epilepsy, as a non-invasive technique with minimal side effects. This approach also takes advantage of the current practical opportunity to utilize growing digital health technology.

  5. Recurrent myocardial infarction: Mechanisms of free-floating adaptation and autonomic derangement in networked cardiac neural control

    Science.gov (United States)

    Ardell, Jeffrey L.; Shivkumar, Kalyanam; Armour, J. Andrew

    2017-01-01

    The cardiac nervous system continuously controls cardiac function whether or not pathology is present. While myocardial infarction typically has a major and catastrophic impact, population studies have shown that longer-term risk for recurrent myocardial infarction and the related potential for sudden cardiac death depends mainly upon standard atherosclerotic variables and autonomic nervous system maladaptations. Investigative neurocardiology has demonstrated that autonomic control of cardiac function includes local circuit neurons for networked control within the peripheral nervous system. The structural and adaptive characteristics of such networked interactions define the dynamics and a new normal for cardiac control that results in the aftermath of recurrent myocardial infarction and/or unstable angina that may or may not precipitate autonomic derangement. These features are explored here via a mathematical model of cardiac regulation. A main observation is that the control environment during pathology is an extrapolation to a setting outside prior experience. Although global bounds guarantee stability, the resulting closed-loop dynamics exhibited while the network adapts during pathology are aptly described as ‘free-floating’ in order to emphasize their dependence upon details of the network structure. The totality of the results provide a mechanistic reasoning that validates the clinical practice of reducing sympathetic efferent neuronal tone while aggressively targeting autonomic derangement in the treatment of ischemic heart disease. PMID:28692680

  6. Recurrent myocardial infarction: Mechanisms of free-floating adaptation and autonomic derangement in networked cardiac neural control.

    Directory of Open Access Journals (Sweden)

    Guy Kember

    Full Text Available The cardiac nervous system continuously controls cardiac function whether or not pathology is present. While myocardial infarction typically has a major and catastrophic impact, population studies have shown that longer-term risk for recurrent myocardial infarction and the related potential for sudden cardiac death depends mainly upon standard atherosclerotic variables and autonomic nervous system maladaptations. Investigative neurocardiology has demonstrated that autonomic control of cardiac function includes local circuit neurons for networked control within the peripheral nervous system. The structural and adaptive characteristics of such networked interactions define the dynamics and a new normal for cardiac control that results in the aftermath of recurrent myocardial infarction and/or unstable angina that may or may not precipitate autonomic derangement. These features are explored here via a mathematical model of cardiac regulation. A main observation is that the control environment during pathology is an extrapolation to a setting outside prior experience. Although global bounds guarantee stability, the resulting closed-loop dynamics exhibited while the network adapts during pathology are aptly described as 'free-floating' in order to emphasize their dependence upon details of the network structure. The totality of the results provide a mechanistic reasoning that validates the clinical practice of reducing sympathetic efferent neuronal tone while aggressively targeting autonomic derangement in the treatment of ischemic heart disease.

  7. Clozapine-Induced Cardiovascular Side Effects and Autonomic Dysfunction: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Jessica W. Y. Yuen

    2018-04-01

    Full Text Available Background: Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal risk for extrapyramidal symptoms. Therapeutic benefits, however, are accompanied by a myriad of cardiometabolic side-effects. The specific reasons for clozapine's high propensity to cause adverse cardiometabolic events remain unknown, but it is believed that autonomic dysfunction may play a role in many of these.Objective: This systematic review summarizes the literature on autonomic dysfunction and related cardiovascular side effects associated with clozapine treatment.Method: A search of the EMBASE, MEDLINE, and EBM Cochrane databases was conducted using the search terms antipsychotic agents, antipsychotic drug*, antipsychotic*, schizophrenia, schizophren*, psychos*, psychotic*, mental ill*, mental disorder*, neuroleptic*, cardiovascular*, cardiovascular diseases, clozapine*, clozaril*, autonomic*, sympathetic*, catecholamine*, norepinephrine, noradrenaline, epinephrine, adrenaline.Results: The search yielded 37 studies that were reviewed, of which only 16 studies have used interventions to manage cardiovascular side effects. Side effects reported in the studies include myocarditis, orthostatic hypotension and tachycardia. These were attributed to sympathetic hyperactivity, decreased vagal contribution, blockade of cholinergic and adrenergic receptors, reduced heart rate variability and elevated catecholamines with clozapine use. Autonomic neuropathy was identified by monitoring blood pressure and heart rate changes in response to stimuli and by spectral analysis of heart rate variability. Metoprolol, lorazepam, atenolol, propranolol, amlodipine, vasopressin and norepinephrine infusion were used to treat tachycardia and fluctuations in blood pressure, yet results were limited to case reports.Conclusion: The results indicate there is a lack of clinical studies investigating autonomic dysfunction and a limited use of interventions to manage

  8. RoBlock: a prototype autonomous manufacturing cell

    Science.gov (United States)

    Baekdal, Lars K.; Balslev, Ivar; Eriksen, Rene D.; Jensen, Soren P.; Jorgensen, Bo N.; Kirstein, Brian; Kristensen, Bent B.; Olsen, Martin M.; Perram, John W.; Petersen, Henrik G.; Petersen, Morten L.; Ruhoff, Peter T.; Skjolstrup, Carl E.; Sorensen, Anders S.; Wagenaar, Jeroen M.

    2000-10-01

    RoBlock is the first phase of an internally financed project at the Institute aimed at building a system in which two industrial robots suspended from a gantry, as shown below, cooperate to perform a task specified by an external user, in this case, assembling an unstructured collection of colored wooden blocks into a specified 3D pattern. The blocks are identified and localized using computer vision and grasped with a suction cup mechanism. Future phases of the project will involve other processes such as grasping and lifting, as well as other types of robot such as autonomous vehicles or variable geometry trusses. Innovative features of the control software system include: The use of an advanced trajectory planning system which ensures collision avoidance based on a generalization of the method of artificial potential fields, the use of a generic model-based controller which learns the values of parameters, including static and kinetic friction, of a detailed mechanical model of itself by comparing actual with planned movements, the use of fast, flexible, and robust pattern recognition and 3D-interpretation strategies, integration of trajectory planning and control with the sensor systems in a distributed Java application running on a network of PC's attached to the individual physical components. In designing this first stage, the aim was to build in the minimum complexity necessary to make the system non-trivially autonomous and to minimize the technological risks. The aims of this project, which is planned to be operational during 2000, are as follows: To provide a platform for carrying out experimental research in multi-agent systems and autonomous manufacturing systems, to test the interdisciplinary cooperation architecture of the Maersk Institute, in which researchers in the fields of applied mathematics (modeling the physical world), software engineering (modeling the system) and sensor/actuator technology (relating the virtual and real worlds) could

  9. A Method for Identifying the Mechanical Parameters in Resistance Spot Welding Machines

    DEFF Research Database (Denmark)

    Wu, Pei; Zhang, Wenqi; Bay, Niels

    2003-01-01

    Mechanical dynamic responses of resistance welding machine have a significant influence on weld quality and electrode service life, it must be considered when the real welding production is carried out or the welding process is stimulated. The mathematical models for characterizing the mechanical...

  10. Overview of the Autonomic Nervous System

    Science.gov (United States)

    ... be reversible or progressive. Anatomy of the autonomic nervous system The autonomic nervous system is the part of ... organs they connect with. Function of the autonomic nervous system The autonomic nervous system controls internal body processes ...

  11. Insecticide resistance in vector Chagas disease: evolution, mechanisms and management.

    Science.gov (United States)

    Mougabure-Cueto, Gastón; Picollo, María Inés

    2015-09-01

    Chagas disease is a chronic parasitic infection restricted to America. The disease is caused by the protozoa Trypanosoma cruzi, which is transmitted to human through the feces of infected triatomine insects. Because no treatment is available for the chronic forms of the disease, vector chemical control represents the best way to reduce the incidence of the disease. Chemical control has been based principally on spraying dwellings with insecticide formulations and led to the reduction of triatomine distribution and consequent interruption of disease transmission in several areas from endemic region. However, in the last decade it has been repeatedly reported the presence triatomnes, mainly Triatoma infestans, after spraying with pyrethroid insecticides, which was associated to evolution to insecticide resistance. In this paper the evolution of insecticide resistance in triatomines is reviewed. The insecticide resistance was detected in 1970s in Rhodnius prolixus and 1990s in R. prolixus and T. infestans, but not until the 2000s resistance to pyrthroids in T. infestans associated to control failures was described in Argentina and Bolivia. The main resistance mechanisms (i.e. enhanced metabolism, altered site of action and reduced penetration) were described in the T. infestans resistant to pyrethrods. Different resistant profiles were demonstrated suggesting independent origin of the different resistant foci of Argentina and Bolivia. The deltamethrin resistance in T. infestans was showed to be controlled by semi-dominant, autosomally inherited factors. Reproductive and developmental costs were also demonstrated for the resistant T. infestans. A discussion about resistance and tolerance concepts and the persistence of T. infestans in Gran Chaco region are presented. In addition, theoretical concepts related to toxicological, evolutionary and ecological aspects of insecticide resistance are discussed in order to understand the particular scenario of pyrethroid

  12. The sites and mechanisms of postoperative insulin resistance

    OpenAIRE

    Nygren, Jonas

    1997-01-01

    The Sites and Mechanisms of Postoperative InsulinResistance by Jonas Nygren, M.D. Departments of Surgery and Endocrinology and Diabetes, Karolinska Hospital and Institute, SE-171 76, Stockholm, Sweden In Sweden with nine million inhabitants, 450,000 operations(outpatients excluded) are performed every year resulting in2,250,000 treatment days in hospital. Surgical operations are part ofthe treatment for 44% of all patients admitted to hospital careoccupying 24% of all ...

  13. Resistance of green lacewing, Chrysoperla carnea Stephens to nitenpyram: Cross-resistance patterns, mechanism, stability, and realized heritability.

    Science.gov (United States)

    Mansoor, Muhammad Mudassir; Raza, Abu Bakar Muhammad; Abbas, Naeem; Aqueel, Muhammad Anjum; Afzal, Muhammad

    2017-01-01

    The green lacewing, Chrysoperla carnea Stephens (Neuroptera: Chrysopidae) is a major generalist predator employed in integrated pest management (IPM) plans for pest control on many crops. Nitenpyram, a neonicotinoid insecticide has widely been used against the sucking pests of cotton in Pakistan. Therefore, a field green lacewing strain was exposed to nitenpyram for five generations to investigate resistance evolution, cross-resistance pattern, stability, realized heritability, and mechanisms of resistance. Before starting the selection with nitenpyram, a field collected strain showed 22.08-, 23.09-, 484.69- and 602.90-fold resistance to nitenpyram, buprofezin, spinosad and acetamiprid, respectively compared with the Susceptible strain. After continuous selection for five generations (G1-G5) with nitenpyram in the laboratory, the Field strain (Niten-SEL) developed a resistance ratio of 423.95 at G6. The Niten-SEL strain at G6 showed no cross-resistance to buprofezin and acetamiprid and negative cross-resistance to spinosad compared with the Field strain (G1). For resistance stability, the Niten-SEL strain was left unexposed to any insecticide for four generations (G6-G9) and bioassay results at G10 showed that resistance to nitenpyram, buprofezin and spinosad was stable, while resistance to acetamiprid was unstable. The realized heritability values were 0.97, 0.16, 0.03, and -0.16 to nitenpyram, buprofezin, acetamiprid and spinosad, respectively, after five generations of selection. Moreover, the enzyme inhibitors (PBO or DEF) significantly decreased the nitenpyram resistance in the resistant strain, suggesting that resistance was due to microsomal oxidases and esterases. These results are very helpful for integration of green lacewings in IPM programs. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Catecholamines and diabetic autonomic neuropathy

    DEFF Research Database (Denmark)

    Hilsted, J

    1995-01-01

    In diabetic patients with autonomic neuropathy plasma noradrenaline concentration, used as an index of sympathetic nervous activity, is low. This decrease is, however, only found in patients with a long duration of diabetes with clinically severe autonomic neuropathy. This apparent insensitivity...... of plasma catecholamine measurements is not due to changes in the clearance of catecholamines in diabetic autonomic neuropathy. The physiological responses to infused adrenaline and to noradrenaline are enhanced, for noradrenaline mainly cardiovascular responses. Adrenoceptors (alpha and beta adrenoceptors......) are not altered in circulating blood cells in diabetic autonomic neuropathy. Thus, a generalized up-regulation of adrenoceptors does not occur in diabetic autonomic neuropathy....

  15. Novel and Reversible Mechanisms of Smoking-Induced Insulin Resistance in Humans

    OpenAIRE

    Bergman, Bryan C.; Perreault, Leigh; Hunerdosse, Devon; Kerege, Anna; Playdon, Mary; Samek, Ali M.; Eckel, Robert H.

    2012-01-01

    Smoking is the most common cause of preventable morbidity and mortality in the United States, in part because it is an independent risk factor for the development of insulin resistance and type 2 diabetes. However, mechanisms responsible for smoking-induced insulin resistance are unclear. In this study, we found smokers were less insulin sensitive compared with controls, which increased after either 1 or 2 weeks of smoking cessation. Improvements in insulin sensitivity after smoking cessation...

  16. Multiple resistance to glyphosate, paraquat and ACCase-inhibiting herbicides in Italian ryegrass populations from California: confirmation and mechanisms of resistance.

    Science.gov (United States)

    Tehranchian, Parsa; Nandula, Vijay; Jugulam, Mithila; Putta, Karthik; Jasieniuk, Marie

    2018-04-01

    Glyphosate, paraquat and acetyl CoA carboxylase (ACCase)-inhibiting herbicides are widely used in California annual and perennial cropping systems. Recently, glyphosate, paraquat, and ACCase- and acetolactate synthase (ALS)-inhibitor resistance was confirmed in several Italian ryegrass populations from the Central Valley of California. This research characterized the possible mechanisms of resistance. Multiple-resistant populations (MR1, MR2) are resistant to several herbicides from at least three modes of action. Dose-response experiments revealed that the MR1 population was 45.9-, 122.7- and 20.5-fold, and the MR2 population was 24.8-, 93.9- and 4.0-fold less susceptible to glyphosate, sethoxydim and paraquat, respectively, than the susceptible (Sus) population. Accumulation of shikimate in Sus plants was significantly greater than in MR plants 32 h after light pretreatments. Glyphosate resistance in MR plants was at least partially due to Pro106-to-Ala and Pro106-to-Thr substitutions at site 106 of 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). EPSPS gene copy number and expression level were similar in plants from the Sus and MR populations. An Ile1781-to-Leu substitution in ACCase gene of MR plants conferred a high level of resistance to sethoxydim and cross-resistance to other ACCase-inhibitors. Radiolabeled herbicide studies and phosphorimaging indicated that MR plants had restricted translocation of 14 C-paraquat to untreated leaves compared to Sus plants. This study shows that multiple herbicide resistance in Italian ryegrass populations in California, USA, is due to both target-site and non-target-site resistance mechanisms. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  17. Autonomous Navigation for Autonomous Underwater Vehicles Based on Information Filters and Active Sensing

    Directory of Open Access Journals (Sweden)

    Tianhong Yan

    2011-11-01

    Full Text Available This paper addresses an autonomous navigation method for the autonomous underwater vehicle (AUV C-Ranger applying information-filter-based simultaneous localization and mapping (SLAM, and its sea trial experiments in Tuandao Bay (Shangdong Province, P.R. China. Weak links in the information matrix in an extended information filter (EIF can be pruned to achieve an efficient approach-sparse EIF algorithm (SEIF-SLAM. All the basic update formulae can be implemented in constant time irrespective of the size of the map; hence the computational complexity is significantly reduced. The mechanical scanning imaging sonar is chosen as the active sensing device for the underwater vehicle, and a compensation method based on feedback of the AUV pose is presented to overcome distortion of the acoustic images due to the vehicle motion. In order to verify the feasibility of the navigation methods proposed for the C-Ranger, a sea trial was conducted in Tuandao Bay. Experimental results and analysis show that the proposed navigation approach based on SEIF-SLAM improves the accuracy of the navigation compared with conventional method; moreover the algorithm has a low computational cost when compared with EKF-SLAM.

  18. Autonomous navigation for autonomous underwater vehicles based on information filters and active sensing.

    Science.gov (United States)

    He, Bo; Zhang, Hongjin; Li, Chao; Zhang, Shujing; Liang, Yan; Yan, Tianhong

    2011-01-01

    This paper addresses an autonomous navigation method for the autonomous underwater vehicle (AUV) C-Ranger applying information-filter-based simultaneous localization and mapping (SLAM), and its sea trial experiments in Tuandao Bay (Shangdong Province, P.R. China). Weak links in the information matrix in an extended information filter (EIF) can be pruned to achieve an efficient approach-sparse EIF algorithm (SEIF-SLAM). All the basic update formulae can be implemented in constant time irrespective of the size of the map; hence the computational complexity is significantly reduced. The mechanical scanning imaging sonar is chosen as the active sensing device for the underwater vehicle, and a compensation method based on feedback of the AUV pose is presented to overcome distortion of the acoustic images due to the vehicle motion. In order to verify the feasibility of the navigation methods proposed for the C-Ranger, a sea trial was conducted in Tuandao Bay. Experimental results and analysis show that the proposed navigation approach based on SEIF-SLAM improves the accuracy of the navigation compared with conventional method; moreover the algorithm has a low computational cost when compared with EKF-SLAM.

  19. Mechanisms of current conduction in Pt/BaTiO3/Pt resistive switching cell

    International Nuclear Information System (INIS)

    Pan, R.K.; Zhang, T.J.; Wang, J.Y.; Wang, J.Z.; Wang, D.F.; Duan, M.G.

    2012-01-01

    The 80-nm-thickness BaTiO 3 (BT) thin film was prepared on the Pt/Ti/SiO 2 /Si substrate by the RF magnetron sputtering technique. The Pt/BT/Pt/Ti/SiO 2 /Si structure was investigated using X-ray diffraction and scanning electron microscopy. The current–voltage characteristic measurements were performed. The bipolar resistive switching behavior was found in the Pt/BT/Pt cell. The current–voltage curves were well fitted in different voltage regions at the high resistance state (HRS) and the low resistance state (LRS), respectively. The conduction mechanisms are concluded to be Ohmic conduction and Schottky emission at the LRS, while space-charge-limited conduction and Poole–Frenkel emission at the HRS. The electroforming and switching processes were explained in terms of the valence change mechanism, in which oxygen vacancies play a key role in forming conducting paths. - Highlights: ►Pt/BaTiO 3 /Pt cell shows the bipolar resistive switching behavior. ►The current–voltage curves were well fitted for different conduction mechanisms. ►The electroforming and switching processes were explained.

  20. Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals.

    Science.gov (United States)

    Ahmed, Asma; Felmlee, Daniel J

    2015-12-18

    There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR) rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.

  1. On the mechanism of chloroquine resistance in Plasmodium falciparum.

    KAUST Repository

    Chinappi, Mauro

    2010-11-19

    Resistance to chloroquine of malaria strains is known to be associated with a parasite protein named PfCRT, the mutated form of which is able to reduce chloroquine accumulation in the digestive vacuole of the pathogen. Whether the protein mediates extrusion of the drug acting as a channel or as a carrier and which is the protonation state of its chloroquine substrate is the subject of a scientific debate. We present here an analytical approach that explores which combination of hypotheses on the mechanism of transport and the protonation state of chloroquine are consistent with available equilibrium experimental data. We show that the available experimental data are not, by themselves, sufficient to conclude whether the protein acts as a channel or as a transporter, which explains the origin of their different interpretation by different authors. Interestingly, though, each of the two models is only consistent with a subset of hypotheses on the protonation state of the transported molecule. The combination of these results with a sequence and structure analysis of PfCRT, which strongly suggests that the molecule is a carrier, indicates that the transported species is either or both the mono and di-protonated forms of chloroquine. We believe that our results, besides shedding light on the mechanism of chloroquine resistance in P. falciparum, have implications for the development of novel therapies against resistant malaria strains and demonstrate the usefulness of an approach combining systems biology strategies with structural bioinformatics and experimental data.

  2. On the mechanism of chloroquine resistance in Plasmodium falciparum.

    KAUST Repository

    Chinappi, Mauro; Via, Allegra; Marcatili, Paolo; Tramontano, Anna

    2010-01-01

    Resistance to chloroquine of malaria strains is known to be associated with a parasite protein named PfCRT, the mutated form of which is able to reduce chloroquine accumulation in the digestive vacuole of the pathogen. Whether the protein mediates extrusion of the drug acting as a channel or as a carrier and which is the protonation state of its chloroquine substrate is the subject of a scientific debate. We present here an analytical approach that explores which combination of hypotheses on the mechanism of transport and the protonation state of chloroquine are consistent with available equilibrium experimental data. We show that the available experimental data are not, by themselves, sufficient to conclude whether the protein acts as a channel or as a transporter, which explains the origin of their different interpretation by different authors. Interestingly, though, each of the two models is only consistent with a subset of hypotheses on the protonation state of the transported molecule. The combination of these results with a sequence and structure analysis of PfCRT, which strongly suggests that the molecule is a carrier, indicates that the transported species is either or both the mono and di-protonated forms of chloroquine. We believe that our results, besides shedding light on the mechanism of chloroquine resistance in P. falciparum, have implications for the development of novel therapies against resistant malaria strains and demonstrate the usefulness of an approach combining systems biology strategies with structural bioinformatics and experimental data.

  3. On the Mechanism of Chloroquine Resistance in Plasmodium falciparum

    Science.gov (United States)

    Marcatili, Paolo; Tramontano, Anna

    2010-01-01

    Resistance to chloroquine of malaria strains is known to be associated with a parasite protein named PfCRT, the mutated form of which is able to reduce chloroquine accumulation in the digestive vacuole of the pathogen. Whether the protein mediates extrusion of the drug acting as a channel or as a carrier and which is the protonation state of its chloroquine substrate is the subject of a scientific debate. We present here an analytical approach that explores which combination of hypotheses on the mechanism of transport and the protonation state of chloroquine are consistent with available equilibrium experimental data. We show that the available experimental data are not, by themselves, sufficient to conclude whether the protein acts as a channel or as a transporter, which explains the origin of their different interpretation by different authors. Interestingly, though, each of the two models is only consistent with a subset of hypotheses on the protonation state of the transported molecule. The combination of these results with a sequence and structure analysis of PfCRT, which strongly suggests that the molecule is a carrier, indicates that the transported species is either or both the mono and di-protonated forms of chloroquine. We believe that our results, besides shedding light on the mechanism of chloroquine resistance in P. falciparum, have implications for the development of novel therapies against resistant malaria strains and demonstrate the usefulness of an approach combining systems biology strategies with structural bioinformatics and experimental data. PMID:21124966

  4. Exploiting Drug Addiction Mechanisms to Select against MAPKi-Resistant Melanoma.

    Science.gov (United States)

    Hong, Aayoung; Moriceau, Gatien; Sun, Lu; Lomeli, Shirley; Piva, Marco; Damoiseaux, Robert; Holmen, Sheri L; Sharpless, Norman E; Hugo, Willy; Lo, Roger S

    2018-01-01

    Melanoma resistant to MAPK inhibitors (MAPKi) displays loss of fitness upon experimental MAPKi withdrawal and, clinically, may be resensitized to MAPKi therapy after a drug holiday. Here, we uncovered and therapeutically exploited the mechanisms of MAPKi addiction in MAPKi-resistant BRAF MUT or NRAS MUT melanoma. MAPKi-addiction phenotypes evident upon drug withdrawal spanned transient cell-cycle slowdown to cell-death responses, the latter of which required a robust phosphorylated ERK (pERK) rebound. Generally, drug withdrawal-induced pERK rebound upregulated p38-FRA1-JUNB-CDKN1A and downregulated proliferation, but only a robust pERK rebound resulted in DNA damage and parthanatos-related cell death. Importantly, pharmacologically impairing DNA damage repair during MAPKi withdrawal augmented MAPKi addiction across the board by converting a cell-cycle deceleration to a caspase-dependent cell-death response or by furthering parthanatos-related cell death. Specifically in MEKi-resistant NRAS MUT or atypical BRAF MUT melanoma, treatment with a type I RAF inhibitor intensified pERK rebound elicited by MEKi withdrawal, thereby promoting a cell death-predominant MAPKi-addiction phenotype. Thus, MAPKi discontinuation upon disease progression should be coupled with specific strategies that augment MAPKi addiction. Significance: Discontinuing targeted therapy may select against drug-resistant tumor clones, but drug-addiction mechanisms are ill-defined. Using melanoma resistant to but withdrawn from MAPKi, we defined a synthetic lethality between supraphysiologic levels of pERK and DNA damage. Actively promoting this synthetic lethality could rationalize sequential/rotational regimens that address evolving vulnerabilities. Cancer Discov; 8(1); 74-93. ©2017 AACR. See related commentary by Stern, p. 20 This article is highlighted in the In This Issue feature, p. 1 . ©2017 American Association for Cancer Research.

  5. BART: The Czech Autonomous Observatory

    Czech Academy of Sciences Publication Activity Database

    Nekola, Martin; Hudec, René; Jelínek, M.; Kubánek, P.; Štrobl, Jan; Polášek, Cyril

    2010-01-01

    Roč. 2010, Spec. Is. (2010), 103986/1-103986/5 ISSN 1687-7969. [Workshop on Robotic Autonomous Observatories. Málaga, 18.05.2009-21.05.2009] R&D Projects: GA ČR GA205/08/1207 Grant - others:ESA(XE) ESA-PECS project No. 98023; Spanish Ministry of Education and Science(ES) AP2003-1407 Institutional research plan: CEZ:AV0Z10030501 Keywords : robotic telescope * BART * gamma ray bursts Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics http://www.hindawi.com/journals/aa/2010/103986.html

  6. Biomechanical walking mechanisms underlying the metabolic reduction caused by an autonomous exoskeleton.

    Science.gov (United States)

    Mooney, Luke M; Herr, Hugh M

    2016-01-28

    Ankle exoskeletons can now reduce the metabolic cost of walking in humans without leg disability, but the biomechanical mechanisms that underlie this augmentation are not fully understood. In this study, we analyze the energetics and lower limb mechanics of human study participants walking with and without an active autonomous ankle exoskeleton previously shown to reduce the metabolic cost of walking. We measured the metabolic, kinetic and kinematic effects of wearing a battery powered bilateral ankle exoskeleton. Six participants walked on a level treadmill at 1.4 m/s under three conditions: exoskeleton not worn, exoskeleton worn in a powered-on state, and exoskeleton worn in a powered-off state. Metabolic rates were measured with a portable pulmonary gas exchange unit, body marker positions with a motion capture system, and ground reaction forces with a force-plate instrumented treadmill. Inverse dynamics were then used to estimate ankle, knee and hip torques and mechanical powers. The active ankle exoskeleton provided a mean positive power of 0.105 ± 0.008 W/kg per leg during the push-off region of stance phase. The net metabolic cost of walking with the active exoskeleton (3.28 ± 0.10 W/kg) was an 11 ± 4 % (p = 0.019) reduction compared to the cost of walking without the exoskeleton (3.71 ± 0.14 W/kg). Wearing the ankle exoskeleton significantly reduced the mean positive power of the ankle joint by 0.033 ± 0.006 W/kg (p = 0.007), the knee joint by 0.042 ± 0.015 W/kg (p = 0.020), and the hip joint by 0.034 ± 0.009 W/kg (p = 0.006). This study shows that the ankle exoskeleton does not exclusively reduce positive mechanical power at the ankle joint, but also mitigates positive power at the knee and hip. Furthermore, the active ankle exoskeleton did not simply replace biological ankle function in walking, but rather augmented the total (biological + exoskeletal) ankle moment and power. This study

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

    OpenAIRE

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

    2015-01-01

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

  8. Overview on mechanisms of acetic acid resistance in acetic acid bacteria.

    Science.gov (United States)

    Wang, Bin; Shao, Yanchun; Chen, Fusheng

    2015-02-01

    Acetic acid bacteria (AAB) are a group of gram-negative or gram-variable bacteria which possess an obligate aerobic property with oxygen as the terminal electron acceptor, meanwhile transform ethanol and sugar to corresponding aldehydes, ketones and organic acids. Since the first genus Acetobacter of AAB was established in 1898, 16 AAB genera have been recorded so far. As the main producer of a world-wide condiment, vinegar, AAB have evolved an elegant adaptive system that enables them to survive and produce a high concentration of acetic acid. Some researches and reviews focused on mechanisms of acid resistance in enteric bacteria and made the mechanisms thoroughly understood, while a few investigations did in AAB. As the related technologies with proteome, transcriptome and genome were rapidly developed and applied to AAB research, some plausible mechanisms conferring acetic acid resistance in some AAB strains have been published. In this review, the related mechanisms of AAB against acetic acid with acetic acid assimilation, transportation systems, cell morphology and membrane compositions, adaptation response, and fermentation conditions will be described. Finally, a framework for future research for anti-acid AAB will be provided.

  9. Taxane resistance in breast cancer: mechanisms, predictive biomarkers and circumvention strategies.

    Science.gov (United States)

    Murray, S; Briasoulis, E; Linardou, H; Bafaloukos, D; Papadimitriou, C

    2012-11-01

    Taxanes are established in the treatment of metastatic breast cancer (MBC) and early breast cancer (EBC) as potent chemotherapy agents. However, their therapeutic usefulness is limited by de-novo refractoriness or acquired resistance, which are common drawbacks to most anti-cancer cytotoxics. Considering that the taxanes will remain principle chemotherapeutic agents for the treatment of breast cancer, we reviewed known mechanisms of resistance in with an outlook of optimizing their clinical use. We searched the PubMed and MEDLINE databases for articles (from inception through to 9th January 2012; last search 10/01/2012) and journals known to publish information relevant to taxane chemotherapy. We imposed no language restrictions. Search terms included: cancer, breast cancer, response, resistance, taxane, paclitaxel, docetaxel, taxol. Due to the possibility of alternative mechanisms of resistance all combination chemotherapy treated data sets were removed from our overview. Over-expression of the MDR-1 gene product Pgp was extensively studied in vitro in association with taxane resistance, but data are conflicting. Similarly, the target components microtubules, which are thought to mediate refractoriness through alterations of the expression pattern of tubulins or microtubule associated proteins and the expression of alternative tubulin isoforms, failed to confirm such associations. Little consensus has been generated for reported associations between taxane-sensitivity and mutated p53, or taxane-resistance and overexpression of Bcl-2, Bcl-xL or NFkB. In contrary sufficient in vitro data support an association of spindle assembly checkpoint (SAC) defects with resistance. Clinical data have been limited and inconsistent, which relate to the variety of methods used, lack of standardization of cut-offs for quantitation, differences in clinical endpoints measured and in methods of tissue collection preparation and storage, and study/patient heterogeneity. The most

  10. Mechanism of sulfonylurea herbicide resistance in the broadleaf weed, Kochia scoparia

    International Nuclear Information System (INIS)

    Saari, L.L.; Cotterman, J.C.; Primiani, M.M.

    1990-01-01

    Selection of kochia (Kochia scoparia) biotypes resistant to the sulfonylurea herbicide chlorsulfuron has occurred through the continued use of this herbicide in monoculture cereal-growing areas in the United States. The apparent sulfonylurea resistance observed in kochia was confirmed in greenhouse tests. Fresh and dry weight accumulation in the resistance kochia was 2- to >350-fold higher in the presence of four sulfonylurea herbicides as compared to the susceptible biotype. Acetolactate synthase (ALS) activity isolated from sulfonylurea-resistant kochia was less sensitive to inhibition by three classes of ALS-inhibiting herbicides, sulfonylureas, imidazolinones, and sulfonanilides. The decrease in ALS sensitivity to inhibition (as measured by the ratio of resistant I 50 to susceptible I 50 ) was 5- to 28-fold, 2- to 6-fold, and 20-fold for sulfonylurea herbicides, imidazolinone herbicides, and a sulfonanilide herbicide, respectively. No differences were observed in the ALS-specific activities or the rates of [ 14 C]chlorsulfuron uptake, translocation, and metabolism between susceptible and resistant kochia biotypes. The K m values for pyruvate using ALS from susceptible and resistant kochia were 2.13 and 1.74 mM, respectively. Based on these results, the mechanism of sulfonylurea resistance in this kochia biotype is due solely to a less sulfonylurea-sensitive ALS enzyme

  11. A Secure, Scalable and Elastic Autonomic Computing Systems Paradigm: Supporting Dynamic Adaptation of Self-* Services from an Autonomic Cloud

    Directory of Open Access Journals (Sweden)

    Abdul Jaleel

    2018-05-01

    Full Text Available Autonomic computing embeds self-management features in software systems using external feedback control loops, i.e., autonomic managers. In existing models of autonomic computing, adaptive behaviors are defined at the design time, autonomic managers are statically configured, and the running system has a fixed set of self-* capabilities. An autonomic computing design should accommodate autonomic capability growth by allowing the dynamic configuration of self-* services, but this causes security and integrity issues. A secure, scalable and elastic autonomic computing system (SSE-ACS paradigm is proposed to address the runtime inclusion of autonomic managers, ensuring secure communication between autonomic managers and managed resources. Applying the SSE-ACS concept, a layered approach for the dynamic adaptation of self-* services is presented with an online ‘Autonomic_Cloud’ working as the middleware between Autonomic Managers (offering the self-* services and Autonomic Computing System (requiring the self-* services. A stock trading and forecasting system is used for simulation purposes. The security impact of the SSE-ACS paradigm is verified by testing possible attack cases over the autonomic computing system with single and multiple autonomic managers running on the same and different machines. The common vulnerability scoring system (CVSS metric shows a decrease in the vulnerability severity score from high (8.8 for existing ACS to low (3.9 for SSE-ACS. Autonomic managers are introduced into the system at runtime from the Autonomic_Cloud to test the scalability and elasticity. With elastic AMs, the system optimizes the Central Processing Unit (CPU share resulting in an improved execution time for business logic. For computing systems requiring the continuous support of self-management services, the proposed system achieves a significant improvement in security, scalability, elasticity, autonomic efficiency, and issue resolving time

  12. DualTrust: A Trust Management Model for Swarm-Based Autonomic Computing Systems

    Energy Technology Data Exchange (ETDEWEB)

    Maiden, Wendy M. [Washington State Univ., Pullman, WA (United States)

    2010-05-01

    Trust management techniques must be adapted to the unique needs of the application architectures and problem domains to which they are applied. For autonomic computing systems that utilize mobile agents and ant colony algorithms for their sensor layer, certain characteristics of the mobile agent ant swarm -- their lightweight, ephemeral nature and indirect communication -- make this adaptation especially challenging. This thesis looks at the trust issues and opportunities in swarm-based autonomic computing systems and finds that by monitoring the trustworthiness of the autonomic managers rather than the swarming sensors, the trust management problem becomes much more scalable and still serves to protect the swarm. After analyzing the applicability of trust management research as it has been applied to architectures with similar characteristics, this thesis specifies the required characteristics for trust management mechanisms used to monitor the trustworthiness of entities in a swarm-based autonomic computing system and describes a trust model that meets these requirements.

  13. Mechanisms of antimicrobial resistant Salmonella enterica transmission associated with starling-livestock interactions.

    Science.gov (United States)

    Carlson, James C; Hyatt, Doreene R; Ellis, Jeremy W; Pipkin, David R; Mangan, Anna M; Russell, Michael; Bolte, Denise S; Engeman, Richard M; DeLiberto, Thomas J; Linz, George M

    2015-08-31

    Bird-livestock interactions have been implicated as potential sources for bacteria within concentrated animal feeding operations (CAFO). European starlings (Sturnus vulgaris) in particular are known to contaminate cattle feed and water with Salmonella enterica through their fecal waste. We propose that fecal waste is not the only mechanisms through which starlings introduce S. enterica to CAFO. The goal of this study was to assess if starlings can mechanically move S. enterica. We define mechanical movement as the transportation of media containing S. enterica, on the exterior of starlings within CAFO. We collected 100 starlings and obtained external wash and gastrointestinal tract (GI) samples. We also collected 100 samples from animal pens. Within each pen we collected one cattle fecal, feed, and water trough sample. Isolates from all S. enterica positive samples were subjected to antimicrobial susceptibility testing. All sample types, including 17% of external starling wash samples, contained S. enterica. All sample types had at least one antimicrobial resistant (AMR) isolate and starling GI samples harbored multidrug resistant S. enterica. The serotypes isolated from the starling external wash samples were all found in the farm environment and 11.8% (2/17) of isolates from positive starling external wash samples were resistant to at least one class of antibiotics. This study provides evidence of a potential mechanism of wildlife introduced microbial contamination in CAFO. Mechanical movement of microbiological hazards, by starlings, should be considered a potential source of bacteria that is of concern to veterinary, environmental and public health. Published by Elsevier B.V.

  14. Mesoporous silica nanoparticles loading doxorubicin reverse multidrug resistance: performance and mechanism

    Science.gov (United States)

    Shen, Jianan; He, Qianjun; Gao, Yu; Shi, Jianlin; Li, Yaping

    2011-10-01

    Multidrug resistance (MDR) is one of the major obstacles for successful chemotherapy in cancer. One of the effective approaches to overcome MDR is to use nanoparticle-mediated drug delivery to increase drug accumulation in drug resistant cancer cells. In this work, we first report that the performance and mechanism of an inorganic engineered delivery system based on mesoporous silica nanoparticles (MSNs) loading doxorubicin (DMNs) to overcome the MDR of MCF-7/ADR (a DOX-resistant and P-glycoprotein (P-gp) over-expression cancer cell line). The experimental results showed that DMNs could enhance the cellular uptake of doxorubicin (DOX) and increase the cell proliferation suppression effect of DOX against MCF-7/ADR cells. The IC50 of DMNs against MCF-7/ADR cells was 8-fold lower than that of free DOX. However, an improved effect of DOX in DMNs against MCF-7 cells (a DOX-sensitive cancer cell line) was not found. The increased cellular uptake and nuclear accumulation of DOX delivered by DMNs in MCF-7/ADR cells was confirmed by confocal laser scanning microscopy, and could result from the down-regulation of P-gp and bypassing the efflux action by MSNs themselves. The cellular uptake mechanism of DMNs indicated that the macropinocytosis was one of the pathways for the uptake of DMNs by MCF-7/ADR cells. The in vivo biodistribution showed that DMNs induced a higher accumulation of DOX in drug resistant tumors than free DOX. These results suggested that MSNs could be an effective delivery system to overcome multidrug resistance.

  15. Efflux as a mechanism of antimicrobial drug resistance in clinical relevant microorganisms: the role of efflux inhibitors.

    Science.gov (United States)

    Willers, Clarissa; Wentzel, Johannes Frederik; du Plessis, Lissinda Hester; Gouws, Chrisna; Hamman, Josias Hendrik

    2017-01-01

    Microbial resistance against antibiotics is a serious threat to the effective treatment of infectious diseases. Several mechanisms exist through which microorganisms can develop resistance against antimicrobial drugs, of which the overexpression of genes to produce efflux pumps is a major concern. Several efflux transporters have been identified in microorganisms, which infer resistance against specific antibiotics and even multidrug resistance. Areas covered: This paper focuses on microbial resistance against antibiotics by means of the mechanism of efflux and gives a critical overview of studies conducted to overcome this problem by combining efflux pump inhibitors with antibiotics. Information was obtained from a literature search done with MEDLINE, Pubmed, Scopus, ScienceDirect, OneSearch and EBSCO host. Expert opinion: Efflux as a mechanism of multidrug resistance has presented a platform for improved efficacy against resistant microorganisms by co-administration of efflux pump inhibitors with antimicrobial agents. Although proof of concept has been shown for this approach with in vitro experiments, further research is needed to develop more potent inhibitors with low toxicity which is clinically effective.

  16. Autonomic computing enabled cooperative networked design

    CERN Document Server

    Wodczak, Michal

    2014-01-01

    This book introduces the concept of autonomic computing driven cooperative networked system design from an architectural perspective. As such it leverages and capitalises on the relevant advancements in both the realms of autonomic computing and networking by welding them closely together. In particular, a multi-faceted Autonomic Cooperative System Architectural Model is defined which incorporates the notion of Autonomic Cooperative Behaviour being orchestrated by the Autonomic Cooperative Networking Protocol of a cross-layer nature. The overall proposed solution not only advocates for the inc

  17. Quantitative proteomics as a tool to identify resistance mechanisms in erlotinib-resistant subclones of the non-small cell lung cancer cell line HCC827

    DEFF Research Database (Denmark)

    Jacobsen, Kirstine

    , which in 43-50% of cases are caused by a secondary mutation (T790M) in EGFR. Importantly, a majority of resistance cases are still unexplained (Lin & Bivona, 2012). Our aim is to identify novel resistance mechanisms – and potentially new drug targets - in erlotinib-resistant subclones of the NSCLC cell...... of erlotinib, and in biological triplicates on a Q-Exactive mass spectrometer. Only proteins identified with minimum 2 unique peptides and in minimum 2 of 3 replicates were accepted. Results: Importantly, the resistant clones did not acquire the T790M or other EGFR or KRAS mutations, potentiating...... the identification of novel resistance mechanisms. We identified 2875 cytoplasmic proteins present in all 4 cell lines. Of these 87, 56 and 23 are upregulated >1.5 fold; and 117, 72 and 32 are downregulated >1.5 fold, respectively, in the 3 resistant clones compared to the parental cell line. By network analysis, we...

  18. A molecular dynamics investigation on the crizotinib resistance mechanism of C1156Y mutation in ALK

    International Nuclear Information System (INIS)

    Sun, Hui-Yong; Ji, Feng-Qin

    2012-01-01

    Highlights: ► The study revealed the detailed resistance mechanism of the non-active mutation C1156Y in ALK. ► C1156Y leads to crizotinib displacement and conformational changes in the binding cavity. ► The conformations cause a decline in the vdW and electrostatic energy between crizotinib and ALK. -- Abstract: Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor that has recently been approved in the US for the treatment of non-small cell lung carcinoma (NSCLC). Despite its outstanding safety and efficacy, several resistant mutations against crizotinib have been detected in the treatment of NSCLC. However, in contrast to the widely accepted mechanism of steric hindrance by mutations at the active site, the mechanism by which the C1156Y non-active site mutation confers resistance against crizotinib remains unclear. In the present study, the resistance mechanism of C1156Y in ALK was investigated using molecular dynamics simulations. The results suggest that despite the non-active site mutation, C1156Y causes the dislocation of crizotinib as well as the indirect conformational changes in the binding cavity, which results in a marked decrease in the van der Waals and electrostatic interactions between crizotinib and ALK. The obtained results provide a detailed explanation of the resistance caused by C1156Y and may give a vital clue for the design of drugs to combat crizotinib resistance.

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

    Science.gov (United States)

    Ruiz, Joaquim

    2003-05-01

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

  20. Molecular mechanisms of drug resistance in natural Leishmania populations vary with genetic background.

    Directory of Open Access Journals (Sweden)

    Saskia Decuypere

    Full Text Available The evolution of drug-resistance in pathogens is a major global health threat. Elucidating the molecular basis of pathogen drug-resistance has been the focus of many studies but rarely is it known whether a drug-resistance mechanism identified is universal for the studied pathogen; it has seldom been clarified whether drug-resistance mechanisms vary with the pathogen's genotype. Nevertheless this is of critical importance in gaining an understanding of the complexity of this global threat and in underpinning epidemiological surveillance of pathogen drug resistance in the field. This study aimed to assess the molecular and phenotypic heterogeneity that emerges in natural parasite populations under drug treatment pressure. We studied lines of the protozoan parasite Leishmania (L. donovani with differential susceptibility to antimonial drugs; the lines being derived from clinical isolates belonging to two distinct genetic populations that circulate in the leishmaniasis endemic region of Nepal. Parasite pathways known to be affected by antimonial drugs were characterised on five experimental levels in the lines of the two populations. Characterisation of DNA sequence, gene expression, protein expression and thiol levels revealed a number of molecular features that mark antimonial-resistant parasites in only one of the two populations studied. A final series of in vitro stress phenotyping experiments confirmed this heterogeneity amongst drug-resistant parasites from the two populations. These data provide evidence that the molecular changes associated with antimonial-resistance in natural Leishmania populations depend on the genetic background of the Leishmania population, which has resulted in a divergent set of resistance markers in the Leishmania populations. This heterogeneity of parasite adaptations provides severe challenges for the control of drug resistance in the field and the design of molecular surveillance tools for widespread

  1. Molecular mechanisms and theranostic potential of miRNAs in drug resistance of gastric cancer.

    Science.gov (United States)

    Yang, Wanli; Ma, Jiaojiao; Zhou, Wei; Cao, Bo; Zhou, Xin; Yang, Zhiping; Zhang, Hongwei; Zhao, Qingchuan; Fan, Daiming; Hong, Liu

    2017-11-01

    Systemic chemotherapy is a curative approach to inhibit gastric cancer cells proliferation. Despite the great progress in anti-cancer treatment achieved during the last decades, drug resistance and treatment refractoriness still extensively persists. Recently, accumulating studies have highlighted the role of miRNAs in drug resistance of gastric cancers by modulating some drug resistance-related proteins and genes expression. Pre-clinical reports indicate that miRNAs might serve as ideal biomarkers and potential targets, thus holding great promise for developing targeted therapy and personalized treatment for the patients with gastric cancer. Areas covered: This review provide a comprehensive overview of the current advances of miRNAs and molecular mechanisms underlying miRNA-mediated drug resistance in gastric cancer. We particularly focus on the potential values of drug resistance-related miRNAs as biomarkers and novel targets in gastric cancer therapy and envisage the future research developments of these miRNAs and challenges in translating the new findings into clinical applications. Expert opinion: Although the concrete mechanisms of miRNAs in drug resistance of gastric cancer have not been fully clarified, miRNA may be a promising theranostic approach. Further studies are still needed to facilitate the clinical applications of miRNAs in drug resistant gastric cancer.

  2. Elastin and Mechanics of Pig Pericardial Resistance Arteries (pPRA)

    DEFF Research Database (Denmark)

    Bloksgaard, Maria; Leurgans, Thomas; Rosenstand, Kristoffer

    Resistance arteries are remodeled in hypertension and diabetes. Elastin was reported to play a role herein. The parietal pericardium is opened during cardio-thoracic surgeries and might be a valuable biopsy for research in cardio-vascular diseases. We tested the hypothesis that resistance arteries...... can be isolated from the pericardium to study the micro-architecture of elastin and vascular wall mechanics. The pericardium of pigs served to test the hypothesis. pPRAs were microdissected. Their structure was examined using multiphoton excitation fluorescence microscopy. Diameter......-tension and pressure-diameter-length relationships were recorded in myographs. Findings are compared to rodent mesenteric resistance arteries and –basilar arteries (rMRA, rBA) with comparable lumen diameter (±300µm at 100mmHg). pPRA have no clear external elastic lamina (present in rMRA, but not rBA), scant elastin...

  3. The Mechanisms of Maize Resistance to Fusarium verticillioides by comprehensive analysis of RNA-seq Data

    Directory of Open Access Journals (Sweden)

    Yanping Wang

    2016-11-01

    Full Text Available Fusarium verticillioides is the most commonly reported fungal species responsible for ear rot of maize which substantially reduces grain yield. It also results in a substantial accumulation of mycotoxins that give rise to toxic response when ingested by animals and humans. For inefficient control by chemical and agronomic measures, it thus becomes more desirable to select more resistant varieties. However, the molecular mechanisms underlying the infection process remain poorly understood, which hampers the application of quantitative resistance in breeding programs. Here, we reveal the disease-resistance mechanism of the maize inbred line of BT-1 which displays high resistance to ear rot using RNA high throughput sequencing. By analyzing RNA-seq data from the BT-1 kernels before and after F. verticillioides inoculation, we found that transcript levels of genes associated with key pathways are dramatically changed compared with the control treatment. Differential gene expression in ear rot resistant and susceptible maize was confirmed by RNA microarray and qRT-PCR analyses. Further investigation suggests that the small heat shock protein family, some secondary metabolites, and the signaling pathways of abscisic acid (ABA, jasmonic acid (JA or salicylic acids (SA may be involved in the pathogen-associated molecular pattern-triggered immunity against F. verticillioides. These data will not only provide new insights into the molecular resistant mechanisms against fungi invading, but may also result in the identification of key molecular factors associated with ear rot resistance in maize.

  4. Discovery of Organophosphate Resistance-Related Genes Associated With Well-known Resistance Mechanisms of Plutella xylostella (L.) (Lepidoptera: Plutellidae) by RNA-Seq.

    Science.gov (United States)

    Hsu, Ju-Chun; Lin, Yu-Yu; Chang, Chia-Che; Hua, Kuo-Hsun; Chen, Mei-Ju May; Huang, Li-Hsin; Chen, Chien-Yu

    2016-04-22

    Pesticide resistance poses many challenges for pest control, particularly for destructive pests such as diamondback moths (Plutella xylostella). Organophosphates have been used in the field since the 1950s, leading to selection for resistance-related gene variants and the development of resistance to new insecticides in the diamondback moth. Identifying actual and potential genes involved in resistance could offer solutions for control. This study established resistant diamondback moth strains from two different collections using mevinphos. Two sets of transcriptome sequencing (RNA-Seq) data were generated for pairs of mevinphos-resistant versus susceptible (wild-type) strains. One susceptible strain containing 14 giga base pairs was assembled into a reference-based assembly using published scaffold sequences as reference. Differential expression data between resistant and susceptible strains revealed 944 transcripts (803 with annotations) showing upregulation and 427 transcripts (150 with annotations) showing downregulation. Around 6.8% of the differential expression transcripts (65) could be categorized as associated with well-known resistance mechanisms such as penetration, detoxification, and behavior response; of these 65 transcripts, 38 showed upregulation, and 12 relating to penetration were upregulated when the transcripts of 19 cytochrome P450s, 2 zeta-class glutathione S-transferases, and 4 ATP-binding cassette transporters showed upregulation. In addition, 11 groups of transcripts related to olfactory perception appeared to be downregulated in trade-off situations. Quantitative polymerase chain reaction expression results were consistent with RNA-Seq data. Possible roles of these differentially expressed genes in resistance mechanisms are discussed in this study. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Environmentally Friendly Coating Technology for Autonomous Corrosion Control

    Science.gov (United States)

    Calle, Luz M.; Li, Wenyan; Buhrow, Jerry W.; Johnsey, Marissa N.; Jolley, Scott T.; Pearman, Benjamin P.; Zhang, Xuejun; Fitzpatrick, Lilliana; Gillis, Mathew; Blanton, Michael; hide

    2016-01-01

    This work concerns the development of environmentally friendly encapsulation technology, specifically designed to incorporate corrosion indicators, inhibitors, and self-healing agents into a coating, in such a way that the delivery of the indicators and inhibitors is triggered by the corrosion process, and the delivery of self-healing agents is triggered by mechanical damage to the coating. Encapsulation of the active corrosion control ingredients allows the incorporation of desired autonomous corrosion control functions such as: early corrosion detection, hidden corrosion detection, corrosion inhibition, and self-healing of mechanical damage into a coating. The technology offers the versatility needed to include one or several corrosion control functions into the same coating.The development of the encapsulation technology has progressed from the initial proof-of-concept work, in which a corrosion indicator was encapsulated into an oil-core (hydrophobic) microcapsule and shown to be delivered autonomously, under simulated corrosion conditions, to a sophisticated portfolio of micro carriers (organic, inorganic, and hybrid) that can be used to deliver a wide range of active corrosion ingredients at a rate that can be adjusted to offer immediate as well as long-term corrosion control. The micro carriers have been incorporated into different coating formulas to test and optimize the autonomous corrosion detection, inhibition, and self-healing functions of the coatings. This paper provides an overview of progress made to date and highlights recent technical developments, such as improved corrosion detection sensitivity, inhibitor test results in various types of coatings, and highly effective self-healing coatings based on green chemistry.

  6. Central nervous system involvement in the autonomic responses to psychological distress

    NARCIS (Netherlands)

    de Morree, H.M.; Szabó, B.M.; Rutten, G.J.; Kop, W.J.

    2013-01-01

    Psychological distress can trigger acute coronary syndromes and sudden cardiac death in vulnerable patients. The primary pathophysiological mechanism that plays a role in stress-induced cardiac events involves the autonomic nervous system, particularly disproportional sympathetic activation and

  7. Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals

    Directory of Open Access Journals (Sweden)

    Asma Ahmed

    2015-12-01

    Full Text Available There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.

  8. Mechanisms of hexavalent chromium resistance and removal by microorganisms.

    Science.gov (United States)

    Joutey, Nezha Tahri; Sayel, Hanane; Bahafid, Wifak; El Ghachtouli, Naïma

    2015-01-01

    Chromium has been and is extensively used worldwide in multiple industrial processes and is routinely discharged to the environment from such processes. Therefore, this heavy metal is a potential threat to the environment and to public health, primarily because it is non-biodegradable and environmentally persistent. Chromium exists in several oxidation states, the most stable of which are trivalent Cr(Ill) and hexavalent Cr(VI) species. Each species possesses its own individual chemical characteristics and produces its own biological effects. For example, Cr (Ill) is an essential oligoelement for humans, whereas Cr(VI) is carcinogenic and mutagenic. Several chemical methods are used to remove Cr(VI) from contaminated sites. Each of these methods has advantages and disadvantages. Currently, bioremediation is often the preferred method to deal with Cr contaminated sites, because it is eco-friendly, cost-effective and is a "natural" technology. Many yeast, bacterial and fungal species have been assessed for their suitability to reduce or remove Cr(VI) contamination. The mechanisms by which these microorganisms resist and reduce Cr(VI) are variable and are species dependent. There are several Cr-resistance mechanisms that are displayed by microorganisms. These include active efflux of Cr compounds, metabolic reduction of Cr(VI) to Cr (ill), and either intercellular or extracellular prec1p1tation. Microbial Cr (VI) removal typically involves three stages: binding of chromium to the cell surface, translocation of chromium into the cell, and reduction of Cr(VI) to Cr (ill). Cr(VI) reduction by microorganisms may proceed on the cell surface, outside the cell, or intracellularly, either directly via chromate reductase enzymes, or indirectly via metabolite reduction of Cr(VI). The uptake of chromium ions is a biphasic process. The primary step is known as biosorption, a metabolic energyindependent process. Thereafter, bioaccumulation occurs, but is much slower, and is

  9. Investigation of Resistance to Mechanical Effect of Braille Formed on Different Materials

    Directory of Open Access Journals (Sweden)

    Ingrida VENYTĖ

    2014-06-01

    Full Text Available Qualitative analysis of stresses emerged in paperboard during Braille embossing, using specialized polarimetric equipment, was carried out. Resistance to mechanical effect of Braille dot surfaces, formed with different printing types on different materials (paper, paperboard, polymer, textile, Al foil was investigated. It was determined that Braille dot height change after period mechanical effect is different.

  10. On-electrode autonomous current generator for multi-frequency EIT

    International Nuclear Information System (INIS)

    Jivet, I; Dragoi, B

    2008-01-01

    The paper presents an autonomous programmable current generator module for multi-frequency EIT systems. The module incorporates all stages from the sine wave generation with frequency and amplitude tuning, D/A converter and filter, a high output resistance voltage-to-current converter to the associated digital communication and control. The paper presents in depth the original digital quadrature signal generator and the output current generator with a high resistance. The other main blocks of the design use current practice specifications, since recent technological solutions proposed in the literature were found appropriate. The proposed signal generator circuit, characterized by a very low complexity, is analyzed in its capacity to produce multiple accurate signals up to 1 MHz in frequency. The precision output current source uses a modified current conveyor of type CCII with a high output resistance and low distortion. The output current frequency spectrum and linearity parameters obtained in the simulations are also described. The simulation results indicate a good linearity and high output resistance with an acceptable output voltage swing. The calculated performance parameters are validated with simulations, and future work for the prototype fabrication of the IC is outlined

  11. Influence of Brazilian vegetable oils on mechanical resistence of hair fiber

    Directory of Open Access Journals (Sweden)

    Maria Valéria Velasco

    2015-02-01

    Full Text Available Associating the global trend of incorporating active compounds and plants in cosmetic formulations and the vast Brazilian biodiversity, the present work aimed to study the incorporation of Brazilian vegetable oils in hair conditioner formulations, evaluating the mechanical resistance of hair fibers. The following oils were incorporated into base formulations at 5.0 % (w/w: babassu, buriti, andiroba and pequi. The formulations were applied to samples of Caucasian hair, followed by several washing steps, then the evaluation of mechanical strength. It was found that there was no statistically significant difference in mechanical resistance between samples treated with oils and the control between the first and seventh wash cycles. This fact can be explained by the possible low penetration of oils into the cortex, a region responsible for the mechanical properties of the hair fiber, since the grease composition disfavors its diffusion. The common effects of vegetable oils on the cuticle, such as filling in cracks or cavities, lubrication, and increased protein hydrophobicity cannot be excluded. The oils tested in this work were not able to raise or protect hair tresses. However, additional studies are required in order to establish the effects of oil treatments, particularly in damaged hair.

  12. Understanding the molecular mechanism(s) of hepatitis C virus (HCV) induced interferon resistance.

    Science.gov (United States)

    Qashqari, Hanadi; Al-Mars, Amany; Chaudhary, Adeel; Abuzenadah, Adel; Damanhouri, Ghazi; Alqahtani, Mohammed; Mahmoud, Maged; El Sayed Zaki, Maysaa; Fatima, Kaneez; Qadri, Ishtiaq

    2013-10-01

    Hepatitis C virus (HCV) is one of the foremost causes of chronic liver disease affecting over 300 million globally. HCV contains a positive-stranded RNA of ~9600 nt and is surrounded by the 5' and 3'untranslated regions (UTR). The only successful treatment regimen includes interferon (IFN) and ribavirin. Like many other viruses, HCV has also evolved various mechanisms to circumvent the IFN response by blocking (1) downstream signaling actions via STAT1, STAT2, IRF9 and JAK-STAT pathways and (2) repertoire of IFN Stimulatory Genes (ISGs). Several studies have identified complex host demographic and genetic factors as well as viral genetic heterogeneity associated with outcomes of IFN therapy. The genetic predispositions of over 2000 ISGS may render the patients to become resistant, thus identification of such parameters within a subset of population are necessary for management corollary. The ability of various HCV genotypes to diminish IFN antiviral responses plays critical role in the establishment of chronic infection at the acute stage of infection, thus highlighting importance of the resistance in HCV treated groups. The recently defined role of viral protein such as C, E2, NS3/NS4 and NS5A proteins in inducing the IFN resistance are discussed in this article. How the viral and host genetic composition and epistatic connectivity among polymorphic genomic sites synchronizes the evolutionary IFN resistance trend remains under investigation. However, these signals may have the potential to be employed for accurate prediction of therapeutic outcomes. In this review article, we accentuate the significance of host and viral components in IFN resistance with the aim to determine the successful outcome in patients. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Insights into the background of autonomic medicine.

    Science.gov (United States)

    Laranjo, Sérgio; Geraldes, Vera; Oliveira, Mário; Rocha, Isabel

    2017-10-01

    Knowledge of the physiology underlying the autonomic nervous system is pivotal for understanding autonomic dysfunction in clinical practice. Autonomic dysfunction may result from primary modifications of the autonomic nervous system or be secondary to a wide range of diseases that cause severe morbidity and mortality. Together with a detailed history and physical examination, laboratory assessment of autonomic function is essential for the analysis of various clinical conditions and the establishment of effective, personalized and precise therapeutic schemes. This review summarizes the main aspects of autonomic medicine that constitute the background of cardiovascular autonomic dysfunction. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. A molecular dynamics investigation on the crizotinib resistance mechanism of C1156Y mutation in ALK

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Hui-Yong [Shandong University of Technology, Zibo 255049 (China); Ji, Feng-Qin, E-mail: fengqinji@mail.hzau.edu.cn [National Key Laboratory of Crop Genetic Improvement, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Center for Bioinformatics, Huazhong Agricultural University, Wuhan 430070 (China)

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer The study revealed the detailed resistance mechanism of the non-active mutation C1156Y in ALK. Black-Right-Pointing-Pointer C1156Y leads to crizotinib displacement and conformational changes in the binding cavity. Black-Right-Pointing-Pointer The conformations cause a decline in the vdW and electrostatic energy between crizotinib and ALK. -- Abstract: Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor that has recently been approved in the US for the treatment of non-small cell lung carcinoma (NSCLC). Despite its outstanding safety and efficacy, several resistant mutations against crizotinib have been detected in the treatment of NSCLC. However, in contrast to the widely accepted mechanism of steric hindrance by mutations at the active site, the mechanism by which the C1156Y non-active site mutation confers resistance against crizotinib remains unclear. In the present study, the resistance mechanism of C1156Y in ALK was investigated using molecular dynamics simulations. The results suggest that despite the non-active site mutation, C1156Y causes the dislocation of crizotinib as well as the indirect conformational changes in the binding cavity, which results in a marked decrease in the van der Waals and electrostatic interactions between crizotinib and ALK. The obtained results provide a detailed explanation of the resistance caused by C1156Y and may give a vital clue for the design of drugs to combat crizotinib resistance.

  15. Experimental dynamical characterization of five autonomous chaotic oscillators with tunable series resistance

    Energy Technology Data Exchange (ETDEWEB)

    Minati, Ludovico, E-mail: lminati@ieee.org, E-mail: ludovico.minati@unitn.it [MR-Lab, Center for Mind/Brain Science, University of Trento, Trento, Italy and Scientific Department, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan (Italy)

    2014-09-01

    In this paper, an experimental characterization of the dynamical properties of five autonomous chaotic oscillators, based on bipolar-junction transistors and obtained de-novo through a genetic algorithm in a previous study, is presented. In these circuits, a variable resistor connected in series to the DC voltage source acts as control parameter, for a range of which the largest Lyapunov exponent, correlation dimension, approximate entropy, and amplitude variance asymmetry are calculated, alongside bifurcation diagrams and spectrograms. Numerical simulations are compared to experimental measurements. The oscillators can generate a considerable variety of regular and chaotic sine-like and spike-like signals.

  16. Complexity of resistance mechanisms to imipenem in intensive care unit strains of Pseudomonas aeruginosa.

    Science.gov (United States)

    Fournier, Damien; Richardot, Charlotte; Müller, Emeline; Robert-Nicoud, Marjorie; Llanes, Catherine; Plésiat, Patrick; Jeannot, Katy

    2013-08-01

    Pseudomonas aeruginosa can become resistant to carbapenems by both intrinsic (mutation-driven) and transferable (β-lactamase-based) mechanisms. Knowledge of the prevalence of these various mechanisms is important in intensive care units (ICUs) in order to define optimal prevention and therapeutic strategies. A total of 109 imipenem-non-susceptible (MIC >4 mg/L) strains of P. aeruginosa were collected in June 2010 from the ICUs of 26 French public hospitals. Their resistance mechanisms were characterized by phenotypic, enzymatic, western blotting and molecular methods. Single or associated imipenem resistance mechanisms were identified among the 109 strains. Seven isolates (6.4%) were found to produce a metallo-β-lactamase (one VIM-1, four VIM-2, one VIM-4 and one IMP-29). Porin OprD was lost in 94 (86.2%) strains as a result of mutations or gene disruption by various insertion sequences (ISPa1635, ISPa1328, IS911, ISPs1, IS51, IS222 and ISPa41). Thirteen other strains were shown to be regulatory mutants in which down-regulation of oprD was coupled with overexpressed efflux pumps CzcCBA (n = 1), MexXY (n = 9) and MexEF-OprN (n = 3). The lack of OprD was due to disruption of the oprD promoter by ISPsy2 in one strain and alteration of the porin signal sequence in another. Imipenem resistance in ICU P. aeruginosa strains may result from multiple mechanisms involving metallo-β-lactamase gene acquisition and genetic events (mutations and ISs) inactivating oprD, turning down its expression while increasing efflux activities or preventing insertion of porin OprD in the outer membrane. This diversity of mechanisms allows P. aeruginosa, more than any other nosocomial pathogen, to rapidly adapt to carbapenems in ICUs.

  17. Autonomic Nervous System Disorders

    Science.gov (United States)

    Your autonomic nervous system is the part of your nervous system that controls involuntary actions, such as the beating of your heart ... breathing and swallowing Erectile dysfunction in men Autonomic nervous system disorders can occur alone or as the result ...

  18. The analysis of mechanism of rhenium-coated tools' wear-resistance rising

    Directory of Open Access Journals (Sweden)

    Daniel Petrosyan

    2017-06-01

    Full Text Available It is proposed to obtain wear-resistant layers on the hard-alloy materials by thermochemical treatment. In the different field of production – mechanical engineering, metallurgy and military technologies, with machine parts demanding high wearproof and corrosion-proof machinery parts on the surfaces of syntheses of diamonds, with metal surface thermal-diffusion with rhenium, to receive diffusion wearing layers for the first time. A method for thermochemical treatment of hard alloy plates has been investigated, allowing to raise the wear-resistance of cutting and mining tools.

  19. Biochemical mechanisms of resistance to p-nitrochlorobenzene of karst caves microorganisms

    Directory of Open Access Journals (Sweden)

    O. S. Suslova

    2015-08-01

    Full Text Available The biochemical mechanisms of resistance to persistent organic xenobiotic p-nitrochlorobenzene (NCB of bacterial strains isolated from two cave clays ecosystems – Mushkarova Yama (Podolia, Ukraine and Kuybyshevskaya (Western Caucasus, Abkhazia have been established. It has been determined that chemoorganotrophic karst caves strains could interact with NCB and transform it reducing the nitro group with formation of p-chloroaniline (ClA followed by further destruction of NCB aromatic ring. This explained high resistance of caves strains to NCB. The studied strains could potentially be used in wastewater treatment from nitrochloraromatic compounds.

  20. Insecticide resistance mechanisms associated with different environments in the malaria vector Anopheles gambiae: a case study in Tanzania.

    Science.gov (United States)

    Nkya, Theresia E; Akhouayri, Idir; Poupardin, Rodolphe; Batengana, Bernard; Mosha, Franklin; Magesa, Stephen; Kisinza, William; David, Jean-Philippe

    2014-01-25

    Resistance of mosquitoes to insecticides is a growing concern in Africa. Since only a few insecticides are used for public health and limited development of new molecules is expected in the next decade, maintaining the efficacy of control programmes mostly relies on resistance management strategies. Developing such strategies requires a deep understanding of factors influencing resistance together with characterizing the mechanisms involved. Among factors likely to influence insecticide resistance in mosquitoes, agriculture and urbanization have been implicated but rarely studied in detail. The present study aimed at comparing insecticide resistance levels and associated mechanisms across multiple Anopheles gambiae sensu lato populations from different environments. Nine populations were sampled in three areas of Tanzania showing contrasting agriculture activity, urbanization and usage of insecticides for vector control. Insecticide resistance levels were measured in larvae and adults through bioassays with deltamethrin, DDT and bendiocarb. The distribution of An. gambiae sub-species and pyrethroid target-site mutations (kdr) were investigated using molecular assays. A microarray approach was used for identifying transcription level variations associated to different environments and insecticide resistance. Elevated resistance levels to deltamethrin and DDT were identified in agriculture and urban areas as compared to the susceptible strain Kisumu. A significant correlation was found between adult deltamethrin resistance and agriculture activity. The subspecies Anopheles arabiensis was predominant with only few An. gambiae sensu stricto identified in the urban area of Dar es Salaam. The L1014S kdr mutation was detected at elevated frequency in An gambiae s.s. in the urban area but remains sporadic in An. arabiensis specimens. Microarrays identified 416 transcripts differentially expressed in any area versus the susceptible reference strain and supported the impact

  1. Autonomous authority in relation to the staff regulations of autonomous parliaments

    Directory of Open Access Journals (Sweden)

    Rafael Cano Silva

    2018-04-01

    Full Text Available The statutes of Autonomous Parliaments are parliamentary administrative norms approved by each legislative chamber by virtue of their parliamentary autonomy. However, the parliamentary autonomy of each autonomous parliament does not have the same normative aspect for these purposes. It is studied in this article as despite having the Constitution as a common element, it is essential the special attribution that each autonomous chamber has and that the jurisprudence, both of the Constitutional Court, and that of the Supreme Court, has put in value, question that is included in the section related to the jurisprudence. In conclusion, the bureaucratic organization, in what refers to personal media, may be substantially different in each one of the legislative assemblies, as analyzed in the conclusions of this study.

  2. A molecular dynamics investigation into the mechanisms of alectinib resistance of three ALK mutants.

    Science.gov (United States)

    He, Muyang; Li, Weikang; Zheng, Qingchuan; Zhang, Hongxing

    2018-01-11

    Alectinib, a highly selective next-genetation anaplastic lymphoma kinase (ALK) inhibitor, has demonstrated promising antitumor activity in patients with ALK-positive non-small cell lung carcinomas (NSCLC). However, the therapeutic benefits of alectinib is inescapably hampered by the development of acquired resistant mutations in ALK. Despite the availability of ample experimental mutagenesis data, the molecular origin and the structural motifs under alectinib binding affinity deficiencies are still ambiguous. Here, molecular dynamics (MD) simulations and molecular mechanics generalized born surface area (MM-GBSA) calculation approaches were employed to elucidate the mechanisms of alectinib resistance induced by the mutations I1171N, V1180L, and L1198F. The MD results reveal that the studied mutations could trigger the dislocation of alectinib as well as conformational changes at the inhibitor binding site, thus induce the interactional changes between alectinib and mutants. The most influenced regions are the ligand binding entrance and the hinge region, which are considered to be the dominant binding motifs accounting for the binding affinity loss in mutants. The "key and lock mechanism" between the ethyl group at position 9 of alectinib and a recognition cavity in the hinge region of ALK is presented to illustrate the major molecular origin of drug resistance. Our results provide mechanistic insight into the effect of ALK mutations resistant to alectinib, which could contribute to further rational design of inhibitors to combat the acquired resistance. © 2018 Wiley Periodicals, Inc.

  3. Nanoparticle mechanics: deformation detection via nanopore resistive pulse sensing

    Science.gov (United States)

    Darvish, Armin; Goyal, Gaurav; Aneja, Rachna; Sundaram, Ramalingam V. K.; Lee, Kidan; Ahn, Chi Won; Kim, Ki-Bum; Vlahovska, Petia M.; Kim, Min Jun

    2016-07-01

    Solid-state nanopores have been widely used in the past for single-particle analysis of nanoparticles, liposomes, exosomes and viruses. The shape of soft particles, particularly liposomes with a bilayer membrane, can greatly differ inside the nanopore compared to bulk solution as the electric field inside the nanopores can cause liposome electrodeformation. Such deformations can compromise size measurement and characterization of particles, but are often neglected in nanopore resistive pulse sensing. In this paper, we investigated the deformation of various liposomes inside nanopores. We observed a significant difference in resistive pulse characteristics between soft liposomes and rigid polystyrene nanoparticles especially at higher applied voltages. We used theoretical simulations to demonstrate that the difference can be explained by shape deformation of liposomes as they translocate through the nanopores. Comparing our results with the findings from electrodeformation experiments, we demonstrated that the rigidity of liposomes can be qualitatively compared using resistive pulse characteristics. This application of nanopores can provide new opportunities to study the mechanics at the nanoscale, to investigate properties of great value in fundamental biophysics and cellular mechanobiology, such as virus deformability and fusogenicity, and in applied sciences for designing novel drug/gene delivery systems.Solid-state nanopores have been widely used in the past for single-particle analysis of nanoparticles, liposomes, exosomes and viruses. The shape of soft particles, particularly liposomes with a bilayer membrane, can greatly differ inside the nanopore compared to bulk solution as the electric field inside the nanopores can cause liposome electrodeformation. Such deformations can compromise size measurement and characterization of particles, but are often neglected in nanopore resistive pulse sensing. In this paper, we investigated the deformation of various

  4. Transferability of MCR-1/2 Polymyxin Resistance: Complex Dissemination and Genetic Mechanism.

    Science.gov (United States)

    Feng, Youjun

    2018-03-09

    Polymyxins, a group of cationic antimicrobial polypeptides, act as a last-resort defense against lethal infections by carbapenem-resistant Gram-negative pathogens. Recent emergence and fast spread of mobilized colistin resistance determinant mcr-1 argue the renewed interest of colistin in clinical therapies, threatening global public health and agriculture production. This mini-review aims to present an updated overview of mcr-1, covering its global dissemination, the diversity of its hosts/plasmid reservoirs, the complexity in the genetic environment adjacent to mcr-1, the appearance of new mcr-like genes, and the molecular mechanisms for mobilized colistin resistance determinant 1/2 (MCR-1/2).

  5. Enhanced mechanical properties and increased corrosion resistance of a biodegradable magnesium alloy by plasma electrolytic oxidation (PEO)

    International Nuclear Information System (INIS)

    White, Leon; Koo, Youngmi; Neralla, Sudheer; Sankar, Jagannathan; Yun, Yeoheung

    2016-01-01

    Highlights: • Plasma electrolytic oxidation (PEO) method was developed to control corrosion, porosity, and mechanical property. • Mechanical properties of PEO-coated AZ31 alloys were affected by the different electrolyte. • Mechanical properties and corrosion resistance of PEO-coated AZ31 alloys were compared with uncoated one. - Abstract: We report the enhanced mechanical properties of AZ31 magnesium alloys by plasma electrolytic oxidation (PEO) coating in NaOH, Na_2SiO_3, KF and NaH_2PO_4·2H_2O containing electrolytes. Mechanical properties including wear resistance, surface hardness and elastic modulus were increased for PEO-coated AZ31 Mg alloys (PEO-AZ31). DC polarization in Hank's solution indicating that the corrosion resistance significantly increased for PEO-coating in KF-contained electrolyte. Based on these results, the PEO coating method shows promising potential for use in biodegradable implant applications where tunable corrosion and mechanical properties are needed.

  6. Enhanced mechanical properties and increased corrosion resistance of a biodegradable magnesium alloy by plasma electrolytic oxidation (PEO)

    Energy Technology Data Exchange (ETDEWEB)

    White, Leon; Koo, Youngmi [FIT BEST Laboratory, Engineering Research Center, Department of Chemical, Biological, and Bio Engineering, North Carolina A& T State University, Greensboro, NC 27411 (United States); Neralla, Sudheer [Jet-Hot LLC, Burlington, NC 27215 (United States); Sankar, Jagannathan [FIT BEST Laboratory, Engineering Research Center, Department of Chemical, Biological, and Bio Engineering, North Carolina A& T State University, Greensboro, NC 27411 (United States); Yun, Yeoheung, E-mail: yyun@ncat.edu [FIT BEST Laboratory, Engineering Research Center, Department of Chemical, Biological, and Bio Engineering, North Carolina A& T State University, Greensboro, NC 27411 (United States)

    2016-06-15

    Highlights: • Plasma electrolytic oxidation (PEO) method was developed to control corrosion, porosity, and mechanical property. • Mechanical properties of PEO-coated AZ31 alloys were affected by the different electrolyte. • Mechanical properties and corrosion resistance of PEO-coated AZ31 alloys were compared with uncoated one. - Abstract: We report the enhanced mechanical properties of AZ31 magnesium alloys by plasma electrolytic oxidation (PEO) coating in NaOH, Na{sub 2}SiO{sub 3}, KF and NaH{sub 2}PO{sub 4}·2H{sub 2}O containing electrolytes. Mechanical properties including wear resistance, surface hardness and elastic modulus were increased for PEO-coated AZ31 Mg alloys (PEO-AZ31). DC polarization in Hank's solution indicating that the corrosion resistance significantly increased for PEO-coating in KF-contained electrolyte. Based on these results, the PEO coating method shows promising potential for use in biodegradable implant applications where tunable corrosion and mechanical properties are needed.

  7. Research Update: Nanogenerators for self-powered autonomous wireless sensors

    Science.gov (United States)

    Khan, Usman; Hinchet, Ronan; Ryu, Hanjun; Kim, Sang-Woo

    2017-07-01

    Largely distributed networks of sensors based on the small electronics have great potential for health care, safety, and environmental monitoring. However, in order to have a maintenance free and sustainable operation, such wireless sensors have to be self-powered. Among various energies present in our environment, mechanical energy is widespread and can be harvested for powering the sensors. Piezoelectric and triboelectric nanogenerators (NGs) have been recently introduced for mechanical energy harvesting. Here we introduce the architecture and operational modes of self-powered autonomous wireless sensors. Thereafter, we review the piezoelectric and triboelectric NGs focusing on their working mechanism, structures, strategies, and materials.

  8. Mechanisms of antibiotic resistance to enrofloxacin in uropathogenic Escherichia coli in dog.

    Science.gov (United States)

    Piras, Cristian; Soggiu, Alessio; Greco, Viviana; Martino, Piera Anna; Del Chierico, Federica; Putignani, Lorenza; Urbani, Andrea; Nally, Jarlath E; Bonizzi, Luigi; Roncada, Paola

    2015-09-08

    Escherichia coli (E. coli) urinary tract infections (UTIs) are becoming a serious problem both for pets and humans (zoonosis) due to the close contact and to the increasing resistance to antibiotics. This study has been performed in order to unravel the mechanism of induced enrofloxacin resistance in canine E. coli isolates that represent a good tool to study this pathology. The isolated E. coli has been induced with enrofloxacin and studied through 2D DIGE and shotgun MS. Discovered differentially expressed proteins are principally involved in antibiotic resistance and linked to oxidative stress response, to DNA protection and to membrane permeability. Moreover, since enrofloxacin is an inhibitor of DNA gyrase, the overexpression of DNA starvation/stationary phase protection protein (Dsp) could be a central point to discover the mechanism of this clone to counteract the effects of enrofloxacin. In parallel, the dramatic decrease of the synthesis of the outer membrane protein W, which represents one of the main gates for enrofloxacin entrance, could explain additional mechanism of E. coli defense against this antibiotic. All 2D DIGE and MS data have been deposited into the ProteomeXchange Consortium with identifier PXD002000 and DOI http://dx.doi.org/10.6019/PXD002000. This article is part of a Special Issue entitled: HUPO 2014. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Epileptic Seizures are Reduced by Autonomic Biofeedback Therapy Through Enhancement of Fronto-limbic Connectivity: A Controlled Trial and Neuroimaging Study

    Directory of Open Access Journals (Sweden)

    Yoko Nagai

    2018-01-01

    Interpretation: Our clinical study provides evidence for autonomic biofeedback therapy as an effective and potent behavioral intervention for patients with drug-resistant epilepsy. This approach is non-pharmacological, non-invasive and seemingly side-effect free.

  10. Investigating the molecular mechanisms of organophosphate and pyrethroid resistance in the fall armyworm Spodoptera frugiperda.

    Directory of Open Access Journals (Sweden)

    Renato A Carvalho

    Full Text Available The fall armyworm Spodoptera frugiperda is an economically important pest of small grain crops that occurs in all maize growing regions of the Americas. The intensive use of chemical pesticides for its control has led to the selection of resistant populations, however, to date, the molecular mechanisms underlying resistance have not been characterised. In this study the mechanisms involved in the resistance of two S. frugiperda strains collected in Brazil to chlorpyrifos (OP strain or lambda-cyhalothrin (PYR strain were investigated using molecular and genomic approaches. To examine the possible role of target-site insensitivity the genes encoding the organophosphate (acetylcholinesterase, AChE and pyrethroid (voltage-gated sodium channel, VGSC target-site proteins were PCR amplified. Sequencing of the S. frugiperda ace-1 gene identified several nucleotide changes in the OP strain when compared to a susceptible reference strain (SUS. These result in three amino acid substitutions, A201S, G227A and F290V, that have all been shown previously to confer organophosphate resistance in several other insect species. Sequencing of the gene encoding the VGSC in the PYR strain, identified mutations that result in three amino acid substitutions, T929I, L932F and L1014F, all of which have been shown previously to confer knockdown/super knockdown-type resistance in several arthropod species. To investigate the possible role of metabolic detoxification in the resistant phenotype of the OP and PYR stains all EST sequences available for S. frugiperda were used to design a gene-expression microarray. This was then used to compare gene expression in the resistant strains with the susceptible reference strain. Members of several gene families, previously implicated in metabolic resistance in other insects were found to be overexpressed in the resistant strains including glutathione S-transferases, cytochrome P450s and carboxylesterases. Taken together these results

  11. Investigating the molecular mechanisms of organophosphate and pyrethroid resistance in the fall armyworm Spodoptera frugiperda.

    Science.gov (United States)

    Carvalho, Renato A; Omoto, Celso; Field, Linda M; Williamson, Martin S; Bass, Chris

    2013-01-01

    The fall armyworm Spodoptera frugiperda is an economically important pest of small grain crops that occurs in all maize growing regions of the Americas. The intensive use of chemical pesticides for its control has led to the selection of resistant populations, however, to date, the molecular mechanisms underlying resistance have not been characterised. In this study the mechanisms involved in the resistance of two S. frugiperda strains collected in Brazil to chlorpyrifos (OP strain) or lambda-cyhalothrin (PYR strain) were investigated using molecular and genomic approaches. To examine the possible role of target-site insensitivity the genes encoding the organophosphate (acetylcholinesterase, AChE) and pyrethroid (voltage-gated sodium channel, VGSC) target-site proteins were PCR amplified. Sequencing of the S. frugiperda ace-1 gene identified several nucleotide changes in the OP strain when compared to a susceptible reference strain (SUS). These result in three amino acid substitutions, A201S, G227A and F290V, that have all been shown previously to confer organophosphate resistance in several other insect species. Sequencing of the gene encoding the VGSC in the PYR strain, identified mutations that result in three amino acid substitutions, T929I, L932F and L1014F, all of which have been shown previously to confer knockdown/super knockdown-type resistance in several arthropod species. To investigate the possible role of metabolic detoxification in the resistant phenotype of the OP and PYR stains all EST sequences available for S. frugiperda were used to design a gene-expression microarray. This was then used to compare gene expression in the resistant strains with the susceptible reference strain. Members of several gene families, previously implicated in metabolic resistance in other insects were found to be overexpressed in the resistant strains including glutathione S-transferases, cytochrome P450s and carboxylesterases. Taken together these results provide

  12. Mechanisms of Acquired Resistance to ALK Inhibitors and the Rationale for Treating ALK-positive Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Isozaki, Hideko [Department of Clinical Pharmaceutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558 (Japan); Takigawa, Nagio, E-mail: ntakigaw@gmail.com [Department of General Internal Medicine 4, Kawasaki Medical School, Okayama 700-8505 (Japan); Kiura, Katsuyuki [Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama 700-8558 (Japan)

    2015-04-30

    The discovery of an echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene led to improved clinical outcomes in patients with lung cancer after the development of the first ALK-targeting agent, crizotinib. Some second-generation ALK tyrosine kinase inhibitors (TKIs), which might be more potent than crizotinib or effective on crizotinib-resistant patients, have been developed. Although these ALK-TKIs show an excellent response initially, most patients eventually acquire resistance. Therefore, careful consideration of the resistance mechanisms might lead to superior therapeutic strategies. Here, we summarize the history of ALK-TKIs and their underlying resistance mechanisms in both the preclinical and clinical settings. In addition, we discuss potential future treatment strategies in ALK-TKI-naïve and -resistant patients with lung cancer harboring the EML4-ALK fusion gene.

  13. Formal Verification of Autonomous Vehicle Platooning

    OpenAIRE

    Kamali, Maryam; Dennis, Louise A.; McAree, Owen; Fisher, Michael; Veres, Sandor M.

    2016-01-01

    The coordination of multiple autonomous vehicles into convoys or platoons is expected on our highways in the near future. However, before such platoons can be deployed, the new autonomous behaviors of the vehicles in these platoons must be certified. An appropriate representation for vehicle platooning is as a multi-agent system in which each agent captures the "autonomous decisions" carried out by each vehicle. In order to ensure that these autonomous decision-making agents in vehicle platoo...

  14. Autonomous Landing on Moving Platforms

    KAUST Repository

    Mendoza Chavez, Gilberto

    2016-08-01

    This thesis investigates autonomous landing of a micro air vehicle (MAV) on a nonstationary ground platform. Unmanned aerial vehicles (UAVs) and micro air vehicles (MAVs) are becoming every day more ubiquitous. Nonetheless, many applications still require specialized human pilots or supervisors. Current research is focusing on augmenting the scope of tasks that these vehicles are able to accomplish autonomously. Precise autonomous landing on moving platforms is essential for self-deployment and recovery of MAVs, but it remains a challenging task for both autonomous and piloted vehicles. Model Predictive Control (MPC) is a widely used and effective scheme to control constrained systems. One of its variants, output-feedback tube-based MPC, ensures robust stability for systems with bounded disturbances under system state reconstruction. This thesis proposes a MAV control strategy based on this variant of MPC to perform rapid and precise autonomous landing on moving targets whose nominal (uncommitted) trajectory and velocity are slowly varying. The proposed approach is demonstrated on an experimental setup.

  15. Mechanism by which arylamine N-acetyltransferase 1 ablation causes insulin resistance in mice

    DEFF Research Database (Denmark)

    Camporez, João Paulo; Wang, Yongliang; Faarkrog, Kasper

    2017-01-01

    A single-nucleotide polymorphism in the human arylamine N-acetyltransferase 2 (Nat2) gene has recently been identified as associated with insulin resistance in humans. To understand the cellular and molecular mechanisms by which alterations in Nat2 activity might cause insulin resistance, we...... examined murine ortholog Nat1 knockout (KO) mice. Nat1 KO mice manifested whole-body insulin resistance, which could be attributed to reduced muscle, liver, and adipose tissue insulin sensitivity. Hepatic and muscle insulin resistance were associated with marked increases in both liver and muscle...... adipose tissue, and hepatocytes. Taken together, these studies demonstrate that Nat1 deletion promotes reduced mitochondrial activity and is associated with ectopic lipid-induced insulin resistance. These results provide a potential genetic link among mitochondrial dysfunction with increased ectopic lipid...

  16. Single or in Combination Antimicrobial Resistance Mechanisms of Klebsiella pneumoniae Contribute to Varied Susceptibility to Different Carbapenems

    Science.gov (United States)

    Tsai, Yu-Kuo; Liou, Ci-Hong; Fung, Chang-Phone; Lin, Jung-Chung; Siu, L. Kristopher

    2013-01-01

    Resistance to carbapenems has been documented by the production of carbapenemase or the loss of porins combined with extended-spectrum β-lactamases or AmpC β-lactamases. However, no complete comparisons have been made regarding the contributions of each resistance mechanism towards carbapenem resistance. In this study, we genetically engineered mutants of Klebsiella pneumoniae with individual and combined resistance mechanisms, and then compared each resistance mechanism in response to ertapenem, imipenem, meropenem, doripenem and other antibiotics. Among the four studied carbapenems, ertapenem was the least active against the loss of porins, cephalosporinases and carbapenemases. In addition to the production of KPC-2 or NDM-1 alone, resistance to all four carbapenems could also be conferred by the loss of two major porins, OmpK35 and OmpK36, combined with CTX-M-15 or DHA-1 with its regulator AmpR. Because the loss of OmpK35/36 alone or the loss of a single porin combined with bla CTX-M-15 or bla DHA-1-ampR expression was only sufficient for ertapenem resistance, our results suggest that carbapenems other than ertapenem should still be effective against these strains and laboratory testing for non-susceptibility to other carbapenems should improve the accurate identification of these isolates. PMID:24265784

  17. Resistance mechanisms of linezolid-nonsusceptible enterococci in Korea: low rate of 23S rRNA mutations in Enterococcus faecium.

    Science.gov (United States)

    Lee, Sae-Mi; Huh, Hee Jae; Song, Dong Joon; Shim, Hyang Jin; Park, Kyung Sun; Kang, Cheol-In; Ki, Chang-Seok; Lee, Nam Yong

    2017-12-01

    To investigate linezolid-resistance mechanisms in linezolid-nonsusceptible enterococci (LNSE) isolated from a tertiary hospital in Korea. Enterococcal isolates exhibiting linezolid MICs ≥4 mg l -1 that were isolated between December 2011 and May 2016 were investigated by PCR and sequencing for mutations in 23S rRNA or ribosomal proteins (L3, L4 and L22) and for the presence of cfr, cfr(B) and optrA genes.Results/Key findings. Among 135 LNSE (87 Enterococcus faecium and 48 Enterococcus faecalis isolates), 39.1 % (34/87) of E. faecium and 18.8 % (9/48) of E. faecalis isolates were linezolid-resistant. The optrA carriage was the dominant mechanism in E. faecalis: 13 isolates, including 10 E. faecalis [70 % (7/10) linezolid-resistant and 30 % (3/10) linezolid-intermediate] and three E. faecium [33.3 % (1/3) linezolid-resistant and 66.7 % (2/3) linezolid-intermediate], contained the optrA gene. G2576T mutations in the 23S rRNA gene were detected only in E. faecium [14 isolates; 71.4 % (10/14) linezolid-resistant and 28.6 % (4/14) linezolid-intermediate]. One linezolid-intermediate E. faecium harboured a L22 protein alteration (Ser77Thr). No isolates contained cfr or cfr(B) genes and any L3 or L4 protein alterations. No genetic mechanism of resistance was identified for 67.6 % (23/34) of linezolid-resistant E. faecium. A low rate of 23S rRNA mutations and the absence of known linezolid-resistance mechanisms in the majority of E. faecium isolates suggest regional differences in the mechanisms of linezolid resistance and the possibility of additional mechanisms.

  18. Monosodium glutamate neonatal treatment induces cardiovascular autonomic function changes in rodents

    Directory of Open Access Journals (Sweden)

    Signorá Peres Konrad

    2012-10-01

    Full Text Available OBJECTIVES: The aim of this study was to evaluate cardiovascular autonomic function in a rodent obesity model induced by monosodium glutamate injections during the first seven days of life. METHOD: The animals were assigned to control (control, n = 10 and monosodium glutamate (monosodium glutamate, n = 13 groups. Thirty-three weeks after birth, arterial and venous catheters were implanted for arterial pressure measurements, drug administration, and blood sampling. Baroreflex sensitivity was evaluated according to the tachycardic and bradycardic responses induced by sodium nitroprusside and phenylephrine infusion, respectively. Sympathetic and vagal effects were determined by administering methylatropine and propranolol. RESULTS: Body weight, Lee index, and epididymal white adipose tissue values were higher in the monosodium glutamate group in comparison to the control group. The monosodium glutamate-treated rats displayed insulin resistance, as shown by a reduced glucose/insulin index (-62.5%, an increased area under the curve of total insulin secretion during glucose overload (39.3%, and basal hyperinsulinemia. The mean arterial pressure values were higher in the monosodium glutamate rats, whereas heart rate variability (>7 times, bradycardic responses (>4 times, and vagal (~38% and sympathetic effects (~36% were reduced as compared to the control group. CONCLUSION: Our results suggest that obesity induced by neonatal monosodium glutamate treatment impairs cardiac autonomic function and most likely contributes to increased arterial pressure and insulin resistance.

  19. The autonomic nervous system and cardiac GLP-1 receptors control heart rate in mice

    Directory of Open Access Journals (Sweden)

    Laurie L. Baggio

    2017-11-01

    Conclusions: GLP-1R agonists increase HR through multiple mechanisms, including regulation of autonomic nervous system function, and activation of the atrial GLP-1R. Surprisingly, the isolated atrial GLP-1R does not transduce a direct chronotropic effect following exposure to GLP-1R agonists in the intact heart, or isolated atrium, ex vivo. Hence, cardiac GLP-1R circuits controlling HR require neural inputs and do not function in a heart-autonomous manner.

  20. A mechanism of acquired resistance to complement-mediated lysis by Entamoeba histolytica.

    Science.gov (United States)

    Gutiérrez-Kobeh, L; Cabrera, N; Pérez-Montfort, R

    1997-04-01

    Some Entamoeba histolytica strains resist complement-mediated lysis by serum. Susceptible and resistant strains activate the complement system equivalently, but resistant amebas evade killing by membrane attack complexes. Our objective was to determine the mechanism by which trophozoites of E. histolytica resist lysis by human serum. Amebas were made resistant to lysis by incubation with increasing concentrations of normal human serum. The possibility that resistant cells ingest membrane attack complexes was explored by subcellular fractionation of susceptible and resistant trophozoites treated with sublytic concentrations of human serum containing radiolabeled C9. In both cases, most of the label was in the fractions containing plasma membrane. The susceptible strain consistently showed more label associated with these fractions than the resistant strain. Thus, the possibility that the membrane attack complexes were released to the medium was explored. Both resistant and susceptible trophozoites release to the medium similar amounts of material excluded by Sepharose CL-2B in the presence or absence of normal human serum. Labeled C9 elutes together with the main bulk of proteins from the medium: this indicates that it is not in vesicles or high molecular weight aggregates. Coincubation of susceptible amebas with lysates of resistant trophozoites confers resistance to susceptible cells within 30 min. Resistance to lysis by serum can also be acquired by susceptible amebas after coincubation with lysates from human erythrocytes or after feeding them with whole human red blood cells. Resistant but not susceptible trophozoites show intense immunofluorescent staining on their surface with anti-human erythrocytic membrane antibody. These results suggest that amebas acquire resistance to lysis by serum by incorporating into their membranes complement regulatory proteins.

  1. Effect of mechanical properties on erosion resistance of ductile materials

    Science.gov (United States)

    Levin, Boris Feliksovih

    Solid particle erosion (SPE) resistance of ductile Fe, Ni, and Co-based alloys as well as commercially pure Ni and Cu was studied. A model for SPE behavior of ductile materials is presented. The model incorporates the mechanical properties of the materials at the deformation conditions associated with SPE process, as well as the evolution of these properties during the erosion induced deformation. An erosion parameter was formulated based on consideration of the energy loss during erosion, and incorporates the material's hardness and toughness at high strain rates. The erosion model predicts that materials combining high hardness and toughness can exhibit good erosion resistance. To measure mechanical properties of materials, high strain rate compression tests using Hopkinson bar technique were conducted at strain rates similar to those during erosion. From these tests, failure strength and strain during erosion were estimated and used to calculate toughness of the materials. The proposed erosion parameter shows good correlation with experimentally measured erosion rates for all tested materials. To analyze subsurface deformation during erosion, microhardness and nanoindentation tests were performed on the cross-sections of the eroded materials and the size of the plastically deformed zone and the increase in materials hardness due to erosion were determined. A nanoindentation method was developed to estimate the restitution coefficient within plastically deformed regions of the eroded samples which provides a measure of the rebounding ability of a material during particle impact. An increase in hardness near the eroded surface led to an increase in restitution coefficient. Also, the stress rates imposed below the eroded surface were comparable to those measured during high strain-rate compression tests (10sp3-10sp4 ssp{-1}). A new parameter, "area under the microhardness curve" was developed that represents the ability of a material to absorb impact energy. By

  2. Mechanisms of pyrethroid resistance inHaematobia irritans (Muscidae from Mato Grosso do Sul state, Brazil

    Directory of Open Access Journals (Sweden)

    Antonio Thadeu Medeiros Barros

    Full Text Available Horn fly resistance to pyrethroid insecticides occurs throughout Brazil, but knowledge about the involved mechanisms is still in an incipient stage. This survey was aimed to identify the mechanisms of horn fly resistance to cypermethrin in Mato Grosso do Sul state, Brazil. Impregnated filter paper bioassays using cypermethrin, synergized or not with piperonyl butoxide (PBO and triphenyl phosphate (TPP, were conducted from March 2004 to June 2005 in horn fly populations (n = 33 from all over the state. All populations were highly resistant to cypermethrin, with resistance factors (RF ranging from 89.4 to 1,020.6. Polymerase chain reaction (PCR assays to detect the knockdown resistance (kdr mutation also were performed in 16 samples. The kdr mutation was found in 75% of the tested populations, mostly with relatively low frequencies (<20%, and was absent in some highly resistant populations. Addition of TPP did not significantly reduce the LC50 in any population. However, PBO reduced LC50s above 40-fold in all tested populations, resulting in RFs ≤ 10 in most cases. Horn fly resistance to cypermethrin is widespread in the state, being primarily caused by an enhanced activity of P450 mono-oxygenases and secondarily by reduced target site sensitivity.

  3. Resistive thrust production can be as crucial as added mass mechanisms for inertial undulatory swimmers

    Science.gov (United States)

    Piñeirua, M.; Godoy-Diana, R.; Thiria, B.

    2015-08-01

    In this Rapid Communication, we address a crucial point regarding the description of moderate to high Reynolds numbers aquatic swimmers. For decades, swimming animals have been classified in two different families of propulsive mechanisms based on the Reynolds number: the resistive swimmers, using local friction to produce the necessary thrust force for locomotion at low Reynolds number, and the reactive swimmers, lying in the high Reynolds range, and using added mass acceleration (described by perfect fluid theory). However, inertial swimmers are also systems that dissipate energy, due to their finite size, therefore involving strong resistive contributions, even for high Reynolds numbers. Using a complete model for the hydrodynamic forces, involving both reactive and resistive contributions, we revisit here the physical mechanisms responsible for the thrust production of such swimmers. We show, for instance, that the resistive part of the force balance is as crucial as added mass effects in the modeling of the thrust force, especially for elongated species. The conclusions brought by this work may have significant contributions to the understanding of complex swimming mechanisms, especially for the future design of artificial swimmers.

  4. Pyridostigmine Improves the Effects of Resistance Exercise Training after Myocardial Infarction in Rats

    Science.gov (United States)

    Feriani, Daniele J.; Coelho-Júnior, Hélio J.; de Oliveira, Juliana C. M. F.; Delbin, Maria A.; Mostarda, Cristiano T.; Dourado, Paulo M. M.; Caperuto, Érico C.; Irigoyen, Maria C. C.; Rodrigues, Bruno

    2018-01-01

    Myocardial infarction (MI) remains the leading cause of morbidity and mortality worldwide. Exercise training and pharmacological treatments are important strategies to minimize the deleterious effects of MI. However, little is known about the effects of resistance training combined with pyridostigmine bromide (PYR) treatment on cardiac and autonomic function, as well as on the inflammatory profile after MI. Thus, in the present study, male Wistar rats were randomly assigned into: control (Cont); sedentary infarcted (Inf); PYR – treated sedentary infarcted rats (Inf+P); infarcted rats undergoing resistance exercise training (Inf+RT); and infarcted rats undergoing PYR treatment plus resistance training (Inf+RT+P). After 12 weeks of resistance training (15–20 climbs per session, with a 1-min rest between each climb, at a low to moderate intensity, 5 days a week) and/or PYR treatment (0.14 mg/mL of drink water), hemodynamic function, autonomic modulation, and cytokine expressions were evaluated. We observed that 3 months of PYR treatment, either alone or in combination with exercise, can improve the deleterious effects of MI on left ventricle dimensions and function, baroreflex sensitivity, and autonomic parameters, as well as systemic and tissue inflammatory profile. Furthermore, additional benefits in a maximal load test and anti-inflammatory state of skeletal muscle were found when resistance training was combined with PYR treatment. Thus, our findings suggest that the combination of resistance training and PYR may be a good therapeutic strategy since they promote additional benefits on skeletal muscle anti-inflammatory profile after MI. PMID:29483876

  5. Use of mutagenesis, genetic mapping and next generation transcriptomics to investigate insecticide resistance mechanisms.

    Directory of Open Access Journals (Sweden)

    Predrag Kalajdzic

    Full Text Available Insecticide resistance is a worldwide problem with major impact on agriculture and human health. Understanding the underlying molecular mechanisms is crucial for the management of the phenomenon; however, this information often comes late with respect to the implementation of efficient counter-measures, particularly in the case of metabolism-based resistance mechanisms. We employed a genome-wide insertional mutagenesis screen to Drosophila melanogaster, using a Minos-based construct, and retrieved a line (MiT[w(-]3R2 resistant to the neonicotinoid insecticide Imidacloprid. Biochemical and bioassay data indicated that resistance was due to increased P450 detoxification. Deep sequencing transcriptomic analysis revealed substantial over- and under-representation of 357 transcripts in the resistant line, including statistically significant changes in mixed function oxidases, peptidases and cuticular proteins. Three P450 genes (Cyp4p2, Cyp6a2 and Cyp6g1 located on the 2R chromosome, are highly up-regulated in mutant flies compared to susceptible Drosophila. One of them (Cyp6g1 has been already described as a major factor for Imidacloprid resistance, which validated the approach. Elevated expression of the Cyp4p2 was not previously documented in Drosophila lines resistant to neonicotinoids. In silico analysis using the Drosophila reference genome failed to detect transcription binding factors or microRNAs associated with the over-expressed Cyp genes. The resistant line did not contain a Minos insertion in its chromosomes, suggesting a hit-and-run event, i.e. an insertion of the transposable element, followed by an excision which caused the mutation. Genetic mapping placed the resistance locus to the right arm of the second chromosome, within a ∼1 Mb region, where the highly up-regulated Cyp6g1 gene is located. The nature of the unknown mutation that causes resistance is discussed on the basis of these results.

  6. Autonomic Neuropathy in Diabetes Mellitus

    OpenAIRE

    Verrotti, Alberto; Prezioso, Giovanni; Scattoni, Raffaella; Chiarelli, Francesco

    2014-01-01

    Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes, often overlooked and misdiagnosed. It is a systemic-wide disorder that may be asymptomatic in the early stages. The most studied and clinically important form of DAN is cardiovascular autonomic neuropathy defined as the impairment of autonomic control of the cardiovascular system in patients with diabetes after exclusion of other causes. The reported prevalence of DAN varies widely depending on inconsistent ...

  7. Nonoclusive thrombosis of mechanical mitral valve prosthesis caused by inadequate treatment of anticoagulant therapy resistance

    Directory of Open Access Journals (Sweden)

    Ivanović Branislava

    2008-01-01

    Full Text Available Background. Oral anticoagulants have been used in the prevention of thromboembolic complications for over six decades. A rare, but possible problem in the application of these medications could be resistance to them. Case report. We presented a patient with nonocclusive thrombosis of the mechanical mitral prosthesis due to inadequately treated resistance to peroral anticoagulant therapy. Resistance to oral anticoagulant medications was proven by an increased dosage of warfarin up to 20 mg and, after that, acenokumarol to 15 mg over ten days which did not lead to an increase in the international normalized ratio (INR value over 1.2. On the basis of information that she did not take food rich in vitamin K or medications which could reduce effects of oral anticoagulants, and that she did not have additional illnesses and conditions that could cause an inadequate response to anticoagulant therapy, it was circumstantially concluded that this was a hereditary form of resistance. Because of the existing mechanical prosthetics on the mitral position, low molecular heparin has been introduced into the therapy. The patient reduced it on her own initiative, leading to nonocclusive valvular thrombosis. Conclusion. When associated complications like absolute arrhithmia does not exist, the finding of resistance to oral anticoagulant agents is an indication for the replacement of a mechanical prosthetic with a biological one which has been done in this patients.

  8. Pathogenic Mechanisms of Atrial Fibrillation in Obesity

    Directory of Open Access Journals (Sweden)

    O. M. Drapkina

    2016-01-01

    Full Text Available Atrial fibrillation (AF is one of the most common arrhythmias. It reduces quality of life and its duration due to thromboembolic complications. Obesity contributes to the structural and electrical remodeling of atrial myocardium. This leads to occurrence of ectopic foci in the mouths of the pulmonary veins and the disruption of normal electrical conduction in the atria. Systemic inflammation, myocardial fibrosis, cardiomyocyte overload by Na+ and Ca2+ ions, accumulation in the cells of unoxidized metabolic products, imbalance of the autonomic regulation are considered as the main mechanisms of arrhythmogenic substrate formation. Hypertension, insulin resistance, and obstructive sleep apnea, associated with obesity, increase the risk of development and progression of the arrhythmia. Study of pathogenetic mechanisms of AF in obesity is necessary to develop new strategies for its prevention and the creation of more effective methods of treatment of these patients.

  9. Microglia PACAP and glutamate: Friends or foes in seizure-induced autonomic dysfunction and SUDEP?

    Science.gov (United States)

    Bhandare, Amol M; Kapoor, Komal; Farnham, Melissa M J; Pilowsky, Paul M

    2016-06-01

    Seizure-induced cardiorespiratory autonomic dysfunction is a major cause of sudden unexpected death in epilepsy (SUDEP), and the underlying mechanism is unclear. Seizures lead to increased synthesis, and release of glutamate, pituitary adenylate cyclase activating polypeptide (PACAP), and other neurotransmitters, and cause extensive activation of microglia at multiple regions in the brain including central autonomic cardiorespiratory brainstem nuclei. Glutamate contributes to neurodegeneration, and inflammation in epilepsy. PACAP has neuroprotective, and anti-inflammatory properties, whereas microglia are key players in inflammatory responses in CNS. Seizure-induced increase in PACAP is neuroprotective. PACAP produces neuroprotective effects acting on microglial PAC1 and VPAC1 receptors. Microglia also express glutamate transporters, and their expression can be increased by PACAP in response to harmful or stressful situations such as seizures. Here we discuss the mechanism of autonomic cardiorespiratory dysfunction in seizure, and the role of PACAP, glutamate and microglia in regulating cardiorespiratory brainstem neurons in their physiological state that could provide future therapeutic options for SUDEP. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Molecular Mechanisms of Insulin Resistance Development

    Directory of Open Access Journals (Sweden)

    Vsevolod Arsen'evich Tkachuk

    2014-05-01

    Full Text Available Insulin resistance (IR is a phenomenon associated with an impaired ability of insulin to stimulate glucose uptake by target cells and to reduce the blood glucose level. A response increase in insulin secretion by the pancreas and hyperinsulinemia are compensatory reactions of the body. The development of IR leads to the inability of target cells to respond to insulin that results in developing type 2 diabetes mellitus (T2DM and metabolic syndrome. For this reason, the metabolic syndrome is defined in practice as a combination of IR with one or more pathologies such as T2DM, arterial hypertension, dyslipidemia, abdominal obesity, non-alcoholic fatty liver disease, and some others. However, a combination of high blood glucose and insulin levels always serves as its physiological criterion.IR should be considered as a systemic failure of the endocrine regulation in the body. Physiological causes of IR are diverse. The main ones are nutritional overload and accumulation of certain lipids and their metabolites in cells, low physical activity, chronic inflammation and stress of various nature, including oxidative and endoplasmic reticulum stress (impairment of damaged protein degradation in the cell. Recent studies have demonstrated that these physiological mechanisms likely act through a single intracellular scenario. This is the impairment of signal transduction from the insulin receptor to its targets via the negative feedback mechanism in intracellular insulin-dependent signaling cascades.This review describes the physiological and intracellular mechanisms of insulin action and focuses on their abnormalities upon IR development. Finally, feasible trends in early molecular diagnosis and therapy of IR are discussed.

  11. Where neuroscience and dynamic system theory meet autonomous robotics: a contracting basal ganglia model for action selection.

    Science.gov (United States)

    Girard, B; Tabareau, N; Pham, Q C; Berthoz, A; Slotine, J-J

    2008-05-01

    Action selection, the problem of choosing what to do next, is central to any autonomous agent architecture. We use here a multi-disciplinary approach at the convergence of neuroscience, dynamical system theory and autonomous robotics, in order to propose an efficient action selection mechanism based on a new model of the basal ganglia. We first describe new developments of contraction theory regarding locally projected dynamical systems. We exploit these results to design a stable computational model of the cortico-baso-thalamo-cortical loops. Based on recent anatomical data, we include usually neglected neural projections, which participate in performing accurate selection. Finally, the efficiency of this model as an autonomous robot action selection mechanism is assessed in a standard survival task. The model exhibits valuable dithering avoidance and energy-saving properties, when compared with a simple if-then-else decision rule.

  12. Learning for Autonomous Navigation

    Science.gov (United States)

    Angelova, Anelia; Howard, Andrew; Matthies, Larry; Tang, Benyang; Turmon, Michael; Mjolsness, Eric

    2005-01-01

    Robotic ground vehicles for outdoor applications have achieved some remarkable successes, notably in autonomous highway following (Dickmanns, 1987), planetary exploration (1), and off-road navigation on Earth (1). Nevertheless, major challenges remain to enable reliable, high-speed, autonomous navigation in a wide variety of complex, off-road terrain. 3-D perception of terrain geometry with imaging range sensors is the mainstay of off-road driving systems. However, the stopping distance at high speed exceeds the effective lookahead distance of existing range sensors. Prospects for extending the range of 3-D sensors is strongly limited by sensor physics, eye safety of lasers, and related issues. Range sensor limitations also allow vehicles to enter large cul-de-sacs even at low speed, leading to long detours. Moreover, sensing only terrain geometry fails to reveal mechanical properties of terrain that are critical to assessing its traversability, such as potential for slippage, sinkage, and the degree of compliance of potential obstacles. Rovers in the Mars Exploration Rover (MER) mission have got stuck in sand dunes and experienced significant downhill slippage in the vicinity of large rock hazards. Earth-based off-road robots today have very limited ability to discriminate traversable vegetation from non-traversable vegetation or rough ground. It is impossible today to preprogram a system with knowledge of these properties for all types of terrain and weather conditions that might be encountered.

  13. Embryo mechanics: balancing force production with elastic resistance during morphogenesis.

    Science.gov (United States)

    Davidson, Lance A

    2011-01-01

    Morphogenesis requires the spatial and temporal control of embryo mechanics, including force production and mechanical resistance to those forces, to coordinate tissue deformation and large-scale movements. Thus, biomechanical processes play a key role in directly shaping the embryo. Additional roles for embryo mechanics during development may include the patterning of positional information and to provide feedback to ensure the success of morphogenetic movements in shaping the larval body and organs. To understand the multiple roles of mechanics during development requires familiarity with engineering principles of the mechanics of structures, the viscoelastic properties of biomaterials, and the integration of force and stress within embryonic structures as morphogenesis progresses. In this chapter, we review the basic engineering principles of biomechanics as they relate to morphogenesis, introduce methods for quantifying embryo mechanics and the limitations of these methods, and outline a formalism for investigating the role of embryo mechanics in birth defects. We encourage the nascent field of embryo mechanics to adopt standard engineering terms and test methods so that studies of diverse organisms can be compared and universal biomechanical principles can be revealed. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Fluoroquinolone Resistance Mechanisms in an Escherichia coli Isolate, HUE1, Without Quinolone Resistance-Determining Region Mutations

    Directory of Open Access Journals (Sweden)

    Toyotaka eSato

    2013-05-01

    Full Text Available Fluoroquinolone resistance can cause major clinical problems. Here, we investigated fluoroquinolone resistance mechanisms in a clinical Escherichia coli isolate, HUE1, which had no mutations quinolone resistance-determining regions (QRDRs of DNA gyrase and topoisomerase IV. HUE1 demonstrated MICs that exceeded the breakpoints for ciprofloxacin, levofloxacin, and norfloxacin. HUE1 harbored oqxAB and qnrS1 on distinct plasmids. In addition, it exhibited lower intracellular ciprofloxacin concentrations and higher mRNA expression levels of efflux pumps and their global activators than did reference strains. The genes encoding AcrR (local AcrAB repressor and MarR (MarA repressor were disrupted by insertion of the transposon IS3-IS629 and a frameshift mutation, respectively. A series of mutants derived from HUE1 were obtained by plasmid curing and gene knockout using homologous recombination. Compared to the MICs of the parent strain HUE1, the fluoroquinolone MICs of these mutants indicated that qnrS1, oqxAB, acrAB, acrF, acrD, mdtK, mdfA, and tolC contributed to the reduced susceptibility to fluoroquinolone in HUE1. Therefore, fluoroquinolone resistance in HUE1 is caused by concomitant acquisition of QnrS1 and OqxAB and overexpression of AcrAB−TolC and other chromosome-encoded efflux pumps. Thus, we have demonstrated that QRDR mutations are not absolutely necessary for acquiring fluoroquinolone resistance in E. coli.

  15. Discerning non-autonomous dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Clemson, Philip T.; Stefanovska, Aneta, E-mail: aneta@lancaster.ac.uk

    2014-09-30

    Structure and function go hand in hand. However, while a complex structure can be relatively safely broken down into the minutest parts, and technology is now delving into nanoscales, the function of complex systems requires a completely different approach. Here the complexity clearly arises from nonlinear interactions, which prevents us from obtaining a realistic description of a system by dissecting it into its structural component parts. At best, the result of such investigations does not substantially add to our understanding or at worst it can even be misleading. Not surprisingly, the dynamics of complex systems, facilitated by increasing computational efficiency, is now readily tackled in the case of measured time series. Moreover, time series can now be collected in practically every branch of science and in any structural scale—from protein dynamics in a living cell to data collected in astrophysics or even via social networks. In searching for deterministic patterns in such data we are limited by the fact that no complex system in the real world is autonomous. Hence, as an alternative to the stochastic approach that is predominantly applied to data from inherently non-autonomous complex systems, theory and methods specifically tailored to non-autonomous systems are needed. Indeed, in the last decade we have faced a huge advance in mathematical methods, including the introduction of pullback attractors, as well as time series methods that cope with the most important characteristic of non-autonomous systems—their time-dependent behaviour. Here we review current methods for the analysis of non-autonomous dynamics including those for extracting properties of interactions and the direction of couplings. We illustrate each method by applying it to three sets of systems typical for chaotic, stochastic and non-autonomous behaviour. For the chaotic class we select the Lorenz system, for the stochastic the noise-forced Duffing system and for the non-autonomous

  16. Discerning non-autonomous dynamics

    International Nuclear Information System (INIS)

    Clemson, Philip T.; Stefanovska, Aneta

    2014-01-01

    Structure and function go hand in hand. However, while a complex structure can be relatively safely broken down into the minutest parts, and technology is now delving into nanoscales, the function of complex systems requires a completely different approach. Here the complexity clearly arises from nonlinear interactions, which prevents us from obtaining a realistic description of a system by dissecting it into its structural component parts. At best, the result of such investigations does not substantially add to our understanding or at worst it can even be misleading. Not surprisingly, the dynamics of complex systems, facilitated by increasing computational efficiency, is now readily tackled in the case of measured time series. Moreover, time series can now be collected in practically every branch of science and in any structural scale—from protein dynamics in a living cell to data collected in astrophysics or even via social networks. In searching for deterministic patterns in such data we are limited by the fact that no complex system in the real world is autonomous. Hence, as an alternative to the stochastic approach that is predominantly applied to data from inherently non-autonomous complex systems, theory and methods specifically tailored to non-autonomous systems are needed. Indeed, in the last decade we have faced a huge advance in mathematical methods, including the introduction of pullback attractors, as well as time series methods that cope with the most important characteristic of non-autonomous systems—their time-dependent behaviour. Here we review current methods for the analysis of non-autonomous dynamics including those for extracting properties of interactions and the direction of couplings. We illustrate each method by applying it to three sets of systems typical for chaotic, stochastic and non-autonomous behaviour. For the chaotic class we select the Lorenz system, for the stochastic the noise-forced Duffing system and for the non-autonomous

  17. Structural Discrimination and Autonomous Vehicles

    DEFF Research Database (Denmark)

    Liu, Hin-Yan

    2016-01-01

    This paper examines the potential for structural discrimination to be woven into the fabric of autonomous vehicle developments, which remain underexplored and undiscussed. The prospect for structural discrimination arises as a result of the coordinated modes of autonomous vehicle behaviour...... individual identity, and potentially relative worth, to autonomous vehicles engaging in a crash damage calculus. At the risk of introducing these ideas into the development of autonomous vehicles, this paper hopes to spark a debate to foreclose these eventualities....... that is prescribed by its code. This leads to the potential for individuated outcomes to be networked and thereby multiplied consistently to any number of vehicles implementing such a code. The aggregated effects of such algorithmic policy preferences will thus cumulate in the reallocation of benefits and burdens...

  18. Decentralized Control of Autonomous Vehicles

    Science.gov (United States)

    2003-01-01

    Autonomous Vehicles by John S. Baras, Xiaobo Tan, Pedram Hovareshti CSHCN TR 2003-8 (ISR TR 2003-14) Report Documentation Page Form ApprovedOMB No. 0704...AND SUBTITLE Decentralized Control of Autonomous Vehicles 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 Decentralized Control of Autonomous Vehicles ∗ John S. Baras, Xiaobo Tan, and Pedram

  19. Towards self-healing creep resistant steels

    NARCIS (Netherlands)

    Van der Zwaag, S.; Zhang, S.; Fang, H.; Bruck, E.; Van Dijk, N.H.

    2016-01-01

    We report the main findings of our work on the behaviour of binary Fe-Cu and Fe-Au model alloys designed to explore routes to create new creep resistant steels having an in-built ability to autonomously fill creep induced porosity at grain boundaries. The alloying elements were selected on the basis

  20. Public Health, Ethics, and Autonomous Vehicles.

    Science.gov (United States)

    Fleetwood, Janet

    2017-04-01

    With the potential to save nearly 30 000 lives per year in the United States, autonomous vehicles portend the most significant advance in auto safety history by shifting the focus from minimization of postcrash injury to collision prevention. I have delineated the important public health implications of autonomous vehicles and provided a brief analysis of a critically important ethical issue inherent in autonomous vehicle design. The broad expertise, ethical principles, and values of public health should be brought to bear on a wide range of issues pertaining to autonomous vehicles.

  1. Obstacle avoidance test using a sensor-based autonomous robotic system

    International Nuclear Information System (INIS)

    Fujii, Yoshio; Suzuki, Katsuo

    1998-12-01

    From a viewpoint of reducing personnel radiation exposure of plant staffs working in the high radiation area of nuclear facilities, it is often said to be necessary to develop remote robotic systems, which have great potential of performing various tasks in nuclear facilities. Hence, we developed an advanced remote robotic system, consisting of redundant manipulator and environment-sensing systems, which can be applied to complicated handling tasks under unstructured environment. In the robotic system, various types of sensors for environment-sensing are mounted on the redundant manipulator and sensor-based autonomous capabilities are incorporated. This report describes the results of autonomous obstacle avoidance test which was carried out as follows: manipulating valves at the rear-side of wall, through a narrow window of the wall, with the redundant manipulator mounted on an x-axis driving mechanism. From this test, it is confirmed that the developed robotic system can autonomously achieve handling tasks in limited space as avoiding obstacles, which is supposed to be difficult by a non-redundant manipulator. (author)

  2. New methodology for preventing pressure ulcers using actimetry and autonomous nervous system recording.

    Science.gov (United States)

    Meffre, R; Gehin, C; Schmitt, P M; De Oliveira, F; Dittmar, A

    2006-01-01

    Pressure ulcers constitute an important health problem. They affect lots of people with mobility disorder and they are difficult to detect and prevent because the damage begins on the muscle. This paper proposes a new approach to study pressure ulcers. We aim at developing a methodology to analyse the probability for a patient to develop a pressure ulcer, and that can detect risky situation. The idea is to relate the mobility disorder to autonomic nervous system (ANS) trouble. More precisely, the evaluation of the consequence of the discomfort on the ANS (stress induced by discomfort) can be relevant for the early detection of the pressure ulcer. Mobility is evaluated through movement measurement. This evaluation, at the interface between soft living tissues and any support has to consider the specificity of the human environment. Soft living tissues have non-linear mechanical properties making conventional rigid sensors non suitable for interface parameters measurement. A new actimeter system has been designed in order to study movements of the human body whatever its support while seating. The device is based on elementary active cells. The number of pressure cells can be easily adapted to the application. The spatial resolution is about 4 cm(2). In this paper, we compare activity measurement of a seated subject with his autonomic nervous system activity, recorded by E.motion device. It has been developed in order to record six parameters: skin potential, skin resistance, skin temperature, skin blood rate, instantaneous cardiac frequency and instantaneous respiratory frequency. The design, instrumentation, and first results are presented.

  3. Cancer resistance of SR/CR mice in the genetic knockout backgrounds of leukocyte effector mechanisms: determinations for functional requirements.

    Science.gov (United States)

    Sanders, Anne M; Stehle, John R; Blanks, Michael J; Riedlinger, Gregory; Kim-Shapiro, Jung W; Monjazeb, Arta M; Adams, Jonathan M; Willingham, Mark C; Cui, Zheng

    2010-03-31

    Spontaneous Regression/Complete Resistant (SR/CR) mice are a colony of cancer-resistant mice that can detect and rapidly destroy malignant cells with innate cellular immunity, predominately mediated by granulocytes. Our previous studies suggest that several effector mechanisms, such as perforin, granzymes, or complements, may be involved in the killing of cancer cells. However, none of these effector mechanisms is known as critical for granulocytes. Additionally, it is unclear which effector mechanisms are required for the cancer killing activity of specific leukocyte populations and the survival of SR/CR mice against the challenges of lethal cancer cells. We hypothesized that if any of these effector mechanisms was required for the resistance to cancer cells, its functional knockout in SR/CR mice should render them sensitive to cancer challenges. This was tested by cross breeding SR/CR mice into the individual genetic knockout backgrounds of perforin (Prf-/-), superoxide (Cybb-/), or inducible nitric oxide (Nos2-/). SR/CR mice were bred into individual Prf-/-, Cybb-/-, or Nos2-/- genetic backgrounds and then challenged with sarcoma 180 (S180). Their overall survival was compared to controls. The cancer killing efficiency of purified populations of macrophages and neutrophils from these immunodeficient mice was also examined. When these genetically engineered mice were challenged with cancer cells, the knockout backgrounds of Prf-/-, Cybb-/-, or Nos2-/- did not completely abolish the SR/CR cancer resistant phenotype. However, the Nos2-/- background did appear to weaken the resistance. Incidentally, it was also observed that the male mice in these immunocompromised backgrounds tended to be less cancer-resistant than SR/CR controls. Despite the previously known roles of perforin, superoxide or nitric oxide in the effector mechanisms of innate immune responses, these effector mechanisms were not required for cancer-resistance in SR/CR mice. The resistance was

  4. Mechanism and degree of chemical elements effect on atmosphere corrosion resistance of steels

    International Nuclear Information System (INIS)

    Vu Din' Vuj

    1991-01-01

    It follows from the proposed regression equations that falourable effect of chemical elements on steel resistance to atmospheric corrosion is determined by their ability to increase interatom bond stability in iron crystal lattice and form corrosion products with high protection properties. Element positive influence on steel corrosion resistance decreases in the following order: S, P, Si, Mn, Cu, Cr, Ni, C in semiurban tropical atmosphere and S, Mn, Sr, Cu, Ni, Cr in coastal atmosphere. In the latter case C increases corrosion in a greater degree as compared to P. Small ammounts of Mo decrease steel resistance in semiurban atmosphere and almost do not influence it in the coastal one. Possible mechanisms of individual element influence on steel corrosion resistance are considered

  5. Insecticide resistance in the dengue vector Aedes aegypti from Martinique: distribution, mechanisms and relations with environmental factors.

    Science.gov (United States)

    Marcombe, Sébastien; Mathieu, Romain Blanc; Pocquet, Nicolas; Riaz, Muhammad-Asam; Poupardin, Rodolphe; Sélior, Serge; Darriet, Frédéric; Reynaud, Stéphane; Yébakima, André; Corbel, Vincent; David, Jean-Philippe; Chandre, Fabrice

    2012-01-01

    Dengue is an important mosquito borne viral disease in Martinique Island (French West Indies). The viruses responsible for dengue are transmitted by Aedes aegypti, an indoor day-biting mosquito. The most effective proven method for disease prevention has been by vector control by various chemical or biological means. Unfortunately insecticide resistance has already been observed on the Island and recently showed to significantly reduce the efficacy of vector control interventions. In this study, we investigated the distribution of resistance and the underlying mechanisms in nine Ae. aegypti populations. Statistical multifactorial approach was used to investigate the correlations between insecticide resistance levels, associated mechanisms and environmental factors characterizing the mosquito populations. Bioassays revealed high levels of resistance to temephos and deltamethrin and susceptibility to Bti in the 9 populations tested. Biochemical assays showed elevated detoxification enzyme activities of monooxygenases, carboxylesterases and glutathione S-tranferases in most of the populations. Molecular screening for common insecticide target-site mutations, revealed the presence of the "knock-down resistance" V1016I Kdr mutation at high frequency (>87%). Real time quantitative RT-PCR showed the potential involvement of several candidate detoxification genes in insecticide resistance. Principal Component Analysis (PCA) performed with variables characterizing Ae. aegypti from Martinique permitted to underline potential links existing between resistance distribution and other variables such as agriculture practices, vector control interventions and urbanization. Insecticide resistance is widespread but not homogeneously distributed across Martinique. The influence of environmental and operational factors on the evolution of the resistance and mechanisms are discussed.

  6. Insecticide resistance in the dengue vector Aedes aegypti from Martinique: distribution, mechanisms and relations with environmental factors.

    Directory of Open Access Journals (Sweden)

    Sébastien Marcombe

    Full Text Available Dengue is an important mosquito borne viral disease in Martinique Island (French West Indies. The viruses responsible for dengue are transmitted by Aedes aegypti, an indoor day-biting mosquito. The most effective proven method for disease prevention has been by vector control by various chemical or biological means. Unfortunately insecticide resistance has already been observed on the Island and recently showed to significantly reduce the efficacy of vector control interventions. In this study, we investigated the distribution of resistance and the underlying mechanisms in nine Ae. aegypti populations. Statistical multifactorial approach was used to investigate the correlations between insecticide resistance levels, associated mechanisms and environmental factors characterizing the mosquito populations. Bioassays revealed high levels of resistance to temephos and deltamethrin and susceptibility to Bti in the 9 populations tested. Biochemical assays showed elevated detoxification enzyme activities of monooxygenases, carboxylesterases and glutathione S-tranferases in most of the populations. Molecular screening for common insecticide target-site mutations, revealed the presence of the "knock-down resistance" V1016I Kdr mutation at high frequency (>87%. Real time quantitative RT-PCR showed the potential involvement of several candidate detoxification genes in insecticide resistance. Principal Component Analysis (PCA performed with variables characterizing Ae. aegypti from Martinique permitted to underline potential links existing between resistance distribution and other variables such as agriculture practices, vector control interventions and urbanization. Insecticide resistance is widespread but not homogeneously distributed across Martinique. The influence of environmental and operational factors on the evolution of the resistance and mechanisms are discussed.

  7. Production of sintered alumina from powder; optimization of the sinterized parameters for the maximum mechanical resistence

    International Nuclear Information System (INIS)

    Rocha, J.C. da.

    1981-02-01

    Pure, sinterized alumina and the optimization of the parameters of sinterization in order to obtain the highest mechanical resistence are discussed. Test materials are sinterized from a fine powder of pure alumina (Al 2 O 3 ), α phase, at different temperatures and times, in air. The microstructures are analysed concerning porosity and grain size. Depending on the temperature or the time of sinterization, there is a maximum for the mechanical resistence. (A.R.H.) [pt

  8. [Heart rate variability as a method of assessing the autonomic nervous system in polycystic ovary syndrome].

    Science.gov (United States)

    de Sá, Joceline Cássia Ferezini; Costa, Eduardo Caldas; da Silva, Ester; Azevedo, George Dantas

    2013-09-01

    Polycystic ovary syndrome (PCOS) is an endocrine disorder associated with several cardiometabolic risk factors, such as central obesity, insulin resistance, type 2 diabetes, metabolic syndrome, and hypertension. These factors are associated with adrenergic overactivity, which is an important prognostic factor for the development of cardiovascular disorders. Given the common cardiometabolic disturbances occurring in PCOS women, over the last years studies have investigated the cardiac autonomic control of these patients, mainly based on heart rate variability (HRV). Thus, in this review, we will discuss the recent findings of the studies that investigated the HRV of women with PCOS, as well as noninvasive methods of analysis of autonomic control starting from basic indexes related to this methodology.

  9. Materials learning from life: concepts for active, adaptive and autonomous molecular systems.

    Science.gov (United States)

    Merindol, Rémi; Walther, Andreas

    2017-09-18

    Bioinspired out-of-equilibrium systems will set the scene for the next generation of molecular materials with active, adaptive, autonomous, emergent and intelligent behavior. Indeed life provides the best demonstrations of complex and functional out-of-equilibrium systems: cells keep track of time, communicate, move, adapt, evolve and replicate continuously. Stirred by the understanding of biological principles, artificial out-of-equilibrium systems are emerging in many fields of soft matter science. Here we put in perspective the molecular mechanisms driving biological functions with the ones driving synthetic molecular systems. Focusing on principles that enable new levels of functionalities (temporal control, autonomous structures, motion and work generation, information processing) rather than on specific material classes, we outline key cross-disciplinary concepts that emerge in this challenging field. Ultimately, the goal is to inspire and support new generations of autonomous and adaptive molecular devices fueled by self-regulating chemistry.

  10. Autonomous exoskeleton reduces metabolic cost of human walking.

    Science.gov (United States)

    Mooney, Luke M; Rouse, Elliott J; Herr, Hugh M

    2014-11-03

    Passive exoskeletons that assist with human locomotion are often lightweight and compact, but are unable to provide net mechanical power to the exoskeletal wearer. In contrast, powered exoskeletons often provide biologically appropriate levels of mechanical power, but the size and mass of their actuator/power source designs often lead to heavy and unwieldy devices. In this study, we extend the design and evaluation of a lightweight and powerful autonomous exoskeleton evaluated for loaded walking in (J Neuroeng Rehab 11:80, 2014) to the case of unloaded walking conditions. The metabolic energy consumption of seven study participants (85 ± 12 kg body mass) was measured while walking on a level treadmill at 1.4 m/s. Testing conditions included not wearing the exoskeleton and wearing the exoskeleton, in both powered and unpowered modes. When averaged across the gait cycle, the autonomous exoskeleton applied a mean positive mechanical power of 26 ± 1 W (13 W per ankle) with 2.12 kg of added exoskeletal foot-shank mass (1.06 kg per leg). Use of the leg exoskeleton significantly reduced the metabolic cost of walking by 35 ± 13 W, which was an improvement of 10 ± 3% (p = 0.023) relative to the control condition of not wearing the exoskeleton. The results of this study highlight the advantages of developing lightweight and powerful exoskeletons that can comfortably assist the body during walking.

  11. Effects of CPAP on clinical variables and autonomic modulation in children during an asthma attack.

    Science.gov (United States)

    de Freitas Dantas Gomes, Evelim Leal; Costa, Dirceu; Germano, Sandra Maria; Borges, Pâmela Vieira; Sampaio, Luciana Maria Malosá

    2013-08-01

    Continuous positive airway pressure (CPAP) causes changes in alveolar and intrathoracic pressure and the activation of pulmonary stretch receptors affects the balance of the autonomic nervous system. The acute effects of CPAP on autonomic modulation have been demonstrated in different diseases, but no studies have been carried out addressing CPAP in patients with asthma. The hypothesis tested in the present study is that CPAP can produce an autonomic effect beyond a mechanical effect of bronchial dilatation in children with asthma. The results demonstrated improvements in clinical variables and an increase in vagal tone with the administration of CPAP during an asthma attack, as demonstrated by a diminished respiratory rate and a reduction in signs of respiratory distress. Regarding autonomic modulation, an increase in parasympathetic variables was found, indicating non-cholinergic activation stemming from the persistent increase in peak flow. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Autonomous Congestion Control in Delay-Tolerant Networks

    Science.gov (United States)

    Burleigh, Scott; Jennings, Esther; Schoolcraft, Joshua

    2006-01-01

    This presentation highlights communication congestion control in delay-tolerant networks (DTNs). Large-scale future space exploration will offer complex communication challenges that may be best addressed by establishing a network infrastructure. However, current internet techniques for congestion control are not well suited for operation of a network over interplanetary distances. An alternative, delay-tolerant technique for congestion control in a delay-tolerant network is presented. A simple DTN was constructed and an experimental congestion control mechanism was applied. The mechanism appeared to be effective and each router was able to make its bundle acceptance decisions autonomously. Future research will examine more complex topologies and alternative bundle acceptance rules that might enhance performance.

  13. Behavioural domain knowledge transfer for autonomous agents

    CSIR Research Space (South Africa)

    Rosman, Benjamin S

    2014-11-01

    Full Text Available , and Behavior Transfer in Autonomous Robots, AAAI 2014 Fall Symposium Series, 13-15 November 2014 Behavioural Domain Knowledge Transfer for Autonomous Agents Benjamin Rosman Mobile Intelligent Autonomous Systems Modelling and Digital Science Council...

  14. Testing the permeability and corrosion resistance of micro-mechanically interlocked joints

    DEFF Research Database (Denmark)

    Byskov-Nielsen, Jeppe; Holm, Allan Hjarbæk; Højsholt, Rune

    2011-01-01

    Micro-mechanical interlocking (MMI) can be applied to create new and interesting composite materials. We have employed laser structuring to achieve MMI between stainless steel and plastic with extremely high joint strength. However, the water permeability and corrosion resistance of the joint must...... is conducted. The permeability seems to be consistent with the Hagen–Poiseuille equation independent of the laser structuring technique and is orders of magnitudes larger than the diffusion rate through the plastic. Two different types of corrosion tests have been undertaken, and we show that care must...... be taken in order not to degrade the corrosion resistance of the sample to an unacceptable level....

  15. Mechanical Adaptivity as a Process: Implications to New Materials and Material System Design

    Science.gov (United States)

    2012-08-01

    Mfg / Origami HT Thermal Shape Memory PhotoChem- Mechanical Autonomic Chemo-Mechanical Building Blocks Predictive Models...structure Farkas et al. Chaos 5 1995 Bishop et al. JACS, 2005 Controlling oscillations through medium selection and geometry Controlling...Additive Mfg / Origami HT Thermal Shape Memory PhotoChem- Mechanical Autonomic Chemo-Mechanical Building Blocks Predictive Models

  16. Current challenges in autonomous vehicle development

    Science.gov (United States)

    Connelly, J.; Hong, W. S.; Mahoney, R. B., Jr.; Sparrow, D. A.

    2006-05-01

    The field of autonomous vehicles is a rapidly growing one, with significant interest from both government and industry sectors. Autonomous vehicles represent the intersection of artificial intelligence (AI) and robotics, combining decision-making with real-time control. Autonomous vehicles are desired for use in search and rescue, urban reconnaissance, mine detonation, supply convoys, and more. The general adage is to use robots for anything dull, dirty, dangerous or dumb. While a great deal of research has been done on autonomous systems, there are only a handful of fielded examples incorporating machine autonomy beyond the level of teleoperation, especially in outdoor/complex environments. In an attempt to assess and understand the current state of the art in autonomous vehicle development, a few areas where unsolved problems remain became clear. This paper outlines those areas and provides suggestions for the focus of science and technology research. The first step in evaluating the current state of autonomous vehicle development was to develop a definition of autonomy. A number of autonomy level classification systems were reviewed. The resulting working definitions and classification schemes used by the authors are summarized in the opening sections of the paper. The remainder of the report discusses current approaches and challenges in decision-making and real-time control for autonomous vehicles. Suggested research focus areas for near-, mid-, and long-term development are also presented.

  17. A mechanical-electrical finite element method model for predicting contact resistance between bipolar plate and gas diffusion layer in PEM fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Xinmin; Liu, Dong' an; Peng, Linfa [State Key Laboratory of Mechanical System and Vibration, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240 (China); Ni, Jun [Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109-2125 (United States)

    2008-07-15

    Contact resistance between the bipolar plate (BPP) and the gas diffusion layer (GDL) plays a significant role on the power loss in a proton exchange membrane (PEM) fuel cell. There are two types of contact behavior at the interface of the BPP and GDL, which are the mechanical one and the electrical one. Furthermore, the electrical contact behavior is dependent on the mechanical one. Thus, prediction of the contact resistance is a coupled mechanical-electrical problem. The current FEM models for contact resistance estimation can only simulate the mechanical contact behavior and moreover they are based on the assumption that the contact surface is equipotential, which is not the case in a real BPP/GDL assembly due to the round corner and margin of the BPP. In this study, a mechanical-electrical FEM model was developed to predict the contact resistance between the BPP and GDL based on the experimental interfacial contact resistivity. At first, the interfacial contact resistivity was obtained by experimentally measuring the contact resistance between the GDL and a flat graphite plate of the same material and processing conditions as the BPP. Then, with the interfacial contact resistivity, the mechanical and electrical contact behaviors were defined and the potential distribution of the BPP/GDL assembly was analyzed using the mechanical-electrical FEM model. At last, the contact resistance was calculated according to the potential drop and the current of the contact surface. The numerical results were validated by comparing with those of the model reported previously. The influence of the round corner of the BPP on the contact resistance was also studied and it is found that there exists an optimal round corner that can minimize the contact resistance. This model is beneficial in understanding the mechanical and electrical contact behaviors between the BPP and GDL, and can be used to predict the contact resistance in a new BPP/GDL assembly. (author)

  18. Autonomous learning of robust visual object detection and identification on a humanoid

    NARCIS (Netherlands)

    Leitner, J.; Chandrashekhariah, P.; Harding, S.; Frank, M.; Spina, G.; Förster, A.; Triesch, J.; Schmidhuber, J.

    2012-01-01

    In this work we introduce a technique for a humanoid robot to autonomously learn the representations of objects within its visual environment. Our approach involves an attention mechanism in association with feature based segmentation that explores the environment and provides object samples for

  19. Mechanism of hyperthermic potentiation of cisplatin action in cisplatin-sensitive and -resistant tumour cells

    NARCIS (Netherlands)

    Hettinga, JVE; Lemstra, W; Meijer, C; Dam, WA; Uges, DRA; Konings, AWT; DeVries, EGE; Kampinga, HH

    1997-01-01

    In this study, the mechanism(s) by which heat increases cis-diamminedichloroplatinum (cisplatin, cDDP) sensitivity in cDDP-sensitive and -resistant cell lines of murine as well as human origin were investigated. Heating cells at 43 degrees C during cDDP exposure was found to increase drug

  20. Compact autonomous navigation system (CANS)

    Science.gov (United States)

    Hao, Y. C.; Ying, L.; Xiong, K.; Cheng, H. Y.; Qiao, G. D.

    2017-11-01

    Autonomous navigation of Satellite and constellation has series of benefits, such as to reduce operation cost and ground station workload, to avoid the event of crises of war and natural disaster, to increase spacecraft autonomy, and so on. Autonomous navigation satellite is independent of ground station support. Many systems are developed for autonomous navigation of satellite in the past 20 years. Along them American MANS (Microcosm Autonomous Navigation System) [1] of Microcosm Inc. and ERADS [2] [3] (Earth Reference Attitude Determination System) of Honeywell Inc. are well known. The systems anticipate a series of good features of autonomous navigation and aim low cost, integrated structure, low power consumption and compact layout. The ERADS is an integrated small 3-axis attitude sensor system with low cost and small volume. It has the Earth center measurement accuracy higher than the common IR sensor because the detected ultraviolet radiation zone of the atmosphere has a brightness gradient larger than that of the IR zone. But the ERADS is still a complex system because it has to eliminate many problems such as making of the sapphire sphere lens, birefringence effect of sapphire, high precision image transfer optical fiber flattener, ultraviolet intensifier noise, and so on. The marginal sphere FOV of the sphere lens of the ERADS is used to star imaging that may be bring some disadvantages., i.e. , the image energy and attitude measurements accuracy may be reduced due to the tilt image acceptance end of the fiber flattener in the FOV. Besides Japan, Germany and Russia developed visible earth sensor for GEO [4] [5]. Do we have a way to develop a cheaper/easier and more accurate autonomous navigation system that can be used to all LEO spacecraft, especially, to LEO small and micro satellites? To return this problem we provide a new type of the system—CANS (Compact Autonomous Navigation System) [6].

  1. Acquired resistance to EGFR inhibitors: mechanisms and prevention strategies

    International Nuclear Information System (INIS)

    Viloria-Petit, Alicia M.; Kerbel, Robert S.

    2004-01-01

    Potent and specific, or relatively specific, inhibitors of epidermal growth factor receptor (EGFR) signaling, including monoclonal antibodies and small molecular weight compounds, have been successfully developed. Both types of agent have been found to have significant antitumor activity, especially when used in combination with radio- hormone- and chemotherapy in preclinical studies. Because of the potentiation of the conventional drug activity in these combination settings, inhibitors of EGFR signaling have often been referred to as sensitizers for chemotherapy or radiation, as well as drug resistance reversal agents. Phase II clinical trials in head-and-neck as well as lung cancer suggested this concept of chemosensitization might translate into the clinic, but this remains to be definitively proven in randomized, double-blind Phase III trials. Given the extensive preclinical literature on EGFR blocking drugs and the advanced clinical development of such agents, it is surprising that the possibility of development of acquired resistance to the EGFR inhibitors themselves, a common clinical problem with virtually all other currently used anticancer drugs, remains a largely unexplored subject of investigation. Here we summarize some of the possible mechanisms that can result in acquired resistance to EGFR-targeting drugs. Alternative combination therapies to circumvent and delay this problem are suggested

  2. Structural Studies of Bacterial Enzymes and their Relation to Antibiotic Resistance Mechanisms - Final Paper

    Energy Technology Data Exchange (ETDEWEB)

    Maltz, Lauren [SLAC National Accelerator Lab., Menlo Park, CA (United States)

    2015-08-27

    By using protein crystallography and X-ray diffraction, structures of bacterial enzymes were solved to gain a better understanding of how enzymatic modification acts as an antibacterial resistance mechanism. Aminoglycoside phosphotransferases (APHs) are one of three aminoglycoside modifying enzymes that confer resistance to the aminoglycoside antibiotics via enzymatic modification, rendering many drugs obsolete. Specifically, the APH(2”) family vary in their substrate specificities and also in their preference for the phosphate donor (ADP versus GDP). By solving the structures of members of the APH(2”) family of enzymes, we can see how domain movements are important to their substrate specificity. Our structure of the ternary complex of APH(2”)-IIIa with GDP and kanamycin, when compared to the known structures of APH(2”)-IVa, reveals that there are real physical differences between these two enzymes, a structural finding that explains why the two enzymes differ in their preferences for certain aminoglycosides. Another important group of bacterial resistance enzymes are the Class D β- lactamases. Oxacillinase carbapenemases (OXAs) are part of this enzyme class and have begun to confer resistance to ‘last resort’ drugs, most notably carbapenems. Our structure of OXA-143 shows that the conformational flexibility of a conserved hydrophobic residue in the active site (Val130) serves to control the entry of a transient water molecule responsible for a key step in the enzyme’s mechanism. Our results provide insight into the structural mechanisms of these two different enzymes

  3. A Molecular Modeling Study of the Hydroxyflutamide Resistance Mechanism Induced by Androgen Receptor Mutations

    Directory of Open Access Journals (Sweden)

    Hong-Li Liu

    2017-08-01

    Full Text Available Hydroxyflutamide (HF, an active metabolite of the first generation antiandrogen flutamide, was used in clinic to treat prostate cancer targeting androgen receptor (AR. However, a drug resistance problem appears after about one year’s treatment. AR T877A is the first mutation that was found to cause a resistance problem. Then W741C_T877A and F876L_T877A mutations were also reported to cause resistance to HF, while W741C and F876L single mutations cannot. In this study, molecular dynamics (MD simulations combined with the molecular mechanics generalized Born surface area (MM-GBSA method have been carried out to analyze the interaction mechanism between HF and wild-type (WT/mutant ARs. The obtained results indicate that AR helix 12 (H12 plays a pivotal role in the resistance of HF. It can affect the coactivator binding site at the activation function 2 domain (AF2, surrounded by H3, H4, and H12. When H12 closes to the AR ligand-binding domain (LBD like a lid, the coactivator binding site can be formed to promote transcription. However, once H12 is opened to expose LBD, the coactivator binding site will be distorted, leading to invalid transcription. Moreover, per-residue free energy decomposition analyses indicate that N705, T877, and M895 are vital residues in the agonist/antagonist mechanism of HF.

  4. SEVERAL MECHANISMS OF MERCURY RESISTANCE FOUND IN SOIL ISOLATES FROM PAVLODAR, KAZAKHSTAN

    Science.gov (United States)

    Abdrashitova, Svetlava A., M.A. Ilyushchenko, A. Yu Kalmykv, S.A. Aitkeldieva, Wendy J. Davis-Hoover and Richard Devereux. In press. Several Mechanisms of Mercury Resistance Found in Soil Isolates from Pavlodar, Kazakhstan (Abstract). To be presented at the Battelle Conference on...

  5. Pokeweed Antiviral Protein: Its Cytotoxicity Mechanism and Applications in Plant Disease Resistance

    Directory of Open Access Journals (Sweden)

    Rong Di

    2015-03-01

    Full Text Available Pokeweed antiviral protein (PAP is a 29 kDa type I ribosome inactivating protein (RIP found in pokeweed plants. Pokeweed produces different forms of PAP. This review focuses on the spring form of PAP isolated from Phytolacca americana leaves. PAP exerts its cytotoxicity by removing a specific adenine from the α-sarcin/ricin loop of the large ribosomal RNA. Besides depurination of the rRNA, PAP has additional activities that contribute to its cytotoxicity. The mechanism of PAP cytotoxicity is summarized based on evidence from the analysis of transgenic plants and the yeast model system. PAP was initially found to be anti-viral when it was co-inoculated with plant viruses onto plants. Transgenic plants expressing PAP and non-toxic PAP mutants have displayed broad-spectrum resistance to both viral and fungal infection. The mechanism of PAP-induced disease resistance in transgenic plants is summarized.

  6. The non-protein coding breast cancer susceptibility locus Mcs5a acts in a non-mammary cell-autonomous fashion through the immune system and modulates T-cell homeostasis and functions.

    Science.gov (United States)

    Smits, Bart M G; Sharma, Deepak; Samuelson, David J; Woditschka, Stephan; Mau, Bob; Haag, Jill D; Gould, Michael N

    2011-08-16

    Mechanisms underlying low-penetrance, common, non-protein coding variants in breast cancer risk loci are largely undefined. We showed previously that the non-protein coding mammary carcinoma susceptibility locus Mcs5a/MCS5A modulates breast cancer risk in rats and women. The Mcs5a allele from the Wistar-Kyoto (WKy) rat strain consists of two genetically interacting elements that have to be present on the same chromosome to confer mammary carcinoma resistance. We also found that the two interacting elements of the resistant allele are required for the downregulation of transcript levels of the Fbxo10 gene specifically in T-cells. Here we describe mechanisms through which Mcs5a may reduce mammary carcinoma susceptibility. We performed mammary carcinoma multiplicity studies with three mammary carcinoma-inducing treatments, namely 7,12-dimethylbenz(a)anthracene (DMBA) and N-nitroso-N-methylurea (NMU) carcinogenesis, and mammary ductal infusion of retrovirus expressing the activated HER2/neu oncogene. We used mammary gland and bone marrow transplantation assays to assess the target tissue of Mcs5a activity. We used immunophenotyping assays on well-defined congenic rat lines carrying susceptible and resistant Mcs5a alleles to identify changes in T-cell homeostasis and function associated with resistance. We show that Mcs5a acts beyond the initial step of mammary epithelial cell transformation, during early cancer progression. We show that Mcs5a controls susceptibility in a non-mammary cell-autonomous manner through the immune system. The resistant Mcs5a allele was found to be associated with an overabundance of gd T-cell receptor (TCR)+ T-cells as well as a CD62L (L-selectin)-high population of all T-cell classes. In contrast to in mammary carcinoma, gdTCR+ T-cells are the predominant T-cell type in the mammary gland and were found to be overabundant in the mammary epithelium of Mcs5a resistant congenic rats. Most of them simultaneously expressed the CD4, CD8, and CD161

  7. Basic emotions induced by odorants: a new approach based on autonomic pattern results.

    Science.gov (United States)

    Vernet-Maury, E; Alaoui-Ismaïli, O; Dittmar, A; Delhomme, G; Chanel, J

    1999-02-15

    The aim of this study was to link the effects of odorants with the emotional process, through autonomic nervous system (ANS) responses. Taking Ekman's data and our previous results into account, we tried to verify a possible evocation by odorants of some basic emotions, i.e. anger, fear, sadness, surprise, disgust and happiness. The question investigated was: would it be possible to associate any of these emotions with a pattern of autonomic responses? A total of 15 subjects inhaled five odorants: lavender, ethyl aceto acetate, camphor, acetic acid and butyric acid acting as olfactory stimuli. After inhaling the odorant, subjects were requested to fill out an 11-point hedonic scale to rate its 'pleasantness' vs. 'unpleasantness'. ANS parameters monitored were skin potential and resistance, skin blood flow and temperature, instantaneous respiratory frequency and instantaneous heart rate. Simultaneous recording of these six autonomic parameters permitted the analysis of phasic responses through specific ANS patterns. An analysis of variance made it possible to differentiate among the five odorants. Two-by-two odorant comparisons for autonomic responses using Tukey's HSD multiple comparison test only permitted differentiation between 'pleasant' and 'unpleasant' odors. Camphor was differentiated from both types. For instance, long duration responses were associated with 'unpleasant' odors whereas camphor elicited intermediate responses. Taking into account each subject's preferential channel, it was possible to associate each ANS pattern with a basic emotion by means of a decision tree. The computation of subjects' responses made it possible to associate an odorant with a basic emotion, over the whole group: lavender elicited mostly 'happiness', as did, to a lesser degree ethyl aceto acetate; camphor induced either 'happiness', 'surprise' or 'sadness' according to subjects' past histories; butyric and acetic acids mainly induced negative emotions: 'anger' and 'disgust

  8. Plasmids in Gram negatives: molecular typing of resistance plasmids.

    Science.gov (United States)

    Carattoli, Alessandra

    2011-12-01

    A plasmid is defined as a double stranded, circular DNA molecule capable of autonomous replication. By definition, plasmids do not carry genes essential for the growth of host cells under non-stressed conditions but they have systems which guarantee their autonomous replication also controlling the copy number and ensuring stable inheritance during cell division. Most of the plasmids confer positively selectable phenotypes by the presence of antimicrobial resistance genes. Plasmids evolve as an integral part of the bacterial genome, providing resistance genes that can be easily exchanged among bacteria of different origin and source by conjugation. A multidisciplinary approach is currently applied to study the acquisition and spread of antimicrobial resistance in clinically relevant bacterial pathogens and the established surveillance can be implemented by replicon typing of plasmids. Particular plasmid families are more frequently detected among Enterobacteriaceae and play a major role in the diffusion of specific resistance genes. For instance, IncFII, IncA/C, IncL/M, IncN and IncI1 plasmids carrying extended-spectrum beta-lactamase genes and acquired AmpC genes are currently considered to be "epidemic resistance plasmids", being worldwide detected in Enterobacteriaceae of different origin and sources. The recognition of successful plasmids is an essential first step to design intervention strategies preventing their spread. Copyright © 2011 Elsevier GmbH. All rights reserved.

  9. Phenotypic, fermentation characterization, and resistance mechanism analysis of bacteriophage-resistant mutants of Lactobacillus delbrueckii ssp. bulgaricus isolated from traditional Chinese dairy products.

    Science.gov (United States)

    Deng, Kaibo; Fang, Wei; Zheng, Baodong; Miao, Song; Huo, Guicheng

    2018-03-01

    Bacteriophage infection is a large factor in dairy industrial production failure on the basis of pure inoculation fermentation, and developing good commercial starter cultures from wild dairy products and improving the environmental vigor of starter cultures by enhancing their phage resistance are still the most effective solutions. Here we used a spontaneous isolation method to obtain bacteriophage-resistant mutants of Lactobacillus delbrueckii ssp. bulgaricus strains that are used in traditional Chinese fermented dairy products. We analyzed their phenotypes, fermentation characteristics, and resistance mechanisms. The results showed that bacteriophage-insensitive mutants (BIM) BIM8 and BIM12 had high bacteriophage resistance while exhibiting fermentation and coagulation attributes that were as satisfying as those of their respective parent strains KLDS1.1016 and KLDS1.1028. According to the attachment receptor detection, mutants BIM8 and BIM12 exhibited reduced absorption to bacteriophage phiLdb compared with their respective bacteriophage-sensitive parent strains because of changes to the polysaccharides or teichoic acids connected to their peptidoglycan layer. Additionally, genes, including HSDR, HSDM, and HSDS, encoding 3 subunits of a type I restriction-modification system were identified in their respective parent strains. We also discovered that HSDR and HSDM were highly conserved but that HSDS was variable because it is responsible for the DNA specificity of the complex. The late lysis that occurred only in strain KLDS1.1016 and not in strain KLDS1.1028 suggests that the former and its mutant BIM8 also may have an activatable restriction-modification mechanism. We conclude that the L. bulgaricus BIM8 and BIM12 mutants have great potential in the dairy industry as starter cultures, and their phage-resistance mechanism was effective mainly due to the adsorption interference and restriction-modification system. Copyright © 2018 American Dairy Science

  10. Use of antimicrobials in veterinary medicine and mechanisms of resistance.

    Science.gov (United States)

    Schwarz, S; Chaslus-Dancla, E

    2001-01-01

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

  11. Human Supervision of Multiple Autonomous Vehicles

    Science.gov (United States)

    2013-03-22

    AFRL-RH-WP-TR-2013-0143 HUMAN SUPERVISION OF MULTIPLE AUTONOMOUS VEHICLES Heath A. Ruff Ball...REPORT TYPE Interim 3. DATES COVERED (From – To) 09-16-08 – 03-22-13 4. TITLE AND SUBTITLE HUMAN SUPERVISION OF MULTIPLE AUTONOMOUS VEHICLES 5a...Supervision of Multiple Autonomous Vehicles To support the vision of a system that enables a single operator to control multiple next-generation

  12. Resistance of heat resisting steels and alloys to thermal and mechanical low-cycle fatigue

    International Nuclear Information System (INIS)

    Tulyakov, G.A.

    1980-01-01

    Carried out is a comparative evalUation of resistance of different materials to thermocyclic deformation and fracture on the base of the experimental data on thermal and mechanical low-cycle fatigUe. Considered are peculiarities of thermal fatigue resistance depending on strength and ductility of the material. It is shown, that in the range of the cycle small numbers before the fracture preference is given to the high-ductility cyclically strengthening austenitic steels of 18Cr-10Ni type with slight relation of yield strength to the σsub(0.2)/σsub(B) tensile strength Highly alloyed strength chromium-nickel steels, as well as cyclically destrengthening perlitic and ferritic steels with stronger σsub(0.2)/σsub(B) relation as compared with simple austenitic steels turn to be more long-lived in the range of the cycle great numbers berore fracture. Perlitic steels are stated to have the lowest parameter values of the K crack growth intensity under the similar limiting conditions of the experiment, while steels and alloys with austenite structure-higher values of the K parameter

  13. Synthesis, antitubercular activity and mechanism of resistance of highly effective thiacetazone analogues.

    Directory of Open Access Journals (Sweden)

    Geoffrey D Coxon

    Full Text Available Defining the pharmacological target(s of currently used drugs and developing new analogues with greater potency are both important aspects of the search for agents that are effective against drug-sensitive and drug-resistant Mycobacterium tuberculosis. Thiacetazone (TAC is an anti-tubercular drug that was formerly used in conjunction with isoniazid, but removed from the antitubercular chemotherapeutic arsenal due to toxic side effects. However, several recent studies have linked the mechanisms of action of TAC to mycolic acid metabolism and TAC-derived analogues have shown increased potency against M. tuberculosis. To obtain new insights into the molecular mechanisms of TAC resistance, we isolated and analyzed 10 mutants of M. tuberculosis that were highly resistant to TAC. One strain was found to be mutated in the methyltransferase MmaA4 at Gly101, consistent with its lack of oxygenated mycolic acids. All remaining strains harbored missense mutations in either HadA (at Cys61 or HadC (at Val85, Lys157 or Thr123, which are components of the β-hydroxyacyl-ACP dehydratase complex that participates in the mycolic acid elongation step. Separately, a library of 31 new TAC analogues was synthesized and evaluated against M. tuberculosis. Two of these compounds, 15 and 16, exhibited minimal inhibitory concentrations 10-fold lower than the parental molecule, and inhibited mycolic acid biosynthesis in a dose-dependent manner. Moreover, overexpression of HadAB HadBC or HadABC in M. tuberculosis led to high level resistance to these compounds, demonstrating that their mode of action is similar to that of TAC. In summary, this study uncovered new mutations associated with TAC resistance and also demonstrated that simple structural optimization of the TAC scaffold was possible and may lead to a new generation of TAC-derived drug candidates for the potential treatment of tuberculosis as mycolic acid inhibitors.

  14. Hemodynamic and autonomic nervous system responses to mixed meal ingestion in healthy young and old subjects and dysautonomic patients with postprandial hypotension

    Science.gov (United States)

    Lipsitz, L. A.; Ryan, S. M.; Parker, J. A.; Freeman, R.; Wei, J. Y.; Goldberger, A. L.

    1993-01-01

    BACKGROUND. Although postprandial hypotension is a common cause of falls and syncope in elderly persons and in patients with autonomic insufficiency, the pathophysiology of this disorder remains unknown. METHODS AND RESULTS. We examined the hemodynamic, splanchnic blood pool, plasma norepinephrine (NE), and heart rate (HR) power spectra responses to a standardized 400-kcal mixed meal in 11 healthy young (age, 26 +/- 5 years) and nine healthy elderly (age, 80 +/- 5 years) subjects and 10 dysautonomic patients with symptomatic postprandial hypotension (age, 65 +/- 16 years). Cardiac and splanchnic blood pools were determined noninvasively by radionuclide scans, and forearm vascular resistance was determined using venous occlusion plethysmography. In healthy young and old subjects, splanchnic blood volume increased, but supine blood pressure remained unchanged after the meal. In both groups, HR increased and systemic vascular resistance remained stable. Forearm vascular resistance and cardiac index increased after the meal in elderly subjects, whereas these responses were highly variable and of smaller magnitude in the young. Young subjects demonstrated postprandial increases in low-frequency HR spectral power, representing cardiac sympatho-excitation, but plasma NE remained unchanged. In elderly subjects, plasma NE increased after the meal but without changes in the HR power spectrum. Patients with dysautonomia had a large postprandial decline in blood pressure associated with no change in forearm vascular resistance, a fall in systemic vascular resistance, and reduction in left ventricular end diastolic volume index. HR increased in these patients but without changes in plasma NE or the HR power spectrum. CONCLUSIONS. 1) In healthy elderly subjects, the maintenance of blood pressure homeostasis after food ingestion is associated with an increase in HR, forearm vascular resistance, cardiac index, and plasma NE. In both young and old, systemic vascular resistance is

  15. A Priori User Acceptance and the Perceived Driving Pleasure in Semi-autonomous and Autonomous Vehicles

    DEFF Research Database (Denmark)

    Bjørner, Thomas

    The aim of this minor pilot study is, from a sociological user perspective, to explore a priori user acceptance and the perceived driving pleasure in semi- autonomous and autonomous vehicles. The methods used were 13 in-depth interviews while having participants watch video examples within four...... different scenarios. After each scenario, two different numerical rating scales were used. There was a tendency toward positive attitudes regarding semi- autonomous driving systems, especially the use of a parking assistant and while driving in city traffic congestion. However, there were also major...

  16. Motion Planning of Autonomous Vehicles on a Dual Carriageway without Speed Lanes

    Directory of Open Access Journals (Sweden)

    Rahul Kala

    2015-01-01

    Full Text Available The problem of motion planning of an autonomous vehicle amidst other vehicles on a straight road is considered. Traffic in a number of countries is unorganized, where the vehicles do not move within predefined speed lanes. In this paper, we formulate a mechanism wherein an autonomous vehicle may travel on the “wrong” side in order to overtake a vehicle. Challenges include assessing a possible overtaking opportunity, cooperating with other vehicles, partial driving on the “wrong” side of the road and safely going to and returning from the “wrong” side. The experimental results presented show vehicles cooperating to accomplish overtaking manoeuvres.

  17. Insecticide resistance is mediated by multiple mechanisms in recently introduced Aedes aegypti from Madeira Island (Portugal).

    Science.gov (United States)

    Seixas, Gonçalo; Grigoraki, Linda; Weetman, David; Vicente, José Luís; Silva, Ana Clara; Pinto, João; Vontas, John; Sousa, Carla Alexandra

    2017-07-01

    Aedes aegypti is a major mosquito vector of arboviruses, including dengue, chikungunya and Zika. In 2005, Ae. aegypti was identified for the first time in Madeira Island. Despite an initial insecticide-based vector control program, the species expanded throughout the Southern coast of the island, suggesting the presence of insecticide resistance. Here, we characterized the insecticide resistance status and the underlying mechanisms of two populations of Ae. aegypti from Madeira Island, Funchal and Paúl do Mar. WHO susceptibility bioassays indicated resistance to cyfluthrin, permethrin, fenitrothion and bendiocarb. Use of synergists significantly increased mortality rates, and biochemical assays indicated elevated activities of detoxification enzymes, suggesting the importance of metabolic resistance. Microarray-based transcriptome analysis detected significant upregulation in both populations of nine cytochrome P450 oxidase genes (including four known pyrethroid metabolizing enzymes), the organophosphate metabolizer CCEae3a, Glutathione-S-transferases, and multiple putative cuticle proteins. Genotyping of knockdown resistance loci linked to pyrethroid resistance revealed fixation of the 1534C mutation, and presence with moderate frequencies of the V1016I mutation in each population. Significant resistance to three major insecticide classes (pyrethroid, carbamate and organophosphate) is present in Ae. aegypti from Madeira Island, and appears to be mediated by multiple mechanisms. Implementation of appropriate resistance management strategies including rotation of insecticides with alternative modes of action, and methods other than chemical-based vector control are strongly advised to delay or reverse the spread of resistance and achieve efficient control.

  18. Mechanisms of Linezolid Resistance among Coagulase-Negative Staphylococci Determined by Whole-Genome Sequencing

    Science.gov (United States)

    Tewhey, Ryan; Gu, Bing; Kelesidis, Theodoros; Charlton, Carmen; Bobenchik, April; Hindler, Janet; Schork, Nicholas J.

    2014-01-01

    ABSTRACT Linezolid resistance is uncommon among staphylococci, but approximately 2% of clinical isolates of coagulase-negative staphylococci (CoNS) may exhibit resistance to linezolid (MIC, ≥8 µg/ml). We performed whole-genome sequencing (WGS) to characterize the resistance mechanisms and genetic backgrounds of 28 linezolid-resistant CoNS (21 Staphylococcus epidermidis isolates and 7 Staphylococcus haemolyticus isolates) obtained from blood cultures at a large teaching health system in California between 2007 and 2012. The following well-characterized mutations associated with linezolid resistance were identified in the 23S rRNA: G2576U, G2447U, and U2504A, along with the mutation C2534U. Mutations in the L3 and L4 riboproteins, at sites previously associated with linezolid resistance, were also identified in 20 isolates. The majority of isolates harbored more than one mutation in the 23S rRNA and L3 and L4 genes. In addition, the cfr methylase gene was found in almost half (48%) of S. epidermidis isolates. cfr had been only rarely identified in staphylococci in the United States prior to this study. Isolates of the same sequence type were identified with unique mutations associated with linezolid resistance, suggesting independent acquisition of linezolid resistance in each isolate. PMID:24915435

  19. Vision Based Autonomous Robot Navigation Algorithms and Implementations

    CERN Document Server

    Chatterjee, Amitava; Nirmal Singh, N

    2013-01-01

    This book is devoted to the theory and development of autonomous navigation of mobile robots using computer vision based sensing mechanism. The conventional robot navigation systems, utilizing traditional sensors like ultrasonic, IR, GPS, laser sensors etc., suffer several drawbacks related to either the physical limitations of the sensor or incur high cost. Vision sensing has emerged as a popular alternative where cameras can be used to reduce the overall cost, maintaining high degree of intelligence, flexibility and robustness. This book includes a detailed description of several new approaches for real life vision based autonomous navigation algorithms and SLAM. It presents the concept of how subgoal based goal-driven navigation can be carried out using vision sensing. The development concept of vision based robots for path/line tracking using fuzzy logic is presented, as well as how a low-cost robot can be indigenously developed in the laboratory with microcontroller based sensor systems. The book descri...

  20. Antibiotics Resistance in Rhizobium: Type, Process, Mechanism and Benefit for Agriculture.

    Science.gov (United States)

    Naamala, Judith; Jaiswal, Sanjay K; Dakora, Felix D

    2016-06-01

    The use of high-quality rhizobial inoculants on agricultural legumes has contributed substantially to the N economy of farming systems through inputs from biological nitrogen fixation (BNF). Large populations of symbiotically effective rhizobia should be available in the rhizosphere for symbiotic BNF with host plants. The rhizobial populations should also be able to compete and infect host plants. However, the rhizosphere comprises large populations of different microorganisms. Some of these microorganisms naturally produce antibiotics which are lethal to susceptible rhizobial populations in the soil. Therefore, intrinsic resistance to antibiotics is a desirable trait for the rhizobial population. It increases the rhizobia's chances of growth, multiplication and persistence in the soil. With a large population of rhizobia in the soil, infectivity of host plants and the subsequent BNF efficiency can be guaranteed. This review, therefore, puts together findings by various researchers on antibiotic resistance in bacteria with the main emphasis on rhizobia. It describes the different modes of action of different antibiotics, the types of antibiotic resistance exhibited by rhizobia, the mechanisms of acquisition of antibiotic resistance in rhizobia and the levels of tolerance of different rhizobial species to different antibiotics.

  1. Intelligent autonomous systems 12. Vol. 2. Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sukhan [Sungkyunkwan Univ., Gyeonggi-Do (Korea, Republic of). College of Information and Communication Engineering; Yoon, Kwang-Joon [Konkuk Univ., Seoul (Korea, Republic of); Cho, Hyungsuck [Daegu Gyeongbuk Institute of Science and Technology, Daegu (Korea, Republic of); Lee, Jangmyung (eds.) [Pusan National Univ. (Korea, Republic of). Dept. of Electronics Engineering

    2013-02-01

    Recent research in Intelligent and Autonomous Systems. Volume 2 of the proceedings of the 12th International Conference IAS-12, held June 26-29, 2012, jeju Island, Korea. Written by leading experts in the field. Intelligent autonomous systems are emerged as a key enabler for the creation of a new paradigm of services to humankind, as seen by the recent advancement of autonomous cars licensed for driving in our streets, of unmanned aerial and underwater vehicles carrying out hazardous tasks on-site, and of space robots engaged in scientific as well as operational missions, to list only a few. This book aims at serving the researchers and practitioners in related fields with a timely dissemination of the recent progress on intelligent autonomous systems, based on a collection of papers presented at the 12th International Conference on Intelligent Autonomous Systems, held in Jeju, Korea, June 26-29, 2012. With the theme of ''Intelligence and Autonomy for the Service to Humankind, the conference has covered such diverse areas as autonomous ground, aerial, and underwater vehicles, intelligent transportation systems, personal/domestic service robots, professional service robots for surgery/rehabilitation, rescue/security and space applications, and intelligent autonomous systems for manufacturing and healthcare. This volume 2 includes contributions devoted to Service Robotics and Human-Robot Interaction and Autonomous Multi-Agent Systems and Life Engineering.

  2. The role of the autonomic nervous system in Tourette Syndrome

    Science.gov (United States)

    Hawksley, Jack; Cavanna, Andrea E.; Nagai, Yoko

    2015-01-01

    Tourette Syndrome (TS) is a neurodevelopmental disorder, consisting of multiple involuntary movements (motor tics) and one or more vocal (phonic) tics. It affects up to one percent of children worldwide, of whom about one third continue to experience symptoms into adulthood. The central neural mechanisms of tic generation are not clearly understood, however recent neuroimaging investigations suggest impaired cortico-striato-thalamo-cortical activity during motor control. In the current manuscript, we will tackle the relatively under-investigated role of the peripheral autonomic nervous system, and its central influences, on tic activity. There is emerging evidence that both sympathetic and parasympathetic nervous activity influences tic expression. Pharmacological treatments which act on sympathetic tone are often helpful: for example, Clonidine (an alpha-2 adrenoreceptor agonist) is often used as first choice medication for treating TS in children due to its good tolerability profile and potential usefulness for co-morbid attention-deficit and hyperactivity disorder. Clonidine suppresses sympathetic activity, reducing the triggering of motor tics. A general elevation of sympathetic tone is reported in patients with TS compared to healthy people, however this observation may reflect transient responses coupled to tic activity. Thus, the presence of autonomic impairments in patients with TS remains unclear. Effect of autonomic afferent input to cortico-striato-thalamo-cortical circuit will be discussed schematically. We additionally review how TS is affected by modulation of central autonomic control through biofeedback and Vagus Nerve Stimulation (VNS). Biofeedback training can enable a patient to gain voluntary control over covert physiological responses by making these responses explicit. Electrodermal biofeedback training to elicit a reduction in sympathetic tone has a demonstrated association with reduced tic frequency. VNS, achieved through an implanted device

  3. Autonomous Star Tracker Algorithms

    DEFF Research Database (Denmark)

    Betto, Maurizio; Jørgensen, John Leif; Kilsgaard, Søren

    1998-01-01

    Proposal, in response to an ESA R.f.P., to design algorithms for autonomous star tracker operations.The proposal also included the development of a star tracker breadboard to test the algorithms performances.......Proposal, in response to an ESA R.f.P., to design algorithms for autonomous star tracker operations.The proposal also included the development of a star tracker breadboard to test the algorithms performances....

  4. [Isolation of a carbapenem-resistant K1 serotype Klebsiella pneumonia strain and the study of resistance mechanism].

    Science.gov (United States)

    Zhang, Rong; Wang, Xuan; Lü, Jianxin

    2014-12-16

    To study the virulence and mechanism of carbapenem resistance of a clinical isolate of carbapenem-resistant K1 serotype Klebsiella pneumonia strain. Identification of isolate was carried out with VITEK-2 compact system. Antimicrobial susceptibility was determined by E-test; Metallo β-lactamases and carbapenemases screening were conducted by imipenem-EDTA double disc synergy test and modified Hodge test, respectively.Specific polymerehse chain reaction (PCR) and DNA sequencing were preformed to detect the virulence genes including K1, K2, K5, K20, K54, K57, magA, rmpA, wcaG and a series of β-lactamase resistence genes. Conjunction experiment was also performed. The plasmids of transconjugants were submitted to PCR-based replicon typing (PBRT) method. Molecular typing was performed by multilocus sequence typing (MLST). Antimicrobial susceptibility testing revealed that the Klebsiella pneumonia strain was resistant to most of the antibiotics used in clinic. Phynotype confirmary rest revealed the production of carbapanemases, while Metallo β-lactamases were negative; PCR and DNA sequencing confirmed the isolate was positive for blaKPC-2, blaCTX-M-15, blaTEM-1, blaSHV-1 and virulence genes K1, magA, rmpA, wcaG simultaneously; blaKPC-2 was transferred from donor to Escherichia EC600 by conjunction experiment, while no virulence genes were found in the transconjugants. PBRT revealed that Frep plasmid was found in transconjugants. MLST analysis revealed that this strain belonged to ST23. K1 serotype Klebsiella pneumonia strain carries virulence genes and carbapenem resistance gene blaKPC-2, noteworthily the carbapenem resistance genes can be transferred through horizontal transmission on plasmids.

  5. Genetic analysis to identify good combiners for ToLCV resistance ...

    Indian Academy of Sciences (India)

    2014-11-10

    Nov 10, 2014 ... 2Department of Botany, Udai Pratap Autonomous College, Varanasi 221 002, India. 3AIP-USAID ... there is a possibility of getting hybrid seeds in some com- binations. .... plant growth and resistance to ToLCV disease.

  6. On analysis of operating efficiency of autonomous ventilation systems

    Directory of Open Access Journals (Sweden)

    Kostuganov Arman

    2017-01-01

    Full Text Available The paper deals with the causes and consequences of malfunctioning of natural and mechanical ventilation systems in civil buildings of Russia. Furthermore it gives their classification and analysis based on the literature review. On the basis of the analysis technical solutions for improving the efficiency of ventilation systems in civil buildings are summarized and the field of their application is specified. Among the offered technical solutions the use of autonomous ventilation systems with heat recovery is highlighted as one of the most promising and understudied. Besides it has a wide range of applications. The paper reviews and analyzes the main Russian and foreign designs of ventilation systems with heat recovery that are mostly used in practice. Three types of such systems: UVRK-50, Prana-150, ТеFо are chosen for consideration. The sequence of field tests of selected autonomous ventilation systems have been carried out in order to determine the actual air exchange and efficiency of heat recovery. The paper presents the processed results of the research on the basis of which advantages and disadvantages of the tested ventilation systems are identified and recommendations for engineering and manufacturing of new design models of autonomous ventilation systems with heat recovery are formulated.

  7. Effect of Sleep/Wake Cycle on Autonomic Regulation

    International Nuclear Information System (INIS)

    Jabeen, S.

    2015-01-01

    Objective: To evaluate the association between irregular sleep/wake cycle in shift workers and autonomic regulation. Study Design: Cross-sectional, analytical study. Place and Duration of Study: Dow University Hospital, Karachi, from August to November 2013. Methodology: All health care providers working in rotating shifts making a total (n=104) were included. Instrument was an integrated questionnaire applied to assess autonomic regulation, taken from Kroz et al. on scoring criteria, ranging from 18 - 54, where higher rating signifies strong autonomic regulation, indicating a stable Autonomic Nervous System (ANS) and vice versa. Participants were interviewed and their response was recorded by the investigator. Influence of sleep misalignment was measured quantitatively to extract index of autonomic activity. Results: There was a reduced trend in autonomic strength amongst shift workers. The mean score obtained on the Autonomic Scale was 37.8 ± 5.9. Conclusion: Circadian misalignment has an injurious influence on ANS which might be valuable in controlling autonomic dysfunction that leads to fatal triggers in rotating shift workers. (author)

  8. Effects of the Fourth Ventricle Compression in the Regulation of the Autonomic Nervous System: A Randomized Control Trial

    Directory of Open Access Journals (Sweden)

    Ana Paula Cardoso-de-Mello-e-Mello-Ribeiro

    2015-01-01

    Full Text Available Introduction. Dysfunction of the autonomic nervous system is an important factor in the development of chronic pain. Fourth ventricle compression (CV-4 has been shown to influence autonomic activity. Nevertheless, the physiological mechanisms behind these effects remain unclear. Objectives. This study is aimed at evaluating the effects of fourth ventricle compression on the autonomic nervous system. Methods. Forty healthy adults were randomly assigned to an intervention group, on whom CV-4 was performed, or to a control group, who received a placebo intervention (nontherapeutic touch on the occipital bone. In both groups, plasmatic catecholamine levels, blood pressure, and heart rate were measured before and immediately after the intervention. Results. No effects related to the intervention were found. Although a reduction of norepinephrine, systolic blood pressure, and heart rate was found after the intervention, it was not exclusive to the intervention group. In fact, only the control group showed an increment of dopamine levels after intervention. Conclusion. Fourth ventricle compression seems not to have any effect in plasmatic catecholamine levels, blood pressure, or heart rate. Further studies are needed to clarify the CV-4 physiologic mechanisms and clinical efficacy in autonomic regulation and pain treatment.

  9. Physics Simulation Software for Autonomous Propellant Loading and Gas House Autonomous System Monitoring

    Science.gov (United States)

    Regalado Reyes, Bjorn Constant

    2015-01-01

    1. Kennedy Space Center (KSC) is developing a mobile launching system with autonomous propellant loading capabilities for liquid-fueled rockets. An autonomous system will be responsible for monitoring and controlling the storage, loading and transferring of cryogenic propellants. The Physics Simulation Software will reproduce the sensor data seen during the delivery of cryogenic fluids including valve positions, pressures, temperatures and flow rates. The simulator will provide insight into the functionality of the propellant systems and demonstrate the effects of potential faults. This will provide verification of the communications protocols and the autonomous system control. 2. The High Pressure Gas Facility (HPGF) stores and distributes hydrogen, nitrogen, helium and high pressure air. The hydrogen and nitrogen are stored in cryogenic liquid state. The cryogenic fluids pose several hazards to operators and the storage and transfer equipment. Constant monitoring of pressures, temperatures and flow rates are required in order to maintain the safety of personnel and equipment during the handling and storage of these commodities. The Gas House Autonomous System Monitoring software will be responsible for constantly observing and recording sensor data, identifying and predicting faults and relaying hazard and operational information to the operators.

  10. A Lever Coupling Mechanism in Dual-Mass Micro-Gyroscopes for Improving the Shock Resistance along the Driving Direction

    Directory of Open Access Journals (Sweden)

    Yang Gao

    2017-04-01

    Full Text Available This paper presents the design and application of a lever coupling mechanism to improve the shock resistance of a dual-mass silicon micro-gyroscope with drive mode coupled along the driving direction without sacrificing the mechanical sensitivity. Firstly, the mechanical sensitivity and the shock response of the micro-gyroscope are theoretically analyzed. In the mechanical design, a novel lever coupling mechanism is proposed to change the modal order and to improve the frequency separation. The micro-gyroscope with the lever coupling mechanism optimizes the drive mode order, increasing the in-phase mode frequency to be much larger than the anti-phase one. Shock analysis results show that the micro-gyroscope structure with the designed lever coupling mechanism can notably reduce the magnitudes of the shock response and cut down the stress produced in the shock process compared with the traditional elastic coupled one. Simulations reveal that the shock resistance along the drive direction is greatly increased. Consequently, the lever coupling mechanism can change the gyroscope’s modal order and improve the frequency separation by structurally offering a higher stiffness difference ratio. The shock resistance along the driving direction is tremendously enhanced without loss of the mechanical sensitivity.

  11. Autonomous Deployment and Restoration of Sensor Network using Mobile Robots

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Suzuki

    2010-09-01

    Full Text Available This paper describes an autonomous deployment and restoration of a Wireless Sensor Network (WSN using mobile robots. The authors have been developing an information-gathering system using mobile robots and WSNs in underground spaces in post-disaster environments. In our system, mobile robots carry wireless sensor nodes (SN and deploy them into the environment while measuring Received Signal Strength Indication (RSSI values to ensure communication, thereby enabling the WSN to be deployed and restored autonomously. If the WSN is disrupted, mobile robots restore the communication route by deploying additional or alternate SNs to suitable positions. Utilizing the proposed method, a mobile robot can deploy a WSN and gather environmental information via the WSN. Experimental results using a verification system equipped with a SN deployment and retrieval mechanism are presented.

  12. Autonomous Deployment and Restoration of Sensor Network using Mobile Robots

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Suzuki

    2010-06-01

    Full Text Available This paper describes an autonomous deployment and restoration of a Wireless Sensor Network (WSN using mobile robots. The authors have been developing an information-gathering system using mobile robots and WSNs in underground spaces in post-disaster environments. In our system, mobile robots carry wireless sensor nodes (SN and deploy them into the environment while measuring Received Signal Strength Indication (RSSI values to ensure communication, thereby enabling the WSN to be deployed and restored autonomously. If the WSN is disrupted, mobile robots restore the communication route by deploying additional or alternate SNs to suitable positions. Utilizing the proposed method, a mobile robot can deploy a WSN and gather environmental information via the WSN. Experimental results using a verification system equipped with a SN deployment and retrieval mechanism are presented.

  13. Study on the mechanism of wheat mutants resistance to bi-polaris sorokiniana

    International Nuclear Information System (INIS)

    Sun Guangzu; Wang Guangjin; Tang Fenglan; Liu Lijun; Li Zhongjie

    1992-01-01

    The activities and band number of peroxidase (POD), superoxide dismutase (SOD) and phenylalanine aminolyase (PAL) in plant tissue have been studied after treatment with phytotoxin produced from Bi polaris sorokiniana. The results showed that the activity and band number of these enzymes have been changed markedly. The change in degree of activity for mutants was more than that of the parent, and coincident with the ability of resistance to disease. The authors considered that the toxin tolerance ability and inducibility of SOD and POD by toxin might be one of resistance mechanism of wheat mutant against Bipolaris sorokiniana

  14. Mechanism of Nisin, Pediocin 34, and Enterocin FH99 Resistance in Listeria monocytogenes.

    Science.gov (United States)

    Kaur, Gurpreet; Singh, Tejinder Pal; Malik, Ravinder Kumar; Bhardwaj, Arun

    2012-03-01

    Nisin-, pediocin 34-, and enterocin FH99-resistant variants of Listeria monocytogenes ATCC 53135 were developed. In an attempt to clarify the possible mechanisms underlying bacteriocin resistance in L. monocytogenes ATCC 53135, sensitivity of the resistant strains of L. monocytogenes ATCC 53135 to nisin, pediocin 34, and enterocin FH99 in the absence and presence of different divalent cations was assessed, and the results showed that the addition of divalent cations significantly reduced the inhibitory activity of nisin, pediocin 34, and enterocin FH99 against resistant variants of L. monocytogenes ATCC 53135. The addition of EDTA, however, restored this activity suggesting that the divalent cations seem to affect the initial electrostatic interaction between the positively charged bacteriocin and the negatively charged phospholipids of the membrane. Nisin-, pediocin 34-, and enterocin-resistant variants of L. monocytogenes ATCC 53135 were more resistant to lysozyme as compared to the wild-type strain both in the presence as well as absence of nisin, pediocin 34, and enterocin FH99. Ultra structural profiles of bacteriocin-sensitive L. monocytogenes and its bacteriocin-resistant counterparts revealed that the cells of wild-type strain of L. monocytogenes were maximally in pairs or short chains, whereas, its nisin-, pediocin 34-, and enterocin FH99-resistant variants tend to form aggregates. Results indicated that without a cell wall, the acquired nisin, pediocin 34, and enterocin FH99 resistance of the variants was lost. Although the bacteriocin-resistant variants appeared to lose their acquired resistance toward nisin, pediocin 34, and enterocin FH99, the protoplasts of the resistant variants appeared to be more resistant to bacteriocins than the protoplasts of their wild-type counterparts.

  15. Mining in the Future: Autonomous Robotics for Safer Mines

    CSIR Research Space (South Africa)

    Shahdi, A

    2012-10-01

    Full Text Available ? Require less support infrastructure ? Advanced sensors ? CSIR 2012 Slide 4 Degree of Autonomy ? Teleoperation ? Semi-autonomous ? Autonomous ? CSIR 2012 Slide 5 Mobile Intelligent Autonomous Systems Group ? The Mobile Intelligent Autonomous...

  16. From cooperative to autonomous vehicles

    NARCIS (Netherlands)

    van der Sande, T.P.J.; Nijmeijer, H.; Fossen, T.I.; Pettersen, K.Y.; Nijmeijer, H.

    2017-01-01

    What defines an autonomous vehicle? In this chapter the authors will try to answer this question and formulate the limitations of driver assistance systems as well as for—conditionally—autonomous vehicles . First a short summary of the levels of automation as provided by the society of automotive

  17. Modeling of the bacterial mechanism of methicillin-resistance by a systems biology approach.

    Directory of Open Access Journals (Sweden)

    Ida Autiero

    Full Text Available BACKGROUND: A microorganism is a complex biological system able to preserve its functional features against external perturbations and the ability of the living systems to oppose to these external perturbations is defined "robustness". The antibiotic resistance, developed by different bacteria strains, is a clear example of robustness and of ability of the bacterial system to acquire a particular functional behaviour in response to environmental changes. In this work we have modeled the whole mechanism essential to the methicillin-resistance through a systems biology approach. The methicillin is a beta-lactamic antibiotic that act by inhibiting the penicillin-binding proteins (PBPs. These PBPs are involved in the synthesis of peptidoglycans, essential mesh-like polymers that surround cellular enzymes and are crucial for the bacterium survival. METHODOLOGY: The network of genes, mRNA, proteins and metabolites was created using CellDesigner program and the data of molecular interactions are stored in Systems Biology Markup Language (SBML. To simulate the dynamic behaviour of this biochemical network, the kinetic equations were associated with each reaction. CONCLUSIONS: Our model simulates the mechanism of the inactivation of the PBP by methicillin, as well as the expression of PBP2a isoform, the regulation of the SCCmec elements (SCC: staphylococcal cassette chromosome and the synthesis of peptidoglycan by PBP2a. The obtained results by our integrated approach show that the model describes correctly the whole phenomenon of the methicillin resistance and is able to respond to the external perturbations in the same way of the real cell. Therefore, this model can be useful to develop new therapeutic approaches for the methicillin control and to understand the general mechanism regarding the cellular resistance to some antibiotics.

  18. Polymyxin susceptibility testing, interpretative breakpoints and resistance mechanisms: An update.

    Science.gov (United States)

    Bakthavatchalam, Yamuna Devi; Pragasam, Agila Kumari; Biswas, Indranil; Veeraraghavan, Balaji

    2018-03-01

    Emerging multidrug-resistant (MDR) nosocomial pathogens are a great threat. Polymyxins, an old class of cationic polypeptide antibiotic, are considered as last-resort drugs in treating infections caused by MDR Gram-negative bacteria. Increased use of polymyxins in treating critically ill patients necessitates routine polymyxin susceptibility testing. However, susceptibility testing both of colistin and polymyxin B (PMB) is challenging. In this review, currently available susceptibility testing methods are briefly discussed. The multicomponent composition of colistin and PMB significantly influences susceptibility testing. In addition, poor diffusion in the agar medium, adsorption to microtitre plates and the synergistic effect of the surfactant polysorbate 80 with polymyxins have a great impact on the performance of susceptibility testing methods This review also describes recently identified chromosomal resistance mechanisms, including modification of lipopolysaccharide (LPS) with 4-amino-4-deoxy-l-arabinose (L-Ara4-N) and phosphoethanolamine (pEtN) resulting in alteration of the negative charge, as well as the plasmid-mediated colistin resistance determinants mcr-1, mcr-1.2, mcr-2 and mcr-3. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

  19. Investigation of corrosion resistance of alloys with high mechanical characteristics in some environments of food industry

    International Nuclear Information System (INIS)

    Tremoureux, Yves

    1978-01-01

    This research thesis aimed at improving knowledge in the field of stress-free corrosion of alloys with high mechanical characteristics in aqueous environments, at highlighting some necessary aspects of their behaviour during cleaning or disinfection, and at selecting alloys which possess a good stress-free corrosion resistance in view of a later investigation of their stress corrosion resistance. After a presentation of the metallurgical characteristics of high mechanical strength alloys and the report of a bibliographical study on corrosion resistance of these alloys, the author presents and discusses the results obtained in the study of a possible migration of metallic ions in a milk product which is submitted to a centrifugation, and of the corrosion resistance of selected alloys with respect to the different media they will be in contact with during ultra-centrifugation. The following alloys have been used in this research: Marval 18, Marphynox, Marval X12, 17-4PH steel, Inconel 718 [fr

  20. Autonomous Learner Model Resource Book

    Science.gov (United States)

    Betts, George T.; Carey, Robin J.; Kapushion, Blanche M.

    2016-01-01

    "Autonomous Learner Model Resource Book" includes activities and strategies to support the development of autonomous learners. More than 40 activities are included, all geared to the emotional, social, cognitive, and physical development of students. Teachers may use these activities and strategies with the entire class, small groups, or…

  1. 11th International Symposium on Distributed Autonomous Robotic Systems

    CERN Document Server

    Chirikjian, Gregory

    2014-01-01

    Distributed robotics is a rapidly growing and maturing interdisciplinary research area lying at the intersection of computer science, network science, control theory, and electrical and mechanical engineering. The goal of the Symposium on Distributed Autonomous Robotic Systems (DARS) is to exchange and stimulate research ideas to realize advanced distributed robotic systems. This volume of proceedings includes 31 original contributions presented at the 2012 International Symposium on Distributed Autonomous Robotic Systems (DARS 2012) held in November 2012 at the Johns Hopkins University in Baltimore, MD USA. The selected papers in this volume are authored by leading researchers from Asia, Europa, and the Americas, thereby providing a broad coverage and perspective of the state-of-the-art technologies, algorithms, system architectures, and applications in distributed robotic systems. The book is organized into five parts, representative of critical long-term and emerging research thrusts in the multi-robot com...

  2. Microstructures, mechanical properties and corrosion resistance of Hastelloy C22 coating produced by laser cladding

    International Nuclear Information System (INIS)

    Wang, Qin-Ying; Zhang, Yang-Fei; Bai, Shu-Lin; Liu, Zong-De

    2013-01-01

    Highlights: ► Hastelloy C22 coatings were prepared by diode laser cladding technique. ► Higher laser speed resulted in smaller grain size. ► Size-effect played the key role in the hardness measurements by different ways. ► Coating with higher laser scanning speed displayed higher nano-scratch resistance. ► Small grain size was beneficial for improvement of coating corrosion resistance. -- Abstract: The Hastelloy C22 coatings H1 and H2 were prepared by laser cladding technique with laser scanning speeds of 6 and 12 mm/s, respectively. Their microstructures, mechanical properties and corrosion resistance were investigated. The microstructures and phase compositions were studied by metallurgical microscope, scanning electron microscope and X-ray diffraction analysis. The hardness and scratch resistance were measured by micro-hardness and nanoindentation tests. The polarization curves and electrochemical impedance spectroscopy were tested by electrochemical workstation. Planar, cellular and dendritic solidifications were observed in the coating cross-sections. The coatings metallurgically well-bonded with the substrate are mainly composed of primary phase γ-nickel with solution of Fe, W, Cr and grain boundary precipitate of Mo 6 Ni 6 C. The hardness and corrosion resistance of steel substrate are significantly improved by laser cladding Hastelloy C22 coating. Coating H2 shows higher micro-hardness than that of H1 by 34% and it also exhibits better corrosion resistance. The results indicate that the increase of laser scanning speed improves the microstuctures, mechanical properties and corrosion resistance of Hastelloy C22 coating

  3. Research Progress of the Resistance Mechanism of Non-small Cell Lung Cancer 
to EGFR-TKIs

    Directory of Open Access Journals (Sweden)

    Huihui LIU

    2013-10-01

    Full Text Available Nowadays, lung cancer is the malignant tumor of the highest morbidity and mortality over the world, and non-small cell lung cancer (NSCLC makes up about 80%. There is a great many NSCLC patients have been in advanced stage when diagnosed. As a result, people pay more attention to curing advanced NSCLC. The standard treatment to advanced NSCLC is platinum-based combined chemotherapy. However, chemotherapy drugs usually have limited effects on improving the survival of the patients. Then exploring new therapies is extremely urgent to us. Now, molecular targeted therapy has been the most promising research area for the treatment of NSCLC with researches going deep into pathogenesis and biological behavior of lung cancer. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs have achieved a great success in the treatment of advanced NSCLC. Their representatives are erlotinib and gefitinib. The two drugs have been widely used to treat advanced NSCLCs worldwide, especially for the patients with EGFR activating mutations. However, after a period of treatment (median time is 6 to 12 months, most patients will develop drug resistance to EGFR-TKIs. Intense research in these NSCLCs has identified two major mechanisms of resistance to TKIs: primary and acquired resistances. The research about resistance mechanism of NSCLC to EGFR-TKIs is a hot one because of their excellent effects on improving overall and progression-free survival. The aim of this article was to summarize the development of the resistance mechanisms.

  4. The destiny of the resistance/susceptibility against GCRV is controlled by epigenetic mechanisms in CIK cells.

    Science.gov (United States)

    Shang, Xueying; Yang, Chunrong; Wan, Quanyuan; Rao, Youliang; Su, Jianguo

    2017-07-03

    Hemorrhagic disease caused by grass carp reovirus (GCRV) has severely threatened the grass carp (Ctenopharyngodon idella) cultivation industry. It is noteworthy that the resistance against GCRV infection was reported to be inheritable, and identified at both individual and cellular levels. Therefore, this work was inspired and dedicated to unravel the molecular mechanisms of fate decision post GCRV infection in related immune cells. Foremost, the resistant and susceptible CIK (C. idella kidney) monoclonal cells were established by single cell sorting, subculturing and infection screening successively. RNA-Seq, MeDIP-Seq and small RNA-Seq were carried out with C1 (CIK cells), R2 (resistant cells) and S3 (susceptible cells) groups. It was demonstrated that genome-wide DNA methylation, mRNA and microRNA expression levels in S3 were the highest among three groups. Transcriptome analysis elucidated that pathways associated with antioxidant activity, cell proliferation regulation, apoptosis activity and energy consuming might contribute to the decision of cell fates post infection. And a series of immune-related genes were identified differentially expressed across resistant and susceptible groups, which were negatively modulated by DNA methylation or microRNAs. To conclude, this study systematically uncovered the regulatory mechanism on the resistance from epigenetic perspective and provided potential biomarkers for future studies on resistance breeding.

  5. Physiological Mechanisms behind Differences in Pod Shattering Resistance in Rapeseed (Brassica napus L. Varieties.

    Directory of Open Access Journals (Sweden)

    Jie Kuai

    Full Text Available Pod shattering resistance index (SRI is a key factor affecting the mechanical harvesting of rapeseed. Research on the differences in pod shattering resistance levels of various rapeseed varieties can provide a theoretical basis for varietal breeding and application in mechanical harvesting. The indicators on pod shattering resistance including pod morphology and wall components were evaluated on eight hybrids and open pollinators, respectively, during 2012-2014. The results showed the following: (1 From the current study, SRI varied greatly with variety, and conventional varieties had stronger resistance than hybrid according to the physiological indexes. and (2 Under the experimental conditions, the SRI was linearly related to pod wall weight and the water content in pod walls, and the goodness-of-fit measurements for the regression model of the SRI based on pod wall weight and water content were 0.584** and 0.377*, respectively, reaching the significant level. This illustrated that pod wall weight and the water content in pod walls determined the SRI. (3 Compared with the relative contents of biochemical components in pod walls, the contents of particular biochemical components in pod walls had closer correlations with SRI. Among the biochemical components, the hemicellulose content was the decisive factor for the SRI.

  6. Use and Misuse of Antimicrobial Drugs in Poultry and Livestock: Mechanisms of Antimicrobial Resistance

    Directory of Open Access Journals (Sweden)

    Toni Poole* and Cynthia Sheffield

    2013-07-01

    Full Text Available Food safety begins on the farm with management practices that contribute to an abundant, safe, and affordable food supply. To attain this goal antimicrobials have been used in all stages of food animal production in the United States and elsewhere around the world at one time or another. Among food–production animals antimicrobials are used for growth promotion, disease prophylaxis or disease treatment, and are generally administered to the entire flock or herd. Over many decades bacteria have become resistant to multiple antimicrobial classes in a cumulative manner. Bacteria exhibit a number of well characterized mechanisms of resistance to antimicrobials that include: 1 modification of the antimicrobial; 2 alteration of the drug target; 3 decreased access of drug to target; and 4 implementation of an alternative metabolic pathway not affected by the drug. The mechanisms of resistance are complex and depend on the type of bacterium involved (e.g. Gram–positive or Gram–negative and the class of drug. Some bacterial species have accumulated resistance to nearly all antimicrobial classes due to a combination of intrinsic and acquired processes. This has and will continue to lead to clinical failures of antimicrobial treatment in both human and animal medicine.

  7. Inheritance and mechanism of resistance to herbicides inhibiting acetolactate synthase in Sonchus oleraceus L.

    Science.gov (United States)

    Boutsalis, P; Powles, S B

    1995-07-01

    A biotype of Sonchus oleraceus L. (Compositae) has developed resistance to herbicides inhibiting acetolactate synthase (ALS) following field selection with chlorsulfuron for 8 consecutive years. The aim of this study was to determine the inheritance and mechanism of resistance in this biotype. Determination of ALS activity and inhibition kinetics revealed that Km and Vmax did not vary greatly between the resistant and susceptible biotypes. ALS extracted from the resistant biotype was resistant to five ALS-inhibiting herbicides in an in vitro assay. ALS activity from the resistant biotype was 14 19, 2, 3 and 3 times more resistant to inhibition by chlorsulfuron, sulfometuron, imazethapyr, imazapyr and flumetsulam, respectively, than the susceptible biotype. Hybrids between the resistant and a susceptible biotype were produced, and inheritance was followed through the F1, F2 and F3 generations. F1 hybrids displayed a uniform intermediate level of resistance between resistant and susceptible parents. Three distinct phenotypes, resistant, intermediate and susceptible, were identified in the F2 generation following chlorsulfuron application. A segregation ratio of 1∶2∶1 was observed, indicative of the action of a single, nuclear, incompletely dominant gene. F3 families, derived from intermediate F2 individuals, segregated in a similar manner. Resistance to herbicides inhibiting ALS in this biotype of S. oleraceus is due to the effect of a single gene coding for a resistant form of the target enzyme, ALS.

  8. Transport mechanisms in low-resistance ohmic contacts to p-InP formed by rapid thermal annealing

    DEFF Research Database (Denmark)

    Clausen, Thomas; Leistiko, Otto

    1993-01-01

    process is related to interdiffusion and compound formation between the metal elements and the InP. The onset of low specific contact resistance is characterized by a change in the dominant transport mechanism; from predominantly a combination of thermionic emission and field emission to purely thermionic......Thermionic emission across a very small effective Schottky barrier (0-0.2 eV) are reported as being the dominant transport process mechanism in very low-resistance ohmic contacts for conventional AuZn(Ni) metallization systems top-InP formed by rapid thermal annealing. The barrier modulation...

  9. Linezolid-resistant clinical isolates of enterococci and Staphylococcus cohnii from a multicentre study in China: molecular epidemiology and resistance mechanisms.

    Science.gov (United States)

    Chen, Hongbin; Wu, Weiyuan; Ni, Ming; Liu, Yingmei; Zhang, Jixia; Xia, Fei; He, Wenqiang; Wang, Qi; Wang, Zhanwei; Cao, Bin; Wang, Hui

    2013-10-01

    Genetic characterisation of linezolid-resistant Gram-positive cocci in a multicentre study in China has not been reported previously. To study the mechanism underlying the resistance of linezolid-resistant isolates, nine Enterococcus faecalis, one Enterococcus faecium and three Staphylococcus cohnii isolates with various levels of resistance were collected from five hospitals across China in 2009-2012. The nine E. faecalis isolates were classified into seven sequence types, indicating that these linezolid-resistant E. faecalis isolates were polyclonal. Enterococci isolates had reduced susceptibility to linezolid (MICs of 4-8 mg/L) and had mutation of ribosomal protein L3, with three also having mutation of L4, but without the multidrug resistance gene cfr or the 23S rRNA mutation G2576T. The three S. cohnii isolates were highly resistant to linezolid (MICs of 64 mg/L to >256 mg/L), harboured the cfr gene and had the 23S rRNA mutation G2576T. Southern blotting indicated that the cfr gene of these three isolates resided on different plasmids (pHK01, pRM01 and pRA01). In plasmid pHK01, IS21-558 and the cfr gene were integrated into transposon Tn558. In plasmids pRM01 and pRA01, the cfr gene was flanked by two copies of an IS256-like insertion sequence, indicating that the transferable form of linezolid resistance is conferred by the cfr gene. In conclusion, the emergence of linezolid-resistant Gram-positive cocci in different regions of China is of concern. The cfr gene and the 23S rRNA mutation contribute to high-level linezolid resistance in S. cohnii, and the L3 and L4 mutations are associated with low-level linezolid resistance in enterococci. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  10. Amnioserosa cell constriction but not epidermal actin cable tension autonomously drives dorsal closure.

    Science.gov (United States)

    Pasakarnis, Laurynas; Frei, Erich; Caussinus, Emmanuel; Affolter, Markus; Brunner, Damian

    2016-11-01

    Tissue morphogenesis requires coordination of multiple force-producing components. During dorsal closure in fly embryogenesis, an epidermis opening closes. A tensioned epidermal actin/MyosinII cable, which surrounds the opening, produces a force that is thought to combine with another MyosinII force mediating apical constriction of the amnioserosa cells that fill the opening. A model proposing that each force could autonomously drive dorsal closure was recently challenged by a model in which the two forces combine in a ratchet mechanism. Acute force elimination via selective MyosinII depletion in one or the other tissue shows that the amnioserosa tissue autonomously drives dorsal closure while the actin/MyosinII cable cannot. These findings exclude both previous models, although a contribution of the ratchet mechanism at dorsal closure onset remains likely. This shifts the current view of dorsal closure being a combinatorial force-component system to a single tissue-driven closure event.

  11. Cybersecurity for aerospace autonomous systems

    Science.gov (United States)

    Straub, Jeremy

    2015-05-01

    High profile breaches have occurred across numerous information systems. One area where attacks are particularly problematic is autonomous control systems. This paper considers the aerospace information system, focusing on elements that interact with autonomous control systems (e.g., onboard UAVs). It discusses the trust placed in the autonomous systems and supporting systems (e.g., navigational aids) and how this trust can be validated. Approaches to remotely detect the UAV compromise, without relying on the onboard software (on a potentially compromised system) as part of the process are discussed. How different levels of autonomy (task-based, goal-based, mission-based) impact this remote characterization is considered.

  12. Microstructural Evolution of Advanced Radiation-Resistant ODS Steel with Different Lengths of Mechanical Alloying Time

    Energy Technology Data Exchange (ETDEWEB)

    Noh, Sanghoon; Kim, Ga Eon; Kang, Suk Hoon; Kim, Tae Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-05-15

    Austenitic stainless steel may be one of the candidates because of good strength and corrosion resistance at the high temperatures, however irradiation swelling well occurred to 120dpa at high temperatures and this leads the decrease of the mechanical properties and dimensional stability. Compared to this, ferritic/ martensitic steel is a good solution because of excellent thermal conductivity and good swelling resistance. Unfortunately, the available temperature range of ferritic/martensitic steel is limited up to 650 .deg. C. ODS steel is the most promising structural material because of excellent creep and irradiation resistance by uniformly distributed nano-oxide particles with a high density which is extremely stable at the high temperature in ferritic/martensitic matrix. In this study, powder properties and microstructures of the ODS steel with different length of mechanical alloying time was investigated. The ODS steel milled 5h showed homogeneous grain structure with the highest hardness.

  13. Microstructural Evolution of Advanced Radiation-Resistant ODS Steel with Different Lengths of Mechanical Alloying Time

    International Nuclear Information System (INIS)

    Noh, Sanghoon; Kim, Ga Eon; Kang, Suk Hoon; Kim, Tae Kyu

    2015-01-01

    Austenitic stainless steel may be one of the candidates because of good strength and corrosion resistance at the high temperatures, however irradiation swelling well occurred to 120dpa at high temperatures and this leads the decrease of the mechanical properties and dimensional stability. Compared to this, ferritic/ martensitic steel is a good solution because of excellent thermal conductivity and good swelling resistance. Unfortunately, the available temperature range of ferritic/martensitic steel is limited up to 650 .deg. C. ODS steel is the most promising structural material because of excellent creep and irradiation resistance by uniformly distributed nano-oxide particles with a high density which is extremely stable at the high temperature in ferritic/martensitic matrix. In this study, powder properties and microstructures of the ODS steel with different length of mechanical alloying time was investigated. The ODS steel milled 5h showed homogeneous grain structure with the highest hardness

  14. Anti-Epidermal Growth Factor Receptor Therapy in Head and Neck Squamous Cell Carcinoma: Focus on Potential Molecular Mechanisms of Drug Resistance

    Science.gov (United States)

    Baay, Marc; Wouters, An; Specenier, Pol; Vermorken, Jan B.; Peeters, Marc; Lardon, Filip

    2013-01-01

    Targeted therapy against the epidermal growth factor receptor (EGFR) is one of the most promising molecular therapeutics for head and neck squamous cell carcinoma (HNSCC). EGFR is overexpressed in a wide range of malignancies, including HNSCC, and initiates important signal transduction pathways in HNSCC carcinogenesis. However, primary and acquired resistance are serious problems and are responsible for low single-agent response rate and tumor recurrence. Therefore, an improved understanding of the molecular mechanisms of resistance to EGFR inhibitors may provide valuable indications to identify biomarkers that can be used clinically to predict response to EGFR blockade and to establish new treatment options to overcome resistance. To date, no predictive biomarker for HNSCC is available in the clinic. Therapeutic resistance to anti-EGFR therapy may arise from mechanisms that can compensate for reduced EGFR signaling and/or mechanisms that can modulate EGFR-dependent signaling. In this review, we will summarize some of these molecular mechanisms and describe strategies to overcome that resistance. PMID:23821327

  15. Evaluation of the Mechanical Properties of Gray Cast Iron Using Electrical Resistivity Measurement

    Directory of Open Access Journals (Sweden)

    Bieroński M.

    2016-12-01

    Full Text Available In this paper an attempt to determine the relationship between the electrical resistivity and the tensile strength and hardness of cast iron of carbon equivalent in the range from 3.93% to 4.48%. Tests were performed on the gray cast iron for 12 different melts with different chemical composition. From one melt poured 6 samples. Based on the study of mechanical and electro-resistive determined variation characteristics of tensile strength, hardness and resistivity as a function of the carbon equivalent. Then, regression equations were developed as power functions describing the relationship between the resistivity of castings and their tensile strength and hardness. It was found a high level of regression equations to measuring points, particularly with regard to the relationship Rm=f(ρ. The obtained preliminary results indicate the possibility of application of the method of the resistance to rapid diagnostic casts on the production line, when we are dealing with repeatable production, in this case non variable geometry of the product for which it has been determinated before a regression equation.

  16. Improvement of mechanical properties and corrosion resistance of biodegradable Mg-Nd-Zn-Zr alloys by double extrusion

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xiaobo, E-mail: xbxbzhang2003@163.com [School of Materials Science and Engineering, Nanjing Institute of Technology, Nanjing, 211167 (China); Wang, Zhangzhong [School of Materials Science and Engineering, Nanjing Institute of Technology, Nanjing, 211167 (China); Yuan, Guangyin [National Engineering Research Center of Light Alloy Net Forming, Shanghai Jiao Tong University, Shanghai, 200240 (China); Xue, Yajun [School of Materials Science and Engineering, Nanjing Institute of Technology, Nanjing, 211167 (China)

    2012-08-01

    Highlights: Black-Right-Pointing-Pointer Microstructure of Mg-Nd-Zn-Zr alloys was refined and homogenized by double extrusion process. Black-Right-Pointing-Pointer The mechanical properties of the alloys were significantly enhanced by double extrusion. Black-Right-Pointing-Pointer The biocorrosion resistance of the alloys was improved by double extrusion. - Abstract: Mg-Nd-Zn-Zr alloy is a novel and promising biodegradable magnesium alloy due to good biocompatibility, desired uniform corrosion mode and outstanding corrosion resistance in simulated body fluid (SBF). However, the corrosion resistance and mechanical properties should be improved to meet the requirement of the biodegradable implants, such as plates, screws and cardiovascular stents. In the present study, double extrusion process was adopted to refine microstructure and improve mechanical properties of Mg-2.25Nd-0.11Zn-0.43Zr and Mg-2.70Nd-0.20Zn-0.41Zr alloys. The corrosion resistance of the alloys after double extrusion was also studied. The results show that the microstructure of the alloys under double extrusion becomes much finer and more homogeneous than those under once extrusion. The yield strength, ultimate tensile strength and elongation of the alloys under double extrusion are over 270 MPa, 300 MPa and 32%, respectively, indicating that outstanding mechanical properties of Mg-Nd-Zn-Zr alloy can be obtained by double extrusion. The results of immersion experiment and electrochemical measurements in SBF show that the corrosion resistance of Alloy 1 and Alloy 2 under double extrusion was increased by 7% and 8% respectively compared with those under just once extrusion.

  17. Improvement of mechanical properties and corrosion resistance of biodegradable Mg–Nd–Zn–Zr alloys by double extrusion

    International Nuclear Information System (INIS)

    Zhang, Xiaobo; Wang, Zhangzhong; Yuan, Guangyin; Xue, Yajun

    2012-01-01

    Highlights: ► Microstructure of Mg–Nd–Zn–Zr alloys was refined and homogenized by double extrusion process. ► The mechanical properties of the alloys were significantly enhanced by double extrusion. ► The biocorrosion resistance of the alloys was improved by double extrusion. - Abstract: Mg–Nd–Zn–Zr alloy is a novel and promising biodegradable magnesium alloy due to good biocompatibility, desired uniform corrosion mode and outstanding corrosion resistance in simulated body fluid (SBF). However, the corrosion resistance and mechanical properties should be improved to meet the requirement of the biodegradable implants, such as plates, screws and cardiovascular stents. In the present study, double extrusion process was adopted to refine microstructure and improve mechanical properties of Mg–2.25Nd–0.11Zn–0.43Zr and Mg–2.70Nd–0.20Zn–0.41Zr alloys. The corrosion resistance of the alloys after double extrusion was also studied. The results show that the microstructure of the alloys under double extrusion becomes much finer and more homogeneous than those under once extrusion. The yield strength, ultimate tensile strength and elongation of the alloys under double extrusion are over 270 MPa, 300 MPa and 32%, respectively, indicating that outstanding mechanical properties of Mg–Nd–Zn–Zr alloy can be obtained by double extrusion. The results of immersion experiment and electrochemical measurements in SBF show that the corrosion resistance of Alloy 1 and Alloy 2 under double extrusion was increased by 7% and 8% respectively compared with those under just once extrusion.

  18. The Human Element and Autonomous Ships

    Directory of Open Access Journals (Sweden)

    Sauli Ahvenjärvi

    2016-09-01

    Full Text Available The autonomous ship technology has become a “hot” topic in the discussion about more efficient, environmentally friendly and safer sea transportation solutions. The time is becoming mature for the introduction of commercially sensible solutions for unmanned and fully autonomous cargo and passenger ships. Safety will be the most interesting and important aspect in this development. The utilization of the autonomous ship technology will have many effects on the safety, both positive and negative. It has been announced that the goal is to make the safety of an unmanned ship better that the safety of a manned ship. However, it must be understood that the human element will still be present when fully unmanned ships are being used. The shore-based control of a ship contains new safety aspects and an interesting question will be the interaction of manned and unmanned ships in the same traffic area. The autonomous ship technology should therefore be taken into account on the training of seafarers. Also it should not be forgotten that every single control algorithm and rule of the internal decision making logic of the autonomously navigating ship has been designed and coded by a human software engineer. Thus the human element is present also in this point of the lifetime navigation system of the autonomous ship.

  19. Giant Lysosomes as a Chemotherapy Resistance Mechanism in Hepatocellular Carcinoma Cells.

    Science.gov (United States)

    Colombo, Federico; Trombetta, Elena; Cetrangolo, Paola; Maggioni, Marco; Razini, Paola; De Santis, Francesca; Torrente, Yvan; Prati, Daniele; Torresani, Erminio; Porretti, Laura

    2014-01-01

    Despite continuous improvements in therapeutic protocols, cancer-related mortality is still one of the main problems facing public health. The main cause of treatment failure is multi-drug resistance (MDR: simultaneous insensitivity to different anti-cancer agents), the underlying molecular and biological mechanisms of which include the activity of ATP binding cassette (ABC) proteins and drug compartmentalisation in cell organelles. We investigated the expression of the main ABC proteins and the role of cytoplasmic vacuoles in the MDR of six hepatocellular carcinoma (HCC) cell lines, and confirmed the accumulation of the yellow anti-cancer drug sunitinib in giant (four lines) and small cytoplasmic vacuoles of lysosomal origin (two lines). ABC expression analyses showed that the main ABC protein harboured by all of the cell lines was PGP, whose expression was not limited to the cell membrane but was also found on lysosomes. MTT assays showed that the cell lines with giant lysosomes were more resistant to sorafenib treatment than those with small lysosomes (plysosomes in drug sequestration and MDR in HCC cell lines. The possibility of modulating this mechanism using PGP inhibitors could lead to the development of new targeted strategies to enhance HCC treatment.

  20. Different phenotypic and molecular mechanisms associated with multidrug resistance in Gram-negative clinical isolates from Egypt

    Directory of Open Access Journals (Sweden)

    Helmy OM

    2017-12-01

    Full Text Available Omneya M Helmy, Mona T Kashef Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt Objectives: We set out to investigate the prevalence, different mechanisms, and clonal relatedness of multidrug resistance (MDR among third-generation cephalosporin-resistant Gram-negative clinical isolates from Egypt.Materials and methods: A total of 118 third-generation cephalosporin-resistant Gram-negative clinical isolates were included in this study. Their antimicrobial susceptibility pattern was determined using Kirby–Bauer disk diffusion method. Efflux pump-mediated resistance was tested by the efflux-pump inhibitor-based microplate assay using chlorpromazine. Detection of different aminoglycoside-, β-lactam-, and quinolone-resistance genes was done using polymerase chain reaction. The genetic diversity of MDR isolates was investigated using random amplification of polymorphic DNA.Results: Most of the tested isolates exhibited MDR phenotypes (84.75%. The occurrence of efflux pump-mediated resistance in the different MDR species tested was 40%–66%. Acinetobacter baumannii isolates showed resistance to most of the tested antibiotics, including imipenem. The blaOXA-23-like gene was detected in 69% of the MDR A. baumannii isolates. The MDR phenotype was detected in 65% of Pseudomonas aeruginosa isolates, of which only 23% exhibited efflux pump-mediated resistance. On the contrary, efflux-mediated resistance to piperacillin and gentamicin was recorded in 47.5% of piperacillin-resistant and 25% of gentamicin-resistant MDR Enterobacteriaceae. Moreover, the plasmid-mediated quinolone-resistance genes (aac(6’-Ib-cr, qnrB, and qnrS were detected in 57.6% and 83.33% of quinolone-resistant MDR Escherichia coli and Klebsiella pneumoniae isolates, respectively. The β-lactamase-resistance gene blaSHV-31 was detected for the first time in one MDR K. pneumoniae isolate from an endotracheal tube specimen in Egypt

  1. Connected and autonomous vehicles 2040 vision.

    Science.gov (United States)

    2014-07-01

    The Pennsylvania Department of Transportation (PennDOT) commissioned a one-year project, Connected and Autonomous : Vehicles 2040 Vision, with researchers at Carnegie Mellon University (CMU) to assess the implications of connected and : autonomous ve...

  2. A practical application of the geometrical theory on fibered manifolds to an autonomous bicycle motion in mechanical system with nonholonomic constraints

    Science.gov (United States)

    Haddout, Soufiane

    2018-01-01

    The equations of motion of a bicycle are highly nonlinear and rolling of wheels without slipping can only be expressed by nonholonomic constraint equations. A geometrical theory of general nonholonomic constrained systems on fibered manifolds and their jet prolongations, based on so-called Chetaev-type constraint forces, was proposed and developed in the last decade by O. Krupková (Rossi) in 1990's. Her approach is suitable for study of all kinds of mechanical systems-without restricting to Lagrangian, time-independent, or regular ones, and is applicable to arbitrary constraints (holonomic, semiholonomic, linear, nonlinear or general nonholonomic). The goal of this paper is to apply Krupková's geometric theory of nonholonomic mechanical systems to study a concrete problem in nonlinear nonholonomic dynamics, i.e., autonomous bicycle. The dynamical model is preserved in simulations in its original nonlinear form without any simplifying. The results of numerical solutions of constrained equations of motion, derived within the theory, are in good agreement with measurements and thus they open the possibility of direct application of the theory to practical situations.

  3. ROV90 - A prototype autonomous inspection vehicle

    Energy Technology Data Exchange (ETDEWEB)

    Roedseth, Oe.J.; Hallset, J.O.

    1991-04-01

    Simple autonomous inspection vehicles are suitable for operations where the cost, danger to humans, or area of operation prohibits the use of conventional underwater technology. Autonomous vehicles are, however, in their infancy and few such vehicles are available. There are still some problems to be overcome before this technology becomes useful in commercial applications. We have built ROV90 to investigate these problems. It is a test bed for experimenting with the different parts of an autonomous underwater vehicle. ROV90 will be able to autonomously follow prominent features in the real world, man made or natural. Examples are pipelines or walls in tunnels. ROV90 is tethered, but we are planning to use experience and results from ROV90 to develop av ''real'' autonomous underwater vehicle (AUV) called PISCIS. 11 refs., 8 figs.

  4. Wear resistance and fracture mechanics of WC-Co composites

    International Nuclear Information System (INIS)

    Kaytbay, Saleh; El-Hadek, Medhat

    2014-01-01

    Manufacturing of WC-Co composites using the electroless precipitation method at different sintering temperatures of 1 100, 1 250, 1 350 and 1 500 C was successfully achieved. The chemical composition of the investigated materials was 90 wt.% WC with 10 wt.% Co, and 80 wt.% WC with 20 wt.% Co. The specific density, densification, and Vickers microhardness measurements were found to increase with increased sintering temperature for both the WC-Co compositions. The composites of tungsten carbide with 10 wt.% Co had a higher specific density and Vickers microhardness measurements than those for the composites of tungsten carbide with 20 wt.% Co. Composites with WC-10 wt.% Co had better wear resistance. The stress-strain and transverse rupture strength increased monotonically with the increase in sintering temperatures, agreeing with the material hardness and wear resistance behavior. Fractographical scanning electron microscopy analysis of the fracture surface demonstrated a rough characteristic conical shape failure in the direction of the maximum shear stress. A proposed mechanism for the formation of the conical fracture surface under compression testing is presented. (orig.)

  5. Effects of solution treatment on mechanical properties and corrosion resistance of 4A duplex stainless steel

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Panpan; Wang, Aiqin; Wang, Wenyan [Henan Univ. of Science and Technology, Luoyang (China). School of Material Science and Engineering; Xie, Jingpei [Henan Univ. of Science and Technology, Luoyang (China). Collaborative Innovation Center of Nonferrous Metals

    2018-02-15

    In this study, 4A duplex stainless steels were prepared via remelting in an intermediate frequency furnace and subsequently solution treated at different temperatures. The effects of solution treatment on the mechanical properties and corrosion resistance of 4A duplex stainless steel were investigated. Microstructures were characterized via optical microscopy and scanning electron microscopy. The mechanical properties were evaluated via hardness test, tensile test, and impact test experiments. The point corrosion resistance was studied via chemical immersion and potentiodynamic anodic polarization. The results showed that with increasing solution temperature in the range of 1223 - 1423 K, the tensile strength and hardness first decreased and then increased, and minimum values were obtained at 1323 K. The σ phase precipitated at the boundaries of the α/γ phases in samples solution treated at 1223 K, decreasing both impact energy and pitting potential of the experimental steels. When experimental steels were solution treated at 1373 K for 2 h, a suitable volume fraction of α/γ was uniformly distributed throughout the microstructure, and the steels exhibited optimal mechanical properties and pitting corrosion resistance.

  6. Identification of novel resistance mechanisms to NAMPT inhibition via the de novo NAD+ biosynthesis pathway and NAMPT mutation.

    Science.gov (United States)

    Guo, Jun; Lam, Lloyd T; Longenecker, Kenton L; Bui, Mai H; Idler, Kenneth B; Glaser, Keith B; Wilsbacher, Julie L; Tse, Chris; Pappano, William N; Huang, Tzu-Hsuan

    2017-09-23

    Cancer cells have an unusually high requirement for the central and intermediary metabolite nicotinamide adenine dinucleotide (NAD + ), and NAD + depletion ultimately results in cell death. The rate limiting step within the NAD + salvage pathway required for converting nicotinamide to NAD + is catalyzed by nicotinamide phosphoribosyltransferase (NAMPT). Targeting NAMPT has been investigated as an anti-cancer strategy, and several highly selective small molecule inhibitors have been found to potently inhibit NAMPT in cancer cells, resulting in NAD + depletion and cytotoxicity. To identify mechanisms that could cause resistance to NAMPT inhibitor treatment, we generated a human fibrosarcoma cell line refractory to the highly potent and selective NAMPT small molecule inhibitor, GMX1778. We uncovered novel and unexpected mechanisms of resistance including significantly increased expression of quinolinate phosphoribosyl transferase (QPRT), a key enzyme in the de novo NAD + synthesis pathway. Additionally, exome sequencing of the NAMPT gene in the resistant cells identified a single heterozygous point mutation that was not present in the parental cell line. The combination of upregulation of the NAD + de novo synthesis pathway through QPRT over-expression and NAMPT mutation confers resistance to GMX1778, but the cells are only partially resistant to next-generation NAMPT inhibitors. The resistance mechanisms uncovered herein provide a potential avenue to continue exploration of next generation NAMPT inhibitors to treat neoplasms in the clinic. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Enhanced mechanical properties and increased corrosion resistance of a biodegradable magnesium alloy by plasma electrolytic oxidation (PEO).

    Science.gov (United States)

    White, Leon; Koo, Youngmi; Neralla, Sudheer; Sankar, Jagannathan; Yun, Yeoheung

    2016-06-01

    We report the enhanced mechanical properties of AZ31 magnesium alloys by plasma electrolytic oxidation (PEO) coating in NaOH, Na 2 SiO 3 , KF and NaH 2 PO 4 ·2H 2 O containing electrolytes. Mechanical properties including wear resistance, surface hardness and elastic modulus were increased for PEO-coated AZ31 Mg alloys (PEO-AZ31). DC polarization in Hank's solution indicating that the corrosion resistance significantly increased for PEO-coating in KF-contained electrolyte. Based on these results, the PEO coating method shows promising potential for use in biodegradable implant applications where tunable corrosion and mechanical properties are needed.

  8. Autonomous Cryogenic Load Operations: KSC Autonomous Test Engineer

    Science.gov (United States)

    Shrading, Nicholas J.

    2012-01-01

    The KSC Autonomous Test Engineer (KATE) program has a long history at KSC. Now a part of the Autonomous Cryogenic Load Operations (ACLO) mission, this software system has been sporadically developed over the past 20+ years. Originally designed to provide health and status monitoring for a simple water-based fluid system, it was proven to be a capable autonomous test engineer for determining sources of failure in. the system, As part.of a new goal to provide this same anomaly-detection capability for a complicated cryogenic fluid system, software engineers, physicists, interns and KATE experts are working to upgrade the software capabilities and graphical user interface. Much progress was made during this effort to improve KATE. A display ofthe entire cryogenic system's graph, with nodes for components and edges for their connections, was added to the KATE software. A searching functionality was added to the new graph display, so that users could easily center their screen on specific components. The GUI was also modified so that it displayed information relevant to the new project goals. In addition, work began on adding new pneumatic and electronic subsystems into the KATE knowledgebase, so that it could provide health and status monitoring for those systems. Finally, many fixes for bugs, memory leaks, and memory errors were implemented and the system was moved into a state in which it could be presented to stakeholders. Overall, the KATE system was improved and necessary additional features were added so that a presentation of the program and its functionality in the next few months would be a success.

  9. Auxinic herbicides, mechanisms of action, and weed resistance: A look into recent plant science advances

    Directory of Open Access Journals (Sweden)

    Pedro Jacob Christoffoleti

    2015-08-01

    Full Text Available Auxin governs dynamic cellular processes involved at several stages of plant growth and development. In this review, we discuss the mechanisms employed by auxin in light of recent scientific advances, with a focus on synthetic auxins as herbicides and synthetic auxin resistance mechanisms. Two auxin receptors were reported. The plasma membrane receptor ABP1 (Auxin Binding Protein 1 alters the structure and arrangement of actin filaments and microtubules, leading to plant epinasty and reducing peroxisomes and mitochondria mobility in the cell environment. The second auxin receptor is the gene transcription pathway regulated by the SCFTir/AFB ubiquitination complex, which destroys transcription repressor proteins that interrupt Auxin Response Factor (ARF activation. As a result mRNA related with Abscisic Acid (ABA and ethylene are transcribed, producing high quantities of theses hormones. Their associated action leads to high production of Reactive Oxygen Species (ROS, leading to tissue and plant death. Recently, another ubiquitination pathway which is described as a new auxin signaling route is the F-box protein S-Phase Kinase-Associated Protein 2A (SKP2A. It is active in cell division regulation and there is evidence that auxin herbicides can deregulate the SKP2A pathway, which leads to severe defects in plant development. In this discussion, we propose that SFCSKP2A auxin binding site alteration could be a new auxinic herbicide resistance mechanism, a concept which may contribute to the current progress in plant biology in its quest to clarify the many questions that still surround auxin herbicide mechanisms of action and the mechanisms of weed resistance.

  10. Investigation of the electroforming and resistive switching mechanisms in Fe-doped SrTiO3 thin films

    International Nuclear Information System (INIS)

    Menke, Tobias

    2009-01-01

    To overcome the physical limits of todays memory technologies new concepts are needed. The resistive random access memory (RRAM), which bases on a nonvolatile and repeatable change of the resistance by external electrical stimuli, seems to be one promising candidate. Within the scope of this work, the model system Strontium titanate (SrTiO 3 ) has been investigated to get a deeper understanding of the underlying physical mechanism related to the resistance change. The electrical properties of SrTiO 3 (STO) can be modulated from a band insulator to metallic conduction by a self-doping with oxygen vacancies which act as shallow donors. A local accumulation or depletion of oxygen vacancies at the vicinity of the surface will lead to a local redox process which is responsible for the resistance change. To study the influence of the interfaces on the switching properties of SrTiO 3 thin films, epitaxial films of Fe-doped SrTiO 3 were grown on different bottom electrodes (SrRuO 3 , LaNiO 3 und Nb:STO) by a ''Pulsed Laser Deposition'' technique. An atomic force microscope equipped with a conductive tip (LC-AFM) allowed studying the conductivity of the deposited films on the nanometer scale. Resistive switching of lateral structures smaller than ∝5 nm could be realized which represents the potential of this material for a further downscaling of RRAM devices. The deposition of top electrodes, made of Platinum or Titanium, allowed the electrical characterization of metal-insulator-metal (MIM) structures. An extensive investigation of pristine MIM-devices by impedance spectroscopy showed the big impact of the metal-insulator interface on the overall device resistance. Furthermore, a chemical polarization was studied by dynamical current sweeps and identified as a volatile resistance variation. Usually a forming procedure is needed to ''enable'' the resistive switching properties in MIM devices. The electroforming of these devices was extensively studied and could be

  11. Perinatal acquisition of drug-resistant HIV-1 infection: mechanisms and long-term outcome

    Directory of Open Access Journals (Sweden)

    Dollfus Catherine

    2009-09-01

    Full Text Available Abstract Background Primary-HIV-1-infection in newborns that occurs under antiretroviral prophylaxis that is a high risk of drug-resistance acquisition. We examine the frequency and the mechanisms of resistance acquisition at the time of infection in newborns. Patients and Methods We studied HIV-1-infected infants born between 01 January 1997 and 31 December 2004 and enrolled in the ANRS-EPF cohort. HIV-1-RNA and HIV-1-DNA samples obtained perinatally from the newborn and mother were subjected to population-based and clonal analyses of drug resistance. If positive, serial samples were obtained from the child for resistance testing. Results Ninety-two HIV-1-infected infants were born during the study period. Samples were obtained from 32 mother-child pairs and from another 28 newborns. Drug resistance was detected in 12 newborns (20%: drug resistance to nucleoside reverse transcriptase inhibitors was seen in 10 cases, non-nucleoside reverse transcriptase inhibitors in two cases, and protease inhibitors in one case. For 9 children, the detection of the same resistance mutations in mothers' samples (6 among 10 available and in newborn lymphocytes (6/8 suggests that the newborn was initially infected by a drug-resistant strain. Resistance variants were either transmitted from mother-to-child or selected during subsequent temporal exposure under suboptimal perinatal prophylaxis. Follow-up studies of the infants showed that the resistance pattern remained stable over time, regardless of antiretroviral therapy, suggesting the early cellular archiving of resistant viruses. The absence of resistance in the mother of the other three children (3/10 and neonatal lymphocytes (2/8 suggests that the newborns were infected by a wild-type strain without long-term persistence of resistance when suboptimal prophylaxis was stopped. Conclusion This study confirms the importance of early resistance genotyping of HIV-1-infected newborns. In most cases (75%, drug

  12. Resistance to Linezolid

    DEFF Research Database (Denmark)

    Vester, Birte; Ntokou, Eleni

    2017-01-01

    Linezolid is an antimicrobial agent that binds to the bacterial ribosome and thereby inhibits protein synthesis. Soon after its release as a clinical drug, it became clear that bacteria could become resistant to linezolid. The resistance mechanisms are mainly causing alteration of the drug target...... site, but probably efflux might also play a role. The resistance is still rare in surveillance studies, but outbreaks of resistant clones from hospitals have been observed. So far the main mechanisms of resistance are occurrence of mutations in ribosomal genes or obtaining plasmids with a gene coding...... for a methyltransferase providing resistance. The most obvious way to avoid resistance may be development of derivatives of linezolid overcoming the known resistance mechanisms....

  13. Some resistance mechanisms to ultraviolet radiation; Algunos mecanismos de resistencia a radiacion ultravioleta

    Energy Technology Data Exchange (ETDEWEB)

    Alcantara D, D. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    2002-12-15

    The cyclical exposure of bacterial cells to the ultraviolet light (UV) it has as consequence an increment in the resistance to the lethal effects of this type of radiation, increment that happens as a result of a selection process of favorable genetic mutations induced by the same UV light. With object to study the reproducibility of the genetic changes and the associate mechanisms to the resistance to UV in the bacteria Escherichia coli, was irradiated cyclically with UV light five different derived cultures of a single clone, being obtained five stumps with different resistance grades. The genetic mapping Hfr revealed that so much the mutation events like of selection that took place during the adaptation to the UV irradiation, happened of random manner, that is to say, each one of the resistant stumps it is the result of the unspecified selection of mutations arisen at random in different genes related with the repair and duplication of the DNA. (Author)

  14. An addressable conducting network for autonomic structural health management of composite structures

    International Nuclear Information System (INIS)

    Takahashi, Kosuke; Park, Jong Se; Thomas Hahn, H

    2010-01-01

    The electrical resistance change method (ERCM) has long been an area of interest as an in-service health monitoring system. To apply the ERCM to existing structures, a new concept, the addressable conducting network (ACN), is proposed for autonomic structural health management of graphite/polymer composites. The ACN consists of two sets of conducting lines normal to each other, where one set resides on the top surface of the laminate and the other on the bottom surface. Damage can be detected by monitoring the resistance change 'through the laminate thickness' between two lines. By using a thermally mendable polymer as the matrix, the same conducting lines can be used to supply the electric current needed for resistive heating, thereby allowing the detected damage to be healed. As shown experimentally, the electrical resistance change method using an ACN distinguishes between laminates made of properly and improperly cured prepreg as well as revealing damage generated during three-point bending tests. Finite element analysis was performed to examine the feasibility of the ACN and indicated that the damage can be easily located from the spatial distribution of resistance changes and that the damaged area can be locally heated by supplying a large amount of current to selected conducting lines

  15. An addressable conducting network for autonomic structural health management of composite structures

    Science.gov (United States)

    Takahashi, Kosuke; Park, Jong Se; Hahn, H. Thomas

    2010-10-01

    The electrical resistance change method (ERCM) has long been an area of interest as an in-service health monitoring system. To apply the ERCM to existing structures, a new concept, the addressable conducting network (ACN), is proposed for autonomic structural health management of graphite/polymer composites. The ACN consists of two sets of conducting lines normal to each other, where one set resides on the top surface of the laminate and the other on the bottom surface. Damage can be detected by monitoring the resistance change 'through the laminate thickness' between two lines. By using a thermally mendable polymer as the matrix, the same conducting lines can be used to supply the electric current needed for resistive heating, thereby allowing the detected damage to be healed. As shown experimentally, the electrical resistance change method using an ACN distinguishes between laminates made of properly and improperly cured prepreg as well as revealing damage generated during three-point bending tests. Finite element analysis was performed to examine the feasibility of the ACN and indicated that the damage can be easily located from the spatial distribution of resistance changes and that the damaged area can be locally heated by supplying a large amount of current to selected conducting lines.

  16. Mechanics based model for predicting structure-induced rolling resistance (SRR) of the tire-pavement system

    Science.gov (United States)

    Shakiba, Maryam; Ozer, Hasan; Ziyadi, Mojtaba; Al-Qadi, Imad L.

    2016-11-01

    The structure-induced rolling resistance of pavements, and its impact on vehicle fuel consumption, is investigated in this study. The structural response of pavement causes additional rolling resistance and fuel consumption of vehicles through deformation of pavement and various dissipation mechanisms associated with inelastic material properties and damping. Accurate and computationally efficient models are required to capture these mechanisms and obtain realistic estimates of changes in vehicle fuel consumption. Two mechanistic-based approaches are currently used to calculate vehicle fuel consumption as related to structural rolling resistance: dissipation-induced and deflection-induced methods. The deflection-induced approach is adopted in this study, and realistic representation of pavement-vehicle interactions (PVIs) is incorporated. In addition to considering viscoelastic behavior of asphalt concrete layers, the realistic representation of PVIs in this study includes non-uniform three-dimensional tire contact stresses and dynamic analysis in pavement simulations. The effects of analysis type, tire contact stresses, pavement viscoelastic properties, pavement damping coefficients, vehicle speed, and pavement temperature are then investigated.

  17. Impaired neural structure and function contributing to autonomic symptoms in congenital central hypoventilation syndrome.

    Science.gov (United States)

    Harper, Ronald M; Kumar, Rajesh; Macey, Paul M; Harper, Rebecca K; Ogren, Jennifer A

    2015-01-01

    Congenital central hypoventilation syndrome (CCHS) patients show major autonomic alterations in addition to their better-known breathing deficiencies. The processes underlying CCHS, mutations in the PHOX2B gene, target autonomic neuronal development, with frame shift extent contributing to symptom severity. Many autonomic characteristics, such as impaired pupillary constriction and poor temperature regulation, reflect parasympathetic alterations, and can include disturbed alimentary processes, with malabsorption and intestinal motility dyscontrol. The sympathetic nervous system changes can exert life-threatening outcomes, with dysregulation of sympathetic outflow leading to high blood pressure, time-altered and dampened heart rate and breathing responses to challenges, cardiac arrhythmia, profuse sweating, and poor fluid regulation. The central mechanisms contributing to failed autonomic processes are readily apparent from structural and functional magnetic resonance imaging studies, which reveal substantial cortical thinning, tissue injury, and disrupted functional responses in hypothalamic, hippocampal, posterior thalamic, and basal ganglia sites and their descending projections, as well as insular, cingulate, and medial frontal cortices, which influence subcortical autonomic structures. Midbrain structures are also compromised, including the raphe system and its projections to cerebellar and medullary sites, the locus coeruleus, and medullary reflex integrating sites, including the dorsal and ventrolateral medullary nuclei. The damage to rostral autonomic sites overlaps metabolic, affective and cognitive regulatory regions, leading to hormonal disruption, anxiety, depression, behavioral control, and sudden death concerns. The injuries suggest that interventions for mitigating hypoxic exposure and nutrient loss may provide cellular protection, in the same fashion as interventions in other conditions with similar malabsorption, fluid turnover, or hypoxic exposure.

  18. Impaired Neural Structure and Function Contributing to Autonomic Symptoms in Congenital Central Hypoventilation Syndrome

    Directory of Open Access Journals (Sweden)

    Ronald M Harper

    2015-10-01

    Full Text Available Congenital central hypoventilation syndrome (CCHS patients show major autonomic alterations in addition to their better-known breathing deficiencies. The processes underlying CCHS, mutations in the PHOX2B gene, target autonomic neuronal development, with frame shift extent contributing to symptom severity. Many autonomic characteristics, such as impaired pupillary constriction and poor temperature regulation, reflect parasympathetic alterations, and can include disturbed alimentary processes, with malabsorption and intestinal motility dyscontrol. The sympathetic nervous system changes can exert life-threatening outcomes, with dysregulation of sympathetic outflow leading to high blood pressure, time-altered and dampened heart rate and breathing responses to challenges, cardiac arrhythmia, profuse sweating, and poor fluid regulation. The central mechanisms contributing to failed autonomic processes are readily apparent from structural and functional magnetic resonance imaging studies, which reveal substantial cortical thinning, tissue injury, and disrupted functional responses in hypothalamic, hippocampal, posterior thalamic, and basal ganglia sites and their descending projections, as well as insular, cingulate, and medial frontal cortices, which influence subcortical autonomic structures. Midbrain structures are also compromised, including the raphe system and its projections to cerebellar and medullary sites, the locus coeruleus, and medullary reflex integrating sites, including the dorsal and ventrolateral medullary nuclei. The damage to rostral autonomic sites overlaps metabolic, affective and cognitive regulatory regions, leading to hormonal disruption, anxiety, depression, behavioral control, and sudden death concerns. The injuries suggest that interventions for mitigating hypoxic exposure and nutrient loss may provide cellular protection, in the same fashion as interventions in other conditions with similar malabsorption, fluid turnover

  19. Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism

    Science.gov (United States)

    Gorbunova, Vera; Hine, Christopher; Tian, Xiao; Ablaeva, Julia; Gudkov, Andrei V.; Nevo, Eviatar; Seluanov, Andrei

    2012-01-01

    Blind mole rats Spalax (BMR) are small subterranean rodents common in the Middle East. BMR is distinguished by its adaptations to life underground, remarkable longevity (with a maximum documented lifespan of 21 y), and resistance to cancer. Spontaneous tumors have never been observed in spalacids. To understand the mechanisms responsible for this resistance, we examined the growth of BMR fibroblasts in vitro of the species Spalax judaei and Spalax golani. BMR cells proliferated actively for 7–20 population doublings, after which the cells began secreting IFN-β, and the cultures underwent massive necrotic cell death within 3 d. The necrotic cell death phenomenon was independent of culture conditions or telomere shortening. Interestingly, this cell behavior was distinct from that observed in another long-lived and cancer-resistant African mole rat, Heterocephalus glaber, the naked mole rat in which cells display hypersensitivity to contact inhibition. Sequestration of p53 and Rb proteins using SV40 large T antigen completely rescued necrotic cell death. Our results suggest that cancer resistance of BMR is conferred by massive necrotic response to overproliferation mediated by p53 and Rb pathways, and triggered by the release of IFN-β. Thus, we have identified a unique mechanism that contributes to cancer resistance of this subterranean mammal extremely adapted to life underground. PMID:23129611

  20. Cisplatin as an Anti-Tumor Drug: Cellular Mechanisms of Activity, Drug Resistance and Induced Side Effects

    International Nuclear Information System (INIS)

    Florea, Ana-Maria; Büsselberg, Dietrich

    2011-01-01

    Platinum complexes are clinically used as adjuvant therapy of cancers aiming to induce tumor cell death. Depending on cell type and concentration, cisplatin induces cytotoxicity, e.g., by interference with transcription and/or DNA replication mechanisms. Additionally, cisplatin damages tumors via induction of apoptosis, mediated by the activation of various signal transduction pathways, including calcium signaling, death receptor signaling, and the activation of mitochondrial pathways. Unfortunately, neither cytotoxicity nor apoptosis are exclusively induced in cancer cells, thus, cisplatin might also lead to diverse side-effects such as neuro- and/or renal-toxicity or bone marrow-suppression. Moreover, the binding of cisplatin to proteins and enzymes may modulate its biochemical mechanism of action. While a combination-chemotherapy with cisplatin is a cornerstone for the treatment of multiple cancers, the challenge is that cancer cells could become cisplatin-resistant. Numerous mechanisms of cisplatin resistance were described including changes in cellular uptake, drug efflux, increased detoxification, inhibition of apoptosis and increased DNA repair. To minimize cisplatin resistance, combinatorial therapies were developed and have proven more effective to defeat cancers. Thus, understanding of the biochemical mechanisms triggered by cisplatin in tumor cells may lead to the design of more efficient platinum derivates (or other drugs) and might provide new therapeutic strategies and reduce side effects

  1. Cisplatin as an Anti-Tumor Drug: Cellular Mechanisms of Activity, Drug Resistance and Induced Side Effects

    Energy Technology Data Exchange (ETDEWEB)

    Florea, Ana-Maria [Department of Neuropathology, Heinrich-Heine University, Düsseldorf (Germany); Büsselberg, Dietrich, E-mail: dib2015@qatar-med.cornell.edu [Weil Cornell Medical College in Qatar, Qatar Foundation-Education City, P.O. Box 24144, Doha (Qatar)

    2011-03-15

    Platinum complexes are clinically used as adjuvant therapy of cancers aiming to induce tumor cell death. Depending on cell type and concentration, cisplatin induces cytotoxicity, e.g., by interference with transcription and/or DNA replication mechanisms. Additionally, cisplatin damages tumors via induction of apoptosis, mediated by the activation of various signal transduction pathways, including calcium signaling, death receptor signaling, and the activation of mitochondrial pathways. Unfortunately, neither cytotoxicity nor apoptosis are exclusively induced in cancer cells, thus, cisplatin might also lead to diverse side-effects such as neuro- and/or renal-toxicity or bone marrow-suppression. Moreover, the binding of cisplatin to proteins and enzymes may modulate its biochemical mechanism of action. While a combination-chemotherapy with cisplatin is a cornerstone for the treatment of multiple cancers, the challenge is that cancer cells could become cisplatin-resistant. Numerous mechanisms of cisplatin resistance were described including changes in cellular uptake, drug efflux, increased detoxification, inhibition of apoptosis and increased DNA repair. To minimize cisplatin resistance, combinatorial therapies were developed and have proven more effective to defeat cancers. Thus, understanding of the biochemical mechanisms triggered by cisplatin in tumor cells may lead to the design of more efficient platinum derivates (or other drugs) and might provide new therapeutic strategies and reduce side effects.

  2. Autonomous exoskeleton reduces metabolic cost of human walking during load carriage

    Science.gov (United States)

    2014-01-01

    Background Many soldiers are expected to carry heavy loads over extended distances, often resulting in physical and mental fatigue. In this study, the design and testing of an autonomous leg exoskeleton is presented. The aim of the device is to reduce the energetic cost of loaded walking. In addition, we present the Augmentation Factor, a general framework of exoskeletal performance that unifies our results with the varying abilities of previously developed exoskeletons. Methods We developed an autonomous battery powered exoskeleton that is capable of providing substantial levels of positive mechanical power to the ankle during the push-off region of stance phase. We measured the metabolic energy consumption of seven subjects walking on a level treadmill at 1.5 m/s, while wearing a 23 kg vest. Results During the push-off portion of the stance phase, the exoskeleton applied positive mechanical power with an average across the gait cycle equal to 23 ± 2 W (11.5 W per ankle). Use of the autonomous leg exoskeleton significantly reduced the metabolic cost of walking by 36 ± 12 W, which was an improvement of 8 ± 3% (p = 0.025) relative to the control condition of not wearing the exoskeleton. Conclusions In the design of leg exoskeletons, the results of this study highlight the importance of minimizing exoskeletal power dissipation and added limb mass, while providing substantial positive power during the walking gait cycle. PMID:24885527

  3. Differences in autonomic nerve function in patients with silent and symptomatic myocardial ischaemia.

    Science.gov (United States)

    Shakespeare, C. F.; Katritsis, D.; Crowther, A.; Cooper, I. C.; Coltart, J. D.; Webb-Peploe, M. W.

    1994-01-01

    BACKGROUND--Autonomic neuropathy provides a mechanism for the absence of symptoms in silent myocardial ischaemia, but characterisation of the type of neuropathy is lacking. AIM--To characterise and compare autonomic nerve function in patients with silent and symptomatic myocardial ischaemia. METHODS AND RESULTS--The Valsalva manoeuvre, heart rate variation (HRV) in response to deep breathing and standing, lower body negative pressure, isometric handgrip, and the cold pressor test were performed by patients with silent (n = 25) and symptomatic (n = 25) ambulatory ischaemia and by controls (n = 21). No difference in parasympathetic efferent function between patients with silent and symptomatic ischaemia was recorded, but both had significantly less HRV in response to standing than the controls (p < 0.005 for silent and p < 0.01 for symptomatic). Patients with silent ischaemia showed an increased propensity for peripheral vasodilatation compared with symptomatic patients (p < 0.02) and controls (p < 0.04). Impaired sympathetic function was found in patients with pure silent ischaemia (n = 4) compared with the remaining patients with silent ischaemia whose pain pathways were presumed to be intact. CONCLUSIONS--Patients with silent ischaemia and pain pathways presumed to be intact have an enhanced peripheral vasodilator response, and if this applied to the coronary vasculature it could provide a mechanism for limiting ischaemia to below the pain threshold. Patients with pure silent ischaemia have evidence of sympathetic autonomic dysfunction. Images PMID:8297687

  4. Autonomous power networks based power system

    International Nuclear Information System (INIS)

    Jokic, A.; Van den Bosch, P.P.J.

    2006-01-01

    This paper presented the concept of autonomous networks to cope with this increased complexity in power systems while enhancing market-based operation. The operation of future power systems will be more challenging and demanding than present systems because of increased uncertainties, less inertia in the system, replacement of centralized coordinating activities by decentralized parties and the reliance on dynamic markets for both power balancing and system reliability. An autonomous network includes the aggregation of networked producers and consumers in a relatively small area with respect to the overall system. The operation of an autonomous network is coordinated and controlled with one central unit acting as an interface between internal producers/consumers and the rest of the power system. In this study, the power balance problem and system reliability through provision of ancillary services was formulated as an optimization problem for the overall autonomous networks based power system. This paper described the simulation of an optimal autonomous network dispatching in day ahead markets, based on predicted spot prices for real power, and two ancillary services. It was concluded that large changes occur in a power systems structure and operation, most of them adding to the uncertainty and complexity of the system. The introduced concept of an autonomous power network-based power system was shown to be a realistic and consistent approach to formulate and operate a market-based dispatch of both power and ancillary services. 9 refs., 4 figs

  5. Advancing Autonomous Operations for Deep Space Vehicles

    Science.gov (United States)

    Haddock, Angie T.; Stetson, Howard K.

    2014-01-01

    Starting in Jan 2012, the Advanced Exploration Systems (AES) Autonomous Mission Operations (AMO) Project began to investigate the ability to create and execute "single button" crew initiated autonomous activities [1]. NASA Marshall Space Flight Center (MSFC) designed and built a fluid transfer hardware test-bed to use as a sub-system target for the investigations of intelligent procedures that would command and control a fluid transfer test-bed, would perform self-monitoring during fluid transfers, detect anomalies and faults, isolate the fault and recover the procedures function that was being executed, all without operator intervention. In addition to the development of intelligent procedures, the team is also exploring various methods for autonomous activity execution where a planned timeline of activities are executed autonomously and also the initial analysis of crew procedure development. This paper will detail the development of intelligent procedures for the NASA MSFC Autonomous Fluid Transfer System (AFTS) as well as the autonomous plan execution capabilities being investigated. Manned deep space missions, with extreme communication delays with Earth based assets, presents significant challenges for what the on-board procedure content will encompass as well as the planned execution of the procedures.

  6. Effect of vanadium of mechanical behavior, machinability and wear resistance of aluminium grain refined by Ti+B

    International Nuclear Information System (INIS)

    Zaid, A.I.O.; Hamid, A.A.A.

    1999-01-01

    It is well established that aluminum and its alloys are industrially grain refined by adding either Ti or Ti-B to improve their mechanical behavior and surface finish. In a previous paper, it was found that the grain refining efficiency of aluminum master alloys containing Ti or Ti+B was enhanced by addition of small amounts of other elements including vanadium. V. Therefore, it is anticipated that such an element will improve mechanical behavior, machinability and wear resistance of aluminum and its alloys. In this paper, the effect of vanadium addition, up to 0.3% on mechanical behavior is investigated. Machinability was assessed under different cutting conditions: speed, feed and depth of cut and finally the wear resistance was determined at different loads and speeds. The results indicated that improvement in hardness and mechanical strength were achieved by the addition of V that addition of more than 0.2%V resulted in little or no improvement. Similarly, addition of V resulted in improvement of surface quality under the different cutting conditions of speed, feed and depth of cut, and resistance to wear. However addition of more than 0.2% V resulted in increase of wear rate and change of wear mechanisms. (author)

  7. Cuando nos quedamos solos: Resistir en la incertidumbre Prácticas de emancipación y autonomía When we stay alone: Resist in uncertainty. Emancipation and empowerment practices

    Directory of Open Access Journals (Sweden)

    Ester Jordana Lluch

    2013-03-01

    Full Text Available

    Ante la incertidumbre que nos rodea se plantea la necesidad de resistir en la universidad sin ningún diagnóstico del presente. Sin embargo, podemos partir de las críticas a dos de los rasgos de la universidad moderna que la han caracterizado: autonomía y emancipación. Trataremos de vislumbrar qué prácticas de resistencia puedan tener lugar aquí y ahora, reelaborando críticamente ambos principios a partir de las reflexiones de Jacques Rancière y Michel Foucault.

     

    In view of the uncertainty that surrounds us, there appears the need to resist in the university without any diagnosis of the present. For it, we can depart from the critiques to two of the features that have been characterized the modern university: autonomy and emancipation. We will to try to glimpse what practices of resistance could take place here and now, re-elaborating critically both principles using the reflections of Jacques Rancière and Michel Foucault.

     

  8. Ester-free Thiol-X Resins: New Materials with Enhanced Mechanical Behavior and Solvent Resistance.

    Science.gov (United States)

    Podgórski, Maciej; Becka, Eftalda; Chatani, Shunsuke; Claudino, Mauro; Bowman, Christopher N

    A series of thiol-Michael and radical thiol-ene network polymers were successfully prepared from ester-free as well as ester-containing monomer formulations. Polymerization reaction rates, dynamic mechanical analysis, and solvent resistance experiments were performed and compared between compositions with varied ester loading. The incorporation of ester-free alkyl thiol, vinyl sulfone and allylic monomers significantly improved the mechanical properties when compared with commercial, mercaptopropionate-based thiol-ene or thiol-Michael networks. For polymers with no hydrolytically degradable esters, glass transition temperatures (T g 's) as high as 100 °C were achieved. Importantly, solvent resistance tests demonstrated enhanced stability of ester-free formulations over PETMP-based polymers, especially in concentrated basic solutions. Kinetic analysis showed that glassy step-growth polymers are readily formed at ambient conditions with conversions reaching 80% and higher.

  9. Transcriptional Network Analysis Reveals Drought Resistance Mechanisms of AP2/ERF Transgenic Rice

    Directory of Open Access Journals (Sweden)

    Hongryul Ahn

    2017-06-01

    Full Text Available This study was designed to investigate at the molecular level how a transgenic version of rice “Nipponbare” obtained a drought-resistant phenotype. Using multi-omics sequencing data, we compared wild-type rice (WT and a transgenic version (erf71 that had obtained a drought-resistant phenotype by overexpressing OsERF71, a member of the AP2/ERF transcription factor (TF family. A comprehensive bioinformatics analysis pipeline, including TF networks and a cascade tree, was developed for the analysis of multi-omics data. The results of the analysis showed that the presence of OsERF71 at the source of the network controlled global gene expression levels in a specific manner to make erf71 survive longer than WT. Our analysis of the time-series transcriptome data suggests that erf71 diverted more energy to survival-critical mechanisms related to translation, oxidative response, and DNA replication, while further suppressing energy-consuming mechanisms, such as photosynthesis. To support this hypothesis further, we measured the net photosynthesis level under physiological conditions, which confirmed the further suppression of photosynthesis in erf71. In summary, our work presents a comprehensive snapshot of transcriptional modification in transgenic rice and shows how this induced the plants to acquire a drought-resistant phenotype.

  10. Chromium-modified a-C films with advanced structural, mechanical and corrosive-resistant characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Ming, Miao Yi [International Chinese-Belarusian scientific laboratory on vacuum-plasma technology, Nanjing University of Science and Technology, Nanjing 210094 (China); Francisk Skorina Gomel State University, Gomel 246019 (Belarus); Jiang, Xiaohong, E-mail: jxh0668@sina.com [International Chinese-Belarusian scientific laboratory on vacuum-plasma technology, Nanjing University of Science and Technology, Nanjing 210094 (China); Francisk Skorina Gomel State University, Gomel 246019 (Belarus); Piliptsou, D.G., E-mail: pdg_@mail.ru [International Chinese-Belarusian scientific laboratory on vacuum-plasma technology, Nanjing University of Science and Technology, Nanjing 210094 (China); Francisk Skorina Gomel State University, Gomel 246019 (Belarus); Zhuang, Yuzhao; Rogachev, A.V.; Rudenkov, A.S. [International Chinese-Belarusian scientific laboratory on vacuum-plasma technology, Nanjing University of Science and Technology, Nanjing 210094 (China); Francisk Skorina Gomel State University, Gomel 246019 (Belarus); Balmakou, A. [Faculty of Material Science and Technology, Slovak University of Technology, Trnava 91724 (Slovakia)

    2016-08-30

    Highlights: • Influence of the chromium interlayer on the structure and mechanical properties of a-C:Cr films. • Residual stress and wear of a-C:Cr and Cr/a-C varies due to their phase and surface morphology. • Chromium-modified a-C films with advanced structural, mechanical and corrosive-resistant characteristics. - Abstract: To improve structural, mechanical and chemical properties of diamond-like carbon films, we developed amorphous carbon chromium-modified composite films fabricated by means of cathode magnetic filtered arc deposition. The properties were analyzed by Raman spectroscopy, X-ray photoelectron spectroscopy and atomic force microscopy for the purpose of the structure characterization, elemental analysis and topology examination. Moreover, we also assessed residual stress, the coefficient of friction, hardness, the elastic modulus and corrosion parameters through X-ray double-crystal surface profilometry, tribo-testing, nanoindenter-testing, as well as contact angle measurements and potentiodynamic polarization analysis. As a result of a comparative analysis, we revealed a substantial improvement in the characteristics of developed composite films in comparison with amorphous carbon films. For example, Cr-modification is resulted, in greater integrated performance, toughness and corrosion resistance; the residual stress was reduced substantially.

  11. Autonomous Science Analysis with the New Millennium Program-Autonomous Sciencecraft Experiment

    Science.gov (United States)

    Doggett, T.; Davies, A. G.; Castano, R. A.; Baker, V. R.; Dohm, J. M.; Greeley, R.; Williams, K. K.; Chien, S.; Sherwood, R.

    2002-12-01

    The NASA New Millennium Program (NMP) is a testbed for new, high-risk technologies, including new software and hardware. The Autonomous Sciencecraft Experiment (ASE) will fly on the Air Force Research Laboratory TechSat-21 mission in 2006 is such a NMP mission, and is managed by the Jet Propulsion Laboratory, California Institute of Technology. TechSat-21 consists of three satellites, each equipped with X-band Synthetic Aperture Radar (SAR) that will occupy a 13-day repeat track Earth orbit. The main science objectives of ASE are to demonstrate that process-related change detection and feature identification can be conducted autonomously during space flight, leading to autonomous onboard retargeting of the spacecraft. This mission will observe transient geological and environmental processes using SAR. Examples of geologic processes that may be observed and investigated include active volcanism, the movement of sand dunes and transient features in desert environments, water flooding, and the formation and break-up of lake ice. Science software onboard the spacecraft will allow autonomous processing and formation of SAR images and extraction of scientific information. The subsequent analyses, performed on images formed onboard from the SAR data, will include feature identification using scalable feature "templates" for each target, change detection through comparison of current and archived images, and science discovery, a search for other features of interest in each image. This approach results in obtaining the same science return for a reduced amount of resource use (such as downlink) when compared to that from a mission operating without ASE technology. Redundant data is discarded. The science-driven goals of ASE will evolve during the ASE mission through onboard replanning software that can re-task satellite operations. If necessary, as a result of a discovery made autonomously by onboard science processing, existing observation sequences will be pre-empted to

  12. Autonomous search

    CERN Document Server

    Hamadi, Youssef; Saubion, Frédéric

    2012-01-01

    Autonomous combinatorial search (AS) represents a new field in combinatorial problem solving. Its major standpoint and originality is that it considers that problem solvers must be capable of self-improvement operations. This is the first book dedicated to AS.

  13. Ester-free Thiol-X Resins: New Materials with Enhanced Mechanical Behavior and Solvent Resistance

    OpenAIRE

    Podgórski, Maciej; Becka, Eftalda; Chatani, Shunsuke; Claudino, Mauro; Bowman, Christopher N.

    2015-01-01

    A series of thiol-Michael and radical thiol-ene network polymers were successfully prepared from ester-free as well as ester-containing monomer formulations. Polymerization reaction rates, dynamic mechanical analysis, and solvent resistance experiments were performed and compared between compositions with varied ester loading. The incorporation of ester-free alkyl thiol, vinyl sulfone and allylic monomers significantly improved the mechanical properties when compared with commercial, mercapto...

  14. Ground Operations Autonomous Control and Integrated Health Management

    Science.gov (United States)

    Daniels, James

    2014-01-01

    The Ground Operations Autonomous Control and Integrated Health Management plays a key role for future ground operations at NASA. The software that is integrated into this system is called G2 2011 Gensym. The purpose of this report is to describe the Ground Operations Autonomous Control and Integrated Health Management with the use of the G2 Gensym software and the G2 NASA toolkit for Integrated System Health Management (ISHM) which is a Computer Software Configuration Item (CSCI). The decision rationale for the use of the G2 platform is to develop a modular capability for ISHM and AC. Toolkit modules include knowledge bases that are generic and can be applied in any application domain module. That way, there's a maximization of reusability, maintainability, and systematic evolution, portability, and scalability. Engine modules are generic, while application modules represent the domain model of a specific application. Furthermore, the NASA toolkit, developed since 2006 (a set of modules), makes it possible to create application domain models quickly, using pre-defined objects that include sensors and components libraries for typical fluid, electrical, and mechanical systems.

  15. Molecular epidemiology, antimicrobial susceptibilities and resistance mechanisms of Streptococcus pyogenes isolates resistant to erythromycin and tetracycline in Spain (1994–2006

    Directory of Open Access Journals (Sweden)

    Rubio-López Virginia

    2012-09-01

    Full Text Available Abstract Background Group A Streptococcus (GAS causes human diseases ranging in severity from uncomplicated pharyngitis to life-threatening necrotizing fasciitis and shows high rates of macrolide resistance in several countries. Our goal is to identify antimicrobial resistance in Spanish GAS isolates collected between 1994 and 2006 and to determine the molecular epidemiology (emm/T typing and PFGE and resistance mechanisms of those resistant to erythromycin and tetracycline. Results Two hundred ninety-five out of 898 isolates (32.8% were erythromycin resistant, with the predominance of emm4T4, emm75T25, and emm28T28, accounting the 67.1% of the 21 emm/T types. Spread of emm4T4, emm75T25 and emm28T28 resistant clones caused high rates of macrolide resistance. The distribution of the phenotypes was M (76.9%, cMLSB (20.3%, iMLSB (2.7% with the involvement of the erythromycin resistance genes mef(A (89.5%, msr(D (81.7%, erm(B (37.3% and erm(A (35.9%. Sixty-one isolates were tetracycline resistant, with the main representation of the emm77T28 among 20 emm/T types. To note, the combination of tet(M and tet(O tetracycline resistance genes were similar to tet(M alone reaching values close to 40%. Resistance to both antibiotics was detected in 19 isolates of 7 emm/T types, being emm11T11 and the cMLSB phenotype the most frequent ones. erm(B and tet(M were present in almost all the strains, while erm(A, mef(A, msr(D and tet(O appeared in less than half of them. Conclusions Spanish GAS were highly resistant to macrolides meanwhile showed minor resistance rate to tetracycline. A remarkable correlation between antimicrobial resistance and emm/T type was noticed. Clonal spread of emm4T4, emm75T25 and emm28T28 was the main responsable for macrolide resistance where as that emm77T28 clones were it to tetraclycline resistance. A wide variety of macrolide resistance genes were responsible for three macrolide resistance phenotypes.

  16. Perception, Planning, Control, and Coordination for Autonomous Vehicles

    Directory of Open Access Journals (Sweden)

    Scott Drew Pendleton

    2017-02-01

    Full Text Available Autonomous vehicles are expected to play a key role in the future of urban transportation systems, as they offer potential for additional safety, increased productivity, greater accessibility, better road efficiency, and positive impact on the environment. Research in autonomous systems has seen dramatic advances in recent years, due to the increases in available computing power and reduced cost in sensing and computing technologies, resulting in maturing technological readiness level of fully autonomous vehicles. The objective of this paper is to provide a general overview of the recent developments in the realm of autonomous vehicle software systems. Fundamental components of autonomous vehicle software are reviewed, and recent developments in each area are discussed.

  17. Energy homeostasis, autonomic activity and obesity

    NARCIS (Netherlands)

    Scheurink, AJW; Balkan, B; Nyakas, C; vanDijk, G; Steffens, AB; Bohus, B

    1995-01-01

    Obesity is often accompanied by alterations in both sympathetic and parasympathetic autonomic functions. The present paper summarizes the results of a number of studies designed to investigate autonomic functioning in normal, genetically, and experimentally obese rats, Particular emphasis is given

  18. The role of the autonomic nervous system in hypertension: a bond graph model study

    International Nuclear Information System (INIS)

    Chen, Shuzhen; Gong, Yuexian; Dai, Kaiyong; Sui, Meirong; Yu, Yi; Ning, Gangmin; Zhang, Shaowen

    2008-01-01

    A bond graph model of the cardiovascular system with embedded autonomic nervous regulation was developed for a better understanding of the role of the autonomic nervous system (ANS) in hypertension. The model is described by a pump model of the heart and a detailed representation of the head and neck, pulmonary, coronary, abdomen and extremity circulation. It responds to sympathetic and parasympathetic activities by modifying systemic peripheral vascular resistance, heart rate, ventricular end-systolic elastance and venous unstressed volumes. The impairment of ANS is represented by an elevation of the baroreflex set point. The simulation results show that, compared with normotensive, in hypertension the systolic and diastolic blood pressure (SBP/DBP) rose from 112/77 mmHg to 144/94 mmHg and the left ventricular wall thickness (LVWT) increased from 10 mm to 12.74 mm. In the case that ANS regulation was absent, both the SBP and DBP further increased by 8 mmHg and the LVWT increased to 13.22 mm. The results also demonstrate that when ANS regulation is not severely damaged, e.g. the baroreflex set point is 97 mmHg, it still has an effect in preventing the rapid rise of blood pressure in hypertension; however, with the worsening of ANS regulation, its protective role weakens. The results agree with human physiological and pathological features in hemodynamic parameters and carotid baroreflex function curves, and indicate the role of ANS in blood pressure regulation and heart protection. In conclusion, the present model may provide a valid approach to study the pathophysiological conditions of the cardiovascular system and the mechanism of ANS regulation

  19. Visually induced nausea causes characteristic changes in cerebral, autonomic and endocrine function in humans.

    Science.gov (United States)

    Farmer, Adam D; Ban, Vin F; Coen, Steven J; Sanger, Gareth J; Barker, Gareth J; Gresty, Michael A; Giampietro, Vincent P; Williams, Steven C; Webb, Dominic L; Hellström, Per M; Andrews, Paul L R; Aziz, Qasim

    2015-03-01

    An integrated understanding of the physiological mechanisms involved in the genesis of nausea remains lacking. We aimed to describe the psychophysiological changes accompanying visually induced motion sickness, using a motion video, hypothesizing that differences would be evident between subjects who developed nausea in comparison to those who did not. A motion, or a control, stimulus was presented to 98 healthy subjects in a randomized crossover design. Validated questionnaires and a visual analogue scale (VAS) were used for the assessment of anxiety and nausea. Autonomic and electrogastrographic activity were measured at baseline and continuously thereafter. Plasma vasopressin and ghrelin were measured in response to the motion video. Subjects were stratified into quartiles based on VAS nausea scores, with the upper and lower quartiles considered to be nausea sensitive and resistant, respectively. Twenty-eight subjects were exposed to the motion video during functional neuroimaging. During the motion video, nausea-sensitive subjects had lower normogastria/tachygastria ratio and cardiac vagal tone but higher cardiac sympathetic index in comparison to the control video. Furthermore, nausea-sensitive subjects had decreased plasma ghrelin and demonstrated increased activity of the left anterior cingulate cortex. Nausea VAS scores correlated positively with plasma vasopressin and left inferior frontal and middle occipital gyri activity and correlated negatively with plasma ghrelin and brain activity in the right cerebellar tonsil, declive, culmen, lingual gyrus and cuneus. This study demonstrates that the subjective sensation of nausea is associated with objective changes in autonomic, endocrine and brain networks, and thus identifies potential objective biomarkers and targets for therapeutic interventions. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  20. Cardiovascular autonomic control during short-term thermoneutral and cool head-out immersion.

    Science.gov (United States)

    Mourot, Laurent; Bouhaddi, Malika; Gandelin, Emmanuel; Cappelle, Sylvie; Dumoulin, Gilles; Wolf, Jean-Pierre; Rouillon, Jean Denis; Regnard, Jacques

    2008-01-01

    Moderately cold head-out water immersion stimulates both baro- and cold-receptors, and triggers complex and contradictory effects on the cardiovascular system and its autonomic nervous control. To assess the effects of water immersion and cold on cardiovascular status and related autonomic nervous activity. Hemodynamic variables and indexes of autonomic nervous activity (analysis of heart rate and blood pressure variability) were evaluated in 12 healthy subjects during 3 exposures of 20 min each in the upright position, i.e., in air (AIR, 24-25 degrees C), and during head-out water immersion at 35-36 degrees C (WIn) and 26-27 degrees C (WIc). Plasma noradrenaline, systolic and diastolic blood pressure, and total peripheral resistances were reduced during WIn compared to AIR (263.9 +/- 39.4 vs. 492.5 +/- 35.7 pg x ml(-1), 116.5 +/- 3.7 and 65.4 +/- 1.7 mmHg vs. 140.8 +/- 4.7 and 89.8 +/- 2.8 mmHg, 14.1 +/- 1.0 vs. 16.3 +/- 0.9 mmHg x L(-1) x min, respectively) while they were increased during WIc (530.8 +/- 84.7 pg ml(-1), 148.0 +/- 7.0 mmHg, 80.8 +/- 3.0 mmHg, and 25.8 +/- 1.9 mmHg x L(-1) x min, respectively). The blood pressure variability was reduced to the same extent during WIc and Win compared to AIR. Heart rate decreased during WIn (67.8 +/- 2.7 vs. 81.2 +/- 2.7 bpm during AIR), in parallel with an increased cardiac parasympathetic activity. This pattern was strengthened during WIc (55.3 +/- 2.2 bpm). Thermoneutral WI lowered sympathetic activity and arterial tone, while moderate whole-body skin cooling triggered vascular sympathetic activation. Conversely, both WI and cold triggered cardiac parasympathetic activation, highlighting a complex autonomic control of the cardiovascular system.

  1. Vitamin D in the Spectrum of Prediabetes and Cardiovascular Autonomic Dysfunction.

    Science.gov (United States)

    Dimova, Rumyana; Tankova, Tsvetalina; Chakarova, Nevena

    2017-09-01

    Vitamin D is a fat-soluble secosteroid hormone with pleiotropic effects. 1,25-Dihydroxyvitamin D coordinates the biosynthesis of neurotransmitters in the central nervous system, which regulate cardiovascular autonomic function and may explain its putative role in the development of cardiovascular autonomic neuropathy (CAN). CAN is an independent risk factor for mortality in patients with diabetes and prediabetes and is associated with an increased risk of developing type 2 diabetes and cardiovascular disease. Accumulating data indicate the presence of peripheral nerve injury at these early stages of dysglycemia and its multifactorial pathogenesis. Prediabetes is associated with vitamin D insufficiency. Vitamin D is proposed to prevent the progression of glucose intolerance. The putative underlying mechanisms include maintenance of the intracellular calcium concentration, direct stimulation of insulin receptor expression, and enhancement of the insulin response to glucose transporters. Vitamin D exerts a protective effect on peripheral nerve fibers by decreasing the demyelination process and inducing axonal regeneration. The effects of vitamin D supplementation on glucose tolerance and related autonomic nerve dysfunction have been a recent focus of scientific interest. Although well-designed observational studies are available, the causative relation between vitamin D deficiency, glucose intolerance, and CAN is still debatable. One reason might be that interventional studies are unpersuasive with regard to the beneficial clinical effects of vitamin D supplementation. Because of its favorable side effect profile, vitamin D supplementation might represent an attractive therapeutic option for treating the pandemic prevalence of prediabetes and vitamin D deficiency. Vitamin D supplementation can improve glucose tolerance and cardiovascular autonomic function and can thus reduce cardiovascular mortality among subjects with different stages of glucose intolerance and

  2. Resistance mechanisms to plant viruses: an overview

    NARCIS (Netherlands)

    Goldbach, R.W.; Bucher, E.C.; Prins, A.H.

    2003-01-01

    To obtain virus-resistant host plants, a range of operational strategies can be followed nowadays. While for decades plant breeders have been able to introduce natural resistance genes in susceptible genotypes without knowing precisely what these resistance traits were, currently a growing number of

  3. Glass-ceramics frits for high mechanical resistance glazes

    International Nuclear Information System (INIS)

    Gajek, M.; Lis, J.; Partyka, J.; Wojczyk, M.

    2004-01-01

    The obtaining and application of glass-ceramics frits for glazes were discussed by many authors. This glazes are characterized by raised mechanical parameters and chemical resistance. Factors, that determines crystallization process are initial composition, heat treatment and nucleation agents. The kind of crystalline phases, crystal habit and the content of residual glass phase play the decisive role in the strengthening of the glaze. In this paper are shown results of investigation over controlled crystallization in the ternary systems; Li 2 O-Al 2 O 3 -SiO 2 , CaO-Al 2 O 3 -SiO 2 , ZnO-Al 2 O 3 -SiO 2 , MgO-Al 2 O 3 -SiO 2 , with or without nucleation agents. (author)

  4. Mycoplasma bovis: Mechanisms of Resistance and Trends in Antimicrobial Susceptibility.

    Science.gov (United States)

    Lysnyansky, Inna; Ayling, Roger D

    2016-01-01

    Mycoplasma bovis is a cell-wall-less bacterium and belongs to the class Mollicutes. It is the most important etiological agent of bovine mycoplasmoses in North America and Europe, causing respiratory disease, mastitis, otitis media, arthritis, and reproductive disease. Clinical disease associated with M. bovis is often chronic, debilitating, and poorly responsive to antimicrobial therapy, resulting in significant economic loss, the full extent of which is difficult to estimate. Until M. bovis vaccines are universally available, sanitary control measures and antimicrobial treatment are the only approaches that can be used in attempts to control M. bovis infections. However, in vitro studies show that many of the current M. bovis isolates circulating in Europe have high minimum inhibitory concentrations (MIC) for many of the commercially available antimicrobials. In this review we summarize the current MIC trends indicating the development of antimicrobial resistance in M. bovis as well as the known molecular mechanisms by which resistance is acquired.

  5. Mycoplasma bovis: mechanisms of resistance and trends in antimicrobial susceptibility

    Directory of Open Access Journals (Sweden)

    Inna eLysnyansky

    2016-04-01

    Full Text Available Mycoplasma bovis is a cell-wall-less bacterium and belongs to the class Mollicutes. It is the most important etiological agent of bovine mycoplasmoses in North America and Europe, causing respiratory disease, mastitis, otitis media, arthritis, and reproductive disease. Clinical disease associated with M. bovis is often chronic, debilitating, and poorly responsive to antimicrobial therapy, resulting in significant economic loss, the full extent of which is difficult to estimate. Until M. bovis vaccines are universally available, sanitary control measures and antimicrobial treatment are the only approaches that can be used in attempts to control M. bovis infections. However, in vitro studies show that many of the current M. bovis isolates circulating in Europe have high minimum inhibitory concentrations (MIC for many of the commercially available antimicrobials. In this review we summarize the current MIC trends indicating the development of antimicrobial resistance in M. bovis as well as the known molecular mechanisms by which resistance is acquired.

  6. Towards mechanisms-guided resistivity-based monitoring of damage evolution in laminated composites

    KAUST Repository

    Lubineau, Gilles

    2013-04-05

    A convenient health monitoring technique for detecting degradation in laminated composite is to monitor the change of electrical resistance along multiple conduction paths within the structure. Yet, the relations between the global modification of resistivity and the exact underlying damage map is still unclear that makes diffcult to interpret these nondestructive-testing results. The challenge is then to be able to reconstruct from these global observation the underlying damage map. This is even more diffcult due to the numerous underlying damage mechanisms that can take place either at the inter laminar of intra laminar level. This paper intends to provide some preliminary insights about strategies to recover the damage state based only on global measurements. We focus here on transverse cracking detection. We introduce the homogenization process that defines at the meso scale an equivalent homogeneous ply that is energetically equivalent to the cracked one. This can be used as a first tool to reconstruct damage maps based on global resistivity measurements.

  7. Comparison of three control methods for an autonomous vehicle

    Science.gov (United States)

    Deshpande, Anup; Mathur, Kovid; Hall, Ernest

    2010-01-01

    The desirability and challenge of developing a completely autonomous vehicle and the rising need for more efficient use of energy by automobiles motivate this research- a study for an optimum solution to computer control of energy efficient vehicles. The purpose of this paper is to compare three control methods - mechanical, hydraulic and electric that have been used to convert an experimental all terrain vehicle to drive by wire which would eventually act as a test bed for conducting research on various technologies for autonomous operation. Computer control of basic operations in a vehicle namely steering, braking and speed control have been implemented and will be described in this paper. The output from a 3 axis motion controller is used for this purpose. The motion controller is interfaced with a software program using WSDK (Windows Servo Design Kit) as an intermediate tuning layer for tuning and parameter settings in autonomous operation. The software program is developed in C++. The voltage signal sent to the motion controller can be varied through the control program for desired results in controlling the steering motor, activating the hydraulic brakes and varying the vehicle's speed. The vehicle has been tested for its basic functionality which includes testing of street legal operations and also a 1000 mile test while running in a hybrid mode. The vehicle has also been tested for control when it is interfaced with devices such as a keyboard, joystick and sensors under full autonomous operation. The vehicle is currently being tested in various safety studies and is being used as a test bed for experiments in control courses and research studies. The significance of this research is in providing a greater understanding of conventional driving controls and the possibility of improving automobile safety by removing human error in control of a motor vehicle.

  8. Research Institute for Autonomous Precision Guided Systems

    National Research Council Canada - National Science Library

    Rogacki, John R

    2007-01-01

    ... vehicles, cooperative flight of autonomous aerial vehicles using GPS and vision information, cooperative and sharing of information in search missions involving multiple autonomous agents, multi-scale...

  9. Modeling the autonomic and metabolic effects of obstructive sleep apnea: A simulation study.

    Directory of Open Access Journals (Sweden)

    Limei eCheng

    2012-01-01

    Full Text Available Long term exposure to intermittent hypoxia and sleep fragmentation introduced by recurring obstructive sleep apnea has been linked to subsequent cardiovascular disease and Type 2 diabetes. The underlying mechanisms remain unclear, but impairment of the normal interactions among the systems that regulate autonomic and metabolic function is likely involved. We have extended an existing integrative model of respiratory, cardiovascular and sleep-wake state control, to incorporate a sub-model of glucose-insulin-fatty acid regulation. This computational model is capable of simulating the complex dynamics of cardiorespiratory control, chemoreflex and state-related control of breath-to-breath ventilation, state-related and chemoreflex control of upper airway potency, respiratory and circulatory mechanics, as well as the metabolic control of glucose insulin dynamics and its interactions with the autonomic control. The interactions between autonomic and metabolic control include the circadian regulation of epinephrine secretion, epinephrine regulation on dynamic fluctuations in glucose and free-fatty acid in plasma, metabolic coupling among tissues and organs provided by insulin and epinephrine, as well as the effect of insulin on peripheral vascular sympathetic activity. These model simulations provide insight into the relative importance of the various mechanisms that determine the acute and chronic physiological effects of sleep-disordered breathing. The model can also be used to investigate the effects of a variety of interventions, such as different glucose clamps, the intravenous glucose tolerance test and the application of continuous positive airway pressure on obstructive sleep apnea subjects. As such, this model provides the foundation on which future efforts to simulate disease progression and the long-term effects of pharmacological intervention can be based.

  10. Adaptive Control Allocation for Fault Tolerant Overactuated Autonomous Vehicles

    Science.gov (United States)

    2007-11-01

    Tolerant Overactuated Autonomous Vehicles Casavola, A.; Garone, E. (2007) Adaptive Control Allocation for Fault Tolerant Overactuated Autonomous ...Adaptive Control Allocation for Fault Tolerant Overactuated Autonomous Vehicles 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...Tolerant Overactuated Autonomous Vehicles 3.2 - 2 RTO-MP-AVT-145 UNCLASSIFIED/UNLIMITED Control allocation problem (CAP) - Given a virtual input v(t

  11. Overfeeding, autonomic regulation and metabolic consequences.

    NARCIS (Netherlands)

    Scheurink, A.J.W.; Balkan, B; Strubbe, J.H.; van Dijk, G.; Steffens, A.B

    The autonomic nervous system plays an important role in the regulation of body processes in health and disease. Overfeeding and obesity (a disproportional increase of the fat mass of the body) are often accompanied by alterations in both sympathetic and parasympathetic autonomic functions. The

  12. Autonomic dysfunction in different subtypes of multiple system atrophy.

    Science.gov (United States)

    Schmidt, Claudia; Herting, Birgit; Prieur, Silke; Junghanns, Susann; Schweitzer, Katherine; Globas, Christoph; Schöls, Ludger; Reichmann, Heinz; Berg, Daniela; Ziemssen, Tjalf

    2008-09-15

    Multiple system atrophy (MSA) can clinically be divided into the cerebellar (MSA-C) and the parkinsonian (MSA-P) variant. However, till now, it is unknown whether autonomic dysfunction in these two entities differs regarding severity and profile. We compared the pattern of autonomic dysfunction in 12 patients with MSA-C and 26 with MSA-P in comparison with 27 age- and sex-matched healthy controls using a standard battery of autonomic function tests and a structured anamnesis of the autonomic nervous system. MSA-P patients complained significantly more often about the symptoms of autonomic dysfunctions than MSA-C patients, especially regarding vasomotor, secretomotor, and gastrointestinal subsystems. However, regarding cardiovascular, sudomotor pupil, urogenital, and sleep subsystems, there were no significant quantitative or qualitative differences as analyzed by autonomic anamnesis and testing. Our results suggest that there are only minor differences in the pattern of autonomic dysfunction between the two clinical MSA phenotypes. (c) 2007 Movement Disorder Society.

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

    Directory of Open Access Journals (Sweden)

    Flávia Regina da Costa

    2014-02-01

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

  14. Network analysis of S. aureus response to ramoplanin reveals modules for virulence factors and resistance mechanisms and characteristic novel genes.

    Science.gov (United States)

    Subramanian, Devika; Natarajan, Jeyakumar

    2015-12-10

    Staphylococcus aureus is a major human pathogen and ramoplanin is an antimicrobial attributed for effective treatment. The goal of this study was to examine the transcriptomic profiles of ramoplanin sensitive and resistant S. aureus to identify putative modules responsible for virulence and resistance-mechanisms and its characteristic novel genes. The dysregulated genes were used to reconstruct protein functional association networks for virulence-factors and resistance-mechanisms individually. Strong link between metabolic-pathways and development of virulence/resistance is suggested. We identified 15 putative modules of virulence factors. Six hypothetical genes were annotated with novel virulence activity among which SACOL0281 was discovered to be an essential virulence factor EsaD. The roles of MazEF toxin-antitoxin system, SACOL0202/SACOL0201 two-component system and that of amino-sugar and nucleotide-sugar metabolism in virulence are also suggested. In addition, 14 putative modules of resistance mechanisms including modules of ribosomal protein-coding genes and metabolic pathways such as biotin-synthesis, TCA-cycle, riboflavin-biosynthesis, peptidoglycan-biosynthesis etc. are also indicated. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. The nanocoherer: an electrically and mechanically resettable resistive switching device based on gold clusters assembled on paper

    Science.gov (United States)

    Minnai, Chloé; Mirigliano, Matteo; Brown, Simon A.; Milani, Paolo

    2018-03-01

    We report the realization of a resettable resistive switching device based on a nanostructured film fabricated by supersonic cluster beam deposition of gold clusters on plain paper substrates. Through the application of suitable voltage ramps, we obtain, in the same device, either a complex pattern of resistive switchings, or reproducible and stable switchings between low resistance and high resistance states, with an amplitude up to five orders of magnitude. Our device retains a state of internal resistance following the history of the applied voltage similar to that reported for memristors. The two different switching regimes in the same device are both stable, the transition between them is reversible, and it can be controlled by applying voltage ramps or by mechanical deformation of the substrate. The device behavior can be related to the formation, growth and breaking of junctions between the loosely aggregated gold clusters forming the nanostructured films. The fact that our cluster-assembled device is mechanically resettable suggests that it can be considered as the analog of the coherer: a switching device based on metallic powders used for the first radio communication system.

  16. Mechanical Properties and Thermal Shock Resistance Analysis of BNNT/Si3N4 Composites

    Science.gov (United States)

    Wang, Shouren; Wang, Gaoqi; Wen, Daosheng; Yang, Xuefeng; Yang, Liying; Guo, Peiquan

    2018-04-01

    BNNT/Si3N4 ceramic composites with different weight amount of BNNT fabricated by hot isostatic pressing were introduced. The mechanical properties and thermal shock resistance of the composites were investigated. The results showed that BNNT-added ceramic composites have a finer and more uniform microstructure than that of BNNT-free Si3N4 ceramic because of the retarding effect of BNNT on Si3N4 grain growth. The addition of 1.5 wt.% BNNT results in simultaneous increase in flexural strength, fracture toughness, and thermal shock resistance. The analysis of the results indicates that BNNT brings many thermal transport channels in the microstructure, increasing the efficiency of thermal transport, therefore results in increase of thermal shock resistance. In addition, BNNT improves the residual flexural strength of composites by crack deflection, bridging, branching and pinning, which increase the crack propagation resistance.

  17. The Bering Autonomous Target Detection

    DEFF Research Database (Denmark)

    Jørgensen, John Leif; Denver, Troelz; Betto, Maurizio

    2003-01-01

    An autonomous asteroid target detection and tracking method has been developed. The method features near omnidirectionality and focus on high speed operations and completeness of search of the near space rather than the traditional faint object search methods, employed presently at the larger...... telescopes. The method has proven robust in operation and is well suited for use onboard spacecraft. As development target for the method and the associated instrumentation the asteroid research mission Bering has been used. Onboard a spacecraft, the autonomous detection is centered around the fully...... autonomous star tracker the Advanced Stellar Compass (ASC). One feature of this instrument is that potential targets are registered directly in terms of date, right ascension, declination, and intensity, which greatly facilitates both tracking search and registering. Results from ground and inflight tests...

  18. A biorobotic pectoral fin for autonomous undersea vehicles.

    Science.gov (United States)

    Tangorra, James L; Davidson, S Naomi; Madden, Peter G; Lauder, George V; Hunter, Ian W

    2006-01-01

    A biorobotic fin for autonomous undersea vehicles (AUVs) was developed based on studies of the anatomy, kinematics, and hydrodynamics of the bluegill sunfish pectoral fin. The biorobotic fin was able to produce many of the complex fin motions used by the sunfish during steady swimming and was used to investigate mechanisms of thrust production and control. This biorobotic fin is an excellent experimental tool and is an important first step towards developing propulsive devices that give AUVs maneuvering characteristics that match and exceed those of highly maneuverable fish.

  19. Recent Developments on Microencapsulation for Autonomous Corrosion Protection

    Science.gov (United States)

    Calle, Luz M.; Li, Wenyan; Buhrow, Jerry W.; Fitzpatrick, Lilliana; Jolley, Scott T.; Surma, Jan M.; Pearman, Benjamin P.; Zhang, Xuejun

    2014-01-01

    This work concerns recent progress in the development of a multifunctional smart coating based on microencapsulation for the autonomous control of corrosion. Microencapsulation allows the incorporation of desired corrosion control functionalities, such as early corrosion detection and inhibition through corrosion controlled release of corrosion indicators and inhibitors, as well as self-healing agent release when mechanical damage occurs.While proof-of-concept results have been reported previously, more recent efforts have been concentrated in technical developments to improve coating compatibility, synthesis procedure scalability, as well as fine tuning the release property of encapsulated active agents.

  20. BRAF-mutant melanoma: treatment approaches, resistance mechanisms, and diagnostic strategies

    Directory of Open Access Journals (Sweden)

    Spagnolo F

    2015-01-01

    Full Text Available Francesco Spagnolo,1 Paola Ghiorzo,2,3 Laura Orgiano,4 Lorenza Pastorino,2,3 Virginia Picasso,4 Elena Tornari,4 Vincenzo Ottaviano,4 Paola Queirolo4 1Department of Plastic and Reconstructive Surgery, IRCCS Azienda Ospedaliera Universitaria San Martino, IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy; 2Department of Internal Medicine and Medical Specialties (DiMI, University of Genoa, Genova, Italy; 3Genetics of Rare Cancers, IRCCS Azienda Ospedaliera Universitaria San Martino, IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy; 4Department of Medical Oncology, IRCCS Azienda Ospedaliera Universitaria San Martino, IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy Abstract: BRAF inhibitors vemurafenib and dabrafenib achieved improved overall survival over chemotherapy and have been approved for the treatment of BRAF-mutated metastatic melanoma. More recently, the combination of BRAF inhibitor dabrafenib with MEK inhibitor trametinib has shown improved progression-free survival, compared to dabrafenib monotherapy, in a Phase II study and has received approval by the US Food and Drug Administration. However, even when treated with the combination, most patients develop mechanisms of acquired resistance, and some of them do not achieve tumor regression at all, because of intrinsic resistance to therapy. Along with the development of BRAF inhibitors, immunotherapy made an important step forward: ipilimumab, an anti-CTLA-4 monoclonal antibody, was approved for the treatment of metastatic melanoma; anti-PD-1 agents achieved promising results in Phase I/II trials, and data from Phase III studies will be ready soon. The availability of such drugs, which are effective regardless of BRAF status, has made the therapeutic approach more complex, as first-line treatment with BRAF inhibitors may not be the best choice for all BRAF-mutated patients. The aim of this paper is to review the systemic therapeutic options

  1. Autonomic Dysfunction in Patients with Mild to Moderate Alzheimer's Disease

    DEFF Research Database (Denmark)

    Jensen-Dahm, Christina; Waldemar, Gunhild; Staehelin Jensen, Troels

    2015-01-01

    BACKGROUND: Autonomic function has received little attention in Alzheimer's disease (AD). AD pathology has an impact on brain regions which are important for central autonomic control, but it is unclear if AD is associated with disturbance of autonomic function. OBJECTIVE: To investigate autonomic...

  2. Wear Resistance and Mechanical Behaviour of Epoxy/Mollusk Shell Biocomposites developed for Structural Applications

    Directory of Open Access Journals (Sweden)

    I.O. Oladele

    2016-09-01

    Full Text Available Epoxy resin is one of the strongest commercially exploitable thermosetting polymers in the polymer family; however its expensive nature in comparison with other thermosetting polymers such as vinylester and polyester limits its applications as a structural material. Inexpensive fillers on the other hand, especially those derived from agro-industrial wastes are very important in reducing the overall cost of polymer composites and furthermore influential in enhancing some of their engineering properties. In the present study, the wear resistance and mechanical behaviour of epoxy polymer matrix filled with <75 and 75 μm calcined particles of African land snail shells have been comparatively investigated. The wear resistance and the mechanical behaviour of the composites were studied via Taber Abraser and INSTRON universal testing machine. Also, the elemental constituents of the calcined snail shell and the epoxy biocomposites were characterized by X-Ray Fluorescence Spectroscopy and Scanning Electron Microscopy/Energy Dispersion Spectroscopy. From the experimental results, it was observed that, at the highest filler loading, smaller particle size presented a biocomposite with significant enhancement in wear and mechanical properties. However, it was also observed that increase in particle size showed no significant enhancement in the mechanical properties of the biocomposites.

  3. Development of a resilient mechanical sealing solution to resist electro corrosion in ultrapure feedwater applications

    Energy Technology Data Exchange (ETDEWEB)

    Loenhout, Gerard van [Flowservice Flow Solutions Division, Etten-Leur (Netherlands); Enders, Klaus; Schmerberg, Rainer [Vattenfall Europe Generation AG, Peitz (Germany)

    2012-11-01

    Ever since the introduction of mechanical seals on high speed boiler feed pumps in the sixties, mechanical seals have proven to be a reliable, cost effective sealing method. However, since the introduction of combined water treatment chemistry used in today's modern fossil-fuelled power stations, keeping mechanical seal reliability high, became a challenge. A pragmatic approach is presented. A resilient sealing solution was developed to resist electro corrosion for such critical feed water pumps. (orig.)

  4. Advanced Autonomous Systems for Space Operations

    Science.gov (United States)

    Gross, A. R.; Smith, B. D.; Muscettola, N.; Barrett, A.; Mjolssness, E.; Clancy, D. J.

    2002-01-01

    New missions of exploration and space operations will require unprecedented levels of autonomy to successfully accomplish their objectives. Inherently high levels of complexity, cost, and communication distances will preclude the degree of human involvement common to current and previous space flight missions. With exponentially increasing capabilities of computer hardware and software, including networks and communication systems, a new balance of work is being developed between humans and machines. This new balance holds the promise of not only meeting the greatly increased space exploration requirements, but simultaneously dramatically reducing the design, development, test, and operating costs. New information technologies, which take advantage of knowledge-based software, model-based reasoning, and high performance computer systems, will enable the development of a new generation of design and development tools, schedulers, and vehicle and system health management capabilities. Such tools will provide a degree of machine intelligence and associated autonomy that has previously been unavailable. These capabilities are critical to the future of advanced space operations, since the science and operational requirements specified by such missions, as well as the budgetary constraints will limit the current practice of monitoring and controlling missions by a standing army of ground-based controllers. System autonomy capabilities have made great strides in recent years, for both ground and space flight applications. Autonomous systems have flown on advanced spacecraft, providing new levels of spacecraft capability and mission safety. Such on-board systems operate by utilizing model-based reasoning that provides the capability to work from high-level mission goals, while deriving the detailed system commands internally, rather than having to have such commands transmitted from Earth. This enables missions of such complexity and communication` distances as are not

  5. Characterization of the abomasal transcriptome for mechanisms of resistance to gastrointestinal nematodes in cattle

    Science.gov (United States)

    2011-01-01

    The response of the abomasal transcriptome to gastrointestinal parasites was evaluated in parasite-susceptible and parasite-resistant Angus cattle using RNA-seq at a depth of 23.7 million sequences per sample. These cattle displayed distinctly separate resistance phenotypes as assessed by fecal egg counts. Approximately 65.3% of the 23 632 bovine genes were expressed in the fundic abomasum. Of these, 13 758 genes were expressed in all samples tested and likely represent core components of the bovine abomasal transcriptome. The gene (BT14427) with the most abundant transcript, accounting for 10.4% of sequences in the transcriptome, is located on chromosome 29 and has unknown functions. Additionally, PIGR (1.6%), Complement C3 (0.7%), and Immunoglobulin J chain (0.5%) were among the most abundant transcripts in the transcriptome. Among the 203 genes impacted, 64 were significantly over-expressed in resistant animals at a stringent cutoff (FDR parasite resistance in cattle. Our results provide insights into the development of host immunity to gastrointestinal nematode infection and will facilitate understanding of mechanism underlying host resistance. PMID:22129081

  6. A Primer on Autonomous Aerial Vehicle Design.

    Science.gov (United States)

    Coppejans, Hugo H G; Myburgh, Herman C

    2015-12-02

    There is a large amount of research currently being done on autonomous micro-aerial vehicles (MAV), such as quadrotor helicopters or quadcopters. The ability to create a working autonomous MAV depends mainly on integrating a simultaneous localization and mapping (SLAM) solution with the rest of the system. This paper provides an introduction for creating an autonomous MAV for enclosed environments, aimed at students and professionals alike. The standard autonomous system and MAV automation are discussed, while we focus on the core concepts of SLAM systems and trajectory planning algorithms. The advantages and disadvantages of using remote processing are evaluated, and recommendations are made regarding the viability of on-board processing. Recommendations are made regarding best practices to serve as a guideline for aspirant MAV designers.

  7. Cyber Security Considerations for Autonomous Tactical Wheeled Vehicles

    Science.gov (United States)

    2016-04-01

    Update Will Enable Autonomous Driving. Retrieved August 6, 2015, from http://spectrum.ieee.org/: http://spectrum.ieee.org/ cars -that-think...Cyber Security Considerations for Autonomous Tactical Wheeled Vehicles 1 UNCLASSIFIED Cyber Security Considerations for... Autonomous Tactical Wheeled Vehicles Sebastian C Iovannitti 4/1/2016 Submitted to Lawrence Technological University College of Management in

  8. Investigation of the electroforming and resistive switching mechanisms in Fe-doped SrTiO{sub 3} thin films

    Energy Technology Data Exchange (ETDEWEB)

    Menke, Tobias

    2009-11-27

    To overcome the physical limits of todays memory technologies new concepts are needed. The resistive random access memory (RRAM), which bases on a nonvolatile and repeatable change of the resistance by external electrical stimuli, seems to be one promising candidate. Within the scope of this work, the model system Strontium titanate (SrTiO{sub 3}) has been investigated to get a deeper understanding of the underlying physical mechanism related to the resistance change. The electrical properties of SrTiO{sub 3} (STO) can be modulated from a band insulator to metallic conduction by a self-doping with oxygen vacancies which act as shallow donors. A local accumulation or depletion of oxygen vacancies at the vicinity of the surface will lead to a local redox process which is responsible for the resistance change. To study the influence of the interfaces on the switching properties of SrTiO{sub 3} thin films, epitaxial films of Fe-doped SrTiO{sub 3} were grown on different bottom electrodes (SrRuO{sub 3}, LaNiO{sub 3} und Nb:STO) by a ''Pulsed Laser Deposition'' technique. An atomic force microscope equipped with a conductive tip (LC-AFM) allowed studying the conductivity of the deposited films on the nanometer scale. Resistive switching of lateral structures smaller than {proportional_to}5 nm could be realized which represents the potential of this material for a further downscaling of RRAM devices. The deposition of top electrodes, made of Platinum or Titanium, allowed the electrical characterization of metal-insulator-metal (MIM) structures. An extensive investigation of pristine MIM-devices by impedance spectroscopy showed the big impact of the metal-insulator interface on the overall device resistance. Furthermore, a chemical polarization was studied by dynamical current sweeps and identified as a volatile resistance variation. Usually a forming procedure is needed to ''enable'' the resistive switching properties in MIM devices

  9. Functional Characterization of Bacteria Isolated from Ancient Arctic Soil Exposes Diverse Resistance Mechanisms to Modern Antibiotics

    Science.gov (United States)

    Perron, Gabriel G.; Whyte, Lyle; Turnbaugh, Peter J.; Goordial, Jacqueline; Hanage, William P.; Dantas, Gautam; Desai, Michael M.

    2015-01-01

    Using functional metagenomics to study the resistomes of bacterial communities isolated from different layers of the Canadian high Arctic permafrost, we show that microbial communities harbored diverse resistance mechanisms at least 5,000 years ago. Among bacteria sampled from the ancient layers of a permafrost core, we isolated eight genes conferring clinical levels of resistance against aminoglycoside, β-lactam and tetracycline antibiotics that are naturally produced by microorganisms. Among these resistance genes, four also conferred resistance against amikacin, a modern semi-synthetic antibiotic that does not naturally occur in microorganisms. In bacteria sampled from the overlaying active layer, we isolated ten different genes conferring resistance to all six antibiotics tested in this study, including aminoglycoside, β-lactam and tetracycline variants that are naturally produced by microorganisms as well as semi-synthetic variants produced in the laboratory. On average, we found that resistance genes found in permafrost bacteria conferred lower levels of resistance against clinically relevant antibiotics than resistance genes sampled from the active layer. Our results demonstrate that antibiotic resistance genes were functionally diverse prior to the anthropogenic use of antibiotics, contributing to the evolution of natural reservoirs of resistance genes. PMID:25807523

  10. Spontaneous bacteriocin resistance in Listeria monocytogenes as a susceptibility screen for identifying different mechanisms of resistance and modes of action by bacteriocins of lactic acid bacteria.

    Science.gov (United States)

    Macwana, Sunita; Muriana, Peter M

    2012-01-01

    A practical system was devised for grouping bacteriocins of lactic acid bacteria (LAB) based on mode of action as determined by changes in inhibitory activity to spontaneously-acquired bacteriocin resistance (Bac(R)). Wild type Listeria monocytogenes 39-2 was sensitive to five bacteriocins produced by 3 genera of LAB: pediocin PA-1 and pediocin Bac3 (Pediococcus), lacticin FS97 and lacticin FS56 (Lactococcus), and curvaticin FS47 (Lactobacillus). A spontaneous Bac(R) derivative of L. monocytogenes 39-2 obtained by selective recovery against lacticin FS56 provided complete resistance to the bacteriocin made by Lactococcus lactis FS56. The lacticin FS56-resistant strain of L. monocyotgenes 39-2 was also cross-resistant to curvaticin FS47 and pediocin PA-1, but not to lacticin FS97 or pediocin Bac3. The same pattern of cross-resistance was also observed with Bac(R) isolates obtained with L. monocytogenes Scott A-2. A spontaneous mutation that renders a strain cross-resistant to different bacteriocins indicates that they share a common mechanism of resistance due to similar modes of action of the bacteriocins. Spontaneous resistance was acquired to other bacteriocins (in aggregate) by following the same procedure against which the Bac(R) strain was still sensitive. In subsequent challenge assays, mixtures of bacteriocins of different modes of action provided greater inhibition than mixtures of bacteriocins of the same mode of action (as determined by our screening method). This study identifies a methodical approach to classify bacteriocins into functional groups based on mechanism of resistance (i.e., mode of action) that could be used for identifying the best mixture of bacteriocins for use as biopreservatives. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Non-equilibrium assembly of microtubules: from molecules to autonomous chemical robots.

    Science.gov (United States)

    Hess, H; Ross, Jennifer L

    2017-09-18

    Biological systems have evolved to harness non-equilibrium processes from the molecular to the macro scale. It is currently a grand challenge of chemistry, materials science, and engineering to understand and mimic biological systems that have the ability to autonomously sense stimuli, process these inputs, and respond by performing mechanical work. New chemical systems are responding to the challenge and form the basis for future responsive, adaptive, and active materials. In this article, we describe a particular biochemical-biomechanical network based on the microtubule cytoskeletal filament - itself a non-equilibrium chemical system. We trace the non-equilibrium aspects of the system from molecules to networks and describe how the cell uses this system to perform active work in essential processes. Finally, we discuss how microtubule-based engineered systems can serve as testbeds for autonomous chemical robots composed of biological and synthetic components.

  12. Exact Solutions for Certain Nonlinear Autonomous Ordinary Differential Equations of the Second Order and Families of Two-Dimensional Autonomous Systems

    Directory of Open Access Journals (Sweden)

    M. P. Markakis

    2010-01-01

    Full Text Available Certain nonlinear autonomous ordinary differential equations of the second order are reduced to Abel equations of the first kind ((Ab-1 equations. Based on the results of a previous work, concerning a closed-form solution of a general (Ab-1 equation, and introducing an arbitrary function, exact one-parameter families of solutions are derived for the original autonomous equations, for the most of which only first integrals (in closed or parametric form have been obtained so far. Two-dimensional autonomous systems of differential equations of the first order, equivalent to the considered herein autonomous forms, are constructed and solved by means of the developed analysis.

  13. Simvastatin-induced cardiac autonomic control improvement in fructose-fed female rats

    Directory of Open Access Journals (Sweden)

    Renata Juliana da Silva

    2011-01-01

    Full Text Available OBJECTIVE: Because autonomic dysfunction has been found to lead to cardiometabolic disorders and because studies have reported that simvastatin treatment has neuroprotective effects, the objective of the present study was to investigate the effects of simvastatin treatment on cardiovascular and autonomic changes in fructose-fed female rats. METHODS: Female Wistar rats were divided into three groups: controls (n=8, fructose (n=8, and fructose+ simvastatin (n=8. Fructose overload was induced by supplementing the drinking water with fructose (100 mg/L, 18 wks. Simvastatin treatment (5 mg/kg/day for 2 wks was performed by gavage. The arterial pressure was recorded using a data acquisition system. Autonomic control was evaluated by pharmacological blockade. RESULTS: Fructose overload induced an increase in the fasting blood glucose and triglyceride levels and insulin resistance. The constant rate of glucose disappearance during the insulin intolerance test was reduced in the fructose group (3.4+ 0.32%/min relative to that in the control group (4.4+ 0.29%/min. Fructose+simvastatin rats exhibited increased insulin sensitivity (5.4+0.66%/min. The fructose and fructose+simvastatin groups demonstrated an increase in the mean arterial pressure compared with controls rats (fructose: 124+2 mmHg and fructose+simvastatin: 126 + 3 mmHg vs. controls: 112 + 2 mmHg. The sympathetic effect was enhanced in the fructose group (73 + 7 bpm compared with that in the control (48 + 7 bpm and fructose+simvastatin groups (31+8 bpm. The vagal effect was increased in fructose+simvastatin animals (84 + 7 bpm compared with that in control (49 + 9 bpm and fructose animals (46+5 bpm. CONCLUSION: Simvastatin treatment improved insulin sensitivity and cardiac autonomic control in an experimental model of metabolic syndrome in female rats. These effects were independent of the improvements in the classical plasma lipid profile and of reductions in arterial pressure. These results

  14. [Macrolide-resistant Streptococcus pneumoniae on the islands of Gran Canaria and Lanzarote (Spain): molecular mechanisms and serogroup relationships].

    Science.gov (United States)

    Artiles, Fernando; Horcajada-Herrera, Iballa; Noguera-Catalán, Javier; Alamo-Antúnez, Isabel; Bordes-Benítez, Ana; Lafarga-Capuz, Bernardo

    2007-11-01

    Macrolide resistance in Streptococcus pneumoniae is coded by the ermB and mefA/E genes. The aim of this study was to determine the status of macrolide-resistance, the molecular mechanisms involved, the serogroup relationships, and the level of co-resistance in S. pneumoniae isolates from Gran Canaria and Lanzarote, in the Canary Islands, Spain. Macrolide resistance phenotypes were investigated in 261 S. pneumoniae clinical isolates over a two-year period (2004 and 2005). Genotypes were determined by PCR (detection of ermB and mefA/E genes). Overall macrolide resistance was 40.6% (106 isolates); 79.2% (84) of resistant isolates presented the MLSB phenotype (98.8% harbored the ermB gene), with a predominance of serogroup 19, and 20.8% (22) presented the M phenotype (77.3% displayed the mefA/E gene), all associated with serogroup 14. Worthy of note, the M phenotype was found in 8 invasive isolates from Lanzarote (80%) all from serogroup 14. The ermB and mefA/E genes were detected in 7 isolates belonging to serogroup 19. Absence of co-resistance was observed most frequently in serogroup 14 (66.7%). Co-resistance with penicillin G, tetracycline, and trimethoprim-sulfamethoxazole was associated with serogroup 19 (36.8%). Two isolates (0.8%) were resistant to telithromycin. The frequency of macrolide resistance mechanisms in the Canary Islands is different from that observed in the rest of Spain, particularly in Lanzarote, where 80% of isolates harbored the mefA/E gene and belonged to serogroup 14.

  15. Motivation Counts: Autonomous But Not Obligated Sharing Promotes Happiness in Preschoolers.

    Science.gov (United States)

    Wu, Zhen; Zhang, Zhen; Guo, Rui; Gros-Louis, Julie

    2017-01-01

    Research has demonstrated that prosocial sharing is emotionally rewarding, which leads to further prosocial actions; such a positive feedback loop suggests a proximal mechanism of human's tendency to act prosocially. However, it leaves open a question as to how the emotional benefits from sharing develop in young children and whether sharing under pressure promotes happiness as well. The current study directly compared 3- and 5-year-old Chinese children's happiness when sharing was autonomous (the recipient did not contribute to getting the reward) with when sharing was obligated (the recipient and the actor jointly earned the reward). We found that children shared more items overall when sharing was obligated than autonomous, demonstrating their conformity to social norms of merit-based sharing. In children who eventually shared with others, 5-year-olds gave out more stickers in the obligated sharing condition than in the autonomous sharing condition, but 3-year-olds shared the same amount between the conditions, suggesting that 5-year-olds adhered to the merit-based sharing norm more strictly than 3-year-olds. Moreover, in the autonomous sharing condition, children displayed greater happiness when they shared with the recipient than when they kept stickers for themselves, suggesting that costly prosocial giving benefited children with positive mood; however, children did not gain happiness when they shared with the recipient in the obligated sharing condition. These findings demonstrate that children's affective benefits depend on the motivation underlying their prosocial behavior, and further imply that normative force and emotional gains may independently drive preschoolers' prosocial behaviors.

  16. Motivation Counts: Autonomous But Not Obligated Sharing Promotes Happiness in Preschoolers

    Directory of Open Access Journals (Sweden)

    Zhen Wu

    2017-05-01

    Full Text Available Research has demonstrated that prosocial sharing is emotionally rewarding, which leads to further prosocial actions; such a positive feedback loop suggests a proximal mechanism of human’s tendency to act prosocially. However, it leaves open a question as to how the emotional benefits from sharing develop in young children and whether sharing under pressure promotes happiness as well. The current study directly compared 3- and 5-year-old Chinese children’s happiness when sharing was autonomous (the recipient did not contribute to getting the reward with when sharing was obligated (the recipient and the actor jointly earned the reward. We found that children shared more items overall when sharing was obligated than autonomous, demonstrating their conformity to social norms of merit-based sharing. In children who eventually shared with others, 5-year-olds gave out more stickers in the obligated sharing condition than in the autonomous sharing condition, but 3-year-olds shared the same amount between the conditions, suggesting that 5-year-olds adhered to the merit-based sharing norm more strictly than 3-year-olds. Moreover, in the autonomous sharing condition, children displayed greater happiness when they shared with the recipient than when they kept stickers for themselves, suggesting that costly prosocial giving benefited children with positive mood; however, children did not gain happiness when they shared with the recipient in the obligated sharing condition. These findings demonstrate that children’s affective benefits depend on the motivation underlying their prosocial behavior, and further imply that normative force and emotional gains may independently drive preschoolers’ prosocial behaviors.

  17. Effects of alpha-glucosylhesperidin on the peripheral body temperature and autonomic nervous system.

    Science.gov (United States)

    Takumi, Hiroko; Fujishima, Noboru; Shiraishi, Koso; Mori, Yuka; Ariyama, Ai; Kometani, Takashi; Hashimoto, Shinichi; Nadamoto, Tomonori

    2010-01-01

    We studied the effects of alpha-glucosylhesperidin (G-Hsp) on the peripheral body temperature and autonomic nervous system in humans. We first conducted a survey of 97 female university students about excessive sensitivity to the cold; 74% of them replied that they were susceptible or somewhat susceptible to the cold. We subsequently conducted a three-step experiment. In the first experiment, G-Hsp (500 mg) was proven to prevent a decrease in the peripheral body temperature under an ambient temperature of 24 degrees C. In the second experiment, a warm beverage containing G-Hsp promoted blood circulation and kept the finger temperature higher for a longer time. We finally used a heart-rate variability analysis to study whether G-Hsp changed the autonomic nervous activity. The high-frequency (HF) component tended to be higher, while the ratio of the low-frequency (LF)/HF components tended to be lower after the G-Hsp administration. These results suggest that the mechanism for temperature control by G-Hsp might involve an effect on the autonomic nervous system.

  18. PHM Enabled Autonomous Propellant Loading Operations

    Science.gov (United States)

    Walker, Mark; Figueroa, Fernando

    2017-01-01

    The utility of Prognostics and Health Management (PHM) software capability applied to Autonomous Operations (AO) remains an active research area within aerospace applications. The ability to gain insight into which assets and subsystems are functioning properly, along with the derivation of confident predictions concerning future ability, reliability, and availability, are important enablers for making sound mission planning decisions. When coupled with software that fully supports mission planning and execution, an integrated solution can be developed that leverages state assessment and estimation for the purposes of delivering autonomous operations. The authors have been applying this integrated, model-based approach to the autonomous loading of cryogenic spacecraft propellants at Kennedy Space Center.

  19. Autonomous Control of Space Reactor Systems

    International Nuclear Information System (INIS)

    Belle R. Upadhyaya; K. Zhao; S.R.P. Perillo; Xiaojia Xu; M.G. Na

    2007-01-01

    Autonomous and semi-autonomous control is a key element of space reactor design in order to meet the mission requirements of safety, reliability, survivability, and life expectancy. Interrestrial nuclear power plants, human operators are available to perform intelligent control functions that are necessary for both normal and abnormal operational conditions

  20. Autonomous Control of Space Reactor Systems

    Energy Technology Data Exchange (ETDEWEB)

    Belle R. Upadhyaya; K. Zhao; S.R.P. Perillo; Xiaojia Xu; M.G. Na

    2007-11-30

    Autonomous and semi-autonomous control is a key element of space reactor design in order to meet the mission requirements of safety, reliability, survivability, and life expectancy. Interrestrial nuclear power plants, human operators are avilable to perform intelligent control functions that are necessary for both normal and abnormal operational conditions.

  1. Molecular mechanisms of bortezomib resistant adenocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Erika Suzuki

    Full Text Available Bortezomib (Velcade™ is a reversible proteasome inhibitor that is approved for the treatment of multiple myeloma (MM. Despite its demonstrated clinical success, some patients are deprived of treatment due to primary refractoriness or development of resistance during therapy. To investigate the role of the duration of proteasome inhibition in the anti-tumor response of bortezomib, we established clonal isolates of HT-29 adenocarcinoma cells adapted to continuous exposure of bortezomib. These cells were ~30-fold resistant to bortezomib. Two novel and distinct mutations in the β5 subunit, Cys63Phe, located distal to the binding site in a helix critical for drug binding, and Arg24Cys, found in the propeptide region were found in all resistant clones. The latter mutation is a natural variant found to be elevated in frequency in patients with MM. Proteasome activity and levels of both the constitutive and immunoproteasome were increased in resistant cells, which correlated to an increase in subunit gene expression. These changes correlated with a more rapid recovery of proteasome activity following brief exposure to bortezomib. Increased recovery rate was not due to increased proteasome turnover as similar findings were seen in cells co-treated with cycloheximide. When we exposed resistant cells to the irreversible proteasome inhibitor carfilzomib we noted a slower rate of recovery of proteasome activity as compared to bortezomib in both parental and resistant cells. Importantly, carfilzomib maintained its cytotoxic potential in the bortezomib resistant cell lines. Therefore, resistance to bortezomib, can be overcome with irreversible inhibitors, suggesting prolonged proteasome inhibition induces a more potent anti-tumor response.

  2. Clinical epidemiology and resistance mechanisms of carbapenem-resistant Acinetobacter baumannii, French Guiana, 2008-2014.

    Science.gov (United States)

    Mahamat, Aba; Bertrand, Xavier; Moreau, Brigitte; Hommel, Didier; Couppie, Pierre; Simonnet, Christine; Kallel, Hatem; Demar, Magalie; Djossou, Felix; Nacher, Mathieu

    2016-07-01

    This study investigated the clinical epidemiology and resistance mechanisms of Acinetobacter baumannii and characterised the clonal diversity of carbapenem-resistant A. baumannii (CRAB) during an ICU-associated outbreak at Cayenne Hospital, French Guiana. All non-duplicate A. baumannii isolates from 2008 to 2014 were tested for antibiotic susceptibility by disk diffusion. Multilocus sequence typing, pulsed-field gel electrophoresis (PFGE) and characterisation of carbapenemase-encoding genes were performed on CRAB. Of the 441 A. baumannii isolates, most were from males (54.0%) and were detected mainly from the ICU (30.8%) and medicine wards (21.8%). In the ICU, strains were mainly isolated from the respiratory tract (44.1%) and bloodstream (14.0%), whereas in medicine wards they mainly were from wound/drainage (36.5%) and bloodstream (25.0%). A. baumannii showed the greatest susceptibility to piperacillin/tazobactam (92.7%), imipenem (92.5%), colistin (95.6%) and amikacin (97.2%), being lower in the ICU and medicine wards compared with other wards. An outbreak of OXA-23-producing CRAB occurred in the 13-bed ICU in 2010. CRAB strains were more co-resistant to other antimicrobials compared with non-CRAB. Molecular genetics analysis revealed five sequence types [ST78, ST107 and ST642 and two new STs (ST830 and ST831)]. Analysis of PFGE profiles indicated cross-transmissions of CRAB within the ICU, between the ICU and one medicine ward during transfer of patients, and within that medicine ward. This study provides the first clinical and molecular data of A. baumannii from French Guiana and the Amazon basin. The ICU was the highest risk unit of this nosocomial outbreak of OXA-23-producing CRAB, which could subsequently disseminate within the hospital. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  3. The treatment of autonomic dysfunction in tetanus

    Directory of Open Access Journals (Sweden)

    T van den Heever

    2017-07-01

    Full Text Available We report a case of generalised tetanus in a 50-year-old female patient after sustaining a wound to her right lower leg. She developed autonomic dysfunction, which included labile hypertension alternating with hypotension and sweating. The autonomic dysfunction was treated successfully with a combination of morphine sulphate infusion, magnesium sulphate, and clonidine. She also received adrenaline and phenylephrine infusions as needed for hypotension. We then discuss the pathophysiology, clinical features and treatment options of autonomic dysfunction.

  4. Swarm autonomic agents with self-destruct capability

    Science.gov (United States)

    Hinchey, Michael G. (Inventor); Sterritt, Roy (Inventor)

    2011-01-01

    Systems, methods and apparatus are provided through which in some embodiments an autonomic entity manages a system by generating one or more stay alive signals based on the functioning status and operating state of the system. In some embodiments, an evolvable synthetic neural system is operably coupled to one or more evolvable synthetic neural systems in a hierarchy. The evolvable neural interface receives and generates heartbeat monitor signals and pulse monitor signals that are used to generate a stay alive signal that is used to manage the operations of the synthetic neural system. In another embodiment an asynchronous Alice signal (Autonomic license) requiring valid credentials of an anonymous autonomous agent is initiated. An unsatisfactory Alice exchange may lead to self-destruction of the anonymous autonomous agent for self-protection.

  5. A Primer on Autonomous Aerial Vehicle Design

    Directory of Open Access Journals (Sweden)

    Hugo H. G. Coppejans

    2015-12-01

    Full Text Available There is a large amount of research currently being done on autonomous micro-aerial vehicles (MAV, such as quadrotor helicopters or quadcopters. The ability to create a working autonomous MAV depends mainly on integrating a simultaneous localization and mapping (SLAM solution with the rest of the system. This paper provides an introduction for creating an autonomous MAV for enclosed environments, aimed at students and professionals alike. The standard autonomous system and MAV automation are discussed, while we focus on the core concepts of SLAM systems and trajectory planning algorithms. The advantages and disadvantages of using remote processing are evaluated, and recommendations are made regarding the viability of on-board processing. Recommendations are made regarding best practices to serve as a guideline for aspirant MAV designers.

  6. F-18-FDG-PET in autonomous goiter

    International Nuclear Information System (INIS)

    Boerner, A.R.; Voth, E.; Schicha, H.

    1999-01-01

    Aim: Gain-of-function mutations of the thyrotropin receptor (TSHR) gene have been invoked as one of the major causes of toxic thyroid adenomas. This study evaluates F-18-FDG-PET in these patients. Methods: Twenty patients with focal autonomous nodules and ten with disseminated autonomy were investigated the day before radioiodine therapy. Twenty patients with cancer of the head or neck and normal thyroid function served as controls. Results: F-18-FDG-Uptake was higher in patients than in controls. Focal autonomous nodules were associated with focally enhanced glucose metabolism. Disseminated autonomous goiters showed various patterns of focal or global hypermetabolism. Conclusion: Autonomous thyroid tissue caused by constitutive mutations of the TSH receptor is characterised by simultaneous increases in glucose and iodine metabolism which are correlated. (orig.) [de

  7. On the influence of Ti-Al intermetallic coating architecture on mechanical properties and wear resistance of end mills

    Science.gov (United States)

    Vardanyan, E. L.; Budilov, V. V.; Ramazanov, K. N.; Ataullin, Z. R.

    2017-07-01

    Thin-film wear-resistant coatings are widely used to increase life and efficiency of metal cutting tools. This paper shows the results of a study on the influence of architecture (number, sequence and thickness of layers) of wear-resistant coatings on physical, mechanical and operational properties of end mills. Coatings consisting of alternating Ti-Al/Ti-Al-N layers of equal thickness demonstrated the best physical and mechanical properties. Durability of coated tools when processing materials from chromium-vanadium steel increased twice as compared to uncoated tools.

  8. Autonomic control of body temperature and blood pressure: influences of female sex hormones.

    Science.gov (United States)

    Charkoudian, Nisha; Hart, Emma C J; Barnes, Jill N; Joyner, Michael J

    2017-06-01

    Female reproductive hormones exert important non-reproductive influences on autonomic regulation of body temperature and blood pressure. Estradiol and progesterone influence thermoregulation both centrally and peripherally, where estradiol tends to promote heat dissipation, and progesterone tends to promote heat conservation and higher body temperatures. Changes in thermoregulation over the course of the menstrual cycle and with hot flashes at menopause are mediated by hormonal influences on neural control of skin blood flow and sweating. The influence of estradiol is to promote vasodilation, which, in the skin, results in greater heat dissipation. In the context of blood pressure regulation, both central and peripheral hormonal influences are important as well. Peripherally, the vasodilator influence of estradiol contributes to the lower blood pressures and smaller risk of hypertension seen in young women compared to young men. This is in part due to a mechanism by which estradiol augments beta-adrenergic receptor mediated vasodilation, offsetting alpha-adrenergic vasoconstriction, and resulting in a weak relationship between muscle sympathetic nerve activity and total peripheral resistance, and between muscle sympathetic nerve activity and blood pressure. After menopause, with the loss of reproductive hormones, sympathetic nerve activity, peripheral resistance and blood pressure become more strongly related, and sympathetic nerve activity (which increases with age) becomes a more important contributor to the prevailing level of blood pressure. Continuing to increase our understanding of sex hormone influences on body temperature and blood pressure regulation will provide important insight for optimization of individualized health care for future generations of women.

  9. Autonomic composite hydrogels by reactive printing: materials and oscillatory response.

    Science.gov (United States)

    Kramb, R C; Buskohl, P R; Slone, C; Smith, M L; Vaia, R A

    2014-03-07

    Autonomic materials are those that automatically respond to a change in environmental conditions, such as temperature or chemical composition. While such materials hold incredible potential for a wide range of uses, their implementation is limited by the small number of fully-developed material systems. To broaden the number of available systems, we have developed a post-functionalization technique where a reactive Ru catalyst ink is printed onto a non-responsive polymer substrate. Using a succinimide-amine coupling reaction, patterns are printed onto co-polymer or biomacromolecular films containing primary amine functionality, such as polyacrylamide (PAAm) or poly-N-isopropyl acrylamide (PNIPAAm) copolymerized with poly-N-(3-Aminopropyl)methacrylamide (PAPMAAm). When the films are placed in the Belousov-Zhabotinsky (BZ) solution medium, the reaction takes place only inside the printed nodes. In comparison to alternative BZ systems, where Ru-containing monomers are copolymerized with base monomers, reactive printing provides facile tuning of a range of hydrogel compositions, as well as enabling the formation of mechanically robust composite monoliths. The autonomic response of the printed nodes is similar for all matrices in the BZ solution concentrations examined, where the period of oscillation decreases in response to increasing sodium bromate or nitric acid concentration. A temperature increase reduces the period of oscillations and temperature gradients are shown to function as pace-makers, dictating the direction of the autonomic response (chemical waves).

  10. Autonomous Vision-Based Tethered-Assisted Rover Docking

    Science.gov (United States)

    Tsai, Dorian; Nesnas, Issa A.D.; Zarzhitsky, Dimitri

    2013-01-01

    Many intriguing science discoveries on planetary surfaces, such as the seasonal flows on crater walls and skylight entrances to lava tubes, are at sites that are currently inaccessible to state-of-the-art rovers. The in situ exploration of such sites is likely to require a tethered platform both for mechanical support and for providing power and communication. Mother/daughter architectures have been investigated where a mother deploys a tethered daughter into extreme terrains. Deploying and retracting a tethered daughter requires undocking and re-docking of the daughter to the mother, with the latter being the challenging part. In this paper, we describe a vision-based tether-assisted algorithm for the autonomous re-docking of a daughter to its mother following an extreme terrain excursion. The algorithm uses fiducials mounted on the mother to improve the reliability and accuracy of estimating the pose of the mother relative to the daughter. The tether that is anchored by the mother helps the docking process and increases the system's tolerance to pose uncertainties by mechanically aligning the mating parts in the final docking phase. A preliminary version of the algorithm was developed and field-tested on the Axel rover in the JPL Mars Yard. The algorithm achieved an 80% success rate in 40 experiments in both firm and loose soils and starting from up to 6 m away at up to 40 deg radial angle and 20 deg relative heading. The algorithm does not rely on an initial estimate of the relative pose. The preliminary results are promising and help retire the risk associated with the autonomous docking process enabling consideration in future martian and lunar missions.

  11. Affective Synchrony and Autonomic Coupling during Cooperation: A Hyperscanning Study

    Directory of Open Access Journals (Sweden)

    Maria Elide Vanutelli

    2017-01-01

    Full Text Available Previous research highlighted that during social interactions people shape each other’s emotional states by resonance mechanisms and synchronized autonomic patterns. Starting from the idea that joint actions create shared emotional experiences, in the present study a social bond was experimentally induced by making subjects cooperate with each other. Participants’ autonomic system activity (electrodermal: skin conductance level and response: SCL, SCR; cardiovascular indices: heart rate: HR was continuously monitored during an attentional couple game. The cooperative motivation was induced by presenting feedback which reinforced the positive outcomes of the intersubjective exchange. 24 participants coupled in 12 dyads were recruited. Intrasubject analyses revealed higher HR in the first part of the task, connoted by increased cognitive demand and arousing social dynamic, while intersubject analysis showed increased synchrony in electrodermal activity after the feedback. Such results encourage the use of hyperscanning techniques to assess emotional coupling in ecological and real-time paradigms.

  12. Mechanical and thermal resistance of multi-material components for ITER

    International Nuclear Information System (INIS)

    Burlet, H.

    2013-01-01

    The First Wall panels for ITER are complex parts composed of stainless steel, copper and beryllium [1]. These materials are joined using diffusion bonding technique. The stainless steel is a commonly used in nuclear reactors 316LN material and acts as a structural material. The copper alloy is a CuCrZr material which acts as a heat sink. The beryllium consisting in tiles and layer is used as the protective plasma facing material. The fabrication of these panels is performed through 2 main steps. The first step consists in welding all together a bi-metallic support structure made from a thick CuCrZr plate embedded with 316LN tubes and bonded to a thick 316LN backing plate with cooling channels. The bonding is performed in a HIP (Hot Isostatic Pressure) facility. The second step is performed at a lower temperature and aims at simultaneously welding by HIP Be onto CuCrZr and ageing the CuCrZr heat sink to obtain the correct mechanical resistance of this alloy reinforced by precipitates. The various joints 316LN/316LN, 316LN/CuCrZr, and CuCrZr/Be are then characterized [2] from a microstructural point of view and by mechanical tests. It is quite hard to characterize the strength of a diffusion bonded joints. Standard tests may be used for homogeneous joints whereas specific tests have been developed to characterize the heterogeneous bonds. To optimize the bond, we performed mainly impact and tensile bi-material tests (Fig 1). Once the manufacture parameters have been optimized, advanced mechanical tests are performed based on Bimetallic CT specimens, axisymmetric notched specimens, 4P bending specimens. Numerical simulations are required to analyse the mechanical response. In order to characterize the fatigue resistance of the joints, specific mock-ups have been designed by the European Fusion Development Agreement EFDA team (Fig 2). Results of heat flux testing will be reviewed for the various joints. The assembly of heterogeneous materials by Hipping is very complex

  13. Acinetobacter spp. Infections in Malaysia: A Review of Antimicrobial Resistance Trends, Mechanisms and Epidemiology.

    Science.gov (United States)

    Mohd Rani, Farahiyah; A Rahman, Nor Iza; Ismail, Salwani; Alattraqchi, Ahmed Ghazi; Cleary, David W; Clarke, Stuart C; Yeo, Chew Chieng

    2017-01-01

    Acinetobacter spp. are important nosocomial pathogens, in particular the Acinetobacter baumannii - calcoaceticus complex, which have become a global public health threat due to increasing resistance to carbapenems and almost all other antimicrobial compounds. High rates of resistance have been reported among countries in Southeast Asia, including Malaysia. In this review, we examine the antimicrobial resistance profiles of Acinetobacter spp. hospital isolates from Malaysia over a period of nearly three decades (1987-2016) with data obtained from various peer-reviewed publications as well as the Malaysian National Surveillance on Antibiotic Resistance (NSAR). NSAR data indicated that for most antimicrobial compounds, including carbapenems, the peak resistance rates were reached around 2008-2009 and thereafter, rates have remained fairly constant (e.g., 50-60% for carbapenems). Individual reports from various hospitals in Peninsular Malaysia do not always reflect the nationwide resistance rates and often showed higher rates of resistance. We also reviewed the epidemiology and mechanisms of resistance that have been investigated in Malaysian Acinetobacter spp. isolates, particularly carbapenem resistance and found that bla OXA-23 is the most prevalent acquired carbapenemase-encoding gene. From the very few published reports and whole genome sequences that are available, most of the Acinetobacter spp. isolates from Malaysia belonged to the Global Clone 2 (GC2) CC92 group with ST195 being the predominant sequence type. The quality of data and analysis in the national surveillance reports could be improved and more molecular epidemiology and genomics studies need to be carried out for further in-depth understanding of Malaysian Acinetobacter spp. isolates.

  14. Autonomic symptoms in idiopathic REM behavior disorder

    DEFF Research Database (Denmark)

    Ferini-Strambi, Luigi; Oertel, Wolfgang; Dauvilliers, Yves

    2014-01-01

    Patients with idiopathic REM sleep behavior disorder (iRBD) are at very high risk of developing neurodegenerative synucleinopathies, which are disorders with prominent autonomic dysfunction. Several studies have documented autonomic dysfunction in iRBD, but large-scale assessment of autonomic...... symptoms has never been systematically performed. Patients with polysomnography-confirmed iRBD (318 cases) and controls (137 healthy volunteers and 181 sleep center controls with sleep diagnoses other than RBD) were recruited from 13 neurological centers in 10 countries from 2008 to 2011. A validated scale...

  15. Bilateral human-robot control for semi-autonomous UAV navigation

    NARCIS (Netherlands)

    Wopereis, Han Willem; Fumagalli, Matteo; Stramigioli, Stefano; Carloni, Raffaella

    2015-01-01

    This paper proposes a semi-autonomous bilateral control architecture for unmanned aerial vehicles. During autonomous navigation, a human operator is allowed to assist the autonomous controller of the vehicle by actively changing its navigation parameters to assist it in critical situations, such as

  16. Effects of insula resection on autonomic nervous system activity

    NARCIS (Netherlands)

    de Morree, Helma; Rutten, Geert-Jan; Szabo, B.M.; Sitskoorn, Margriet; Kop, Wijo

    2016-01-01

    Background: The insula is an essential component of the central autonomic network and plays a critical role in autonomic regulation in response to environmental stressors. The role of the insula in human autonomic regulation has been primarily investigated following cerebrovascular accidents, but

  17. Autonomous Cryogenics Loading Operations Simulation Software: Knowledgebase Autonomous Test Engineer

    Science.gov (United States)

    Wehner, Walter S., Jr.

    2013-01-01

    Working on the ACLO (Autonomous Cryogenics Loading Operations) project I have had the opportunity to add functionality to the physics simulation software known as KATE (Knowledgebase Autonomous Test Engineer), create a new application allowing WYSIWYG (what-you-see-is-what-you-get) creation of KATE schematic files and begin a preliminary design and implementation of a new subsystem that will provide vision services on the IHM (Integrated Health Management) bus. The functionality I added to KATE over the past few months includes a dynamic visual representation of the fluid height in a pipe based on number of gallons of fluid in the pipe and implementing the IHM bus connection within KATE. I also fixed a broken feature in the system called the Browser Display, implemented many bug fixes and made changes to the GUI (Graphical User Interface).

  18. Investigating the mechanisms of glyphosate resistance in goosegrass (Eleusine indica (L.) Gaertn.) by RNA sequencing technology.

    Science.gov (United States)

    Chen, Jingchao; Huang, Hongjuan; Wei, Shouhui; Huang, Zhaofeng; Wang, Xu; Zhang, Chaoxian

    2017-01-01

    Glyphosate is an important non-selective herbicide that is in common use worldwide. However, evolved glyphosate-resistant (GR) weeds significantly affect crop yields. Unfortunately, the mechanisms underlying resistance in GR weeds, such as goosegrass (Eleusine indica (L.) Gaertn.), an annual weed found worldwide, have not been fully elucidated. In this study, transcriptome analysis was conducted to further assess the potential mechanisms of glyphosate resistance in goosegrass. The RNA sequencing libraries generated 24 597 462 clean reads. De novo assembly analysis produced 48 852 UniGenes with an average length of 847 bp. All UniGenes were annotated using seven databases. Sixteen candidate differentially expressed genes selected by digital gene expression analysis were validated by quantitative real-time PCR (qRT-PCR). Among these UniGenes, the EPSPS and PFK genes were constitutively up-regulated in resistant (R) individuals and showed a higher copy number than that in susceptible (S) individuals. The expressions of four UniGenes relevant to photosynthesis were inhibited by glyphosate in S individuals, and this toxic response was confirmed by gas exchange analysis. Two UniGenes annotated as glutathione transferase (GST) were constitutively up-regulated in R individuals, and were induced by glyphosate both in R and S. In addition, the GST activities in R individuals were higher than in S. Our research confirmed that two UniGenes (PFK, EPSPS) were strongly associated with target resistance, and two GST-annotated UniGenes may play a role in metabolic glyphosate resistance in goosegrass. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

  19. Whole transcriptome analysis reveals potential novel mechanisms of low-level linezolid resistance in Enterococcus faecalis.

    Science.gov (United States)

    Hua, Ruoyi; Xia, Yun; Wu, Wenyao; Yan, Jia; Yang, Mi

    2018-03-20

    Linezolid is an oxazolidinone antibiotic commonly used to treat serious infections caused by vancomycin-resistant enterococcus. Recently, low-level linezolid resistant Enterococcus faecalis strains have emerged worldwide, but the resistant mechanisms remain undefined. Whole-transcriptome profiling was performed on an E. faecalis strain P10748 with low-level linezolid resistance in comparison with a linezolid-susceptible strain 3138 and the standard control strain ATCC29212. The functions of differentially expressed genes (DEGs) were predicted, with some DEGs potentially involved in drug resistance were validated by PCR and quantitative PCR (qPCR). RNA-Seq on three E. faecalis strains generated 1920 unigenes, with 98% of them assigned to various function groups. A total of 150 DEGs were identified in the linezolid resistant strain P10748 compared to the linezolid susceptible strains 3138 and ATCC29212. Functional analysis indicated a significant transcriptomic shift to membrane transportation and biofilm formation in strain P10748, with three significantly up-regulated DEGs predicted to be associated with drug resistance through active efflux pumps and biofilm formation. The existence of these three DEGs was further confirmed by PCR and qPCR. The significant upregulation of genes associated with efflux pumps and biofilm formation in the linezolid resistant strain suggests their roles in low-level resistance to linezolid in E. faecalis. Copyright © 2018. Published by Elsevier B.V.

  20. Azole resistance in Candida spp. isolated from Catú Lake, Ceará, Brazil: an efflux-pump-mediated mechanism

    Directory of Open Access Journals (Sweden)

    Raimunda S.N. Brilhante

    2016-03-01

    Full Text Available Abstract Since, there is no study reporting the mechanism of azole resistance among yeasts isolated from aquatic environments; the present study aims to investigate the occurrence of antifungal resistance among yeasts isolated from an aquatic environment, and assess the efflux-pump activity of the azole-resistant strains to better understand the mechanism of resistance for this group of drugs. For this purpose, monthly water and sediment samples were collected from Catú Lake, Ceará, Brazil, from March 2011 to February 2012. The obtained yeasts were identified based on morphological and biochemical characteristics. Of the 46 isolates, 37 were Candida spp., 4 were Trichosporon asahii, 3 were Cryptococcus laurentii, 1 Rhodotorula mucilaginosa, and 1 was Kodamaea ohmeri. These isolates were subjected to broth microdilution assay with amphotericin B, itraconazole, and fluconazole, according to the methodology standardized by the Clinical and Laboratory Standards Institute (CLSI. The minimum inhibitory concentrations (MICs of amphotericin B, itraconazole, and fluconazole were 0.03125–2 µg/mL, 0.0625 to ≥16 µg/mL, and 0.5 to ≥64 µg/mL, respectively, and 13 resistant azole-resistant Candida isolates were detected. A reduction in the azole MICs leading to the phenotypical reversal of the azole resistance was observed upon addition of efflux-pump inhibitors. These findings suggest that the azole resistance among environmental Candida spp. is most likely associated with the overexpression of efflux-pumps.